what is the benefits of utrogeson combined with ecotrin in the first trimester of pregnancy
 

Pills
 

ED Pills

ED Drugs
 

Revascularization Procedures, Prophylaxis Medications



Aseptic Necrosis Medications



Heart Attack (Myocardial Infarction) Medications


Definition of Heart Attack: A heart attack (myocardial infarction) occurs when an area of heart muscle dies or is permanently damaged because of an inadequate supply of oxygen to that area.

Drugs associated with Heart Attack

The following drugs and medications are in some way related to, or used in the treatment of Heart Attack. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

See sub-topics

Topics under Heart Attack Myocardial Infarction, Prophylaxis (39 drugs) Post MI Syndrome (0 drugs) Learn more about Heart Attack (Myocardial Infarction)

Micromedex Care Notes:

Acute Coronary Syndromes Myocardial Infarction

Medical Encyclopedia:

Anesthesia Heart attack

Harvard Health Guide:

Symptoms and treatment for Heart Attack (Myocardial Infarction)
Drug List: Abbokinase Aceon Activase Altace Arthritis-Pain Arthritis-Pain-Formula Ascriptin Ascriptin-Maximum-Strength Aspergum-Gum Aspir-81 Aspir-Low Aspirin-Buffered Aspirin-Lite-Coat Aspirin-Low-Dose Aspiritab Bayer Bayer-Plus Bayer-Low-Adult-Strength-Controlled-Release-Tablets Bayer-Aspirin-With-Calcium Blocadren Buffered-Aspirin Bufferin Bufferin-Arthritis-Strength Bufferin-Extra-Strength Chloromag Coumadin Easprin Ecotrin-Delayed-Release-Tablets Ecotrin-Adult-Low-Strength Ecotrin-Maximum-Strength Empirin Fasprin Fragmin Genacote Halfprin Heparin-Sodium Inderal Integrilin Jantoven Kinlytic Litecoat-Aspirin Lopressor Lovenox Mag-64 Mag-Sr-Sustained-Release-Tablets Mag-Delay Mavik Medi-Seltzer-Effervescent-Tablets Metoprolol-Succinate-Er Minitran-Patch Nitrek-Transdermal Nitro-Td-Patch-A-Transdermal Nitro-Bid-Ointment Nitro-Dur-Patch Nitro-Time-Controlled-Release-Capsules Nitrocot Nitrogard Nitrol-Appli-Kit-Topical Nitrolingual-Pumpspray-Spray Nitromist Nitroquick Nitrostat Norwich-Aspirin Plavix Prinivil Retavase Retavase-Half-Kit Slow-Mag-Sustained-Release-Tablets St-Joseph-Aspirin-Adult-Ec St-Joseph-Aspirin-Adult-Chewable St-Joseph-81-Mg-Adult-Chewable-Tablets Stanback-Analgesic Streptase Tenormin Tnkase Transderm-Nitro Tri-Buffered-Aspirin Univasc Ysp-Aspirin Zestril Zorprin-Controlled-Release-Tablets
read more / Download


Osteoarthritis Medications


Definition of Osteoarthritis: Osteoarthritis is a chronic disease causing deterioration of the joint cartilage (the softer parts of bones, which cushion their connections to each other) and the formation of new bone (bone spurs) at the margins of the joints.

Drugs associated with Osteoarthritis

The following drugs and medications are in some way related to, or used in the treatment of Osteoarthritis. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Learn more about Osteoarthritis

Medical Encyclopedia:

Osteoarthritis

Harvard Health Guide:

Symptoms and treatment for Osteoarthritis

Drugs.com Health Center:

Osteoarthritis
Drug List: A-G-Profen A-Methapred-Solution Aceta-W-Codeine Actiprofen Actron Addaprin Advil Advil-Liqui-Gels Aflaxen Aleve All-Day-Pain-Relief All-Day-Relief Amigesic Amino-Opti-C Anaprox Anaprox-Ds Ansaid Aristocort Aristocort-Forte Arthritis-Pain Arthritis-Pain-Formula Arthrotec Ascriptin Ascriptin-Maximum-Strength Aspercreme-Cream Aspergum-Gum Aspirin-Buffered Aspirin-Lite-Coat Aspiritab Axsain-Cream Bayer Bayer-Plus Bayer-Aspirin-With-Calcium Bextra Buffered-Aspirin Bufferin Bufferin-Arthritis-Strength Bufferin-Extra-Strength Capital-W-Codeine-Suspension Capital-With-Codeine-Suspension Capsicum-Oleoresin Capsin Capzasin-Liquid Capzasin-Back-And-Body Capzasin-Quick-Relief Capzasin-Hp Capzasin-Hp-Arthritis-Formula Capzasin-P-Cream Castiva-Warming-Lotion Cataflam Celebrex Celestone-Solution Celestone-Soluspan Choline-Magnesium-Trisalicylate Clinacort-Injection Clinalog-Injection Clinoril Cocet Cocet-Plus Comfort-Pac-With-Naproxen Cortone-Acetate Cosamin-Ds Cosmegen Cymbalta Daypro Deltasone Depo-Medrol-Suspension Disalcid Dolobid Dolorac Dr-S-Cream Duexis Easprin Ec-Naprosyn-Enteric-Coated-Tablets Ecotrin-Delayed-Release-Tablets Ecotrin-Adult-Low-Strength Ecotrin-Maximum-Strength Empirin Euflexxa Excedrin Excedrin-Extra-Strength Excedrin-Quick-Tab-Peppermint Excedrin-Tension-Headache Ez-Iii Fasprin Feldene Genace Genacote Genpril Glucosamine-Chondroitin-With-Msm Gnp-Capsaicin-Lotion Goodys-Extra-Strength Halfprin Haltran Hyalgan Ibu Ibu-200 Icyhot-Pm-Medicated-Patch Indocin Indocin-Iv Indocin-Sr-Sustained-Release-Capsules Ken-Jec-40-Injection Kenalog-10-Suspension Kenalog-40-Suspension Leader-Naproxen-Sodium Limbrel Limbrel-250 Limbrel-500 Litecoat-Aspirin Lodine Lodine-Xl Medi-Seltzer-Effervescent-Tablets Medrol Medrol-Dosepak Menthac-Arthritis-Cream-With-Capsaicin Methylprednisolone-Dose-Pack Meticorten Midol-Extended-Relief Midol-Ib Mobic Motrin Motrin-Ib Myoflex-Cream Nalfon Naprelan-Sustained-Release-Tablets Naprosyn Norwich-Aspirin Nuprin Orthovisc Orudis Orudis-Kt Oruvail-Extended-Release-Capsules Osteo-Bi-Flex Osteo-Bi-Flex-Advanced Osteo-Bi-Flex-Double-Strength Osteo-Bi-Flex-Plus-Msm Osteo-Bi-Flex-Triple-Strength P-1000 Pan-C-500 Pennsaid Peridin-C Prevacid_Naprapac Prevacid-Naprapac-375 Prevacid-Naprapac-500 Pryflex Q-Profen Qutenza Relafen Relamine Rt-Capsin Rutin Salflex Salonpas-Gel-Patch Salonpas-Pain-Patch-With-Capsaicin Salsitab Same Schiff-Move-Free Schiff-Move-Free-Caplets Sloan-S-Liniment Solu-Medrol-Solution Span-C Stanback-Analgesic Sterapred Sterapred-Ds Supac Supartz Synvisc Synvisc-One Tac-3-Injection Tolectin Tolectin-600 Tolectin-Ds Tri-Buffered-Aspirin Triam-Forte Triamcot-Injection Triamonide-40-Injection Tricosal Trilisate Trixaicin Trixaicin-Hp Tylenol-W-Codeine Tylenol-With-Codeine-3 Tylenol-With-Codeine-4 U-Tri-Lone-Injection Valorin-Extra Vimovo Vioxx Voltaren Voltaren-Gel Voltaren-Xr-Extended-Release-Tablets Vopac Ysp-Aspirin Zorprin-Controlled-Release-Tablets Zostrix-Cream Zostrix-Diabetic-Foot-Pain Zostrix-Foot-Pain Zostrix-Neuropathy Zostrix-Sports Zostrix-Hp
read more / Download


Aquamephyton


Generic Name: phytonadione (fye toe na DYE own)
Brand Names: Mephyton, Vitamin K1

What is Aquamephyton (phytonadione)?

Phytonadione is a man-made form of vitamin K. Phytonadione is important in the production of substances that cause the blood to clot.

Phytonadione is used to treat vitamin K deficiency and to treat certain bleeding or blood clotting problems.

Phytonadione may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Aquamephyton (phytonadione)?

Tell your doctor and dentist that you are taking phytonadione before having any type of surgery.

What should I discuss with my healthcare provider before taking Aquamephyton (phytonadione)?

Phytonadione may affect other medical conditions or treatments. Talk to your doctor before taking phytonadione if you have other health problems or conditions, or if you take other medications.

Phytonadione is in the FDA pregnancy category C. This means that it is not known whether phytonadione will be harmful to an unborn baby. Do not take phytonadione without first talking to your doctor if you are pregnant or could become pregnant during treatment. It is not known whether phytonadione passes into breast milk and if it will affect a nursing baby. Do not take this medication without first talking to your doctor if you are breast-feeding a baby. How should I take Aquamephyton (phytonadione)?

Take phytonadione exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

Take each oral dose with a full glass of water.

Injectable forms of phytonadione are usually administered by a healthcare professional. If you are injecting phytonadione at home, your doctor or nurse will give you detailed instructions regarding preparation, administration, and storage of the medication.

Do not take more phytonadione than is prescribed.

It is important to take phytonadione regularly to get the most benefit.

Your doctor may want you to have blood tests or other medical evaluations during treatment with phytonadione to monitor progress and side effects.

Store phytonadione at room temperature away from moisture and heat. Protect phytonadione from light, as light decreases the effectiveness of the medication. What happens if I miss a dose?

Contact your doctor if you miss a dose of this medication.

What happens if I overdose? Seek emergency medical attention if an overdose is suspected.

Symptoms of a phytonadione overdose are not known.

What should I avoid while taking Aquamephyton (phytonadione)?

Tell your doctor and dentist that you are taking phytonadione before having any type of surgery.

Aquamephyton (phytonadione) side effects Seek emergency medical attention or contact your doctor immediately if you experience any serious side effects from phytonadione such as:

an allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives);

dizziness;

fast or irregular heartbeats; or

increased sweating.

Other less serious side effects may be more likely to occur. Continue to use phytonadione and talk to your doctor if you experience

flushing of the face;

an unusual taste in the mouth; or

pain or irritation at the injection site (injectable form).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Aquamephyton (phytonadione)?

Before taking phytonadione, tell your doctor about all other medicines you are taking, especially any of the following:

warfarin (Coumadin);

mineral oil;

orlistat (Xenical);

cholestyramine (Questran, Prevalite);

a salicylate such as aspirin (Acuprin, Ecotrin, Ascriptin, Bayer, others); choline salicylate and/or magnesium salicylate (Magan, Doan's, Bayer Select Backache Pain Formula, Mobidin, Arthropan, Trilisate, Tricosal), or salsalate (Disalcid);

a nonsteroidal anti-inflammatory drug (NSAID) such as ibuprofen (Motrin, Advil, Nuprin, others), ketoprofen (Orudis, Orudis KT, Oruvail), naproxen (Naprosyn, Anaprox, Aleve), diclofenac (Voltaren, Cataflam), nabumetone (Relafen), oxaprozin (Daypro), piroxicam (Feldene), etodolac (Lodine), fenoprofen (Nalfon), flurbiprofen (Ansaid), indomethacin (Indocin), ketorolac (Toradol), sulindac (Clinoril), or tolmetin (Tolectin); or

an antibiotic.

You may not be able to take phytonadione, or you may require a dosage adjustment or special monitoring during treatment.

Medications other than those listed here may also interact with phytonadione. Tell your doctor about all other prescription and over-the-counter medicines that you take, including vitamins, minerals, and herbal products.

More Aquamephyton resources Aquamephyton Side Effects (in more detail)Aquamephyton Use in Pregnancy & BreastfeedingAquamephyton Drug InteractionsAquamephyton Support Group0 Reviews for Aquamephyton - Add your own review/rating Phytonadione Prescribing Information (FDA) Phytonadione Monograph (AHFS DI) Phytonadione MedFacts Consumer Leaflet (Wolters Kluwer) Mephyton Advanced Consumer (Micromedex) - Includes Dosage Information Mephyton Prescribing Information (FDA) Mephyton MedFacts Consumer Leaflet (Wolters Kluwer) Vitamin K1 Prescribing Information (FDA) Compare Aquamephyton with other medications Hypoprothrombinemia, Anticoagulant InducedHypoprothrombinemia, Not Associated with Anticoagulant TherapyHypoprothrombinemia, ProphylaxisVitamin K Deficiency Where can I get more information? Your pharmacist has more information about phytonadione written for health professionals that you may read.

See also: Aquamephyton side effects (in more detail)


read more / Download


H. pylori eradication agents


A drug may be classified by the chemical type of the active ingredient or by the way it is used to treat a particular condition. Each drug can be classified into one or more drug classes.

Agents used in treatment of Helicobacter Pylori are medicines used for stomach acid inhibition, combined with antibacterial agents. Treatment is for one week with a proton pump inhibitor or an antacid (or antisecretory agents), and two appropriate antibacterial agents. This one week triple therapy does give a good eradication rate.

See also

Medical conditions associated with H. pylori eradication agents:

Helicobacter Pylori Infection Drug List: Prevpac-Therapy-Pack Pylera Helidac-Therapy-Pack
read more / Download


Aspirin


Class: Salicylates
VA Class: CN103
CAS Number: 50-78-2
Brands: Aggrenox, Alka-Seltzer, Anacin, Ascriptin, Ascomp, Aspergum, Bayer, BC Powder, Bufferin, Cope, Damason-P, Darvon, Easprin, Ecotrin, Endodan, Equagesic, Fiorinal, Fortabs, Gelpirin, Genacote, Goody’s, Halfprin, Lanorinal, Micrainin, Norgesic, Percodan, Soma Compound, St. Joseph, Stanbeck Powder, Synalgos-DC, Vanquish, ZORprin

Introduction

NSAIA; salicylate ester of acetic acid.a

Uses for Aspirin Pain

Symptomatic relief of mild to moderate pain.a

Self-medication in children for the temporary relief of minor aches and pains and headache.841

Self-medication in adolescents and adults for the temporary relief of minor aches and pains associated with headache, common cold, toothache, muscular aches, backache, arthritis, menstrual cramps,836 and sore throat.837 840

Self-medication in fixed combination with acetaminophen and caffeine for the temporary relief of mild to moderate pain associated with migraine headache;701 702 703 also can be used for the treatment of severe migraine headache if previous attacks have responded to similar non-opiate analgesics or NSAIAs.701 702 703 778

Fever

Self-medication for reduction of fever associated with colds, sore throats, and teething.837 841 (See Contraindications and see Pediatric Use under Cautions.)

Inflammatory Diseases

Symptomatic treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, spondyloarthropathies, and systemic lupus erythematosus (SLE).a c l m

Rheumatic Fever

Symptomatic treatment of rheumatic fever†.a A drug of choice in patients with mild carditis (without cardiomegaly or CHF, with or without polyarthritis) or with polyarthritis only.h

TIAs and Acute Ischemic Stroke

Reduction of the risk of recurrent TIAs and stroke or death in patients who have had single or multiple TIAs or ischemic stroke (secondary prevention).c 646 682 691 737 818 842 881 m

Prevention of TIAs and stroke in patients undergoing carotid endarterectomy.646 690 769 828 m In patients with asymptomatic or recurrent carotid stenosis who are not candidates for surgery, lifelong prophylaxis with aspirin is recommended by American College of Chest Physicians (ACCP).828

Aspirin, dipyridamole and aspirin, or clopidogrel all considered acceptable options by ACCP, AHA and other clinicians for initial therapy in adults;818 881 in children, aspirin recommended following discontinuance of anticoagulation (e.g., unfractionated or LMW heparin, warfarin).825

Also used in fixed combination with extended-release dipyridamole to reduce the risk of recurrent stroke, death from all vascular causes, or nonfatal MI in patients who have had TIAs or completed ischemic stroke caused by thrombosis.691 716 738 739 743 881 883

Aspirin and dipyridamole combination or clopidogrel monotherapy may be preferable to aspirin monotherapy for secondary prevention based on somewhat greater absolute risk reduction for stroke; weigh benefit against additional costs of therapy.818

Acute treatment of ischemic stroke† when thrombolytic therapy is contraindicated or not indicated.691 699 700 716 818 862 May be safely used with low-dose sub-Q heparin to prevent DVT in such patients.818

Secondary Prevention of CAD and MI

Recommended by ACCP for reduction of the risk of vascular events in all patients with CAD regardless of the presence or absence of clinical manifestations.820 823 828 867

Reduction of the risk of vascular mortality in patients with suspected acute ST-segment elevation MI (AMI).c 579 635 636 646 669 742 765 819 820 821 m

Reduction of the risk of stroke and recurrent infarction in patients surviving an MI (secondary prevention).c 579 635 646 669 742 765 820 821 842 m

Recommended by ACCP for use as monotherapy in low- to moderate-risk post-MI patients in most health-care settings.820

Recommended by American Diabetes Association (ADA) for the prevention of cardiovascular events in diabetic patients who have evidence of large-vessel disease (e.g., history of MI, CABG, stroke or TIA, peripheral vascular disease, claudication, angina). 830 901

Recommended by ACCP for use in combination with short-term oral anticoagulation (e.g., warfarin therapy) in high-risk, post-MI patients (e.g., anterior MI or acute MI with severe left ventricular dysfunction, congestive heart failure, previous emboli, or echocardiographic evidence of mural thrombosis).820

Recommend by ACC and AHA for short-term use in combination withwarfarin in patients with left ventricular thrombus and for long-term use in patients without an increased risk for bleeding.821

Recommended by ACC and AHA for use in combination with long-term warfarin therapy in patients without coronary stents in whom other indications for anticoagulation exist (e.g., atrial fibrillation,cerebral emboli, extensive wall-motion abnormality).821

Recommended by ACCP for use in combination with long-term oral anticoagulation (e.g., warfarin therapy) in post-MI patients where meticulous INR monitoring is standard and routinely accessible.820

Has been used in combination with clopidogrel and other standard therapy (e.g., thrombolytic agents, heparin) during acute MI to reduce mortality, recurrent MI, recurrent ischemia, or stroke.852 853 854 855 856 862

Primary Prevention of CAD and MI

May reduce the risk of a first MI† in certain patient populations (primary prevention).573 574 575 576 658 659 660 661 666 667 668 669 670 671 783 785 786 820 848 851 Balance of risks and benefits is most favorable in patients at moderate to high risk of CHD783 820 (based on age and 10-year risk of cardiac event >10%).668 669 820 832 Use of aspirin in such patients is suggested over either warfarin or no antithrombotic therapy.820

Recommended by ADA for primary prevention in patients with type 1 or type 2 diabetes mellitus who are at high risk for cardiovascular events (i.e., familial history of CHD, smoking, hypertension, obesity, albuminuria, elevated blood cholesterol or triglyceride concentrations) and in whom aspirin is not contraindicated.760 830 901

Benefit appears to be minimal or lacking in women at low risk for CHD, except possibly those ?65 years of age; further study needed.846 847 848 849 850 851

Not currently recommended for primary prevention in the general population without known risk factors.646 658 661 662 669 674 675 676 783 784 847

Unstable Angina or Non-ST-Segment Elevation MI

Reduction of the risk of death and/or nonfatal MI in patients with unstable angina or non-ST-segment elevation (NSTE) acute coronary syndromes (ACSs).c 581 613 614 615 616 617 618 619 620 621 669 682 684 728 736 740 765 775 820 m ACCP recommends use with low molecular weight heparins over unfractionated heparin for the acute treatment of patients with NSTE ACSs.820

In patients with unstable angina or NSTE ACS who are not at high risk for bleeding, ACC and AHA recommend adding clopidogrel to aspirin and heparin therapy for reduction of cardiovascular and cerebrovascular events.765 768 771 820 823 824 833 865 866 867 868 905

In patients with unstable angina and moderate to high-risk features, use in combination with other antiplatelet therapies (e.g., tirofiban, eptifibatide) and heparin recommended by ACC, AHA, and ACCP.820 833

Chronic Stable Angina

Reduction of the risk of MI and/or sudden death in patients with chronic stable angina.c 646 669 680 728 736 820 822 m

May administer with clopidogrel in selected high-risk patients with chronic stable angina.820

Percutaneous Coronary Intervention and Revascularization Procedures

Reduction of cardiovascular risks (e.g., early ischemic complications, graft closure) in patients undergoing percutaneous coronary intervention (PCI) including coronary angioplastyc 646 686 824 865 866 or stent implantation, 686 824 865 866 886 887 888 889 m or CABG.c 646 683 685 781 782 823 m

Pretreatment with aspirin prior to PCI recommended by ACC and AHA.865 867 Adjunctive therapy with a loading dose of a thienopyridine derivative is preferred by ACCP over systemic anticoagulant therapy prior to the procedure.771 824 865

For patients unable to tolerate aspirin, ACC and AHA suggest pretreatment with clopidogrel,865 866 while ACCP suggests pretreatment with clopidogrel or ticlopidine prior to planned PCI.771 824

Continue low-dose aspirin therapy indefinitely as secondary prevention against cardiovascular events following PCI.824 865 867 880 No evidence that such long-term therapy affects the rate of restenosis.686 771 824

Recommended by ACC and AHA in combination with clopidogrel as short-term prophylaxis (?1 month), preferably long-term prophylaxis (?1 year) after PCI in patients with bare-metal stents who are not at high risk for bleeding.821 865 867

Prolonged prophylaxis (?12 months) in combination with a thienopyridine derivative strongly recommended after PCI in patients with drug-eluting stents (DES) who are not at high risk of bleeding.886 887 888 890 891 892 894 902 (See Thrombosis Associated with Drug-eluting Stents under Cautions.)

Use in combination with clopidogrel suggested by ACC and AHA in patients undergoing brachytherapy for restenosis following PCI and stent implantation†.865

Recommended by ACCP for use in all patients undergoing saphenous vein or internal mammary artery bypass grafting (regardless of effect on graft patency) based on indication in all patients with CAD.823 ACC and AHA recommend use after saphenous vein CABG to reduce risk of graft closure.867 885

May be used in combination with oral anticoagulants in patients with saphenous vein bypass grafts who have underlying conditions necessitating use of oral anticoagulants (e.g., prosthetic heart valves).768 823

Embolism Associated with Atrial Fibrillation/Flutter

An alternative or adjunct to oral anticoagulation for reduction of the incidence of thromboembolic episodes in selected patients with chronic atrial fibrillation† or atrial flutter†.744 747 749 773 774 776 826 880

Use of either aspirin or warfarin is suggested by ACC, AHA, and other clinicians in patients with nonvalvular atrial fibrillation with intermediate risk of stroke.826 k n o

Recommended for use in patients with atrial fibrillation at low risk for stroke or who are poor candidates for oral anticoagulation.744 747 748 749 767 773 774 776 826 880 881 k n o

Recommended for use in patients with “lone” atrial fibrillation (e.g., those younger than 75 years of age without prior stroke or TIA) over warfarin because relatively low risk of stroke in these patients does not warrant risks of oral anticoagulation.

Embolism Associated with Valvular Heart Disease

Used as an alternative or adjunct to oral anticoagulation for reduction of the incidence of thromboembolic episodes in selected patients with valvular heart disease†.746 764 827 881

Recommend by ACCP for use in patients with mitral valve prolapse and unexplained symptomatic TIAs.827

Used as an adjunct to warfarin in patients with mitral valve disease associated with rheumatic fever and recurrent embolism despite warfarin therapy.827 881

Thrombosis in Other Arteries and Arteriovenous Communications

Reduction of the risk of stroke and MI in patients undergoing peripheral percutaneous transluminal angioplasty (PTA) with or without stenting.690 828

Reduction of the risk of long-term cardiovascular morbidity and mortality in patients with chronic limb ischemia (e.g., intermittent claudication) resulting from arteriosclerosis.690 769 828 Use of aspirin is suggested by ACCP over clopidogrel in these patients because of cost considerations.828

Prolonging the patency of vascular grafts following peripheral bypass surgery (e.g., prosthetic infrainguinal femoropopliteal).690 769 828 Prophylaxis used in selected patients undergoing other bypass procedures and vascular reconstructions; consult specialized references for additional information.690 769 828

Has been used following initial heparin therapy to reduce the risk of thrombotic occlusion in children with Blalock-Taussig shunts†.662 718 825

Prosthetic Heart Valves

Has been used in conjunction with warfarin to reduce the risk of systemic thromboembolism and death in patients with mechanical prosthetic heart valves†.692 693 694 717 827

In patients with a bioprosthetic valve in the aortic position, ACCP recommends aspirin or warfarin for the first 3 months following valve insertion.827 Follow-up long-term therapy recommended to protect against thromboembolism in patients with bioprosthetic heart valves† who are in sinus rhythm and without risk factors.827

May be added to therapy with a low molecular weight heparin or unfractionated heparin in pregnant women with prosthetic heart valves† who are at high risk for thrombosis.845

Thrombosis Associated with Fontan Procedure

Has been used for prevention of thromboembolic complications following Fontan procedure† (definitive palliative surgical treatment for most congenital univentricular heart lesions) in children.662 825 Antithrombotic therapy effective in <50% of patients and many prophylactic regimens in use; no consensus on optimal regimen.662 825

Pericarditis

Drug of choice for the management of pain associated with acute pericarditis† following MI.635 821

Kawasaki Disease

Treatment of Kawasaki disease; used in conjunction with immune globulin IV (IGIV).636 637 638 662 825

Complications of Pregnancy

Has been used alone or in combination with other drugs (e.g., heparin, corticosteroids, immune globulin) for prevention of complications of pregnancy† (e.g., preeclampsia, pregnancy loss in women with a history of antiphospholipid syndrome and recurrent fetal loss).594 595 596 597 599 600 601 605 626 627 628 647 648 650 651 652 653 654 705 706 707 708 709 710 711 712 713 714 715 726 817 845 857

Use in combination with subcutaneous low-dose unfractionated heparin or a low molecular weight heparin suggested by ACCP in women with a congenital thrombophilic deficit and recurrent spontaneous abortions, a second-trimester or later pregnancy loss, severe or recurrent preeclampsia, or abruption.845

Combined prophylactic therapy with low dosages of aspirin and unfractionated heparin considered the regimen of choice in women with antiphospholipid syndrome and a history of multiple pregnancy losses, followed by postpartum oral anticoagulation therapy.845 Combination prophylactic therapy with aspirin and unfractionated or low molecular weight heparin followed by postpartum anticoagulation suggested in women with antiphospholipid syndrome and a history of multiple pregnancy losses,preeclampsia, intrauterine growth retardation, or abruption.845 857 In women with antiphospholipid syndrome and no prior venous thromboembolism or pregnancy loss, consider clinical surveillance alone or therapy with low-dose unfractionated heparin, once-daily low molecular weight heparin, and/or low dosages of aspirin.647 652 845 857

Routine use of aspirin prophylaxis to reduce the incidence and severity of preeclampsia (even in patients at increased risk of preeclampsia) generally not recommended; 634 705 706 707 712 713 715 can consider prophylaxis in women with prior severe or early-onset preeclampsia, chronic hypertension, severe diabetes, or moderate to severe renal disease.815 816 817 (See Pregnancy under Cautions.)

Prevention of Cancer

Limited data (observational studies) suggest that aspirin or other NSAIAs may reduce the risk of various cancers† (e.g., colorectal, breast, gastric cancer);864 870 871 872 873 such results generally not confirmed in randomized controlled trials.864 874 875 876

Regular use (e.g., daily) associated with a reduction in the risk of recurrent colorectal adenomas and colorectal cancer† in some studies.789 790 791 792 793 794 795 796 797 798 799 800 801 802 803 804 805 806 807 808 809 810 811 812 813 814 815 Beneficial effects of NSAIAs in reducing colorectal cancer risk dissipate following discontinuance of such therapy. Preventive therapy with aspirin currently not recommended because aspirin does not completely eliminate adenomas; aspirin therapy should not be considered a replacement for colorectal cancer screening and surveillance.790 793 794 795 796 814

Aspirin Dosage and Administration Administration

Administer orally; may administer rectally as suppositories in patients who cannot tolerate oral therapy.a

Do not use aspirin preparation if strong vinegar-like odor is present.a

Oral Administration

Usually administer orally with food or a full glass of water (240 mL).a 836 m

Film-coated, extended-release, or enteric-coated may be associated with less GI irritation and/or symptomatic GI disturbances than uncoated tablets.a

Do not use delayed-release or extended-release tablets if rapid response is required.a

Swallow delayed-release and extended-release tablets whole; do not crush or chew.a

Prepare oral solution by dissolving 2 tablets for solution (Alka-Seltzer) in 120 mL of water; ingest the entire solution to ensure adequate dosing.838 843 844

Do not chew aspirin preparations for ?7 days following tonsillectomy or oral surgery;841 837 do not place preparations directly on tooth or gum surface (possible tissue injury from prolonged contact).a

Rectal Administration

Do not administer aspirin tablets rectally.a

Dosage

When used for pain, fever, or inflammatory diseases, attempt to titrate to the lowest effective dosage.a

When used in anti-inflammatory dosages, development of tinnitus can be used as a sign of elevated plasma salicylate concentrations (except in patients with high-frequency hearing impairment).a

Pediatric Patients

Dosage in children should be guided by body weight or body surface area.a 841

Do not use in children and teenagers with varicella or influenza, unless directed by a clinician.841 (See Contraindications under Cautions.)

Pain Oral

Children 2–11 years of age: 1.5 g/m2 daily administered in 4–6 divided doses (maximum 2.5 g/m2 daily).a

Dose may be given every 4 hours as necessary (up to 5 times in 24 hours).841

Dosage for Self-medication of Pain in Children <12 Years of Age841

Age

Weight

Oral Dose

<3 years of age

<14.5 kg

Consult clinician

3–<4 years

14.5–16 kg

160 mg

4–<6 years

16–20.5 kg

240 mg

6–<9 years

20.5–30 kg

320 mg

9–<11 years

30–35 kg

320–400 mg

11 years

35–38 kg

320–480 mg

For self-medication in children ?12 years of age, 325–650 mg every 4 hours (maximum 4 g daily) or 1 g every 6 hours as necessary.836 e

For self-medication in children ?12 years of age, 454 mg (as chewing gum pieces) every 4 hours as necessary (maximum 3.632 g daily).837

For self-medication in children ?12 years of age, 650 mg (as highly buffered effervescent solution [Alka-Seltzer Original]) every 4 hours (maximum 2.6 g daily); alternatively, 1 g (Alka-Seltzer Extra Strength) every 6 hours (maximum 3.5 g daily).843 844

Rectal

Children 2–11 years of age: 1.5 g/m2 daily administered in 4–6 divided doses (maximum 2.5 g/m2 daily).a

Children ?12 years of age: 325–650 mg every 4 hours as necessary (maximum 4 g daily).a

Fever Oral

Children 2–11 years of age: 1.5 g/m2 daily administered in 4–6 divided doses (maximum 2.5 g/m2 daily).a

Dose may be given every 4 hours as necessary (up to 5 times in 24 hours).841

Dosage for Self-medication of Fever in Children <12 Years of Age841

Age

Weight

Oral Dose

<3 years of age

<14.5 kg

Consult physician

3–<4 years

14.5–16 kg

160 mg

4–<6 years

16–20.5 kg

240 mg

6–<9 years

20.5–30 kg

320 mg

9–<11 years

30–35 kg

320–400 mg

11 years

35–38 kg

320–480 mg

Children ?12 years of age: 325–650 mg every 4 hours as necessary (maximum 4 g daily).a

For self-medication in children ?12 years of age, 454 mg (as chewing gum pieces) every 4 hours as necessary (maximum 3.632 g daily).837

Rectal

Children 2–11 years of age: 1.5 g/m2 daily administered in 4–6 divided doses (maximum 2.5 g/m2 daily).a

Children ?12 years of age: 325–650 mg every 4 hours as necessary (maximum 4 g daily).a

Inflammatory Diseases Juvenile Rheumatoid Arthritis Oral

Initially, 90–130 mg/kg daily in divided doses.c m Increase dosage as necessary for anti-inflammatory efficacy; target plasma salicylate concentration is 150–300 mcg/mL.c m Plasma concentrations >200 mcg/mL associated with an increased incidence of toxicity.c m

Rheumatic Fever† Oral

Initially, 90–130 mg/kg daily given in divided doses every 4–6 hours for up to 1–2 weeks for maximal suppression of acute inflammation, followed by 60–70 mg/kg daily in divided doses for 1–6 weeks.a Adjust dosage based on response, tolerance, and plasma salicylate concentrations.a Gradually withdraw over 1–2 weeks.a

Various regimens suggested depending on severity of initial manifestations.a Consult published protocols for more information on specific dosages and schedules.a

Thrombosis Acute Ischemic Stroke† Oral

2–5 mg/kg daily suggested by ACCP following discontinuance of anticoagulant (e.g., unfractionated or LMW heparin, warfarin) therapy.825

Blalock-Taussig Shunt† Oral

5 mg/kg daily has been suggested following intraoperative heparin.825

Fontan Procedure† Oral

5 mg/kg daily has been suggested; optimal duration of therapy unknown.825

Mechanical Prosthetic Heart Valves† Oral

6–20 mg/kg daily in combination with oral anticoagulation for patients with lack of response to oral anticoagulation or contraindication to full-dose oral anticoagulation suggested by ACCP.825

Bioprosthetic Heart Valves† Oral

ACCP suggests same treatment as for adults825 (75–100 mg daily long term in those in sinus rhythm).827

Kawasaki Disease Oral

Initially, 80–100 mg/kg daily given in 4 equally divided doses (in combination with IVIG); initiate within 10 days of onset of fever.636 637 638 639 640 662 825 May be necessary to monitor plasma salicylate concentrations.636 637 638 When fever subsides, decrease dosage to 3–5 mg/kg once daily.636 637 638 639 640 641

Continue indefinitely in those with coronary artery abnormalities;636 637 638 in the absence of such abnormalities, continue for 6–8 weeks after initial onset of illness or until platelet count and erythrocyte sedimentation rate return to normal.636 637 638 662 825

Adults Pain Oral

For self-medication, 325–650 mg every 4 hours (maximum 4 g daily) or 0.5–1 g every 6 hours as necessary.836 e

For self-medication, 454 mg (as chewing gum pieces) every 4 hours as necessary (maximum 3.632 g daily).837

Adults <60 years of age for self-medication: 650 mg (as a highly buffered effervescent solution [Alka-Seltzer Lemon-Lime or Original]) every 4 hours (maximum 2.6 g daily); alternatively, 1 g (Alka-Seltzer Extra Strength) every 6 hours (maximum 3.5 g daily).838 843 844

Adults ?60 years of age for self-medication: 650 mg (as a highly buffered effervescent solution [Alka-Seltzer Lemon-Lime or Original]) every 4 hours (maximum 1.3 g daily); alternatively, 1 g (Alka-Seltzer Extra Strength) every 6 hours (maximum 1.5 g daily).838 843 844

Rectal

325–650 mg every 4 hours as necessary (maximum 4 g daily).a

Pain Associated with Migraine Headache Oral

For self-medication, 500 mg (combined with acetaminophen 500 mg and caffeine 130 mg) as a single dose.701

Fever Oral

325–650 mg every 4 hours as necessary (maximum 4 g daily).a

For self-medication, 454 mg (as chewing gum pieces) every 4 hours as necessary (maximum 3.632 g daily).837

Rectal

325–650 mg every 4 hours as necessary (maximum 4 g daily).a

Inflammatory Diseases Rheumatoid Arthritis and Arthritis and Pleurisy of SLE Oral

Initially, 3 g daily in divided doses.c l m Increase dosage as necessary for anti-inflammatory efficacy; target plasma salicylate concentration is 150–300 mcg/mL.c l m Plasma concentrations >200 mcg/mL associated with an increased incidence of toxicity.c l m

Osteoarthritis Oral

Up to 3 g daily in divided doses.c m

Spondyloarthropathies Oral

Up to 4 g daily in divided doses.c m

Rheumatic Fever† Oral

Initially, 4.9–7.8 g daily in divided doses given for maximal suppression of acute inflammation.a Adjust dosage based on response, tolerance, and plasma salicylate concentrations.a

Various regimens suggested depending on severity of initial manifestations.a Consult published protocols for more information on specific dosages and schedules.a

TIAs and Acute Ischemic Stroke Secondary Prevention Oral

50–325 mg daily in patients who experienced a noncardioembolic stroke or TIA (i.e., atherothrombotic, lacunar, or cryptogenic stroke).a m 646 691 818

Alternatively, 25 mg (in combination with dipyridamole 200 mg) twice daily (morning and evening) or clopidogrel (75 mg daily).738 818

50–100 mg daily suggested by some clinicians for patients at moderate to high risk of bleeding complications.818

Continue secondary prevention indefinitely.646 691 818 m

Acute Treatment† of Ischemic Stroke Oral

160–325 mg daily, initiated within 48 hours of stroke onset in patients who are not receiving thrombolytic therapy and continued for up to 2–4 weeks;691 699 700 818 then aspirin, dipyridamole and aspirin, or clopidogrel for secondary prevention.646 691 699 700 818

CAD and MI Suspected AMI or ACS Oral

160–325 mg as soon as AMI or ACS is suspected (no later than 24 hours after symptom onset), continued daily after MI.c m 579 635 646 669 765 819 820 821 862 (See CAD and MI: Secondary Prevention, under Dosage and Administration.)

Consider adjunctive therapy with clopidogrel (e.g., 300-mg loading dose, then 75 mg daily) for acute ST-segment elevation MI, unless contraindicated.852 853 854 855 856 862

75–325 mg daily initially for non-ST-segment elevation (NSTE) ACS also has been recommended.820

Rectal

300 mg daily may be considered for patients with severe nausea, vomiting, or upper GI tract disorders.821 862

Secondary Prevention Oral

75–325 or 75–162 mg once daily, continued indefinitely, has been recommended;c 635 646 668 669 736 740 765 775 820 821 822 823 828 867 881 m current evidence suggests 75–81 mg daily sufficient for long-term cardiovascular disease prevention and associated with less GI bleeding risk.s

75–162 mg (possibly 75–81 mg)s daily in combination with long-term (up to 4 years), moderate-intensity (target INR: 2–3) oral anticoagulation recommended in post-MI patients where meticulous INR monitoring standard and routinely ac


read more / Download


Boots Epsom Salts B.P.


1. Name Of The Medicinal Product

Epsom Salts (Magnesium Sulphate BP)

Boots Epsom Salts B.P.

2. Qualitative And Quantitative Composition

Magnesium Sulphate 100%

3. Pharmaceutical Form

Powder for oral solution

4. Clinical Particulars 4.1 Therapeutic Indications

For the symptomatic relief of occasional constipation.

4.2 Posology And Method Of Administration

Adults and children over 12 years: 1 to 4g to be taken in warm water, once daily.

Children under 12 years. Not recommended.

4.3 Contraindications

Intestinal obstruction.

4.4 Special Warnings And Precautions For Use

To be used with caution in elderly or debilitated patients and in those with renal insufficiency.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

This product may interact with tetracyclines, digoxin, vitamins and iron and may potentiate tubocurarine during anaesthesia.

4.6 Pregnancy And Lactation

The use of magnesium containing salts in the first trimester of pregnancy should be avoided.

They should only be used after medical advice if the benefits exceed potentially unknown risks of foetal exposure to magnesium. No adverse effects are anticipated in breast fed infants.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Prolonged excessive use of this product may cause alkalosis and hypermagnesaemia.

4.9 Overdose

Excessive amounts of this medicine may cause diarrhoea and dehydration. Hypermagnesaemia and hypercalcaemia may also occur, particularly if there is impaired renal function. Treatment consists of supportive and symptomatic measures with appropriate correction of fluid and electrolyte balance.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Not applicable.

5.2 Pharmacokinetic Properties

Not applicable.

5.3 Preclinical Safety Data

Never undertaken by Abdine Limited. This product was granted a 'Licence as of Right' some 25 years ago.

6. Pharmaceutical Particulars 6.1 List Of Excipients

None.

6.2 Incompatibilities

None are recognised.

6.3 Shelf Life

As packaged for sale: Three years

As reconstituted for use: One day

After first opening the container: One month

6.4 Special Precautions For Storage

Do not store above 25°C

6.5 Nature And Contents Of Container

A spirally wound, varnished, cardboard tub with a press-fit lid or polypropylene jar and cap containing 100g, 150g, 200g, 250g, 300g or 500g.

6.6 Special Precautions For Disposal And Other Handling

Take from 1 to 4g in warm water.

7. Marketing Authorisation Holder

Bell Sons & Co (Druggists) Ltd

Gifford House

Slaidburn Crescent

Southport

Merseyside PR9 9AL

8. Marketing Authorisation Number(S)

PL 03105/0068

9. Date Of First Authorisation/Renewal Of The Authorisation

12 February 1999

10. Date Of Revision Of The Text

29th November 2010

11 DOSIMETRY

(IF APPLICABLE)

12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS

(IF APPLICABLE)


read more / Download


Tekturna


Generic Name: aliskiren (Oral route)

a-lis-KYE-ren

Oral route(Tablet)

Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. Stop therapy as soon as possible when pregnancy is detected .

Commonly used brand name(s)

In the U.S.

Tekturna

Available Dosage Forms:

Tablet

Therapeutic Class: Antihypertensive

Pharmacologic Class: Renin Inhibitor

Uses For Tekturna

Aliskiren is used alone or together with other medicines to treat high blood pressure (hypertension). High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled.

Aliskiren is a renin inhibitor. It works by blocking an enzyme in the body that is necessary to produce a substance that causes blood vessels to tighten. As a result, the blood vessels relax and decreases the blood pressure. When the blood pressure is lowered, the amount of blood and oxygen is increased to the heart.

This medicine is available only with your doctor's prescription.

Before Using Tekturna

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of aliskiren in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of aliskiren in the elderly.

Pregnancy Pregnancy Category Explanation 1st Trimester C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women. 2nd Trimester D Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk. 3rd Trimester D Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk. Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Cyclosporine Itraconazole

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Benazepril Captopril Cilazapril Enalapril Fosinopril Lisinopril Moexipril Perindopril Quinapril Ramipril Rifampin Trandolapril Zofenopril Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

Grapefruit Juice Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

Airway surgery, history of or Angioedema, or history of or Hyperkalemia (high potassium in the blood)—Use with caution. May make these conditions worse. Dehydration or Diarrhea or Hyponatremia (low sodium in the blood) or Hypovolemia (low blood volume) or Vomiting, severe—Use with caution. These conditions may cause the blood pressure to fall too low with this medicine. Kidney disease, severe—Use with caution. The effects may be increased because of slower removal of the medicine from the body. Proper Use of Tekturna

Your doctor will tell you how much of this medicine to use and how often. Your dose may need to be changed several times in order to find out what works best for you. Do not use more medicine or use it more often than your doctor tells you to.

This medicine may be taken with or without food.

In addition to the use of this medicine, treatment for your high blood pressure may include weight control and changes in the types of food you eat, especially for foods that are high in sodium (salt). Your doctor will tell you which of these are most important for you. You should check with your doctor before changing your diet.

Many patients who have high blood pressure will not notice any signs of the problem. In fact, many patients feel normal. It is very important that you take your medicine exactly as directed and that you keep your appointments with your doctor even if you feel well.

Remember that this medicine will not cure your high blood pressure, but it does help control it. You must continue to take it as directed if you expect to lower your blood pressure and keep it down. You may have to take high blood pressure medicine for the rest of your life. If high blood pressure is not treated, it can cause serious problems such as heart failure, blood vessel disease, stroke, or kidney disease.

To help you remember to take your medicine, try to get into the habit of taking it at the same time each day.

You may take this medicine with or without food. High-fat meals may affect absorption of this medicine.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage form (tablets): For high blood pressure: Adults—At first, 150 milligrams (mg) once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 300 mg per day. Children—Use and dose must be determined by your doctor. Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Tekturna

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant (especially in your second or third trimester) can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using this medicine, tell your doctor right away.

This medicine can cause a serious reaction called angioedema. Stop using this medicine and tell your doctor right away if you start to have swelling on your face, lips, tongue, or throat, or if you are having trouble swallowing or breathing.

Dizziness or lightheadedness may occur while you are using this medicine, especially if you have been taking a diuretic (water pill). Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy. If you feel dizzy, lie down so you do not faint. Then sit for a few moments before standing to prevent the dizziness from returning.

Check with your doctor right away if you become sick while taking this medicine, especially if you have severe or continuing nausea, vomiting, or diarrhea. These conditions may cause you to lose too much water, which can cause low blood pressure. You can also lose water by sweating, so use extra care during exercise or hot weather.

Hyperkalemia (high potassium in the blood) may occur while you are using this medicine. Check with your doctor right away if you have the following symptoms: abdominal or stomach pain; confusion; difficulty with breathing; irregular heartbeat; nausea or vomiting; nervousness; numbness or tingling in the hands, feet, or lips; shortness of breath; or weakness or heaviness of the legs.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine several days before having surgery or medical tests.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Tekturna Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Less common Body aches or pain chills cough diarrhea difficulty with breathing ear congestion fever headache loss of voice nasal congestion runny nose sneezing sore throat unusual tiredness or weakness Rare Ankle, knee, or great toe joint pain blood in the urine joint pain joint stiffness or swelling large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs loss of bladder control loss of consciousness lower back or side pain nausea and vomiting pain in the groin or genitals sharp back pain just below the ribs swelling of the feet or lower legs

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common Acid or sour stomach back pain belching dizziness heartburn indigestion muscle aches rash stomach discomfort, upset, or pain stuffy or runny nose

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Tekturna side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Tekturna resources Tekturna Side Effects (in more detail) Tekturna Dosage Tekturna Use in Pregnancy & Breastfeeding Drug Images Tekturna Drug Interactions Tekturna Support Group 23 Reviews for Tekturna - Add your own review/rating Tekturna Prescribing Information (FDA) Tekturna Consumer Overview Tekturna Monograph (AHFS DI) Tekturna MedFacts Consumer Leaflet (Wolters Kluwer) Aliskiren Professional Patient Advice (Wolters Kluwer) Compare Tekturna with other medications High Blood Pressure
read more / Download


ketorolac Nasal


kee-toe-ROLE-ak

Nasal route(Spray)

For short term use only (up to 5 days in adults). Not for use in pediatric patients and not indicated for minor or chronic pain. Contraindicated in patients with peptic ulcer disease, history of gastrointestinal (GI) bleeding or perforation, peri-operative pain in the setting of CABG surgery, advanced renal impairment, risk of renal failure due to volume depletion, cerebrovascular bleeding, hemorrhagic diathesis, incomplete homeostasis, and high risk of bleeding. Use caution with elderly patients due to high risk of GI adverse events and in patients with cardiovascular disease or risk factors for cardiovascular disease .

Commonly used brand name(s)

In the U.S.

Sprix

Available Dosage Forms:

Spray

Pharmacologic Class: NSAID

Chemical Class: Acetic Acid (class)

Uses For ketorolac

Ketorolac nasal spray is used to relieve moderate to moderately severe pain, such as pain that occurs after an operation or other painful procedure. It is a nonsteroidal anti-inflammatory drug (NSAID) that will reduce pain and inflammation.

Ketorolac has side effects that can be very dangerous. The risk of having a serious side effect increases with the amount that is used and the length of time it is used. Ketorolac should not be used for more than 5 days in a row. Before using ketorolac, you should discuss with your doctor the good that ketorolac can do as well as the risks of using it.

ketorolac is available only with your doctor's prescription.

Before Using ketorolac

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For ketorolac, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to ketorolac or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of ketorolac nasal spray in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of ketorolac nasal spray in the elderly. However, because of ketorolac's toxicity, it should be used with caution in the elderly, after less toxic alternatives have been considered or found ineffective. Recommended doses should not be exceeded, and the patient should be carefully monitored during treatment. In addition, elderly patients are more likely to have age-related heart, kidney, liver, stomach, or bowel problems, which may require caution and an adjustment in the dose for patients receiving ketorolac nasal spray.

Pregnancy Pregnancy Category Explanation 1st Trimester C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women. 2nd Trimester C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women. 3rd Trimester D Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk. Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking ketorolac, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using ketorolac with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

Aceclofenac Acemetacin Alclofenac Apazone Aspirin Benoxaprofen Bufexamac Carprofen Clometacin Clonixin Dexketoprofen Diclofenac Diflunisal Dipyrone Droxicam Etodolac Etofenamate Felbinac Fenbufen Fenoprofen Fentiazac Floctafenine Flufenamic Acid Flurbiprofen Ibuprofen Indomethacin Indoprofen Isoxicam Ketoprofen Lornoxicam Meclofenamate Mefenamic Acid Meloxicam Nabumetone Naproxen Niflumic Acid Nimesulide Oxaprozin Oxyphenbutazone Pentoxifylline Phenylbutazone Pirazolac Piroxicam Pirprofen Probenecid Propyphenazone Proquazone Sulindac Suprofen Tenidap Tenoxicam Tiaprofenic Acid Tolmetin Zomepirac

Using ketorolac with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Abciximab Ardeparin Argatroban Beclamide Beta Glucan Bivalirudin Caramiphen Carbamazepine Certoparin Chlormethiazole Cilostazol Citalopram Clopidogrel Clovoxamine Dabigatran Etexilate Dalteparin Danaparoid Desirudin Diazepam Dipyridamole Enoxaparin Escitalopram Ethotoin Felbamate Femoxetine Flesinoxan Fluoxetine Fluvoxamine Fondaparinux Fosphenytoin Gabapentin Ginkgo Heparin Lacosamide Lepirudin Levetiracetam Mephenytoin Mephobarbital Methotrexate Nadroparin Nefazodone Oxcarbazepine Paraldehyde Paramethadione Parnaparin Paroxetine Pemetrexed Phenacemide Phenobarbital Phenytoin Piracetam Pregabalin Protein C Reviparin Rivaroxaban Rufinamide Sertraline Sibutramine Stiripentol Tacrolimus Tiagabine Ticlopidine Tinzaparin Tirofiban Topiramate Trimethadione Valproic Acid Vigabatrin Vilazodone Zimeldine Zonisamide

Using ketorolac with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Acebutolol Acetohexamide Alacepril Alprenolol Amiloride Arotinolol Atenolol Azilsartan Medoxomil Azosemide Befunolol Bemetizide Benazepril Bendroflumethiazide Benzthiazide Betaxolol Bevantolol Bisoprolol Bopindolol Bucindolol Bumetanide Bupranolol Buthiazide Candesartan Cilexetil Canrenoate Captopril Carteolol Carvedilol Celiprolol Chlorothiazide Chlorpropamide Chlorthalidone Cilazapril Clopamide Cyclopenthiazide Cyclosporine Delapril Desvenlafaxine Dilevalol Duloxetine Enalaprilat Enalapril Maleate Eprosartan Esmolol Ethacrynic Acid Fosinopril Furosemide Gliclazide Glimepiride Glipizide Gliquidone Glyburide Hydrochlorothiazide Hydroflumethiazide Imidapril Indapamide Irbesartan Labetalol Landiolol Levobetaxolol Levobunolol Lisinopril Lithium Losartan Mepindolol Methyclothiazide Metipranolol Metolazone Metoprolol Milnacipran Moexipril Nadolol Nebivolol Nipradilol Olmesartan Medoxomil Oxprenolol Penbutolol Pentopril Perindopril Pindolol Piretanide Polythiazide Propranolol Quinapril Ramipril Sotalol Spirapril Spironolactone Talinolol Tasosartan Telmisartan Temocapril Tertatolol Timolol Tolazamide Tolbutamide Torsemide Trandolapril Triamterene Trichlormethiazide Valsartan Venlafaxine Xipamide Zofenopril Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of ketorolac. Make sure you tell your doctor if you have any other medical problems, especially:

Anemia or Congestive heart failure or Crohn's disease, history of or Edema (fluid retention or body swelling) or Heart attack, history of or Heart disease or Hypertension (high blood pressure) or Kidney disease, or history of or Liver disease, or history of or Stroke, history of or Ulcerative colitis, history of—Use with caution. May make these conditions worse. Aspirin-sensitive asthma, history of or Aspirin sensitivity, history of or Bleeding problems or Kidney disease, severe or Major surgery, prior to or Stomach ulcers or bleeding, or history of—Should not be used in patients with these conditions. Heart surgery (e.g., coronary artery bypass graft [CABG])—Should not be used to relieve pain right before or after the surgery. Proper Use of ketorolac

Take ketorolac only as directed by your doctor to benefit your condition as much as possible. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. Do not use it for more than 5 days in a row. The total number of days also includes any doses of ketorolac that may be given in a hospital or clinic setting. Using too much of ketorolac increases the chance of side effects, especially in elderly patients.

ketorolac should come with a medication guide. Read and follow the instructions carefully. Ask your doctor if you have any questions.

ketorolac is only used in the nose. Do not get any of it in your eyes. If it does get in the eyes, rinse them with water right away and call your doctor.

Drink extra fluids while you are using ketorolac. This will keep your kidneys working well and help prevent kidney problems.

To use:

If you are using the nasal spray for the first time, you will need to prime the spray. To do this, pump the bottle five times until some of the medicine sprays out. Now it is ready to use. Gently blow your nose to clear the nostrils. Sit or stand up straight and tilt your head slightly forward. Insert the tip of the bottle into your right nostril. Point the bottle away from the center of your nose. Spray once into your right nostril. If your dose is 2 sprays, spray once into your left nostril the same way. After using the spray, wipe the tip of the bottle with a clean tissue and put the clear plastic cover back on. Do not use the bottle for more than 24 hours after your first dose. Throw the bottle away after 24 hours even if it still has liquid in it. Dosing

The dose of ketorolac will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of ketorolac. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For nasal dosage form (spray): For pain: Adults weighing 50 kilograms (kg) or more—31.5 milligrams (mg) or 1 spray in each nostril every 6 to 8 hours. Your doctor may adjust your dose if needed. However, the dose is usually not more than 126 mg (a total of 8 sprays) per day. Older adults and adults weighing less than 50 kg—15.75 mg or 1 spray in only one nostril every 6 to 8 hours. However, the dose is usually not more than 63 mg (a total of 4 sprays) per day. Children—Use and dose must be determined by your doctor. Missed Dose

If you miss a dose of ketorolac, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Keep the unopened bottle in the refrigerator. Protect it from light and freezing. Once opened, store the bottle at room temperature, away from heat and direct sunlight. Throw away any unused medicine 24 hours after you opened the bottle and used your first dose.

Precautions While Using ketorolac

It is very important that your doctor check your progress while you are using ketorolac. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to use it.

Do not use any other form of ketorolac (such as injection or tablets) or other NSAIDs unless your doctor says it is okay. Some examples of NSAIDs are aspirin, diclofenac, ibuprofen, naproxen, Advil®, Aleve®, Celebrex®, Ecotrin®, Motrin®, or Voltaren®. Also, you should not use ketorolac together with pentoxifylline (Trental®) or probenecid (Benemid®).

Ketorolac may cause bleeding in your stomach or intestines. This problem can happen without warning signs. This is more likely if you have had a stomach ulcer in the past, if you smoke or drink alcohol regularly, if you are over 60 years of age, are in poor health, or are using certain other medicines (such as steroids or a blood thinner). Stop using ketorolac and call your doctor right away if you have bloody or black, tarry stools; severe stomach pain or heartburn; or vomiting of blood or material that looks like coffee grounds.

ketorolac may cause a serious type of allergic reaction called anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash; itching; hoarseness; trouble breathing; trouble swallowing; or any swelling of your hands, face, or mouth while you are using ketorolac.

Ketorolac may increase your risk of having a heart attack. This is more likely in people who already have heart disease. Stop using ketorolac and call your doctor right away if you have chest pain or discomfort; an irregular or fast heart beat; severe indigestion or heartburn; nausea; sweating; or troubled breathing with exertion.

Serious skin reactions can occur during treatment with ketorolac. Stop using ketorolac and check with your doctor right away if you have any of the following symptoms while you are using ketorolac: blistering, peeling, loosening of the skin; chills; cough; diarrhea; fever; itching; joint or muscle pain; red skin lesions; sore throat; sores, ulcers, or white spots in the mouth or on the lips; or unusual tiredness or weakness.

Check with your doctor right away if you have pain or tenderness in the upper stomach; pale stools; dark urine; loss of appetite; nausea; unusual tiredness or weakness; or yellow eyes or skin. These could be symptoms of a serious liver problem.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

ketorolac Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common Abdominal or stomach pain, cramping, or burning bloody or black, tarry stools blurred vision constipation diarrhea dizziness fast, irregular, pounding, or racing heartbeat or pulse headache heartburn indigestion nausea nervousness pale skin pounding in the ears severe stomach pain sweating unusual bleeding or bruising unusual tiredness or weakness vomiting of blood or material that looks like coffee grounds Less common Burning feeling in the chest or stomach chest pain or discomfort decrease in amount or frequency of urine difficult or labored breathing frequent urge to urinate frequent urination increased amount of pale, dilute urine lightheadedness, dizziness, or fainting rapid, shallow breathing shortness of breath troubled breathing with exertion Rare Bleeding gums bloody or cloudy urine blue lips and fingernails chills clay-colored stools confusion cough or hoarseness coughing that sometimes produces a pink frothy sputum dark urine difficult, burning, or painful urination difficulty with swallowing dilated neck veins extreme fatigue general tiredness and weakness increased blood pressure increased sweating increased thirst itching or hives light-colored stools lower back or side pain nosebleeds pain or burning in the throat pinpoint red spots on the skin rash rectal bleeding sores, ulcers, or white spots on the lips or tongue or inside the mouth stomach upset swelling of the face, fingers, feet, or lower legs swollen glands tenderness in the stomach area tightness in the chest unpleasant breath odor upper right abdominal pain vomiting weight gain or loss wheezing yellow eyes or skin Incidence not known Blistering, peeling, or loosening of the skin bloating change in consciousness convulsions difficulty with moving dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position feeling of warmth feeling that others are watching you or controlling your behavior feeling, seeing, or hearing things that are not there fever with or without chills general body swelling joint or muscle pain large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs loss of consciousness muscle aching or cramping muscle pains or stiffness pain or discomfort in the arms, jaw, back, or neck pains in the stomach, side, or abdomen, possibly radiating to the back pale or blue lips, fingernails, or skin puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue red skin lesions, often with a purple center red, irritated eyes redness of the face, neck, arms, and occasionally, upper chest redness, soreness, or itching skin severe mood or mental changes sneezing sores, welting, or blisters swollen joints swollen, painful, or tender lymph glands in the neck, armpit, or groin weakness or heaviness of the legs

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common Acid or sour stomach belching continuing ringing or buzzing or other unexplained noise in the ears drowsiness excess air or gas in the stomach or intestines full feeling hearing loss nasal discomfort passing gas swelling or inflammation of the mouth Less common Runny nose stuffy nose watering of the eyes Rare Abnormal dreams abnormal taste appetite changes bloody nose bruising burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings decreased awareness or responsiveness delusions dementia difficulty with speaking drooling excessive thirst false or unusual sense of well-being feeling of constant movement of self or surroundings feeling sad or empty general feeling of discomfort or illness inability to concentrate increase in body movements irritability lack or loss of strength large, flat, blue, or purplish patches in the skin loss of balance control loss of interest or pleasure muscle trembling, jerking, or stiffness redness, swelling, or soreness of the tongue restlessness seeing, hearing, or feeling things that are not there sensation of spinning shakiness in the legs, arms, hands, or feet shuffling walk sleepiness or unusual drowsiness sleeplessness tiredness trouble concentrating trouble sleeping uncontrolled movements, especially of the face, neck, and back weight loss Incidence not known Burning, dry, or itching eyes eye discharge or excessive tearing flushed, dry skin fruit-like breath odor increased hunger increased urination redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid stiff neck or back unexplained weight loss

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More ketorolac Nasal resources Ketorolac Nasal Use in Pregnancy & Breastfeeding Drug Images Ketorolac Nasal Drug Interactions Ketorolac Nasal Support Group 74 Reviews for Ketorolac Nasal - Add your own review/rating Compare ketorolac Nasal with other medications Pain Postoperative Pain
read more / Download


Vasotec I.V.


Generic Name: enalaprilat (Intravenous route)

en-AL-a-pril-at

Intravenous route(Solution)

ACE inhibitors can cause injury or death to the developing fetus when used during the second and third trimesters. Stop therapy as soon as possible when pregnancy is detected .

Commonly used brand name(s)

In the U.S.

Vasotec I.V.

Available Dosage Forms:

Solution

Therapeutic Class: Antihypertensive

Pharmacologic Class: ACE Inhibitor

Uses For Vasotec I.V.

Enalaprilat injection is used to treat high blood pressure (hypertension). High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled .

Enalaprilat works by blocking an enzyme in the body that is necessary to produce a substance that causes blood vessels to tighten. As a result, the blood vessels relax. This lowers blood pressure and increases the supply of blood and oxygen to the heart .

This medicine is available only with your doctor's prescription .

Before Using Vasotec I.V.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of enalaprilat in the pediatric population. Safety and efficacy have not been established .

Geriatric

No information is available on the relationship of age to the effects of enalaprilat in geriatric patients. However, elderly patients are more likely to have age-related kidney problems, which may require an adjustment of dose in patients receiving enalaprilat .

Pregnancy Pregnancy Category Explanation 1st Trimester C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women. 2nd Trimester D Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk. 3rd Trimester D Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk. Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Allopurinol Alteplase, Recombinant Amiloride Azathioprine Azilsartan Medoxomil Candesartan Cilexetil Canrenoate Eplerenone Eprosartan Interferon Alfa-2a Losartan Olmesartan Medoxomil Potassium Spironolactone Telmisartan Triamterene Valsartan

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Aceclofenac Acemetacin Alclofenac Apazone Aspirin Azosemide Bemetizide Bendroflumethiazide Benoxaprofen Benzthiazide Bromfenac Bufexamac Bumetanide Bupivacaine Buthiazide Capsaicin Carprofen Chlorothiazide Chlorthalidone Clometacin Clomipramine Clonixin Clopamide Cyclopenthiazide Cyclothiazide Dexketoprofen Diclofenac Diflunisal Dipyrone Droxicam Ethacrynic Acid Etodolac Etofenamate Felbinac Fenbufen Fenoprofen Fentiazac Floctafenine Flufenamic Acid Flurbiprofen Furosemide Hydrochlorothiazide Hydroflumethiazide Ibuprofen Indapamide Indomethacin Indoprofen Isoxicam Ketoprofen Ketorolac Lornoxicam Meclofenamate Mefenamic Acid Meloxicam Metformin Methyclothiazide Metolazone Nabumetone Naproxen Niflumic Acid Nimesulide Oxaprozin Oxyphenbutazone Phenylbutazone Pirazolac Piretanide Piroxicam Pirprofen Polythiazide Propyphenazone Proquazone Quinethazone Rifampin Sulindac Suprofen Tenidap Tenoxicam Tiaprofenic Acid Tolmetin Torsemide Trichlormethiazide Trimethoprim Xipamide Zomepirac Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

Angioedema, history of—May increase the risk of this condition occurring again . Dehydration or Diarrhea or Heart failure or Hyponatremia (low sodium in the blood) or Kidney disease—These conditions may cause the blood pressure to fall too low with enalaprilat . Proper Use of Vasotec I.V.

In addition to the use of this medicine, treatment for your high blood pressure may include weight control and changes in the types of foods you eat, especially foods high in sodium. Your doctor will tell you which of these are most important for you. You should check with your doctor before changing your diet.

Many patients who have high blood pressure will not notice any signs of the problem. In fact, many may feel normal. It is very important that you take your medicine exactly as directed and that you keep your appointments with your doctor even if you feel well.

Remember that this medicine will not cure your high blood pressure but it does help control it. Therefore, you must continue to take it as directed if you expect to lower your blood pressure and keep it down. You may have to take high blood pressure medicine for the rest of your life. If high blood pressure is not treated, it can cause serious problems such as heart failure, blood vessel disease, stroke, or kidney disease.

Precautions While Using Vasotec I.V.

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly and to check for unwanted effects .

Stop using this medicine and call your doctor right away if you have swelling of the face, arms, legs, eyes, lips, or tongue, or problems with swallowing or breathing. These are symptoms of a condition called angioedema .

You may experience lightheadedness during the first few days with this medicine. If this becomes severe and you faint, talk to your doctor right away .

Tell your doctor immediately if you have any signs of infection such as chills, sore throat, or fever. These may be symptoms of an immune system condition called neutropenia .

Using this medicine while you are pregnant can harm your unborn baby. If you think you have become pregnant while using the medicine, tell your doctor right away .

Check with your doctor right away if you have symptoms of jaundice (yellow skin or eyes) because these may be signs of a serious liver condition .

This medicine may increase the amount of potassium in your blood. Do not use salt substitutes containing potassium without first checking with your doctor .

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine several days before having surgery or medical tests .

Vasotec I.V. Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

Less common Blurred vision confusion dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly sweating unusual tiredness or weakness Rare Chest pain or discomfort nausea pain or discomfort in arms, jaw, back or neck shortness of breath vomiting

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common Headache Rare Difficulty having a bowel movement (stool) dizziness fever rash

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Vasotec I.V. side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Vasotec I.V. resources Vasotec I.V. Side Effects (in more detail) Vasotec I.V. Support Group 0 Reviews · Be the first to review/rate this drug
read more / Download


Orudis 50


1. Name Of The Medicinal Product

Orudis 50

2. Qualitative And Quantitative Composition

In terms of the active ingredient

Ketoprofen 50mg

3. Pharmaceutical Form

Capsules

4. Clinical Particulars 4.1 Therapeutic Indications

Recommended in the management of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute articular and periarticular disorders, (bursitis, capsulitis, synovitis, tendinitis), cervical spondylitis, low back pain (strain, lumbago, sciatica, fibrositis), painful musculoskeletal conditions, acute gout, dysmenorrhoea and control of pain and inflammation following orthopaedic surgery.

Orudis reduces joint pain and inflammation and facilitates increase in mobility and functional independence.

It does not cure the underlying disease.

4.2 Posology And Method Of Administration

Oral dosage 50 - 100mg twice daily, morning and evening, depending on patient's weight and on the severity of symptoms.

The maximum daily dose is 200mg. The balance of risks and benefits should be carefully considered before commencing treatment with 200mg daily, and higher doses are not recommended (see also section 4.4).

Best results are obtained by titrating dosage to suit each patient: start with a low dosage in mild chronic disease and a high dosage in acute or severe disease. Some patients derive greater benefit by treatment with capsules only, some with a combined capsule/suppository regimen and others with a higher dosage at night time than at early morning. Where patients require a maximum oral dosage initially, an attempt should be made to reduce this dosage for maintenance since lower dosage might be better tolerated for purposes of long-term treatment.

Elderly: The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy.

Paediatric dosage: Not established.

To limit occurrence of gastrointestinal disturbance, capsules should always be taken with food (milk, meals).

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).

4.3 Contraindications

Ketoprofen is contraindicated in patients who have a history of hypersensitivity reactions such as bronchospasm, asthmatic attacks, rhinitis, angioedema, urticaria or other allergic-type reactions to ketoprofen, any other ingredients in this medicine, ASA or other NSAIDs. Severe, rarely fatal, anaphylactic reactions have been reported in such patients (see section 4.8 Undesirable effects).

Ketoprofen is contraindicated in patients with hypersensitivity to any of the excipients of the drug.

Ketoprofen is also contraindicated in the third trimester of pregnancy.

Ketoprofen is contraindicated in the following cases:

- severe heart failure

- active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding)

- history of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy

- haemorrhagic diathesis

- severe hepatic insufficiency

- severe renal insufficiency

- third trimester of pregnancy

Disease in children (safety/dosage during long-term treatment has not been established).

4.4 Special Warnings And Precautions For Use

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2 Posology and method of administration, and GI and cardiovascular risks below).

The use of ketoprofen with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5 Interactions).

Elderly:

The elderly have an increased risk of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation which may be fatal (see Section 4.2 Posology and method of administration).

Cardiovascular, Renal and Hepatic impairment:

At the start of treatment, renal function must be carefully monitored in patients with heart impairment, heart failure, liver dysfunction, cirrhosis and nephrosis, in patients receiving diuretic therapy, in patients with chronic renal impairment, particularly if the patient is elderly. In these patients, administration of ketoprofen may induce a reduction in renal blood flow caused by prostaglandin inhibition and lead to renal decomposition. (see Section 4.3 Contra-indications).

NSAIDs have also been reported to cause nephrotoxicity in various forms and this can lead to interstitial nephritis, nephrotic syndrome and renal failure.

In patients with abnormal liver function tests or with a history of liver disease, transaminase levels should be evaluated periodically, particularly during long-term therapy. Rare cases of jaundice and hepatitis have been described with ketoprofen.

Cardiovascular and cerebrovascular effects

Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long-term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for ketoprofen.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ketoprofen after careful consideration. Similar consideration should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).

Respiratory disorders:

Patients with asthma combined with chronic rhinitis, chronic sinusitis, and/or nasal polyposis have a higher risk of allergy to aspirin and/or NSAIDs than the rest of the population. Administration of this medicinal product can cause asthma attacks or bronchospasm, particularly in subjects allergic to aspirin or NSAIDs (see section 4.3).

Gastrointestinal bleeding, ulceration and perforation:

GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events.

Some epidemiological evidence suggests that ketoprofen may be associated with a high risk of serious gastrointestinal toxicity, relative to some other NSAIDs, especially at high doses (see also section 4.2 and 4.3).

The risk of GI bleeding, ulceration or perforation is higher with increasing NSAlD doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), and in the elderly. These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and section 4.5).

NSAIDs should only be given with care to patients with a history of gastrointestinal disease (e.g. ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see Section 4.8 Undesirable effects).

Patients with a history of gastrointestinal toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding), particularly in the initial stages of treatment.

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as corticosteroids, or anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (see Section 4.5).

When GI bleeding or ulceration occurs in patients receiving ketoprofen, the treatment should be withdrawn.

SLE and mixed connective tissue disease:

In patients with systemic lupus erythematosis (SLE) and mixed connective tissue disorders, there may be an increased risk of aseptic meningitis (see Section 4.8 Undesirable effects).

Female fertility:

The use of ketoprofen, as with other NSAIDs, may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulty conceiving or who are undergoing investigation of infertility, withdrawal of ketoprofen should be considered.

Skin reactions:

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs. Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Treatment should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Infectious disease:

As with other NSAIDs, in the presence of an infectious disease, it should be noted that the anti-inflammatory, analgesic and the antipyretic properties of ketoprofen may mask the usual signs of infection progression such as fever.

Visual disturbances:

If visual disturbances such as blurred vision occur, treatment should be discontinued.

Patients with active or a past history of peptic ulcer.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Anticoagulants (heparin and warfarin) and platelet aggregation inhibitors (i.e. ticlopidine, clopidogrel):

Increased risk of bleeding (see section 4.4).

If coadministration is unavoidable, patient should be closely monitored.

Lithium:

Risk of elevation of lithium plasma levels sometimes reaching toxic levels due to decreased lithium renal excretion. Where necessary, plasma levels should be closely monitored and the lithium dosage levels adjusted during and after NSAIDs therapy.

Other analgesics/NSAIDs (including cyclooxygenase-2 selective inhibitors) and high dose salicylates:

Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects, particularly gastrointestinal ulceration and bleeding. (see Section 4.4 Special warnings and precautions for use).

Methotrexate:

Serious interactions have been recorded after the use of high dose methotrexate with NSAIDs, including ketoprofen, due to decreased elimination of methotrexate. At doses greater than 15mg/week:

Increased risk of haematologic toxicity of methotrexate, particularly if administered at high doses (> 15 mg/week), possibly related to displacement of protein-bound methotrexate and to its decreased renal clearance. At doses lower than 15mg/week: During the first weeks of combination treatment, full blood count should be monitored weekly. If there is any alteration of the renal function or if the patient is elderly, monitoring should be done more frequently.

Mifepristone:

NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.

Pentoxifylline:

There is an increased risk of bleeding. More frequent clinical monitoring and monitoring of bleeding time is required.

Antihypertensive agents: (beta-blockers, angiotensin converting enzyme inhibitors, diuretics):

Risk of decreased antihypertensive potency (inhibition of vasodilator prostaglandins by NSAIDs.

Diuretics:

Risk of reduced diuretic effect. Patients and particularly dehydrated patients taking diuretics are at a greater risk of developing renal failure secondary to a decrease in renal blood flow caused by prostaglandin inhibition. Such patients should be rehydrated before initiating coadministration therapy and renal function monitored when the treatment is started (see section 4.4 Special warnings and precautions for use).

Cardiac glycosides:

NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.

Ciclosporin:

Increased risk of nephrotoxicity, particularly in elderly subjects.

Corticosteroids:

Increased risk of gastrointestinal ulceration or bleeding. (see Section 4.4 Special warnings and precautions for use).

Quinolone antibiotics:

Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

Tacrolimus:

Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus, particularly in elderly subjects.

Thrombolytics:

Increased risk of bleeding.

Probenecid:

Concomitant administration of probenecid may markedly reduce the plasma clearance of ketoprofen.

Anti-platelet agents and Selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding (section 4.4 Special warnings and precautions for use).

ACE inhibitors and Angiotensin II Antagonists:

In patients with compromised renal function (e.g. dehydrated patients or elderly patients the co-administration of an ACE inhibitor or Angiotensin II antagonist and agents that inhibit cyclooxygenase may result in further deterioration of renal function, including possible acute renal failure.

Zidovudine:

Increased risk of haematological toxicity when NSAlDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

4.6 Pregnancy And Lactation

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimester of pregnancy, ketoprofen should not be given unless clearly necessary. If ketoprofen is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:

- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

- renal dysfunction, which may progress to renal failure with oligo-hydroamniosis; the mother and the neonate, at the end of the pregnancy, to:

- possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.

- Inhibition of uterine contractions resulting in delayed or prolonged labour.

Consequently, ketoprofen is contraindicated during the third trimester of pregnancy.

Lactation

No data are available on excretion of ketoprofen in human milk. Ketoprofen is not recommended in nursing mothers.

4.7 Effects On Ability To Drive And Use Machines

Patients should be warned about the potential for somnolence, dizziness or convulsions, drowsiness, fatigue and visual disturbances and be advised not to drive or operate machinery if these symptoms occur.

4.8 Undesirable Effects

The following CIOMS frequency rating is used, when applicable:

Very common (

The following adverse reactions have been reported with Ketoprofen in adults:

Blood and lymphatic system disorders

- rare: haemorrhagic anaemia, anaemia due to bleeding

- not known: agranulocytosis, thrombocytopenia, bone marrow failure, neutropenia

Immune system disorders

- rare: anaphylactic reactions (including shock)

Psychiatric disorders

- not known: mood altered

Nervous system disorders

- uncommon: headache, dizziness, somnolence

- rare: paraesthesia

- not known: convulsions, dysgeusia, depression, confusion, hallucinations, vertigo, malaise, drowsiness, reports of aseptic meningitis (especially in patients with existing auto-immune disorders such as systemic lupus erythematosis, mixed connective tissue disease) with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation (see section 4.4 Special warnings and precautions for use).

Eye disorders

- rare: visual disturbances such as blurred vision (see section 4.4 Special warnings and precautions for use)

- not known: optic neuritis

Ear and labyrinth disorders

- rare: tinnitus

Cardiac disorders

- not known: heart failure, oedema

Vascular disorders

- not known: hypertension, vasodilatation

Respiratory, thoracic and mediastinal disorders

- rare: asthma, asthmatic attack

- not known: bronchospasm (particularly in patients with known hypersensitivity to ASA and other NSAIDs), rhinitis, non-specific allergic reactions, dyspnoea

Gastrointestinal disorders

- common: dyspepsia, nausea, abdominal pain, vomiting

- uncommon: constipation, diarrhoea, flatulence, gastritis

- rare: stomatitis, peptic ulcer

- very rare: pancreatitis (very rare reports of pancreatitis have been noted with NSAIDs)

- not known: exacerbation of colitis and Crohn's disease, gastrointestinal haemorrhage and perforation, gastralgia, melaena, haematemesis

Gastrointestinal bleeding may sometimes be fatal, particularly in the elderly (see section 4.4 Special warnings and precautions for use).

Hepatobiliary disorders

- rare: hepatitis, transaminases increased, elevated serum bilirubin due to hepatitis disorders

- not known: abnormal liver function, jaundice

Skin and subcutaneous disorders

- uncommon: rash, pruritis

- not known: photosensitivity reactions, alopecia, urticaria, angioedema, bullous eruption including Stevens-Johnson syndrome and toxic epidermal necrolysis, exfoliative and bullous dermatoses (including epidermal necrolysis, erythema multiforme), purpura

Renal and urinary disorders

- not known: renal failure acute, tubulointerstitial nephritis, nephritic syndrome, renal function tests abnormal

General disorders and administration site conditions

- uncommon: oedema, fatigue

- not known: headache, taste perversion

Investigations

- rare: weight increased

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with an increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4 Special warnings and precautions for use).

In all cases of major adverse effects Orudis should be withdrawn at once.

4.9 Overdose

Symptoms

Cases of overdose have been reported with doses up to 2.5g of ketoprofen. In most instances, the symptoms observed have been benign and limited to lethargy, drowsiness, nausea, vomiting and epigastric pain. Headache, rarely diarrhoea, disorientation, excitation, coma, dizziness, tinnitus, fainting, occasionally convulsions may also occur. Adverse effects seen after overdose with propionic acid derivatives such as hypotension, bronchospasm and gastro-intestinal haemorrhage should be anticipated.

In cases of significant poisoning, acute renal failure and liver damage are possible.

If renal failure is present, haemodialysis may be useful to remove circulating medicinal product.

Therapeutic measures:

There are no specific antidotes to ketoprofen overdosages. In cases of suspected massive overdosages, a gastric lavage is recommended and symptomatic and supportive treatment should be instituted to compensate for dehydration, to monitor urinary excretion and to correct acidosis, if present.

Within one hour of ingestion, consideration should be given to administering activated charcoal.

Alternatively, in adults, gastric lavage should be considered if the patient presents within 1 hour of ingesting a potentially toxic amount.

Good urine output should be ensured.

Renal and liver function should be closely monitored.

Patients should be observed for at least four hours after ingestion of potentially toxic amounts.

Frequent or prolonged convulsions should be treated with intravenous diazepam.

The benefit of gastric decontamination is uncertain.

Other measures may be indicated by the patient's clinical condition.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Ketoprofen overall has the properties of a potent non-steroidal anti-inflammatory agent. It has the following pharmacological effects.

Anti-inflammatory

It inhibits the development of carageenan-induced abscesses in rats at 1mg/kg and UV-radiation induced erythema in guinea pigs at 6mg/kg. It is also a potent inhibitor of PGE2 and PGF2? synthesis in guinea pigs and human chopped lung preparations.

Analgesic

Ketoprofen effectively reduced visceral pain in mice caused by phenyl benzoquinone or by bradykinin following P.O. administration at about 6mg/kg.

Antipyretic

Ketoprofen (2 and 6mg/kg) inhibited hyperthermia caused by s.c. injection of brewer's yeast in rats and, at 1mg/kg, hyperthermia caused by i.v. administration of antigonococcal vaccine to rabbits.

Ketoprofen at 10mg/kg i.v. did not affect the cardiovascular, respiratory, central nervous system or autonomic nervous systems.

5.2 Pharmacokinetic Properties

Ketoprofen is completely absorbed from Orudis capsules and maximum plasma concentrations occur after ? - 1 hour. It declines thereafter with a elimination half-life of about 2 - 3 hours. There is no accumulation on continued daily dosing.

5.3 Preclinical Safety Data

No additional data of relevance to the prescriber

6. Pharmaceutical Particulars 6.1 List Of Excipients

Lactose, magnesium stearate

Capsule shells (Elanco & Scherer)

Opaque purple cap: Brilliant Blue FCF (E133), Erythrosine (E127), Titanium Dioxide (E171), Gelatin. Opaque green base: Brilliant Blue FCF (E133), Yellow iron Oxide (E172), Titanium Dioxide (E171), Gelatin

Capsule shells (Capsulgel)

Opaque purple cap: Patent Blue V (E131), Erythrosine (E127), Titanium Dioxide (E171), Gelatin. Opaque green base: Yellow iron Oxide (E172), Patent Blue V (E131), Titanium Dioxide (E171), Gelatin

6.2 Incompatibilities

None stated

6.3 Shelf Life

60 months

6.4 Special Precautions For Storage

Store in a dry place below 25°C. Protect from light.

6.5 Nature And Contents Of Container

Cardboard carton containing blister packs of 112 capsules

6.6 Special Precautions For Disposal And Other Handling

None stated.

7. Marketing Authorisation Holder

Sanofi-aventis

One Onslow Street

Guildford

Surrey

GU1 4YS

UK

8. Marketing Authorisation Number(S)

PL 04425/0576

9. Date Of First Authorisation/Renewal Of The Authorisation

13/09/2006

10. Date Of Revision Of The Text

11 May 2011

11. LEGAL CLASSIFICATION

POM


read more / Download


Oruvail I.M. Injection


1. Name Of The Medicinal Product

Oruvail IM Injection

2. Qualitative And Quantitative Composition

In terms of the active ingredient

Ketoprofen BP 100mg in 2 ml.

3. Pharmaceutical Form

Solution for IM injection

4. Clinical Particulars 4.1 Therapeutic Indications

Oruvail injection is recommended in the management of acute exacerbations of:

• Rheumatoid arthritis, osteoarthritis, ankylosing spondylitis.

• Periarticular conditions such as fibrositis, bursitis, capsulitis, tendinitis and tenosynovitis.

• Low back pain of musculoskeletal origin and sciatica.

• Other painful musculoskeletal conditions.

• Acute gout.

• Control of pain and inflammation following orthopaedic surgery.

4.2 Posology And Method Of Administration

Adults: 50 to 100 mg every four hours, repeated up to a maximum of 200 mg in twenty-four hours. Following a satisfactory response, oral therapy should be instituted with ketoprofen capsules. It is recommended that the injection should not normally be continued for longer than three days.

Elderly: The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy.

Paediatric dosage: not established.

Oruvail IM Injection is for intramuscular injection only.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4

4.3 Contraindications

Ketoprofen is contraindicated in patients who have a history of hypersensitivity reactions such as bronchospasm, asthmatic attacks, rhinitis, angioedema, urticaria or other allergic-type reactions to ketoprofen, any other ingredients in this medicine, ASA or other NSAIDs.

Ketoprofen is contraindicated in patients with hypersensitivity to any of the excipients of the drug.

Ketoprofen is also contraindicated in the third trimester of pregnancy.

Ketoprofen is contraindicated in the following cases:

-severe heart failure

-active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding)

-haemorrhagic diathesis

-severe hepatic insufficiency

-severe renal insufficiency

-third trimester of pregnancy

Ketoprofen is contraindicated in cases of cerebrovascular bleeding or any other active bleeding.

Ketoprofen is contraindicated in patients with haemostatic disorders or ongoing anticoagulant therapy.

4.4 Special Warnings And Precautions For Use

Oruvail injection is for intramuscular use only.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2 Posology and method of administration, and GI and cardiovascular risks below).

The use of ketoprofen with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5 Interactions).

Elderly:

The elderly have an increased risk of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation which may be fatal (see Section 4.2 Posology and method of administration).

Cardiovascular, Renal and Hepatic impairment:

At the start of treatment, renal function must be carefully monitored in patients with heart impairment, heart failure, liver dysfunction, cirrhosis and nephrosis, in patients receiving diuretic therapy, in patients with chronic renal impairment, particularly if the patient is elderly. In these patients, administration of ketoprofen may induce a reduction in renal blood flow caused by prostaglandin inhibition and lead to renal decomposition (see Section 4.3 Contra-indications).

Cardiovascular and cerebrovascular effects

Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long-term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for ketoprofen.

Respiratory disorders:

Patients with asthma combined with chronic rhinitis, chronic sinusitis, and/or nasal polyposis have a higher risk of allergy to aspirin and/or NSAIDs than the rest of the population. Administration of this medicinal product can cause asthma attacks or bronchospasm, particularly in subjects allergic to aspirin or NSAIDs (see section 4.3).

Gastrointestinal bleeding, ulceration and perforation:

GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events.

Some epidemiological evidence suggests that ketoprofen may be associated with a high risk of serious gastrointestinal toxicity, relative to some other NSAIDs, especially at high doses (see also section 4.2 and 4.3).

The risk of GI bleeding, ulceration or perforation is higher with increasing NSAlD doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), and in the elderly. These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and section 4.5).

NSAIDs should only be given with care to patients with a history of gastrointestinal disease (e.g. ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see Section 4.8 Undesirable effects).

Patients with a history of gastrointestinal toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding), particularly in the initial stages of treatment.

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (see section 4.5).

When GI bleeding or ulceration occurs in patients receiving ketoprofen, the treatment should be withdrawn.

SLE and mixed connective tissue disease:

In patients with systemic lupus erythematosis (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis (see section 4.8 Undesirable effects).

Impaired female fertility:

The use of ketoprofen, as with other NSAIDs, may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of ketoprofen should be considered.

Skin reactions:

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAlDs (see section 4.8). Patients appear to be at highest risk for these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Treatment should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Infectious disease:

As with other NSAIDs, in the presence of an infectious disease, it should be noted that the anti-inflammatory, analgesic and the antipyretic properties of ketoprofen may mask the usual signs of infection progression such as fever.

Risk of gastrointestinal bleeding: the relative risk increases in subjects who have a low body weight. If gastrointestinal bleeding or ulcer occur, treatment must be discontinued immediately.

Blood counts and liver and kidney function tests should be carried out during long-term treatment.

Hyperkalaemia:

Hyperkalaemia promoted by diabetes or concomitant treatment with potassium-sparing agents (see section 4.5 Interactions).

Potassium levels must be monitored regularly under these circumstances.

In patients with abnormal liver function tests or with a history of liver disease, transaminase levels should be evaluated periodically, particularly during long-term therapy.

Patients with active or a past history of peptic ulcer.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Anticoagulants (heparin and warfarin) and platelet aggregation inhibitors (i.e. ticlopidine, clopidogrel):

Increased risk of bleeding (see section 4.4).

If co-administration is unavoidable, patient should be closely monitored

Lithium:

Risk of elevation of lithium plasma levels, sometimes reaching toxic levels due to decreased lithium renal excretion. Where necessary, plasma lithium levels should be closely monitored and the lithium dosage levels adjusted during and after NSAIDs therapy.

Other analgesics/NSAIDs (including cyclooxygenase-2 selective inhibitors) and high dose salicylates:

Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects, particularly gastrointestinal ulceration and bleeding (see section 4.4 Special warnings and precautions for use).

Methotrexate:

Serious interactions have been recorded after the use of high dose methotrexate with NSAIDs, including ketoprofen, due to decreased elimination of methotrexate. At doses greater than 15mg/week: Increased risk of haematologic toxicity of methotrexate, particularly if administered at high doses (> 15mg/week), possibly related to displacement of protein-bound methotrexate and to its decreased renal clearance.

Allow at least 12 hours between the discontinuation or initiation of ketoprofen treatment and the administration of methotrexate.

At doses lower than 15mg/week: During the first weeks of combination treatment, full blood count should be monitored weekly. If there is any alteration of the renal function or if the patient is elderly, monitoring should be done more frequently.

Mifepristone:

NSAlDs should not be used for 8-12 days after mifepristone administration as NSAlDs can reduce the effect of mifepristone.

Antihypertensive agents (beta-blockers, angiotensin converting enzyme inhibitors, diuretics):

Risk of decreased antihypertensive potency (inhibition of vasodilator prostaglandins by NSAIDs).

Diuretics:

Risk of reduced diuretic effect. Patients and particularly dehydrated patients taking diuretics are at a greater risk of developing renal failure secondary to a decrease in renal blood flow caused by prostaglandin inhibition. Such patients should be rehydrated before initiating co-administration therapy and renal function monitored when the treatment is started (see section 4.4 Special warnings and precautions for use).

Cardiac glycosides:

NSAlDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.

Ciclosporin: Increased risk of nephrotoxicity, particularly in elderly subjects.

Quinolone antibiotics:

Animal data indicate that NSAlDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAlDs and quinolones may have an increased risk of developing convulsions.

Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus, particularly in elderly subjects.

Thrombolytics:

Increased risk of bleeding.

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding (see section 4.4 Special warnings and precautions for use).

ACE inhibitors and Angiotensin II Antagonists:

In patients with compromised renal function (e.g. dehydrated patients or elderly patients the co-administration of an ACE inhibitor or Angiotensin II antagonist and agents that inhibit cyclooxygenase may result in further deterioration of renal function, including possible acute renal failure.

Zidovudine:

Increased risk of haematological toxicity when NSAlDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

Risks related to hyperkalaemia:

Certain medicinal products or therapeutic categories can promote hyperkalaemia, i.e. potassium salts, potassium-sparing diuretics, converting enzyme inhibitors, angiotensin II receptor blockers, NSAIDs, heparins (low molecular-weight or unfractioned), ciclosporin, tacrolimus and trimethoprim. The occurrence of hyperkalaemia can depend on the presence of co-factors. This risk is enhanced when the drugs mentioned above are administered concomitantly.

Risks related to antiplatelet effect:

Several substances are involved in interactions due to their antiplatelet effects: tirofiban, eptifibarid, abcixiab, and iloprost. The use of several antiplatelet drugs enhances the risk of bleeding.

4.6 Pregnancy And Lactation

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimester of pregnancy, ketoprofen should not be given unless clearly necessary. If ketoprofen is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:

- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

- renal dysfunction, which may progress to renal failure with oligo-hydroamniosis; the mother and the neonate, at the end of the pregnancy, to:

- possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.

- Inhibition of uterine contractions resulting in delayed or prolonged labour.

Consequently, ketoprofen is contraindicated during the third trimester of pregnancy.

Lactation

No data are available on excretion of ketoprofen in human milk. Ketoprofen is not recommended in nursing mothers.

4.7 Effects On Ability To Drive And Use Machines

Patients should be warned about the potential for somnolence, dizziness or convulsions and be advised not to drive or operate machinery if these symptoms occur.

Patients should be warned of possible visual disturbances. If patients experience this, they should not drive or use machines.

4.8 Undesirable Effects

Gastrointestinal: The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4) have been r3eported following administration. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely.

Hypersensitivity: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) non-specific allergic reactions and anaphylaxis (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angiodema and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Local reactions can occur and may include pain or a burning sensation. In all cases of major adverse effects Oruvail should be withdrawn at once.

Cardiovascular and cerebrovascular:

Oedema, hypertension, and cardiac failure, have been reported in association with NSAID treatment.

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with an increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).

Other adverse reactions reported less commonly include:

Renal: Nephrotoxicity in various forms, including interstitial nephritis, nephritic syndrome and renal failure.

Hepatic: abnormal liver function, hepatitis and jaundice.

Neurological and special senses: Visual disturbances, optic neuritis, headaches, paraesthesia, reports of aseptic meningitis (especially in patients with existing autoimmune disorders, such as systemic lupus erythematosus, mixed connective tissue disease), with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation (See section 4.4) , depression, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, fatigue and drowsiness.

Haematological: Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.

Dermatological: Bullous reactions including Stevens Johnson Syndrome and Toxic Epidermal Necrolysis (very rare). Photosensitivity.

4.9 Overdose

Symptoms

In adults, the principal signs of overdose are headache, dizziness, drowsiness, nausea, vomiting, diarrhoea and abdominal pain. Disorientation, excitation, coma, tinnitus, fainting, occasionally convulsions may also occur. During severe intoxication, hypotension, respiratory depression and gastrointestinal bleeding have been observed.

Adverse effects seen after overdose with propionic acid derivatives such as hypotension, bronchospasm and gastro-intestinal haemorrhage should be anticipated.

In cases of significant poisoning, acute renal failure and liver damage are possible.

Therapeutic measures:

The patient must be transferred immediately to a specialised hospital setting where symptomatic treatment can begin.

There is no specific antidote.

Good urine output should be ensured.

Renal and liver function should be closely monitored.

Frequent or prolonged convulsions should be treated with intravenous diazepam.

Other measures may be indicated by the patient's clinical condition.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Ketoprofen is a pharmacopoeial non-steroidal anti-inflammatory drug (NSAID). It is a strong inhibitor of prostaglandin synthetase and potent analgesic agent. Studies in vitro and in vivo show that ketoprofen possesses powerful anti-inflammatory, antipyretic, antibradykinin and lysosomal membrane stabilising properties.

5.2 Pharmacokinetic Properties

Peak concentrations of approximately 10 mg/L are reached at about 0.5-0.75 H after a 100 mg dose. The elimination half life is approximately 1.88 H. Apart from earlier Tmax values, there are no significant differences between the pharmacokinetics of Oruvail IM injection and conventional release capsules (Orudis).

5.3 Preclinical Safety Data

No additional data of relevance to the prescriber.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Arginine

BP

Benzyl Alcohol

BP

Citric Acid anhydrous (E330)

BP

Water For Injections

BP

6.2 Incompatibilities

None stated

6.3 Shelf Life

36 months

6.4 Special Precautions For Storage

Store below 30°C. Protect from light.

6.5 Nature And Contents Of Container

Cartons containing 10 ampoules each having 2 ml. of injection.

6.6 Special Precautions For Disposal And Other Handling

None stated

7. Marketing Authorisation Holder

Sanofi-aventis

One Onslow Street

Guildford

Surrey, GU1 4YS, UK

8. Marketing Authorisation Number(S)

PL 04425/0377

9. Date Of First Authorisation/Renewal Of The Authorisation

15 November 2005

10. Date Of Revision Of The Text

11 May 2011

LEGAL CATEGORY

POM


read more / Download


Valsartan / hydrochlorothiazide 80 mg / 12.5 mg film-coated tablets


1. Name Of The Medicinal Product

Valsartan/hydrochlorothiazide 80 mg/12.5 mg film-coated tablets

2. Qualitative And Quantitative Composition

Each film-coated tablet contains 80 mg valsartan and 12.5 mg hydrochlorothiazide.

Excipient:

One tablet contains 16.27 mg lactose.

3. Pharmaceutical Form

Film-coated tablet.

The film-coated tablets are pink, oval, biconvex.

4. Clinical Particulars 4.1 Therapeutic Indications

Treatment of essential hypertension in adults.

Valsartan/hydrochlorothiazide fixed-dose combination is indicated in patients whose blood pressure is not adequately controlled on valsartan or hydrochlorothiazide monotherapy.

4.2 Posology And Method Of Administration

Posology

The recommended dose of Valsartan/hydrochlorothiazide 80 mg/12.5 mg is one film coated tablet once daily. Dose titration with the individual components is recommended. In each case, up- titration of individual components to the next dose should be followed in order to reduce the risk of hypotension and other adverse events.

When clinically appropriate direct change from monotherapy to the fixed dose combination may be considered in patients whose blood pressure is not adequately controlled on valsartan or hydrochlorothiazide monotherapy, provided the recommended dose titration sequence for the individual components is followed.

The clinical response to Valsartan/hydrochlorothiazide should be evaluated after initiating therapy and if blood pressure remains uncontrolled, the dose may be increased by increasing either one of the components to a maximum dose of valsartan/hydrochlorothiazide 320 mg/25 mg.

The antihypertensive effect is substantially present within 2 weeks.

In most patients, maximal effects are observed within 4 weeks. However, in some patients, 4-8 weeks treatment may be required. This should be taken into account during dose-titration.

Method of administration

Valsartan/hydrochlorothiazide can be taken with or without food and should be administered with water.

Special populations

Renal impairment

No dosage adjustment is required for patients with mild to moderate renal impairment (creatinine clearance

Hepatic impairment

In patients with mild to moderate hepatic impairment without cholestasis the dose of valsartan should not exceed 80 mg (see section 4.4). Valsartan/hydrochlorothiazide is contraindicated in patients with severe hepatic impairment (see sections 4.3, 4.4 and 5.2).

Elderly

No dose adjustment is required in elderly patients.

Paediatric patients

Valsartan/hydrochlorothiazide is not recommended for use in children below the age of 18 years due to a lack of data on safety and efficacy.

4.3 Contraindications

- Hypersensitivity to valsartan, hydrochlorothiazide, other sulfonamide-derived medicinal products or to any of the excipients.

- Second and third trimester of pregnancy (section 4.4 and 4.6).

- Severe hepatic impairment, biliary cirrhosis and cholestasis.

- Severe renal impairment (creatinine clearance <30 ml/min), anuria.

- Refractory hypokalaemia, hyponatraemia, hypercalcaemia, and symptomatic hyperuricaemia.

4.4 Special Warnings And Precautions For Use

Serum electrolyte changes

Valsartan

Concomitant use with potassium supplements, potassium sparing diuretics, salt substitutes containing potassium, or other agents that may increase potassium levels (heparin, etc.) is not recommended. Monitoring of potassium should be undertaken as appropriate.

Hydrochlorothiazide

Hypokalaemia has been reported under treatment with thiazide diuretics, including hydrochlorothiazide. Frequent monitoring of serum potassium is recommended.

Treatment with thiazide diuretics, including hydrochlorothiazide, has been associated with hyponatraemia and hypochloroaemic alkalosis. Thiazides, including hydrochlorothiazide, increase the urinary excretion of magnesium, which may result in hypomagnesaemia. Calcium excretion is decreased by thiazide diuretics. This may result in hypercalcaemia.

As for any patient receiving diuretic therapy, periodic determination of serum electrolytes should be performed at appropriate intervals.

Sodium and/or volume-depleted patients

Patients receiving thiazide diuretics, including hydrochlorothiazide, should be observed for clinical signs of fluid or electrolyte imbalance.

In severely sodium-depleted and/or volume-depleted patients such as those receiving high doses of diuretics, symptomatic hypotension may occur in rare cases after initiation of therapy with valsartan and hydrochlorothiazide. Sodium and/or volume depletion should be corrected before starting treatment with combination of valsartan and hydrochlorothiazide.

Patients with severe chronic heart failure or other conditions with stimulation the renin-angiotensin-aldosterone-system

In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure), treatment with angiotensin converting enzyme inhibitors has been associated with oliguria and/or progressive azotemia and in rare cases with acute renal failure. The use of combination of valsartan and hydrochlorothiazide in patients with severe chronic heart failure has not been established.

Hence it cannot be excluded that because of the inhibition of the renin-angiotensin-aldosterone system the application of valsartan and hydrochlorothiazide as well may be associated with impairment of the renal function. Valsartan/hydrochlorothiazide should not be used in these patients.

Renal artery stenosis

Valsartan/hydrochlorothiazide should not be used to treat hypertension in patients with unilateral or bilateral renal artery stenosis or stenosis to a solitary kidney, since blood urea and serum creatinine may increase in such patients.

Primary hyperaldosteronism

Patients with primary aldosteronism should not be treated with Valsartan/hydrochlorothiazide as their renin-angiotensin system is not activated.

Aortic and mitral valve stenosis, hypertrophic cardiomyopathy

As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or hypertrophic obstructive cardiomyopathy (HOCM).

Renal impairment

No doseage adjustment is required for patients with renal impairment with a creatinine clearance

Kidney transplantation

There is currently no experience on the safe use of Valsartan/hydrochlorothiazide in patients who have recently undergone kidney transplantation.

Hepatic impairment

In patients with mild to moderate hepatic impairment without cholestasis Valsartan/hydrochlorothiazide should be used with caution (see sections 4.2 and 5.2).

Systemic lupus erythematosus

Thiazide diuretics, including hydrochlorothiazide, have been reported to exacerbate or activate systemic lupus erythematosus.

Other metabolic disturbances

Thiazide diuretics, including hydrochlorothiazide, may alter glucose tolerance and raise serum levels of cholesterol, triglycerides, and uric acid. In diabetic patients dosage adjustments of insulin or oral hypoglycaemic agents may be required.

Thiazides may reduce urinary calcium excretion and cause an intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcaemia may be evidence of underlying hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.

Photosensitivity

Cases of photosensitivity reactions have been reported with thiazides diuretics (see section 4.8). If photosensitivity reaction occurs during treatment, it is recommended to stop the treatment. If a re-administration of the diuretic is deemed necessary, it is recommended to protect exposed areas to the sun or to artificial UVA.

Pregnancy

Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless continued AIIRAs therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).

General

Caution should be exercised in case of prior hypersensitivity to other angiotensin II receptor antagonists. Hypersensitivity reactions to are more likely in patients with allergy or asthma.

Lactose

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Interactions related to both valsartan and hydrochlorothiazide

Concomitant use not recommended

Lithium

Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant use of ACE inhibitors and thiazides, including hydrochlorothiazide. Due to the lack of experience with concomitant use of valsartan and lithium, this combination is not recommended. If the combination proves necessary, careful monitoring of serum lithium levels is recommended.

Concomitant use requiring caution

Other antihypertensive agents

Valsartan and hydrochlorothiazide combination may increase the effects of other agents with antihypertensive properties (e.g ACEI, beta-blockers, calcium channel blockers).

Pressor amines (e.g. noradrenaline, adrenaline)

Possible decreased response to pressor amines but not sufficient to preclude their use.

Non-steroidal anti-inflammatory medicines (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid >3 g/day), and non-selective NSAIDs

NSAIDS can attenuate the antihypertensive effect of both angiotensin II antagonists and hydrochlorothiazide when administered simultaneously. Furthermore, concomitant use of Valsartan/hydrochlorothiazide and NSAIDs may lead to worsening of renal function and an increase in serum potassium. Therefore, monitoring of renal function at the beginning of the treatment is recommended, as well as adequate hydration of the patient.

Interactions related to valsartan

Concomitant use not recommended

Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium and other substances that may increase potassium levels

If a medicinal product that affects potassium levels is considered necessary in combination with valsartan, monitoring of potassium plasma levels is advised.

No interaction

In drug interaction studies with valsartan, no interactions of clinical significance have been found with valsartan or any of the following substances: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide. Digoxin and indomethacin could interact with the hydrochlorothiazide component of Valsartan/hydrochlorothiazide (see interactions related to hydrochlorothiazide).

Interactions related to hydrochlorothiazide

Concomitant use requiring caution

Medicinal products associated with potassium loss and hypokalaemia (e.g. kaliuretic diuretics, corticosteroids, laxatives, ACTH, amphotericin, carbenoxolone, penicillin G, salicylic acid and derivatives).

If these medicinal products are to be prescribed with the hydrochlorothiazide-valsartan combination, monitoring of potassium plasma levels is advised. These medicinal products may potentiate the effect of hydrochlorothiazide on serum potassium (see section 4.4).

Medicinal products that could induce torsades de pointes

- Class Ia antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide)

- Class III antiarrhythmics (e.g. amiodarone, sotalol, dofetilide, ibutilide)

- Some antipsychotics: (e.g. thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol)

- Others: (e.g. bepridil, cisapride, diphemanil, erythromycin i.v., halofantrin, ketanserin, mizolastin, pentamidine, sparfloxacine, terfenadine, vincamine i.v.).

Due to the risk of hypokalemia, hydrochlorothiazide should be administered with caution when associated with medicinal products that could induce torsades de pointes.

Digitalis glycosides

Thiazide-induced hypokalaemia or hypomagnesaemia may occur as unwanted effect favoring the onset of digitalis-induced cardiac arrhythmias.

Calcium salts and vitamin D

Administration of thiazide diuretics, including hydrochlorothiazide, with vitamin D or with calcium salts may potentiate the rise in serum calcium.

Antidiabetic medicinal agents products (oral medicinal products and insulin)

The treatment with a thiazide may influence the glucose tolerance. Dose adjustment of the antidiabetic medicinal product may be necessary.

Metformin should be used with caution because of the risk of lactic acidosis induced by possible functional renal failure linked to hydrochlorothiazide.

Beta-blockers and diazoxide

Concomitant use of thiazide diuretics, including hydrochlorothiazide, with betablockers may increase the risk of hyperglycaemia. Thiazide diuretics, including hydrochlorothiazide, may enhance the hyperglycaemic effect of diazoxide.

Medicinal products used in the treatment of gout (probenecid, sulfinpyrazone and allopurinol)

Dosage adjustment of uricosuric medications may be necessary as hydrochlorothiazide may raise the level of serum uric acid. Increase of dosage of probenecid or sulfinpyrazone may be necessary. Co-administration of thiazide diuretics, including hydrochlorothiazide, may increase the incidence of hypersensitivity reactions to allopurinol.

Anticholinergic agents (e.g. atropine, biperiden)

The bioavailability of thiazide-type diuretics may be increased by anticholinergic agents, apparently due to a decrease in gastrointestinal motility and the stomach emptying rate.

Amantadine

Thiazides, including hydrochlorothiazide, may increase the risk of adverse effects caused by amantadine.

Colestyramine and colestipol resins

Absorption of thiazide diuretics, including hydrochlorothiazide, is impaired in the presence of anionic exchange resins.

Cytotoxic agents (e.g. cyclophosamide, methotrexate)

Thiazides, including hydrochlorothiazide, may reduce renal excretion of cytotoxic medicinal products and potentiate their myelosuppressive effects.

Nondepolarizing skeletal muscle relaxants (e.g. tubocurarine)

Thiazides, including hydrochlorothiazide, potentiate the action of curare derivatives.

Ciclosporin

Concomitant treatment with ciclosporin may increase the risk of hyperuricaemia and gout-type complications.

Alcohol, anaesthetics and sedatives

Potentiation of orthostatic hypotension may occur.

Methyldopa

There have been isolated reports of haemolytic anaemia in patients receiving concomitant treatment with methyldopa and hydrochlorothiazide.

Carbamazepine

Patients receiving hydrochlorothiazide concomitantly with carbamazepine may develop hyponatremia. Such patients should therefore be advised about the possibility of hyponatraemic reactions, and should be monitored accordingly.

Iodine contrast media

In case of diuretic-induced dehydration, there is an increased risk of acute renal failure, especially with high doses of the iodine product. Patients should be rehydrated before the administration.

4.6 Pregnancy And Lactation

Pregnancy

Given the effects of the individual components in this combination product on pregnancy, the use of Valsartan/hydrochlorothiazide is not recommended during the first trimester of pregnancy (see section 4.4). The use of < Product name > is contra-indicated during the 2nd and 3rd trimester of pregnancy (see section 4.3 and 4.4).

The use of AIIRAs is not recommended during the first trimester of pregnancy (see section 4.4). The use of AIIRAs is contra-indicated during the 2nd and 3rd trimester of pregnancy (see section 4.3 and 4.4).

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II Receptor Inhibitors (AIIRAs), similar risks may exist for this class of drugs. Unless continued ARB therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately and, if appropriate, alternative therapy should be started.

Exposure to AIIRA therapy during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). (See also 5.3 'Preclinical safety data')

Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.

Infants whose mothers have taken AIIRAs should be closely observed for hypotension (see also section 4.3 and 4.4).

There is limited experience with hydrochlorothiazide during pregnancy, especially during the first trimester. Animal studies are insufficient.

Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action of hydrochlorothiazide its use during the second and third trimester may compromise foeto-placental perfusion and may cause foetal and neonatal effects like icterus, disturbance of electrolyte balance and thrombocytopenia.

Hydrochlorothiazide should not be used for gestational oedema, gestational hypertension or preeclampsia due to the risk of decreased plasma volume and placental hypoperfusion, without a beneficial effect on the course of the disease.

Hydrochlorothiazide should not be used for essential hypertension in pregnant women except in rare situations where no other treatment could be used.

Lactation

Because no information is available regarding the use of Valsartan/hydrochlorothiazide during breastfeeding, Valsartan/hydrochlorothiazide is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

4.7 Effects On Ability To Drive And Use Machines

No studies on the effects of valsartan-hydrochlorothiazide combination, on the ability to drive and use machines have been performed. When driving vehicles or operating machines it should be taken into account that occasionally dizziness or weariness may occur.

4.8 Undesirable Effects

Fixed-dose combination

Adverse reactions reported in clinical trials and laboratory findings occurring more frequently with valsartan plus hydrochlorothiazide versus placebo and individual postmarketing reports are presented below according to system organ class. Adverse reactions known to occur with each component given individually but which have not been seen in clinical trials may occur during treatment with valsartan /hydrochlorothiazide.

Adverse reactions are ranked by frequency, the most frequent first, using the following convention: very common (

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Table 1. Frequency of adverse reactions with valsartan/hydrochlorothiazide

Metabolism and nutrition disorders

 

Uncommon

Dehydration

Nervous system disorders

 

Very rare

Dizziness

Uncommon

Paraesthesia

Not known

Syncope

Eye disorders

 

Uncommon

Vision blurred

Ear and labyrinth disorders

 

Uncommon

Tinnitus

Vascular disorders

 

Uncommon

Hypotension

Respiratory, thoracic and mediastinal disorders

 

Uncommon

Cough

Not known

Non cardiogenic pulmonary oedema

Gastrointestinal disorders

 

Very rare

Diarrhoea

Musculoskeletal and connective tissue disorders

 

Uncommon

Myalgia

Very rare

Arthralgia

Renal and urinary disorders

 

Not known

Impaired renal function

General disorders and administration site conditions

 

Uncommon

Fatigue

Investigations

 

Not known

Serum uric acid increased, Serum bilirubin and Serum creatinine increased, Hypokalaemia, Hyponatraemia, Elevation of Blood Urea Nitrogen, Neutropenia

Additional information on individual components

Adverse reactions previously reported with one of the individual components may be potential undesirable effects with combination ofvalsartan and hydrochlorothiazide as well, even if not observed in clinical trials or during postmarketing period.

Table 2. Frequency of adverse reactions with valsartan

Blood and lymphatic system disorders

 

Not known

Decrease in haemoglobin, decrease in haematocrit, thrombocytopenia

Immune system disorders

 

Not known

Other hypersensitivity/allergic reactions including serum sickness

Metabolism and nutrition disorders

 

Not known

Increase of serum potassium

Ear and labyrinth disorders

 

Uncommon

Vertigo

Vascular disorders

 

Not known

Vasculitis

Gastrointestinal disorders

 

Uncommon

Abdominal pain

Hepatobiliary disorders

 

Not known

Elevation of liver function values

Skin and subcutaneous tissue disorders

 

Not known

Angioedema, rash, pruritus

Renal and urinary disorders

 

Not known

Renal failure

Table 3. Frequency of adverse reactions with hydrochlorothiazide

Hydrochlorothiazide has been extensively prescribed for many years, frequently in higher doses than those administered with Valsartan/hydrochlorothiazide. The following adverse reactions have been reported in patients treated with monotherapy of thiazide diuretics, including hydrochlorothiazide:

Blood and lymphatic system disorders

 

Rare

Thrombocytopenia sometimes with purpura

Very rare

Agranulocytosis, leucopenia, haemolytic anaemia, bone marrow depression

Immune system disorders

 

Very rare

Hypersenstivity reactions

Psychiatric disorders

 

Rare

Depression, sleep disturbances

Nervous system disorders

 

Rare

Headache

Cardiac disorders

 

Rare

Cardiac arrhythmias

Vascular disorders

 

Common

Postural hypotension

Respiratory, thoracic and mediastinal disorders

 

Very rare

Respiratory distress including pneumonitis and pulmonary oedema

Gastrointestinal disorders

 

Common

Loss of appetite, mild nausea and vomiting

Rare

Constipation, gastrointestinal discomfort

Very rare

Pancreatitis

Hepatobiliary disorders

 

Rare

Intrahepatic cholestasis or jaundice

Skin and subcutaneous tissue disorders

 

Common

Urticaria and other forms of rash

Rare

Photosensitisation

Very rare

Necrotising vasculitis and toxic epidermal necrolysis, cutaneous lupus erythematosus-like reactions, reactivation of cutaneous lupus erythematosus

Reproductive system and breast disorders

 

Common

Impotence

4.9 Overdose

Symptoms

Overdose with valsartan may result in marked hypotension, which could lead to depressed level of consciousness, circulatory collapse and/or shock. In addition, the following signs and symptoms may occur due to an overdose of the hydrochlorothiazide component: nausea, somnolence, hypovolaemia, and electrolyte disturbances associated with cardiac arrhythmias and muscle spasms.

Treatment

The therapeutic measures depend on the time of ingestion and the type and severity of the symptoms, stabilisation of the circulatory condition being of prime importance.

If hypotension occurs, the patient should be placed in the supine position and salt and volume supplementation should be given rapidly.

Valsartan cannot be eliminated by means of haemodialysis because of its strong plasma binding behaviour whereas clearance of hydrochlorothiazide will be achieved by dialysis.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: angiotensin II antagonists and diuretics, ATC code: C09DA03.

Valsartan/hydrochlorothiazide

In a double-blind, randomised, active-controlled trial in patients not adequately controlled on hydrochlorothiazide 12.5 mg, significantly greater mean systolic/diastolic BP reductions were observed with the combination of valsartan/hydrochlorothiazide 80/12.5 mg (14.9/11.3 mmHg) compared to hydrochlorothiazide 12.5 mg (5.2/2.9 mmHg) and hydrochlorothiazide 25 mg (6.8/5.7 mmHg). In addition, a significantly greater percentage of patients responded (diastolic BP <90 mmHg or reduction

In a double-blind, randomised, active-controlled trial in patients not adequately controlled on valsartan 80 mg, significantly greater mean systolic/diastolic BP reductions were observed with the combination of valsartan/hydrochlorothiazide 80/12.5 mg (9.8/8.2 mmHg) compared to valsartan 80 mg (3.9/5.1 mmHg) and valsartan 160 mg (6.5/6.2 mmHg). In addition, a significantly greater percentage of patients responded (diastolic BP <90 mmHg or reduction

In a double-blind, randomised, placebo-controlled, factorial design trial comparing various dose combinations of valsartan/hydrochlorothiazide to their respective components, significantly greater mean systolic/diastolic BP reductions were observed with the combination of valsartan/hydrochlorothiazide 80/12.5 mg (16.5/11.8 mmHg) compared to placebo (1.9/4.1 mmHg) and both hydrochlorothiazide 12.5 mg (7.3/7.2 mmHg) and valsartan 80 mg (8.8/8.6 mmHg). In addition, a significantly greater percentage of patients responded (diastolic BP <90 mmHg or reduction

Dose-dependent decreases in serum potassium occurred in controlled clinical studies with valsartan + hydrochlorothiazide. Reduction in serum potassium occurred more frequently in patients given 25 mg hydrochlorothiazide than in those given 12.5 mg hydrochlorothiazide. In controlled clinical trials with valsartan/hydrochlorothiazide the potassium lowering effect of hydrochlorothiazide was attenuated by the potassium-sparing effect of valsartan.

Beneficial effects of valsartan in combination with hydrochlorothiazide on cardiovascular mortality and morbidity are currently unknown.

Epidemiological studies have shown that long-term treatment with hydrochlorothiazide reduces the risk of cardiovascular mortality and morbidity.

Valsartan

Valsartan is an orally active and specific angiotensin II (Ang II) receptor antagonist. It acts selectively on the AT1 receptor subtype, which is responsible for the known actions of angiotensin II. The increased plasma levels of Ang II following AT1 receptor blockade with valsartan may stimulate the unblocked AT2 receptor, which appears to counterbalance the effect of the AT1 receptor. Valsartan does not exhibit any partial agonist activity at the AT1 receptor and has much (about 20,000 fold) greater affinity for the AT1 receptor than for the AT2 receptor. Valsartan is not known to bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.

Valsartan does not inhibit ACE, also known as kininase II, which converts Ang I to Ang II and degrades bradykinin. Since there is no effect on ACE and no potentiation of bradykinin or substance P, angiotensin II antagonists are unlikely to be associated with coughing. In clinical trials where valsartan was compared with an ACE inhibitor, the incidence of dry cough was significantly (P <0.05) lower in patients treated with valsartan than in those treated with an ACE inhibitor (2.6% versus 7.9% respectively). In a clinical trial of patients with a history of dry cough during ACE inhibitor therapy, 19.5% of trial subjects receiving valsartan and 19.0% of those receiving a thiazide diuretic experienced cough compared to 68.5% of those treated with an ACE inhibitor (P <0.05).

Administration of valsartan to patients with hypertension results in reduction of blood pressure without affecting pulse rate. In most patients, after administration of a single oral dose, onset of antihypertensive activity occurs within 2 hours, and the peak reduction of blood pressure is achieved within 4-6 hours. The antihypertensive effect persists over 24 hours after dosing. During repeated dosing, the maximum reduction in blood pressure with any dose is generally attained within 2-4 weeks and is sustained during long-term therapy. Combined with hydrochlorothiazide, a significant additional reduction in blood pressure is achieved.

Abrupt withdrawal of valsartan has not been associated with rebound hypertension or other adverse clinical events.

In hypertensive patients with type 2 diabetes and microalbuminuria, valsartan has been shown to reduce the urinary excretion of albumin. The MARVAL (Micro Albuminuria Reduction with Valsartan) study assessed the reduction in urinary albumin excretion (UAE) with valsartan (80-160 mg/od) versus amlodipine (5-10 mg/od), in 332 type 2 diabetic patients (mean age: 58 years; 265 men) with microalbuminuria (valsartan: 58 ?g/min; amlodipine: 55.4 ?g/min), normal or high blood pressure and with preserved renal function (blood creatinine <120 ?mol/l). At 24 weeks, UAE was reduced (p <0.001) by 42% (–24.2 ?g/min; 95% CI: –40.4 to –19.1) with valsartan and approximately 3% (–1.7 ?g/min; 95% CI: –5.6 to 14.9) with amlodipine despite similar rates of blood pressure reduction in both groups. The Diovan Reduction of Proteinuria (DROP) study further examined the efficacy of valsartan in reducing UAE in 391 hypertensive patients (BP=150/88 mmHg) with type 2 diabetes, albuminuria (mean=102 ?g/min; 20–700 ?g/min) and preserved renal function (mean serum creatinine = 80 ?mol/l). Patients were randomised to one of 3 doses of valsartan (160, 320 and 640 mg/od) and treated for 30 weeks. The purpose of the study was to determine the optimal dose of valsartan for reducing UAE in hypertensive patients with type 2 diabetes. At 30 weeks, the percentage change in UAE was significantly reduced by 36% from baseline with valsartan 160 mg (95%CI: 22 to 47%), and by 44% with valsartan 320 mg (95%CI: 31 to 54%). It was concluded that 160-320 mg of valsartan produced clinically relevant reductions in UAE in hypertensive patients with type 2 diabetes.

Hydrochlorothiazide

The site of action of thiazide diuretics is primarily in the renal distal convoluted tubule. It has been shown that there is a high-affinity receptor in the renal cortex as the primary binding site for the thiazide diuretic action and inhibition of NaCl transport in the distal convoluted tubule. The mode of action of thiazides is through inhibition of the Na+Cl- symporter perhaps by competing for the Cl- site, thereby affecting electrolyte reabsorption mechanisms: directly increasing sodium and chloride excretion to an approximately equal extent, and indirectly by this diuretic action reducing plasma volume, with consequent increases in plasma renin activity, aldosterone secretion and urinary potassium loss, and a decrease in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so with co-administration of valsartan the reduction in serum potassium is less pronounced as observed under monotherapy with hydrochlorothiazide.

5.2 Pharmacokinetic Properties

Valsartan/hydrochlorothiazide

The systemic availability of hydrochlorothiazide is reduced by about 30% when co-administered with valsartan. The kinetics of valsartan are not markedly affected by the co-administration of hydrochlorothiazide. This observed interaction has no impact on the combined use of valsartan and hydrochlorothiazide, since controlled clinical trials have shown a clear anti-hypertensive effect, greater than that obtained with either active substance given alone, or placebo.

Valsartan

Absorption

Following oral administration of valsartan alone, peak plasma concentrations of valsartan are reached in 2–4 hours. Mean absolute bioavailability is 23%. Food decreases exposure (as measured by AUC) to


read more / Download


Norinyl-1


Norinyl-1

Please read this leaflet carefully before you start to take Norinyl-1.

This leaflet gives you some information about how to take your pills. The leaflet can’t tell you everything about Norinyl-1. So if you have any questions or are not sure about anything, ask your doctor, clinic or pharmacist.

Some information about Norinyl-1

Norinyl-1 contains two hormones - a progestogen hormone called norethisterone and an oestrogen hormone called mestranol. These two hormones act together to prevent pregnancy.

What is in Norinyl-1?

Each Norinyl-1 pill contains:

1 milligram of norethisterone and 50 micrograms of mestranol (the ‘active’ ingredients); and maize starch, polyvidone, magnesium stearate and lactose (the ‘inactive’ ingredients).

Norinyl-1 pills are white and have the word ‘SEARLE’ on one side and ‘1’ on the other side. They are packed in blister strips and come in packs of 63 pills.

Who supplies Norinyl-1?

Norinyl-1 is supplied by:

PHARMACIA

Pharmacia Limited Ramsgate Road Sandwich Kent CT13 9NJ UK Who makes Norinyl-1?

Norinyl-1 is made by:

Pharmacia Limited Morpeth Northumberland NE61 3YA UK What is Norinyl-1 for?

Norinyl-1 is a combined oral contraceptive pill you take to prevent you becoming pregnant.

Before you take Norinyl-1

Norinyl-1 may not be suitable for all women. Before you take Norinyl-1, make sure your doctor knows if you have ever had any of the following conditions.

Blood clots in the legs, blood clots in varicose veins, the lungs, the brain or elsewhere (coronary and cerebral thrombotic disorders). A heart attack, angina or a stroke. High levels of fats in your blood (hyperlipidaemia or other disorders of body fats). Cancer of the breast, cervix, vagina or womb (mammary or endometrial cancer). If during pregnancy you had: pruritus (itching of the whole body); jaundice, for which your doctor could not find the cause; or pemphigoid gestationis (a rash previously known as herpes gestationis). Certain types of jaundice (Dubin-Johnson or Rotor syndrome). Bad migraines. Vaginal bleeding, for which your doctor could not find the cause. Liver tumours. Liver disease.

If you are pregnant or are trying to get pregnant, you should not take the pill.

What I should know before taking Norinyl-1

If you had irregular periods or no periods in the past, you may stop ovulating (releasing eggs from your ovaries). You may also stop having normal periods after you have stopped using the combined pill. If you have any of these conditions you may find it better to use a different contraceptive method. You should ask your doctor or clinic for advice.

It is possible that sometimes certain long-term diseases may get worse while you are taking the pill. See the section, ‘Reasons for careful medical checks’.

The pill and thrombosis

Some evidence suggests that women who take the pill are more likely to develop various blood circulation disorders than women who don’t take the pill.

A thrombosis is a blood clot. A thrombosis can develop in veins or in arteries and can cause a blockage. The chance of a thrombosis forming in women taking the pill and women not taking the pill is rare. When blood clots form in the arteries they can cause chest pain (angina), strokes (blood clots in or bleeding from the blood vessels in the brain) and heart attacks.

If blood clots form in veins, they can often be treated with no long term long term danger. On rare occasions a piece of thrombosis may break off. It can travel to the lungs to cause a condition called pulmonary embolism. Therefore in rare cases a thrombosis can cause serious permanent disability or could even be fatal.

It is important to note that a thrombosis can form in people who are not taking the pill as well as those who are taking it. The risk is higher in women who take the pill than in women who don’t take the pill, but is not as high as the risk during pregnancy. The excess risk of thrombosis is highest during the first year a woman ever uses a combined oral contraceptive pill.

For healthy non-pregnant women:

the chance of having a blood clot is about 5 in 100,000 each year.

For women taking the pill containing either levongestrel or norethisterone (a second generation pill):

the chance of having a blood clot is about 15 in 100,000 each year.

For women taking the pill containing desogestrel or gestodene (a third generation pill):

the chance of having a blood clot is about 25 in 100,000 each year.

For women who are pregnant:

the chance of having a blood clot is about 60 in 100,000 pregnancies.

The risk of heart attacks and strokes for women who use the combined pill increases with age and smoking. Other conditions also increase the risk of blood clots in the arteries. These include being greatly overweight, having diseased arteries (atherosclerosis), high blood pressure during pregnancy (pre-eclamptic toxaemia), high blood levels of cholesterol, and diabetes. If you have any of these conditions, you should check with your doctor or clinic to see if the pill is suitable for you. Smokers over 35 are usually told to stop taking these pills.

Breast Cancer

Every woman is at risk of breast cancer whether or not she takes the pill. Breast cancer is rare under the age of 40 years, but the risk increases as a woman gets older.

Breast cancer has been found slightly more often in women who take the pill than in women of the same age who do not take the pill. If women stop taking the pill, this reduces the risk so that 10 years after stopping the pill, the risk of finding breast cancer is the same as for women who have never taken the pill. Breast cancer seems less likely to have spread when found in women who take the pill than in women who do not take the pill.

It is not certain whether the pill causes the increased risk of breast cancer. It may be that women taking the pill are examined more often, so that breast cancer is noticed earlier. The risk of finding breast cancer is not affected by how long a woman takes the pill but by the age at which she stops. This is because the risk of breast cancer strongly increases as a woman gets older.

The chart below shows the background chances of breast cancer at various ages for 10,000 women who have never taken the pill (black bars) and for 10,000 women whilst taking the pill and during the 10 years after stopping it (grey bars). The small extra risk of finding breast cancer can be seen for each age group. This small possible additional risk in women who take the pill has to be balanced against the fact that the pill is a very effective contraceptive and it helps prevent cancer of the womb or ovary.

Taking any medicine carries some risk. You can use the information in this leaflet, and the advice your doctor or clinic has given you to weigh up the risks and benefits of taking the pill. Don’t be embarrassed, ask as many questions as you need to.

Reasons for careful medical checks

Your doctor or clinic will give you regular check-ups while you are taking Norinyl-1. Your blood pressure will be checked before you start the pill and then at regular intervals whilst you are on the pill. If your blood pressure goes up, your doctor may tell you to stop taking Norinyl-1. They may also check your breasts and reproductive organs, including taking a cervical smear at regular intervals, if this is considered necessary by the doctor.

Tell your doctor if you have any of the following conditions.

Migraine, asthma, epilepsy, heart or kidney disease, high blood pressure (hypertension) or you have a previous history of these conditions. This is because the pill may cause fluid retention which can make these conditions worse. Diabetes.

If you have any of the following conditions and they appear to get worse or they appear for the first time, your doctor or clinic may tell you to stop taking the pill.

High blood pressure. Diabetes. Multiple sclerosis Tetany (muscle twitches) Breast problems Varicose veins. Migraine. Epilepsy. Kidney disease. Severe depression. Fibroids in your uterus. Gallstones. Liver problems. Sickle-cell anaemia. Diseases of the heart and blood vessels (cardiovascular disease). Otosclerosis (an inherited form of deafness). Porphyria (a metabolic disease). Chloasma (brown patches on your skin which can happen during pregnancy but may not fade completely). Any disease that is likely to get worse during pregnancy.

If you use any combined pill you may retain fluid which can make it uncomfortable to wear contact lenses.

Other medicines and Norinyl-1

Several medicines can interfere with the way the pill works. These include some drugs that treat epilepsy, arthritis, tuberculosis and some antibiotics or sedatives. Other less common medicines may also have this effect. You may have to use another contraceptive method, such as a condom, while you are taking these medicines and during the next seven days. In some situations, your doctor or clinic may tell you to use extra precautions for longer. If while using these extra precautions you run beyond the end of the blister strip, start the next blister strip without a break. Always mention you are on the pill if a doctor, dentist or hospital prescribes you any medicine.

The herbal remedy St John’s wort (Hypericum perforatum) should not be taken at the same time as this medicine. If you already take a St John’s wort preparation, stop taking the St John’s wort and mention it to your doctor.

Blood tests

The pill may affect the results of certain blood tests, so tell your doctor that you are on the pill if you need any blood tests.

How to take Norinyl-1 Starting your first blister strip Take the first pill on your first day of bleeding. This is the day when your period starts. If you are not having periods, ask your doctor or clinic when you should start taking your pill. Take the pill marked with the correct day of the week. You will be protected at once as long as you take a pill every day. You can take the pill at a time that suits you, but you must take it at about the same time every day. Take a pill every day until you finish a blister strip. If you cannot start the pill on the first day of your period you may start to take it on any day up to the fifth day. However, if you do this, you may not be protected for the first seven days, so you should use another method of contraception such as a condom during those days. Starting the next blister strip Once you have finished all 21 pills, stop for seven days. You will probably bleed during some or all of these seven days. Then, start the next blister strip. Do this whether or not you are still bleeding. You will always start the next blister strip on the same day of the week. You are protected during the seven day break, but only if you start to take the next blister strip on time. The first pill in your blister strip is the worst pill of all to miss or take late. What do I do if I have a stomach upset or I am sick?

Norinyl-1 may not work if you are sick or have severe diarrhoea. You should carry on taking your pills as normal, but use a condom while you are ill and for the next seven days. If these seven days run beyond the end of the blister strip, start the next blister strip without a break.

What do I do if I miss a period?

If you have taken all your pills properly, it is very unlikely that you are pregnant. Take your next blister strip as normal. If you have not taken them correctly, see your doctor or clinic at once. You should do the same if you miss a second period. If you do get pregnant whilst you are taking this type of pill there may be a very small increased risk that your baby will have an abnormality. Ask your doctor to discuss this risk with you.

What do I do if my periods are different?

This is normal when you start the pill. You will probably have less bleeding. You may also have a little bleeding while you are taking the pills (this is called ‘break-through bleeding’). If this happens, do not stop taking your pills. This should stop within two or three months. If the bleeding is heavy, do not stop taking the pill but talk to your doctor or clinic. If your periods seem different, do not stop taking the pills and just mention it to your doctor or clinic at your next visit.

What do I do if I am having an operation?

If you are planning to have an operation, which will mean lying in bed for more than a whole day, or any operation on your legs, it is best that you stop taking this type of pill at least four weeks before your operation. This does not apply to some minor operations. You can usually start to take the pill again two weeks after the operation. Talk to your doctor or clinic about another method of contraception you can use until the operation. For example, you may use a progestogen-only pill.

If you are having treatment for varicose veins, stop taking the combined pill four weeks before your treatment and stay off it until 3 months after your last treatment.

What do I do if I have an accident or I am ill?

If you have an accident or illness which means that you will have to stay in bed, it is best to stop taking the pill until you are active again.

Smoking

Smoking increases the risks to your health and some of the risks of taking the pill. It is always best to stop smoking. If you do smoke, your doctor or clinic may tell you to change your method of contraception when you are 35 or over.

What do I do if I want a baby?

If you want to have a baby it is best to wait until you have stopped taking the pill for three months or at least until your regular periods have returned. You can always use another contraceptive method such as a condom. Only rarely do regular periods take some time to return. Once you have had one period, it is easier to work out when your baby is due. However, if you do get pregnant as soon as you stop taking Norinyl-1, this is not harmful.

What do I do if I am changing pill brands?

Take the first pill of your new blister strip on the day immediately after you have finished your old blister strip. Your period will usually be delayed until the new blister strip is finished, but you may have some break-through bleeding during the first few days of the new blister strip. This is quite normal and you will still be protected against pregnancy. If you do have a break, ask your doctor or clinic whether you need an extra contraceptive method such as a condom.

What do I do if I have just had a baby? If you are breast feeding, you should not take the combined pill. This is because the oestrogen in the pill may reduce the amount of milk you produce. You should be able to take the progestogen-only pill instead. Ask your doctor or clinic for advice. If you are not breast feeding, you may start taking the pill 21 days after your baby is born. This will protect you immediately. If you start later than this, you may not be protected until you have taken the pill for seven days. What do I do if I have just had a miscarriage or abortion?

You may be able to start taking the pill immediately. If you can, you will be protected straight away. Ask your doctor or clinic if you should do so.

Overdose

If you take more than the recommended number of pills, or if you discover someone has taken a lot of pills, contact your doctor immediately.

What do I do if I forget to take a pill? If you forget to take a pill take it as soon as you remember and take the next one at your normal time. This may mean taking two pills on the same day. If you are 12 or more hours late in taking one or more pills, it may not work. As soon as you remember, take your last missed pill and carry on taking your pills normally. However, you may not be protected for the next seven days, so either avoid sexual intercourse or use an extra contraceptive method, such as a condom. If you have fewer than seven pills in your blister strip after you have missed taking your pill, you should complete the blister strip and start the next blister strip without a break. This will give you protection from when you took the last missed pill. You may not have a period until the end of two blister strips, but this will not harm you. You may also have some bleeding on days when you take the pill. Norinyl-1 Side Effects

All medicines can sometimes cause problems. If you are worried about side effects, talk to your doctor. These effects should become less of a problem as your body becomes used to the pills. You may notice a change in your sex drive, and have irregular vaginal bleeding or changes in your period.

Other side effects that you might have include nausea, stomach upsets, tender breasts, weight gain, changes in appetite, headaches, depression, high blood pressure, and changes in the way your body breaks down sugars, fats or vitamins. If you have fibroids in your uterus, these may also get worse.

Reasons to get medical help immediately

The cause of these symptoms may have nothing to do with the pill but you may need treatment. Stop taking your pills at once and tell your doctor if you have:

a sudden sharp or severe pain in the chest; suddenly become short of breath or breathing is painful; coughed up blood; painful or inflamed veins in your legs; a crushing type of chest pain or your chest feels heavy; a very first attack of migraine (a bad headache with sickness); migraines which get worse, especially if your sight is affected, you see flashing lights, your limbs feel weak, you lose the sensation or feel a different sensation in your limbs, or you have a fit; sudden and unusual severe headaches; dizziness or you faint; a problem with your sight or speech; swollen arms or legs; jaundice (your skin or the whites of your eyes look yellow); a severe rash; or swelling or tenderness in your stomach. How to store Norinyl-1

Store your Norinyl-1 pills in a dry place, away from direct sunlight and below 25°C. Make sure children cannot see or reach them.

Don’t take Norinyl-1 after the ‘expiry date’ shown on the box. If your pack is out of date, take it to your pharmacist who will get rid of the pills safely.

If you have any comments on the way this leaflet is written, please write to Medical Information at Pharmacia Limited.

This leaflet was written in May 2007.

Norinyl-1 is a contraceptive. It will not protect you against sexually-transmitted diseases including AIDS. For safer sex, use a condom as well as your usual contraceptive.

Norinyl-1 and Pharmacia are registered trademarks.

Ref: NR2_0


read more / Download


Ramipril 1.25 mg Capsules (Winthrop Pharmaceuticals UK Ltd)


1. Name Of The Medicinal Product

Ramipril 1.25 mg Capsules

2. Qualitative And Quantitative Composition

1.25 mg ramipril.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Yellow opaque/white opaque hard gelatin capsules.

4. Clinical Particulars 4.1 Therapeutic Indications - Treatment of hypertension.

- Cardiovascular prevention: reduction of cardiovascular morbidity and mortality in patients with:

    o manifest atherothrombotic cardiovascular disease (history of coronary heart disease or stroke, or peripheral vascular disease) or

o diabetes with at least one cardiovascular risk factor (see section 5.1).

- Treatment of renal disease:     o Incipient glomerular diabetic nephropathy as defined by the presence of microalbuminuria,

o Manifest glomerular diabetic nephropathy as defined by macroproteinuria in patients with at least one cardiovascular risk factor (see section 5.1),

o Manifest glomerular non diabetic nephropathy as defined by macroproteinuria

- Treatment of symptomatic heart failure.

- Secondary prevention after acute myocardial infarction: reduction of mortality from the acute phase of myocardial infarction in patients with clinical signs of heart failure when started > 48 hours following acute myocardial infarction.

4.2 Posology And Method Of Administration

Oral use.

It is recommended that ramipril capsules are taken each day at the same time of the day.

Ramipril capsules can be taken before, with or after meals, because food intake does not modify its bioavailability (see section 5.2).

Ramipril capsules should be swallowed with liquid. They must not be chewed or crushed.

Adults

Diuretic-Treated patients

Hypotension may occur following initiation of therapy with ramipril; this is more likely in patients who are being treated concurrently with diuretics. Caution is therefore recommended since these patients may be volume and/or salt depleted.

If possible, the diuretic should be discontinued 2 to 3 days before beginning therapy with ramipril (see section 4.4).

In hypertensive patients in whom the diuretic is not discontinued, therapy with ramipril should be initiated with a 1.25 mg dose. Renal function and serum potassium should be monitored. The subsequent dosage of ramipril should be adjusted according to blood pressure target.

Hypertension

The dose should be individualised according to the patient profile (see section 4.4) and blood pressure control.

Ramipril may be used in monotherapy or in combination with other classes of antihypertensive medicinal products.

Starting dose

Ramipril should be started gradually with an initial recommended dose of 2.5 mg daily.

Patients with a strongly activated renin-angiotensin-aldosterone system may experience an excessive drop in blood pressure following the initial dose. A starting dose of 1.25 mg is recommended in such patients and the initiation of treatment should take place under medical supervision (see section 4.4).

Titration and maintenance dose

The dose can be doubled at interval of two to four weeks to progressively achieve target blood pressure; the maximum permitted dose of ramipril is 10 mg daily. Usually the dose is administered once daily.

Cardiovascular prevention

Starting dose

The recommended initial dose is 2.5 mg of ramipril once daily.

Titration and maintenance dose

Depending on the patient's tolerability to the active substance, the dose should be gradually increased. It is recommended to double the dose after one or two weeks of treatment and - after another two to three weeks - to increase it up to the target maintenance dose of 10 mg ramipril once daily.

See also posology on diuretic treated patients above.

Treatment of renal disease

In patients with diabetes and microalbuminuria:

Starting dose:

The recommended initial dose is 1.25 mg of ramipril once daily.

Titration and maintenance dose

Depending on the patient's tolerability to the active substance, the dose is subsequently increased. Doubling the once daily dose to 2.5 mg after two weeks and then to 5 mg after a further two weeks is recommended.

In patients with diabetes and at least one cardiovascular risk

Starting dose:

The recommended initial dose is 2.5 mg of ramipril once daily.

Titration and maintenance dose

Depending on the patient's tolerability to the active substance, the dose is subsequently increased. Doubling the daily dose to 5 mg ramipril after one or two weeks and then to 10 mg ramipril after a further two or three weeks is recommended. The target daily dose is 10 mg.

In patients with non- diabetic nephropathy as defined by macroproteinuria

Starting dose:

The recommended initial dose is 1.25 mg of ramipril once daily.

Titration and maintenance dose

Depending on the patient's tolerability to the active substance, the dose is subsequently increased. Doubling the once daily dose to 2.5 mg after two weeks and then to 5 mg after a further two weeks is recommended.

Symptomatic heart failure

Starting dose

In patients stabilized on diuretic therapy, the recommended initial dose is 1.25 mg daily.

Titration and maintenance dose

Ramipril should be titrated by doubling the dose every one to two weeks up to a maximum daily dose of 10 mg. Two administrations per day are preferable.

Secondary prevention after acute myocardial infarction and with heart failure

Starting dose

After 48 hours, following myocardial infarction in a clinically and haemodynamically stable patient, the starting dose is 2.5 mg twice daily for three days. If the initial 2.5 mg dose is not tolerated a dose of 1.25 mg twice a day should be given for two days before increasing to 2.5 mg and 5 mg twice a day. If the dose cannot be increased to 2.5 mg twice a day the treatment should be withdrawn.

See also posology on diuretic treated patients above.

Titration and maintenance dose

The daily dose is subsequently increased by doubling the dose at intervals of one to three days up to the target maintenance dose of 5 mg twice daily.

The maintenance dose is divided in 2 administrations per day where possible.

If the dose cannot be increased to 2.5 mg twice a day treatment should be withdrawn. Sufficient experience is still lacking in the treatment of patients with severe (NYHA IV) heart failure immediately after myocardial infarction. Should the decision be taken to treat these patients, it is recommended that therapy be started at 1.25 mg once daily and that particular caution be exercised in any dose increase.

Special populations

Patients with renal impairment

Daily dose in patients with renal impairment should be based on creatinine clearance (see section 5.2):

- if creatinine clearance is

- if creatinine clearance is between 30-60 ml/min, it is not necessary to adjust the initial dose (2.5 mg/day); the maximal daily dose is 5 mg;

- if creatinine clearance is between 10-30 ml/min, the initial dose is 1.25 mg/day and the maximal daily dose is 5 mg;

- in haemodialysed hypertensive patients: ramipril is slightly dialysable; the initial dose is 1.25 mg/day and the maximal daily dose is 5 mg; the medicinal product should be administered a few hours after haemodialysis is performed.

Patients with hepatic impairment (see section 5.2)

In patients with hepatic impairment, treatment with ramipril must be initiated only under close medical supervision and the maximum daily dose is 2.5 mg ramipril.

Elderly

Initial doses should be lower and subsequent dose titration should be more gradual because of a greater chance of undesirable effects especially in very old and frail patients. A reduced initial dose of 1.25 mg ramipril should be considered.

Paediatric population

Ramipril is not recommended for use in children and adolescents below 18 years of age due to insufficient data on safety and efficacy.

4.3 Contraindications

- Hypersensitivity to the active substance, any of the excipients or any other ACE(Angiotensin Converting Enzyme) inhibitors (see section 6.1).

- History of angioedema (hereditary, idiopathic or due to previous angioedema with ACE inhibitors or AIIRAs).

- Extracorporeal treatments leading to contact of blood with negatively charged surfaces (see section 4.5)

- Significant bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney

- 2nd and 3rd trimester of pregnancy (see sections 4.4 and 4.6)

- Ramipril must not be used in patients with hypotensive or haemodynamically unstable states.

4.4 Special Warnings And Precautions For Use

Special populations

Pregnancy: ACE inhibitors such as ramipril, or Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless continued ACE inhibitor/ AIIRAs therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors/ AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).

o Patients at particular risk of hypotension

- Patients with strongly activated renin-angiotensin-aldosterone system

Patients with strongly activated renin-angiotensin-aldosterone system are at risk of an acute pronounced fall in blood pressure and deterioration of renal function due to ACE inhibition, especially when an ACE inhibitor or a concomitant diuretic is given for the first time or at first dose increase.

Significant activation of renin-angiotensin-aldosterone system is to be anticipated and medical supervision including blood pressure monitoring is necessary, for example in:

• patients with severe hypertension.

• patients with decompensated congestive heart failure

• patients with haemodynamically relevant leftventricular inflow or outflow impediment (e.g.stenosis of the aortic or mitral valve ).

• patients with unilateral renal artery stenosis with a second functional kidney

• patients in whom fluid or salt depletion exists or may develop (including patients with diuretics)

• patients with liver cirrhosis and/or ascites

• patients undergoing major surgery or during anaesthesia with agents that produce hypotension.

Generally, it is recommended to correct dehydration, hypovolaemia or salt depletion before initiating treatment (in patients with heart failure, however, such corrective action must be carefully weighed up against the risk of volume overload).

- Transient or persistent heart failure post MI

- Patients at risk of cardiac or cerebral ischemia in case of acute hypotension

The initial phase of treatment requires special medical supervision.

o Elderly patients

See section 4.2.

Surgery

It is recommended that treatment with angiotensin converting enzyme inhibitors such as ramipril should be discontinued where possible one day before surgery.

Monitoring of renal function

Renal function should be assessed before and during treatment and dosage adjusted especially in the initial weeks of treatment. Particularly careful monitoring is required in patients with renal impairment (see section 4.2). There is a risk of impairment of renal function, particularly in patients with congestive heart failure or after a renal transplant.

Angioedema

Angioedema has been reported in patients treated with ACE inhibitors including ramipril (see section 4.8).

In case of angioedema, ramipril must be discontinued.

Emergency therapy should be instituted promptly. Patient should be kept under observation for at least 12 to 24 hours and discharged after complete resolution of the symptoms.

Intestinal angioedema has been reported in patients treated with ACE inhibitors including ramipril (see section 4.8). These patients presented with abdominal pain (with or without nausea or vomiting).

Anaphylactic reactions during desensitization

The likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom and other allergens are increased under ACE inhibition. A temporary discontinuation of ramipril should be considered prior to desensitization.

Hyperkalaemia

Hyperkalaemia has been observed in some patients treated with ACE inhibitors including ramipril. Patients at risk for development of hyperkalaemia include those with renal insufficiency, age (> 70 years), uncontrolled diabetes mellitus, or those using potassium salts, potassium retaining diuretics and other plasma potassium increasing active substances, or conditions such as dehydration, acute cardiac decompensation, metabolic acidosis. If concomitant use of the above mentioned agents is deemed appropriate, regular monitoring of serum potassium is recommended (see section 4.5).

Neutropenia/agranulocytosis

Neutropenia/agranulocytosis, as well as thrombocytopenia and anaemia, have been rarely seen and bone marrow depression has also been reported. It is recommended to monitor the white blood cell count to permit detection of a possible leucopoenia. More frequent monitoring is advised in the initial phase of treatment and in patients with impaired renal function, those with concomitant collagen disease (e.g. lupus erythematosus or scleroderma), and all those treated with other medicinal products that can cause changes in the blood picture (see sections 4.5 and 4.8).

Ethnic differences

ACE inhibitors cause higher rate of angioedema in black patients than in non black patients.

As with other ACE inhibitors, ramipril may be less effective in lowering blood pressure in black people than in non black patients, possibly because of a higher prevalence of hypertension with low renin level in the black hypertensive population.

Cough

Cough has been reported with the use of ACE inhibitors. Characteristically, the cough is non-productive, persistent and resolves after discontinuation of therapy. ACE inhibitor-induced cough should be considered as part of the differential diagnosis of cough.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Contra-indicated combinations

Extracorporeal treatments leading to contact of blood with negatively charged surfaces such as dialysis or haemofiltration with certain high-flux membranes (e.g. polyacrylonitril membranes) and low density lipoprotein apheresis with dextran sulphate due to increased risk of severe anaphylactoid reactions (see section 4.3). If such treatment is required, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent.

Precautions for use

Potassium salts, heparin, potassium-retaining diuretics and other plasma potassium increasing active substances (including Angiotensin II antagonists, trimethoprim, tacrolimus, ciclosporin): Hyperkalaemia may occur, therefore close monitoring of serum potassium is required.

Antihypertensive agents (e.g. diuretics) and other substances that may decrease blood pressure (e.g. nitrates, tricyclic antidepressants, anaesthetics, acute alcohol intake, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin): Potentiation of the risk of hypotension is to be anticipated (see section 4.2 for diuretics)

Vasopressor sympathomimetics and other substances (e.g. isoproterenol, dobutamine, dopamine, epinephrine) that may reduce the antihypertensive effect of ramipril: Blood pressure monitoring is recommended.

Allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics and other substances that may change the blood cell count: Increased likelihood of haematological reactions (see section 4.4).

Lithium Salts: Excretion of lithium may be reduced by ACE inhibitors and therefore lithium toxicity may be increased.. Lithium levels must be monitored.

Antidiabetic agents including insulin: Hypoglycaemic reactions may occur. Blood glucose monitoring is recommended.

Non-steroidal anti-inflammatory drugs and acetylsalicylic acid: Reduction of the antihypertensive effect of ramipril is to be anticipated. Furthermore, concomitant treatment of ACE inhibitors and NSAIDs may lead to an increased risk of worsening of renal function and to an increase in kalaemia.

4.6 Pregnancy And Lactation

Ramipril is not recommended during the first trimester of pregnancy (see section 4.4) and contraindicated during the second and third trimesters of pregnancy (see section 4.3).

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started.

ACE inhibitor/ Angiotensin II Receptor Antagonist (AIIRA) therapy exposure during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). (See also 5.3 'Preclinical safety data'). Should exposure to ACE inhibitor have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Newborns whose mothers have taken ACE inhibitors should be closely observed for hypotension, oliguria and hyperkalaemia (see also sections 4.3 and 4.4).

Because insufficient information is available regarding the use of ramipril during breastfeeding (see section 5.2), ramipril is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

4.7 Effects On Ability To Drive And Use Machines

Some adverse effects (e.g. symptoms of a reduction in blood pressure such as dizziness) may impair the patient's ability to concentrate and react and, therefore, constitute a risk in situations where these abilities are of particular importance (e.g. operating a vehicle or machinery).

This can happen especially at the start of treatment, or when changing over from other preparations. After the first dose or subsequent increases in dose it is not advisable to drive or operate machinery for several hours.

4.8 Undesirable Effects

The safety profile of ramipril includes persistent dry cough and reactions due to hypotension. Serious adverse reactions include angioedema, hyperkalaemia, renal or hepatic impairment, pancreatitis, severe skin reactions and neutropenia/agranulocytosis.

Adverse reactions frequency is defined using the following convention:

Very common (

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

 

 

Common

Uncommon

Rare

Very rare

Not known

Cardiac disorders

 

 

Myocardial ischaemia including angina pectoris or myocardial infarction, tachycardia, arrhythmia, palpitations, oedema peripheral

 

 

 

 

 

 

Blood and lymphatic system disorders

 

 

 

Eosinophilia

White blood cell count decreased (including neutropenia or agranulocytosis), red blood cell count decreased, haemoglobin decreased, platelet count decreased

 

 

Bone marrow failure, pancytopenia, haemolytic anaemia

Nervous system disorders

 

Headache, dizziness

Vertigo, paraesthesia, ageusia, dysgeusia,

Tremor, balance disorder

 

 

Cerebral ischaemia including ischaemic stroke and transient ischaemic attack, psychomotor skills impaired, burning sensation, parosmia

Eye disorders

 

 

 

Visual disturbance including blurred vision

Conjunctivitis

 

 

 

 

Ear and labyrinth disorders

 

 

 

 

Hearing impaired, tinnitus

 

 

 

 

Respiratory, thoracic and mediastinal disorders

 

Non-productive tickling cough, bronchitis, sinusitis, dyspnoea

Bronchospasm including asthma aggravated, nasal congestion

 

 

 

 

 

 

Gastrointestinal disorders

 

 

Gastrointestinal inflammation, digestive disturbances, abdominal discomfort, dyspepsia, diarrhoea, nausea, vomiting

Pancreatitis (cases of fatal outcome have been very exceptionally reported with ACE inhibitors), pancreatic enzymes increased, small bowel angioedema, abdominal pain upper including gastritis, constipation, dry mouth

Glossitis

 

 

Aphtous stomatitis

Renal and urinary disorders

 

 

 

Renal impairment including renal failure acute, urine output increased, worsening of a pre-existing proteinuria, blood urea increased, blood creatinine increased

 

 

 

 

 

 

 

Skin and subcutaneous tissue disorders

 

Rash in particular maculo-papular

Angioedema; very exceptionally, the airway obstruction resulting from angioedema may have a fatal outcome; pruritus, hyperhidrosis

Exfoliative dermatitis, urticaria, onycholysis,

Photosensitivity reaction

Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, psoriasis aggravated, dermatitis psoriasiform, pemphigoid or lichenoid exanthema or enanthema, alopecia

Musculoskeletal and connective tissue disorders

 

Muscle spasms, myalgia

Arthralgia

 

 

 

 

 

 

Metabolism and nutrition disorders

 

Blood potassium increased

Anorexia, decreased appetite,

 

 

 

 

Blood sodium decreased

Vascular disorders

 

Hypotension, orthostatic blood pressure decreased, syncope

Flushing

Vascular stenosis, hypoperfusion, vasculitis

 

 

Raynaud's phenomenon

General disorders and administration site conditions

 

Chest pain, fatigue

Pyrexia

Asthenia

 

 

 

 

Immune system disorders

 

 

 

 

 

 

 

 

 

Anaphylactic or anaphylactoid reactions, antinuclear antibody increased

Hepatobiliary disorders

 

 

Hepatic enzymes and/or bilirubin conjugated increased,

Jaundice cholestatic, hepatocellular damage

 

 

Acute hepatic failure, cholestatic or cytolytic hepatitis (fatal outcome has been very exceptional).

Reproductive system and breast disorders

 

 

Transient erectile impotence, libido decreased

 

 

 

 

 

Gynaecomastia

Psychiatric disorders

 

 

Depressed mood, anxiety, nervousness, restlessness, sleep disorder including somnolence

 

Confusional state

 

 

Disturbance in attention

4.9 Overdose

Symptoms associated with overdosage of ACE inhibitors may include excessive peripheral vasodilatation (with marked hypotension, shock), bradycardia, electrolyte disturbances, and renal failure. The patient should be closely monitored and the treatment should be symptomatic and supportive. Suggested measures include primary detoxification (gastric lavage, administration of adsorbents) and measures to restore haemodynamic stability, including, administration of alpha 1 adrenergic agonists or angiotensin II (angiotensinamide) administration. Ramiprilat, the active metabolite of ramipril is poorly removed from the general circulation by haemodialysis.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: ACE Inhibitors, plain, ATC code C09AA05.

Mechanism of action

Ramiprilat, the active metabolite of the prodrug ramipril, inhibits the enzyme dipeptidylcarboxypeptidase I (synonyms: angiotensin-converting enzyme; kininase II). In plasma and tissue this enzyme catalyses the conversion of angiotensin I to the active vasoconstrictor substance angiotensin II, as well as the breakdown of the active vasodilator bradykinin. Reduced angiotensin II formation and inhibition of bradykinin breakdown lead to vasodilatation.

Since angiotensin II also stimulates the release of aldosterone, ramiprilat causes a reduction in aldosterone secretion. The average response to ACE inhibitor monotherapy was lower in black (Afro-Caribbean) hypertensive patients (usually a low-renin hypertensive population) than in non-black patients.

Pharmacodynamic effects

Antihypertensive properties:

Administration of ramipril causes a marked reduction in peripheral arterial resistance. Generally, there are no major changes in renal plasma flow and glomerular filtration rate. Administration of ramipril to patients with hypertension leads to a reduction in supine and standing blood pressure without a compensatory rise in heart rate.

In most patients the onset of the antihypertensive effect of a single dose becomes apparent 1 to 2 hours after oral administration. The peak effect of a single dose is usually reached 3 to 6 hours after oral administration. The antihypertensive effect of a single dose usually lasts for 24 hours.

The maximum antihypertensive effect of continued treatment with ramipril is generally apparent after 3 to 4 weeks. It has been shown that the antihypertensive effect is sustained under long term therapy lasting 2 years.

Abrupt discontinuation of ramipril does not produce a rapid and excessive rebound increase in blood pressure.

Heart failure:

In addition to conventional therapy with diuretics and optional cardiac glycosides, ramipril has been shown to be effective in patients with functional classes II-IV of the New-York Heart Association. The drug had beneficial effects on cardiac haemodynamics (decreased left and right ventricular filling pressures, reduced total peripheral vascular resistance, increased cardiac output and improved cardiac index). It also reduced neuroendocrine activation.

Clinical efficacy and safety

Cardiovascular prevention/Nephroprotection;

A preventive placebo-controlled study (the HOPE-study), was carried out in which ramipril was added to standard therapy in more than 9,200 patients. Patients with increased risk of cardiovascular disease following either atherothrombotic cardiovascular disease (history of coronary heart disease, stroke or peripheral vascular disease) or diabetes mellitus with at least one additional risk factor (documented microalbuminuria, hypertension, elevated total cholesterol level, low high-density lipoprotein cholesterol level or cigarette smoking) were included in the study.

The study showed that ramipril statistically significantly decreases the incidence of myocardial infarction, death from cardiovascular causes and stroke, alone and combined (primary combined events).

The HOPE Study: Main Results;

 

 

Ramipril

Placebo

relative risk

(95% confidence interval)

p-value

 

 

%

%

 

 

 

 

All patients

n=4,645

N=4,652

 

 

Primary combined events

14.0

17.8

0.78 (0.70-0.86)

<0.001

Myocardial infarction

9.9

12.3

0.80 (0.70-0.90)

<0.001

Death from cardiovascular causes

6.1

8.1

0.74 (0.64-0.87)

<0.001

Stroke

3.4

4.9

0.68 (0.56-0.84)

<0.001

 

 

 

 

 

 

 

 

 

 

Secondary endpoints

 

 

 

 

Death from any cause

10.4

12.2

0.84 (0.75-0.95)


read more / Download


Brevinor Tablets


Brevinor

Please read this leaflet carefully before you start to take Brevinor. This leaflet gives you some information about how to take your pills. The leaflet can't tell you everything about Brevinor. So if you have any questions or are not sure about anything, ask your doctor, clinic or pharmacist.

Some information about Brevinor

Brevinor contains two hormones - a progestogen hormone called norethisterone and an oestrogen hormone called ethinylestradiol. These two hormones act together to prevent pregnancy.

What is in Brevinor?

Each Brevinor pill contains:

500 micrograms of norethisterone and 35 micrograms of ethinylestradiol (the 'active' ingredients); and maize starch, polyvidone, magnesium stearate, lactose and colouring E132 (the 'inactive' ingredients).

Brevinor pills are blue and have the word 'SEARLE' on one side and 'BX' on the other side. They are packed in blister strips and come in packs of 63 pills.

One of the active ingredients in this medicine is ethinylestradiol. This is the new name for ethinyloestradiol. The ingredient itself has not changed.

Who supplies Brevinor?

Brevinor is supplied by:

Pharmacia Limited Ramsgate Road Sandwich Kent CT13 9NJ UK Who makes Brevinor?

Brevinor is made by:

Pharmacia Limited Morpeth Northumberland NE61 3YA UK What is Brevinor for?

Brevinor is a combined oral contraceptive pill you take to prevent you becoming pregnant.

Before you take Brevinor

Brevinor may not be suitable for all women. Before you take Brevinor, make sure your doctor knows if you have ever had any of the following conditions.

Blood clots in the legs, blood clots in varicose veins, the lungs, the brain or elsewhere (coronary and cerebral thrombotic disorders). A heart attack, angina or a stroke. High levels of fats in your blood (hyperlipidaemia or other disorders of body fats). Cancer of the breast, cervix, vagina or womb. If during pregnancy you had: pruritus (itching of the whole body); jaundice, for which your doctor could not find the cause; or pemphigoid gestationis (a rash previously known as herpes gestationis). Certain types of jaundice (Dubin-Johnson or Rotor syndrome). Bad migraines. Vaginal bleeding, for which your doctor could not find the cause. Liver tumours. Liver disease.

If you are pregnant or are trying to get pregnant, you should not take the pill.

What I should know before taking Brevinor

If you had irregular periods or no periods in the past, you may stop ovulating (releasing eggs from your ovaries). You may also stop having normal periods after you have stopped using the combined pill. If you have any of these conditions you may find it better to use a different contraceptive method. You should ask your doctor or clinic for advice. It is possible that sometimes certain long-term diseases may get worse while you are taking the pill. See the section, 'Reasons for careful medical checks'.

The pill and thrombosis

Some evidence suggests that women who take the pill are more likely to develop various blood circulation disorders than women who don't take the pill. A thrombosis is a blood clot. A thrombosis can develop in veins or in arteries and can cause a blockage. The chance of a thrombosis forming in women taking the pill and women not taking the pill is rare. When blood clots form in the arteries they can cause chest pain (angina), strokes (blood clots in or bleeding from the blood vessels in the brain) and heart attacks.

If blood clots form in veins, they can often be treated with no long term danger. On rare occasions a piece of thrombosis may break off. It can travel to the lungs to cause a condition called pulmonary embolism. Therefore in rare cases a thrombosis can cause serious permanent disability or could even be fatal.

It is important to note that a thrombosis can form in people who are not taking the pill as well as those who are taking it. The risk is higher in women who take the pill than in women who don't take the pill, but is not as high as the risk during pregnancy. The excess risk of thrombosis is highest during the first year a woman ever uses a combined oral contraceptive pill.

For healthy non-pregnant women: the chance of having a blood clot is about 5 in 100,000 each year.

For women taking the pill containing either levongestrel or norethisterone (a second generation pill): the chance of having a blood clot is about 15 in 100,000 each year.

For women taking the pill containing desogestrel or gestodene (a third generation pill): the chance of having a blood clot is about 25 in 100,000 each year.

For women who are pregnant: the chance of having a blood clot is about 60 in 100,000 pregnancies.

The risk of heart attacks and strokes for women who use the combined pill increases with age and smoking. Other conditions also increase the risk of blood clots in the arteries. These include being greatly overweight, having diseased arteries (atherosclerosis), high blood pressure during pregnancy (pre-eclamptic toxaemia), high blood levels of cholesterol, and diabetes. If you have any of these conditions, you should check with your doctor or clinic to see if the pill is suitable for you. Smokers over 35 are usually told to stop taking these pills.

Breast Cancer

Every woman is at risk of breast cancer whether or not she takes the pill. Breast cancer is rare under the age of 40 years, but the risk increases as a woman gets older.

Breast cancer has been found slightly more often in women who take the pill than in women of the same age who do not take the pill. If women stop taking the pill, this reduces the risk so that 10 years after stopping the pill, the risk of finding breast cancer is the same as for women who have never taken the pill. Breast cancer seems less likely to have spread when found in women who take the pill than in women who do not take the pill.

It is not certain whether the pill causes the increased risk of breast cancer. It may be that women taking the pill are examined more often, so that breast cancer is noticed earlier. The risk of finding breast cancer is not affected by how long a woman takes the pill but by the age at which she stops. This is because the risk of breast cancer strongly increases as a woman gets older.

The chart below shows the background chances of breast cancer at various ages for 10,000 women who have never taken the pill (black bars) and for 10,000 women whilst taking the pill and during the 10 years after stopping it (grey bars). The small extra risk of finding breast cancer can be seen for each age group. This small possible additional risk in women who take the pill has to be balanced against the fact that the pill is a very effective contraceptive and it helps prevent cancer of the womb or ovary.

The following information describes the estimated number of breast cancers found in women of various ages who never took the Pill, or who took the Pill for 5 years and then stopped. For women who took the Pill, the information gives the total number of breast cancers found during the time that they were taking the Pill and during the 10 years after they stopped taking it.

For women under 20 years of age who never took the Pill, 4 out of 10,000 had breast cancer and of those who had taken the Pill, 4.5 out of 10,000 had breast cancer.

For women between the ages of 20 and 24 who never took the Pill, 16 out of 10,000 had breast cancer and of those who had taken the Pill, 17.5 out of 10,000 had breast cancer.

For women between the ages of 25 and 29 who never took the Pill, 44 out of 10,000 had breast cancer and of those who had taken the Pill, 48.7 out of 10,000 had breast cancer.

For women between the ages of 30 and 34 who never took the Pill, 100 out of 10,000 had breast cancer and of those who had taken the Pill, 111 out of 10,000 had breast cancer.

For women between the ages of 35 and 39 who never took the Pill, 160 out of 10,000 had breast cancer and of those who had taken the Pill, 181 out of 10,000 had breast cancer.

For women between the ages of 40 and 44 who never took the Pill, 230 out of 10,000 had breast cancer and of those who had taken the Pill, 262 out of 10,000 had breast cancer.

Taking any medicine carries some risk. You can use the information in this leaflet, and the advice your doctor or clinic has given you to weigh up the risks and benefits of taking the pill. Don't be embarrassed, ask as may questions as you need to.

Reasons for careful medical checks

Your doctor or clinic will give you regular checkups while you are taking Brevinor. Your blood pressure will be checked before you start the pill and then at regular intervals whilst you are on the pill. If your blood pressure goes up, your doctor may tell you to stop taking Brevinor. They may also check your breasts and reproductive organs, including taking a cervical smear at regular intervals, if this is considered necessary by the doctor.

Tell your doctor if you have any of the following conditions.

Migraine, asthma, epilepsy, heart or kidney disease, high blood pressure (hypertension) or you have a previous history of these conditions. This is because the pill may cause fluid retention which can make these conditions worse. Diabetes.

If you have any of the following conditions and they appear to get worse or they appear for the first time, your doctor or clinic may tell you to stop taking the pill.

High blood pressure. Diabetes. Multiple sclerosis Tetany (muscle twitches) Breast problems. Varicose veins. Migraine. Epilepsy. Kidney disease. Severe depression. Fibroids in your uterus. Gallstones. Liver problems. Sickle-cell anaemia. Diseases of the heart and blood vessels (cardiovascular disease). Otosclerosis (an inherited form of deafness). Porphyria (a metabolic disease). Chloasma (brown patches on your skin which can happen during pregnancy but may not fade completely). Any disease that is likely to get worse during pregnancy.

If you use any combined pill you may retain fluid which can make it uncomfortable to wear contact lenses

Other medicines and Brevinor

Several medicines can interfere with the way the pill works. These include some drugs that treat epilepsy, arthritis, tuberculosis and some antibiotics or sedatives. Other less common medicines may also have this effect. You may have to use another contraceptive method, such as a condom, while you are taking these medicines and during the next seven days. In some situations, your doctor or clinic may tell you to use extra precautions for longer. If while using these extra precautions you run beyond the end of the blister strip, start the next blister strip without a break. Always mention you are on the pill if a doctor, dentist or hospital prescribes you any medicine.

The herbal remedy St John's wort (Hypericum perforatum) should not be taken at the same time as this medicine. If you already take a St John's wort preparation, stop taking the St John's wort and mention it to your doctor.

Blood tests

The pill may affect the results of certain blood tests, so tell your doctor that you are on the pill if you need any blood tests.

How to take Brevinor Starting your first blister strip Take the first pill on your first day of bleeding. This is the day when your period starts. If you are not having periods, ask your doctor or clinic when you should start taking your pill. Take the pill marked with the correct day of the week. You will be protected at once as long as you take a pill every day. You can take the pill at a time that suits you, but you must take it at about the same time every day. Take a pill every day until you finish a blister strip. If you cannot start the pill on the first day of your period you may start to take it on any day up to the fifth day. However, if you do this, you may not be protected for the first seven days, so you should use another method of contraception such as the condom during those days. Starting the next blister strip Once you have finished all 21 pills, stop for seven days. You will probably bleed during some or all of these seven days. Then, start the next blister strip. Do this whether or not you are still bleeding. You will always start the next blister strip on the same day of the week. You are protected during the seven day break, but only if you start the next blister strip on time. The first pill in your blister strip is the worst pill of all to miss or take late. What do I do if I have a stomach upset or I am sick?

Brevinor may not work if you are sick or have severe diarrhoea. You should carry on taking your pills as normal, but use a condom while you are ill and for the next seven days. If these seven days run beyond the end of the blister strip, start the next blister strip without a break

What do I do if I miss a period?

If you have taken all your pills properly, it is very unlikely that you are pregnant. Take your next blister strip as normal. If you have not taken them correctly, see your doctor or clinic at once. You should do the same if you miss a second period. If you do get pregnant whilst you are taking the pill there may be a very small increased risk that your baby will have an abnormality. Ask your doctor to discuss this risk with you.

What do I do if my periods are different?

This is normal when you start the pill. You will probably have less bleeding. You may also have a little bleeding while you are taking the pills (this is called 'break-through bleeding'). If this happens, do not stop taking your pills. This should stop within two or three months. If the bleeding is heavy, do not stop taking the pill but talk to your doctor or clinic. If your periods seem different, do not stop taking the pills and just mention it to your doctor or nurse at your next visit.

What do I do if I am having an operation?

If you are planning to have an operation, which will mean lying in bed for more than a whole day, or any operation on your legs, it is best that you stop taking this type of pill at least four weeks before your operation. This does not apply to some minor operations. You can usually start to take the pill again two weeks after the operation. Talk to your doctor or clinic about another method of contraception you can use until the operation. For example, you may use a progestogen-only pill.

If you are having treatment for varicose veins, stop taking the combined pill four weeks before your treatment and stay off it until 3 months after your last treatment.

What do I do if I have an accident or I am ill

If you have an accident or illness which means that you will have to stay in bed, it is best to stop taking the pill until you are active again.

Smoking

Smoking increases the risks to your health and some of the risks of taking the pill. It is always best to stop smoking. If you do smoke, your doctor or clinic may tell you to change your method of contraception when you are 35 or over.

What do I do if I want a baby?

If you want to have a baby it is best to wait until you have stopped taking the pill for three months or at least until your regular periods have returned. You can always use another contraceptive method such as a condom. Only rarely do regular periods take some time to return. Once you have had one period, it is easier to work out when your baby is due. However, if you do get pregnant as soon as you stop taking Brevinor, this is not harmful.

What do I do if I am changing pill brands?

Take the first pill of your new blister strip on the day immediately after you have finished your old blister strip. Your period will usually be delayed until the new blister strip is finished, but you may have some break-through bleeding during the first few days of the new blister strip. This is quite normal and you will still be protected against pregnancy. If you do have a break, ask your doctor or clinic whether you need an extra contraceptive method such as a condom.

What do I do if I have just had a baby? If you are breast feeding, you should not take the combined pill. This is because the oestrogen in the pill may reduce the amount of milk you produce. You should be able to take the progestogen-only pill instead. Ask your doctor or clinic for advice. If you are not breast feeding, you may start taking the pill 21 days after your baby is born. This will protect you immediately. If you start later than this, you may not be protected until you have taken the pill for seven days. What do I do if I have just had a miscarriage or abortion?

You may be able to start taking the pill immediately. If you can, you will be protected straight away. Ask your doctor or clinic if you should do so.

Overdose

If you take more than the recommended number of pills, or if you discover someone has taken a lot of pills, contact your doctor immediately.

What do I do if I forget to take a pill? If you forget to take a pill take it as soon as you remember and take the next one at your normal time. This may mean taking two pills on the same day If you are 12 or more hours late in taking one or more pills, it may not work. As soon as you remember, take your last missed pill and carry on taking your pills normally. However, you may not be protected for the next seven days, so either avoid sexual intercourse or use an extra contraceptive method, such as a condom. If you have fewer than seven pills in your blister strip after you have missed taking your pill, you should complete the blister strip and start the next blister strip without a break. This will give you protection from when you took the last missed pill. You may not have a period until the end of two blister strips, but this will not harm you. You may also have some bleeding on days when you take the pill. Brevinor Tablets Side Effects

All medicines can sometimes cause problems. If you are worried about side effects, talk to your doctor. These effects should become less of a problem as your body becomes used to the pills.

You may notice a change in your sex drive, and have irregular vaginal bleeding or changes in your period.

Other side effects that you might have include nausea, stomach upsets, tender breasts, weight gain, changes in appetite, headaches, depression, high blood pressure, and changes in the way your body breaks down sugars, fats or vitamins. If you have fibroids in your uterus, these may also get worse.

Reasons to get medical help immediately

The cause of these symptoms may have nothing to do with the pill but you may need treatment. Stop taking your pills at once and tell your doctor if you have:

a sudden sharp or severe pain in the chest; suddenly become short of breath or breathing is painful; coughed up blood; painful or inflamed veins in your legs; a crushing type of chest pain or your chest feels heavy; a very first attack of migraine (a bad headache with sickness); migraines which get worse, especially if your sight is affected, you see flashing lights, your limbs feel weak, you lose the sensation or feel a different sensation in your limbs, or you fit; sudden and unusual severe headaches; a problem with your sight or speech; swollen arms or legs; jaundice (your skin or the whites of your eyes look yellow); a severe rash; or swelling or tenderness in your stomach. How to store Brevinor

Store your Brevinor pills in a dry place, away from direct sunlight and below 25°C. Make sure that children cannot see or reach them.

Don't take Brevinor after the 'expiry date' shown on the box. If your pack is out of date, take it to your pharmacist who will get rid of the pills safely.

If you have any comments on the way this leaflet is written, please write to Medical Information at Pharmacia Limited, Milton Keynes.

This leaflet was revised in December 2006.

Brevinor is a contraceptive. It will not protect against sexually-transmitted diseases including AIDS. For safer sex, use a condom as well as your usual contraceptive.

Brevinor and Pharmacia are registered trademarks. 063/316


read more / Download


Ramipril 10mg Tablets


1. Name Of The Medicinal Product

Ramipril 10mg Tablets

2. Qualitative And Quantitative Composition

10 mg ramipril.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Tablet

White to almost white, oblong tablets with a score-line.

Upper stamp: HMO/HMO

Lower stamp: anonymous

4. Clinical Particulars 4.1 Therapeutic Indications

- Treatment of hypertension.

- Cardiovascular prevention: reduction of cardiovascular morbidity and mortality in patients with:

o manifest atherothrombotic cardiovascular disease (history of coronary heart disease or stroke, or peripheral vascular disease) or

o diabetes with at least one cardiovascular risk factor (see section 5.1).

- Treatment of renal disease:

o Incipient glomerular diabetic nephropathy as defined by the presence of microalbuminuria,

o Manifest glomerular diabetic nephropathy as defined by macroproteinuria in patients with at least one cardiovascular risk factor (see section 5.1),

o Manifest glomerular non diabetic nephropathy as defined by macroproteinuria

- Treatment of symptomatic heart failure.

- Secondary prevention after acute myocardial infarction: reduction of mortality from the acute phase of myocardial infarction in patients with clinical signs of heart failure when started> 48 hours following acute myocardial infarction.

4.2 Posology And Method Of Administration

Oral use.

It is recommended that RAMIPRIL is taken each day at the same time of the day.

RAMIPRIL can be taken before, with or after meals, because food intake does not modify its bioavailability (see section 5.2).

RAMIPRIL has to be swallowed with liquid. It must not be chewed or crushed.

Adults

Diuretic-Treated patients

Hypotension may occur following initiation of therapy with RAMIPRIL; this is more likely in patients who are being treated concurrently with diuretics. Caution is therefore recommended since these patients may be volume and/or salt depleted.

If possible, the diuretic should be discontinued 2 to 3 days before beginning therapy with RAMIPRIL (see section 4.4).

In hypertensive patients in whom the diuretic is not discontinued, therapy with RAMIPRIL should be initiated with a 1.25 mg dose. Renal function and serum potassium should be monitored. The subsequent dosage of RAMIPRIL should be adjusted according to blood pressure target.

Hypertension

The dose should be individualised according to the patient profile (see section 4.4) and blood pressure control.

RAMIPRIL may be used in monotherapy or in combination with other classes of antihypertensive medicinal products.

Starting dose

RAMIPRIL should be started gradually with an initial recommended dose of 2.5 mg daily.

Patients with a strongly activated renin-angiotensin-aldosterone system may experience an excessive drop in blood pressure following the initial dose. A starting dose of 1.25 mg is recommended in such patients and the initiation of treatment should take place under medical supervision (see section 4.4).

Titration and maintenance dose

The dose can be doubled at interval of two to four weeks to progressively achieve target blood

pressure; the maximum permitted dose of RAMIPRIL is 10 mg daily. Usually the dose is administered once daily.

Cardiovascular prevention

Starting dose

The recommended initial dose is 2.5 mg of RAMIPRIL once daily.

Titration and maintenance dose

Depending on the patient's tolerability to the active substance, the dose should be gradually increased. It is recommended to double the dose after one or two weeks of treatment and - after another two to three weeks - to increase it up to the target maintenance dose of 10 mg RAMIPRIL once daily.

See also posology on diuretic treated patients above.

Treatment of renal disease

In patients with diabetes and microalbuminuria:

Starting dose:

The recommended initial dose is 1.25 mg of RAMIPRIL once daily.

Titration and maintenance dose

Depending on the patient's tolerability to the active substance, the dose is subsequently increased. Doubling the once daily dose to 2.5 mg after two weeks and then to 5 mg after a further two weeks is recommended.

In patients with diabetes and at least one cardiovascular risk

Starting dose:

The recommended initial dose is 2.5 mg of RAMIPRIL once daily.

Titration and maintenance dose

Depending on the patient's tolerability to the active substance, the dose is subsequently increased. Doubling the daily dose to 5 mg RAMIPRIL after one or two weeks and then to 10 mg RAMIPRIL after a further two or three weeks is recommended. The target daily dose is 10 mg.

In patients with non- diabetic nephropathy as defined by macroproteinuria

Starting dose:

The recommended initial dose is 1.25 mg of RAMIPRIL once daily.

Titration and maintenance dose

Depending on the patient's tolerability to the active substance, the dose is subsequently increased. Doubling the once daily dose to 2.5 mg after two weeks and then to 5 mg after a further two weeks is recommended.

Symptomatic heart failure

Starting dose

In patients stabilized on diuretic therapy, the recommended initial dose is 1.25 mg daily.

Titration and maintenance dose

RAMIPRIL should be titrated by doubling the dose every one to two weeks up to a maximum daily dose of 10 mg. Two administrations per day are preferable.

Secondary prevention after acute myocardial infarction and with heart failure

Starting dose

After 48 hours, following myocardial infarction in a clinically and haemodynamically stable patient, the starting dose is 2.5 mg twice daily for three days. If the initial 2.5 mg dose is not tolerated a dose of 1.25 mg twice a day should be given for two days before increasing to 2.5 mg and 5 mg twice a day. If the dose cannot be increased to 2.5 mg twice a day the treatment should be withdrawn.

See also posology on diuretic treated patients above.

Titration and maintenance dose

The daily dose is subsequently increased by doubling the dose at intervals of one to three days up to the target maintenance dose of 5 mg twice daily.

The maintenance dose is divided in 2 administrations per day where possible.

If the dose cannot be increased to 2.5 mg twice a day treatment should be withdrawn. Sufficient experience is still lacking in the treatment of patients with severe (NYHA IV) heart failure immediately after myocardial infarction. Should the decision be taken to treat these patients, it is recommended that therapy be started at 1.25 mg once daily and that particular caution be exercised in any dose increase.

Special populations

Patients with renal impairment

Daily dose in patients with renal impairment should be based on creatinine clearance (see section 5.2):

- if creatinine clearance is

- if creatinine clearance is between 30-60 ml/min, it is not necessary to adjust the initial dose (2.5 mg/day); the maximal daily dose is 5 mg;

- if creatinine clearance is between 10-30 ml/min, the initial dose is 1.25 mg/day and the maximal daily dose is 5 mg;

- in haemodialysed hypertensive patients: ramipril is slightly dialysable; the initial dose is 1.25 mg/day and the maximal daily dose is 5 mg; the medicinal product should be administered few hours after haemodialysis is performed.

Patients with hepatic impairment (see section 5.2)

In patients with hepatic impairment, treatment with RAMIPRIL must be initiated only under close medical supervision and the maximum daily dose is 2.5 mg RAMIPRIL.

Elderly

Initial doses should be lower and subsequent dose titration should be more gradual because of greater chance of undesirable effects especially in very old and frail patients. A reduced initial dose of 1.25 mg ramipril should be considered.

Paediatric population

RAMIPRIL is not recommended for use in children and adolescents below 18 years of age due to insufficient data on safety and efficacy.

4.3 Contraindications

- Hypersensitivity to the active substance, to any of the excipients or any other ACE (Angiotensin Converting Enzyme) inhibitors (see section 6.1)

- History of angioedema (hereditary, idiopathic or due to previous angioedema with ACE inhibitors or AIIRAs)

- Extracorporeal treatments leading to contact of blood with negatively charged surfaces (see section 4.5)

- Significant bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney

- 2nd and 3rd trimester of pregnancy (see sections 4.4 and 4.6)

- Ramipril must not be used in patients with hypotensive or haemodynamically unstable states.

4.4 Special Warnings And Precautions For Use

Special populations

Pregnancy: ACE inhibitors such as ramipril, or Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless continued ACE inhibitor/ AIIRAs therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors/ AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).

Patients at particular risk of hypotension

Patients with strongly activated renin-angiotensin-aldosterone system:

Patients with strongly activated renin-angiotensin-aldosterone system are at risk of an acute pronounced fall in blood pressure and deterioration of renal function due to ACE inhibition, especially when an ACE inhibitor or a concomitant diuretic is given for the first time or at first dose increase.

Significant activation of renin-angiotensin-aldosterone system is to be anticipated and medical supervision including blood pressure monitoring is necessary, for example in:

- patients with severe hypertension

- patients with decompensated congestive heart failure

- patients with haemodynamically relevant left ventricular inflow or outflow impediment (e.g. stenosis of the aortic or mitral valve)

- patients with unilateral renal artery stenosis with a second functional kidney

- patients in whom fluid or salt depletion exists or may develop (including patients with diuretics)

- patients with liver cirrhosis and/or ascites

- patients undergoing major surgery or during anaesthesia with agents that produce hypotension.

Generally, it is recommended to correct dehydration, hypovolaemia or salt depletion before initiating treatment (in patients with heart failure, however, such corrective action must be carefully weighed out against the risk of volume overload).

Transient or persistent heart failure post MI

Patients at risk of cardiac or cerebral ischemia in case of acute hypotension

The initial phase of treatment requires special medical supervision.

Elderly patients

See section 4.2.

Surgery

It is recommended that treatment with angiotensin converting enzyme inhibitors such as ramipril should be discontinued where possible one day before surgery.

Monitoring of renal function

Renal function should be assessed before and during treatment and dosage adjusted especially in the initial weeks of treatment. Particularly careful monitoring is required in patients with renal impairment (see section 4.2). There is a risk of impairment of renal function, particularly in patients with congestive heart failure or after a renal transplant.

Angioedema

Angioedema has been reported in patients treated with ACE inhibitors including ramipril (see

section 4.8).

In case of angioedema, RAMIPRIL must be discontinued.

Emergency therapy should be instituted promptly. Patient should be kept under observation for at least 12 to 24 hours and discharged after complete resolution of the symptoms.

Intestinal angioedema has been reported in patients treated with ACE inhibitors including RAMIPRIL (see section 4.8). These patients presented with abdominal pain (with or without nausea or vomiting).

Anaphylactic reactions during desensitization

The likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom and other allergens are increased under ACE inhibition. A temporary discontinuation of RAMIPRIL should be considered prior to desensitization.

Hyperkalaemia

Hyperkalaemia has been observed in some patients treated with ACE inhibitors including RAMIPRIL. Patients at risk for development of hyperkalaemia include those with renal insufficiency, age (> 70 years), uncontrolled diabetes mellitus, or those using potassium salts, potassium retaining diuretics and other plasma potassium increasing active substances, or conditions such as dehydration, acute cardiac decompensation, metabolic acidosis. If concomitant use of the above mentioned agents is deemed appropriate, regular monitoring of serum potassium is recommended (see section 4.5).

Neutropenia/agranulocytosis

Neutropenia/agranulocytosis, as well as thrombocytopenia and anaemia, have been rarely seen and bone marrow depression has also been reported. It is recommended to monitor the white blood cell count to permit detection of a possible leucopoenia. More frequent monitoring is advised in the initial phase of treatment and in patients with impaired renal function, those with concomitant collagen disease (e.g. lupus erythematosus or scleroderma), and all those treated with other medicinal products that can cause changes in the blood picture (see sections 4.5 and 4.8).

Ethnic differences

ACE inhibitors cause higher rate of angioedema in black patients than in non black patients.

As with other ACE inhibitors, ramipril may be less effective in lowering blood pressure in black people than in non black patients, possibly because of a higher prevalence of hypertension with low renin level in the black hypertensive population.

Cough

Cough has been reported with the use of ACE inhibitors. Characteristically, the cough is nonproductive, persistent and resolves after discontinuation of therapy. ACE inhibitor-induced cough should be considered as part of the differential diagnosis of cough.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Contra-indicated combinations

Extracorporeal treatments leading to contact of blood with negatively charged surfaces such as dialysis or haemofiltration with certain high-flux membranes (e.g. polyacrylonitril membranes) and low density lipoprotein apheresis with dextran sulphate due to increased risk of severe anaphylactoid reactions (see section 4.3). If such treatment is required, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent.

Precautions for use

Potassium salts, heparin, potassium-retaining diuretics and other plasma potassium increasing active substances (including Angiotensin II antagonists, trimethoprim, tacrolimus, ciclosporin): Hyperkalaemia may occur, therefore close monitoring of serum potassium is required.

Antihypertensive agents (e.g. diuretics) and other substances that may decrease blood pressure (e.g.nitrates, tricyclic antidepressants, anaesthetics, acute alcohol intake, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin): Potentiation of the risk of hypotension is to be anticipated (see section 4.2 for diuretics)

Vasopressor sympathomimetics and other substances (e.g. isoproterenol, dobutamine, dopamine, epinephrine) that may reduce the antihypertensive effect of RAMIPRIL: Blood pressure monitoring is recommended.

Allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics and other substances that may change the blood cell count: Increased likelihood of haematological reactions (see section 4.4).

Lithium salts: Excretion of lithium may be reduced by ACE inhibitors and therefore lithium toxicity may be increased. Lithium level must be monitored.

Antidiabetic agents including insulin: Hypoglycaemic reactions may occur. Blood glucose monitoring is recommended.

Non-steroidal anti-inflammatory drugs and acetylsalicylic acid: Reduction of the antihypertensive effect of RAMIPRIL is to be anticipated. Furthermore, concomitant treatment of ACE inhibitors and NSAIDs may lead to an increased risk of worsening of renal function and to an increase in kalaemia.

4.6 Pregnancy And Lactation

RAMIPRIL is not recommended during the first trimester of pregnancy (see section 4.4) and contraindicated during the second and third trimesters of pregnancy (see section 4.3).

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started. ACE inhibitor/ Angiotensin II Receptor Antagonist (AIIRA) therapy exposure during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). (See also 5.3 'Preclinical safety data'). Should exposure to ACE inhibitor have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Newborns whose mothers have taken ACE inhibitors should be closely observed for hypotension, oliguria and hyperkalaemia (see also sections 4.3 and 4.4).

Because insufficient information is available regarding the use of ramipril during breastfeeding (see section 5.2), ramipril is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

4.7 Effects On Ability To Drive And Use Machines

Some adverse effects (e.g. symptoms of a reduction in blood pressure such as dizziness) may impair the patient's ability to concentrate and react and, therefore, constitute a risk in situations where these abilities are of particular importance (e.g. operating a vehicle or machinery).

This can happen especially at the start of treatment, or when changing over from other preparations. After the first dose or subsequent increases in dose it is not advisable to drive or operate machinery for several hours.

4.8 Undesirable Effects

The safety profile of ramipril includes persistent dry cough and reactions due to hypotension. Serious adverse reactions include angioedema, hyperkalaemia, renal or hepatic impairment, pancreatitis, severe skin reactions and neutropenia/agranulocytosis.

Adverse reactions frequency is defined using the following convention:

Very common (

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

 

 

Common

Uncommon

Rare

Very rare

Not known

Cardiac disorders

 

 

Myocardial ischaemia including angina pectoris or myocardial infarction, tachycardia, arrhythmia, palpitations, oedema peripheral

 

 

 

 

 

 

Blood and lymphatic system disorders

 

 

 

Eosinophilia

White blood cell count decreased (including neutropenia or agranulocytosis), red blood cell count decreased, haemoglobin decreased, platelet count decreased

 

 

Bone marrow failure, pancytopenia, haemolytic anaemia

Nervous system disorders

 

Headache, dizziness

Vertigo, paraesthesia, ageusia, dysgeusia,

Tremor, balance disorder

 

 

Cerebral ischaemia including ischaemic stroke and transient ischaemic attack, psychomotor skills impaired, burning sensation, parosmia

Eye disorders

 

 

 

Visual disturbance including blurred vision

Conjunctivitis

 

 

 

 

Ear and labyrinth disorders

 

 

 

 

Hearing impaired, tinnitus

 

 

 

 

Respiratory, thoracic and mediastinal disorders

 

Non-productive tickling cough, bronchitis, sinusitis, dyspnoea

Bronchospasm including asthma aggravated, nasal congestion

 

 

 

 

 

 

Gastrointestinal disorders

 

 

Gastrointestinal inflammation, digestive disturbances, abdominal discomfort, dyspepsia, diarrhoea, nausea, vomiting

Pancreatitis (cases of fatal outcome have been very exceptionally reported with ACE inhibitors), pancreatic enzymes increased, small bowel angioedema, abdominal pain upper including gastritis, constipation, dry mouth

Glossitis

 

 

Aphtous stomatitis

Renal and urinary disorders

 

 

 

Renal impairment including renal failure acute, urine output increased, worsening of a pre-existing proteinuria, blood urea increased, blood creatinine increased

 

 

 

 

 

 

 

Skin and subcutaneous tissue disorders

 

Rash in particular maculo-papular

Angioedema; very exceptionally, the airway obstruction resulting from angioedema may have a fatal outcome; pruritus, hyperhidrosis

Exfoliative dermatitis, urticaria, onycholysis,

Photosensitivity reaction

Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, psoriasis aggravated, dermatitis psoriasiform, pemphigoid or lichenoid exanthema or enanthema, alopecia

Musculoskeletal and connective tissue disorders

 

Muscle spasms, myalgia

Arthralgia

 

 

 

 

 

 

Metabolism and nutrition disorders

 

Blood potassium increased

Anorexia, decreased appetite,

 

 

 

 

Blood sodium decreased

Vascular disorders

 

Hypotension, orthostatic blood pressure decreased, syncope

Flushing

Vascular stenosis, hypoperfusion, vasculitis

 

 

Raynaud's phenomenon

General disorders and administration site conditions

 

Chest pain, fatigue

Pyrexia

Asthenia

 

 

 

 

Immune system disorders

 

 

 

 

 

 

 

 

 

Anaphylactic or anaphylactoid reactions, antinuclear antibody increased

Hepatobiliary disorders

 

 

Hepatic enzymes and/or bilirubin conjugated increased,

Jaundice cholestatic, hepatocellular damage

 

 

Acute hepatic failure, cholestatic or cytolytic hepatitis (fatal outcome has been very exceptional).

Reproductive system and breast disorders

 

 

Transient erectile impotence, libido decreased

 

 

 

 

 

Gynaecomastia

Psychiatric disorders

 

 

Depressed mood, anxiety, nervousness, restlessness, sleep disorder including somnolence

 

Confusional state

 

 

Disturbance in attention

4.9 Overdose

Symptoms associated with overdosage of ACE inhibitors may include excessive peripheral

vasodilatation (with marked hypotension, shock), bradycardia, electrolyte disturbances, and renal failure. The patient should be closely monitored and the treatment should be symptomatic and supportive. Suggested measures include primary detoxification (gastric lavage, administration of adsorbents) and measures to restore haemodynamic stability, including, administration of alpha 1 adrenergic agonists or angiotensin II (angiotensinamide) administration. Ramiprilat, the active metabolite of ramipril is poorly removed from the general circulation by haemodialysis.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: ACE Inhibitors, plain, ATC code C09AA05.

Mechanism of action

Ramiprilat, the active metabolite of the prodrug ramipril, inhibits the enzyme dipeptidylcarboxypeptidase I (synonyms: angiotensin-converting enzyme; kininase II). In plasma and tissue this enzyme catalyses the conversion of angiotensin I to the active vasoconstrictor substance angiotensin II, as well as the breakdown of the active vasodilator bradykinin. Reduced angiotensin II formation and inhibition of bradykinin breakdown lead to vasodilatation.

Since angiotensin II also stimulates the release of aldosterone, ramiprilat causes a reduction in aldosterone secretion. The average response to ACE inhibitor monotherapy was lower in black (Afro-Caribbean) hypertensive patients (usually a low-renin hypertensive population) than in non-black patients.

Pharmacodynamic effects

Antihypertensive properties:

Administration of ramipril causes a marked reduction in peripheral arterial resistance. Generally, there are no major changes in renal plasma flow and glomerular filtration rate. Administration of ramipril to patients with hypertension leads to a reduction in supine and standing blood pressure without a compensatory rise in heart rate.

In most patients the onset of the antihypertensive effect of a single dose becomes apparent 1 to 2 hours after oral administration. The peak effect of a single dose is usually reached 3 to 6 hours after oral administration. The antihypertensive effect of a single dose usually lasts for 24 hours.

The maximum antihypertensive effect of continued treatment with ramipril is generally apparent after 3 to 4 weeks. It has been shown that the antihypertensive effect is sustained under long term therapy lasting 2 years.

Abrupt discontinuation of ramipril does not produce a rapid and excessive rebound increase in blood pressure.

Heart failure:

In addition to conventional therapy with diuretics and optional cardiac glycosides, ramipril has been shown to be effective in patients with functional classes II-IV of the New-York Heart Association. The drug had beneficial effects on cardiac haemodynamics (decreased left and right ventricular filling pressures, reduced total peripheral vascular resistance, increased cardiac output and improved cardiac index). It also reduced neuroendocrine activation.

Clinical efficacy and safety

Cardiovascular prevention/Nephroprotection;

A preventive placebo-controlled study (the HOPE-study), was carried out in which ramipril was added to standard therapy in more than 9,200 patients. Patients with increased risk of cardiovascular disease following either atherothrombotic cardiovascular disease (history of coronary heart disease, stroke or peripheral vascular disease) or diabetes mellitus with at least one additional risk factor (documented microalbuminuria, hypertension, elevated total cholesterol level, low high-density lipoprotein cholesterol level or cigarette smoking) were included in the study.

The study showed that ramipril statistically significantly decreases the incidence of myocardial infarction, death from cardiovascular causes and stroke, alone and combined (primary combined events).

The HOPE Study: Main Results;

 

 

Ramipril

Placebo

relative risk

(95% confidence interval)

p-value

 

 

%

%

 

 

 

 

All patients

n=4,645

N=4,652

 

 

Primary combined events

14.0

17.8

0.78 (0.70-0.86)

<0.001

Myocardial infarction

9.9

12.3

0.80 (0.70-0.90)

<0.001

Death from cardiovascular causes

6.1

8.1

0.74 (0.64-0.87)

<0.001

Stroke

3.4

4.9

0.68 (0.56-0.84)

<0.001

 

 

 

 

 

 

 

 

 

 

Secondary endpoints

 

 

 

 

Death from any cause

10.4

12.2

0.84 (0.75-0.95)

0.005

Need for Revascularisation

16.0

18.3

0.85 (0.77-0.94)

0.002

Hospitalisation for unstable angina

12.1

12.3

0.98 (0.87-1.10)

NS

Hospitalisation for heart failure


read more / Download


Capoten


Generic Name: captopril (KAP toe pril)
Brand Names: Capoten

What is captopril?

Captopril is an ACE inhibitor. ACE stands for angiotensin converting enzyme.

Captopril is used to treat high blood pressure (hypertension), congestive heart failure, kidney problems caused by diabetes, and to improve survival after a heart attack.

Captopril may also be used for purposes not listed in this medication guide.

What is the most important information I should know about captopril? Do not use captopril if you are pregnant. Captopril can cause injury or death to the unborn baby if you take the medicine during your second or third trimester. Drinking alcohol can further lower your blood pressure and may increase certain side effects of captopril. Do not use salt substitutes or potassium supplements while taking captopril, unless your doctor has told you to.

Conditions that may cause very low blood pressure include: vomiting, diarrhea, heavy sweating, heart disease, dialysis, a low salt diet, or taking diuretics (water pills). Follow your doctor's instructions about the type and amount of liquids you should drink while taking captopril. Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting.

What should I discuss with my healthcare provider before taking captopril? You should not use this medication if you are allergic to captopril or to any other ACE inhibitor, such as benazepril (Lotensin), fosinopril (Monopril), enalapril (Vasotec), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), or trandolapril (Mavik).

To make sure you can safely take captopril, tell your doctor if you have any of these other conditions:

kidney disease (or if you are on dialysis);

liver disease;

heart disease or congestive heart failure;

diabetes; or

a connective tissue disease such as Marfan syndrome, Sjogren's syndrome, lupus, scleroderma, or rheumatoid arthritis.

FDA pregnancy category D. Do not use captopril if you are pregnant. Stop using this medication and tell your doctor right away if you become pregnant. Captopril can cause injury or death to the unborn baby if you take the medicine during your second or third trimester. Use effective birth control while taking captopril. Captopril can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are using captopril. How should I take captopril?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results.

Captopril is usually taken 1 hour before meals. Follow your doctor's instructions.

Conditions that may cause very low blood pressure include: vomiting, diarrhea, heavy sweating, heart disease, dialysis, a low salt diet, or taking diuretics (water pills). Follow your doctor's instructions about the type and amount of liquids you should drink while taking captopril. Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting.

Your blood pressure will need to be checked often. Your kidney or liver function may also need to be tested. Visit your doctor regularly.

If you need surgery, tell the surgeon ahead of time that you are using captopril. You may need to stop using the medicine for a short time.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Store at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use.

See also: Capoten dosage (in more detail)

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose? Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include feeling extremely dizzy or light-headed, or fainting.

What should I avoid while taking captopril? Drinking alcohol can further lower your blood pressure and may increase certain side effects of captopril. Do not use salt substitutes or potassium supplements while taking captopril, unless your doctor has told you to. Captopril side effects Get emergency medical help if you have any of these signs of an allergic reaction: hives; severe stomach pain; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

feeling light-headed, fainting;

urinating more or less than usual, or not at all;

fever, chills, body aches, flu symptoms;

pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;

easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;

fast, pounding, or uneven heartbeats;

chest pain; or

swelling, rapid weight gain.

Less serious side effects may include:

cough;

loss of taste sensation, loss of appetite;

dizziness, drowsiness, headache;

sleep problems (insomnia);

dry mouth, sores inside your mouth or on your lips;

nausea, diarrhea, constipation; or

mild skin itching or rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect captopril?

Tell your doctor about all other medicines you use, especially:

gold injections to treat arthritis;

lithium (Lithobid, Eskalith);

a potassium supplement such as K-Dur, Klor-Con;

salt substitutes that contain potassium;

drugs that can dilate blood vessels, such as alprostadil (Caverject, Edex), nitroglycerin (Nitro Dur, Nitrolingual, Nitrostat, Transderm Nitro, and others), nitroprusside (Nitropress), nesiritide (Natrecor), minoxidil (Loniten), or isosorbide dinitrate (Imdur, Isordil);

aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others; or

a diuretic (water pill).

This list is not complete and other drugs may interact with captopril. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Capoten resources Capoten Side Effects (in more detail)Capoten DosageCapoten Use in Pregnancy & BreastfeedingDrug ImagesCapoten Drug InteractionsCapoten Support Group0 Reviews for Capoten - Add your own review/rating Capoten Prescribing Information (FDA) Capoten Monograph (AHFS DI) Capoten Advanced Consumer (Micromedex) - Includes Dosage Information Capoten Consumer Overview Capoten MedFacts Consumer Leaflet (Wolters Kluwer) Captopril Professional Patient Advice (Wolters Kluwer) Compare Capoten with other medications CystinuriaDiabetic Kidney DiseaseHeart FailureHigh Blood PressureHypertensive EmergencyLeft Ventricular Dysfunction Where can I get more information? Your pharmacist can provide more information about captopril.

See also: Capoten side effects (in more detail)


read more / Download


losartan


loe-SAR-tan

Oral route(Tablet)

Drugs that act directly on the renin-angiotensin system can cause injury or death to the developing fetus when used during the second and third trimesters. Stop therapy as soon as possible when pregnancy is detected .

Commonly used brand name(s)

In the U.S.

Cozaar

Available Dosage Forms:

Tablet

Therapeutic Class: Cardiovascular Agent

Pharmacologic Class: Angiotensin II Receptor Antagonist

Uses For losartan

Losartan is used to treat high blood pressure (hypertension). High blood pressure adds to the work load of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled.

Losartan works by blocking the action of a substance in the body that causes blood vessels to tighten. As a result, losartan relaxes blood vessels. This lowers blood pressure.

Losartan is also used to decrease the risk of stroke in patients with high blood pressure and a condition called left ventricular hypertrophy (LVH). LVH is an enlargement of the left pumping chamber of the heart and can cause problems with the way the heart pumps blood.

Losartan is also used to treat a condition called diabetic nephropathy. Diabetic nephropathy is a complication of type 2 diabetes which causes the kidneys to not work properly.

Losartan is available only with your doctor's prescription.

Before Using losartan

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For losartan, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to losartan or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Studies on losartan have been done only in adult patients, and there is no specific information comparing use of losartan in children younger than 6 years of age with use in other age groups.

Geriatric

losartan has been tested in a limited number of patients 65 years of age or older and has not been shown to cause different side effects or problems in older people than it does in younger adults.

Pregnancy Pregnancy Category Explanation 1st Trimester C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women. 2nd Trimester D Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk. 3rd Trimester D Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk. Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking losartan, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using losartan with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Benazepril Enalapril Enalaprilat Lisinopril Lithium Moexipril Perindopril Quinapril Ramipril Trandolapril

Using losartan with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Bromfenac Celecoxib Diclofenac Diflunisal Etodolac Fenoprofen Fluconazole Flurbiprofen Ibuprofen Indomethacin Ketoprofen Ketorolac Magnesium Salicylate Meclofenamate Mefenamic Acid Meloxicam Nabumetone Naproxen Nepafenac Oxaprozin Piroxicam Rifampin Salsalate Sulindac Tolmetin Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of losartan. Make sure you tell your doctor if you have any other medical problems, especially:

Kidney disease or Liver disease—Effects may be increased because of slower removal of losartan from the body Proper Use of losartan

Make certain your health care professional knows if you are on any special diet, such as a low-sodium diet.

To help you remember to take your medicine, try to get into the habit of taking it at the same time each day.

In addition to the use of the medicine your doctor has prescribed, treatment for your high blood pressure may include weight control and care in the types of foods you eat, especially foods high in sodium. Your doctor will tell you which of these are most important for you. You should check with your doctor before changing your diet.

Many patients who have high blood pressure will not notice any signs of the problem. In fact, many may feel normal. It is very important that you take your medicine exactly as directed and that you keep your appointments with your doctor even if you feel well.

Remember that losartan will not cure your high blood pressure but it does help control it. Therefore, you must continue to take it as directed if you expect to lower your blood pressure and keep it down. You may have to take high blood pressure medicine for the rest of your life . If high blood pressure is not treated, it can cause serious problems such as heart failure, blood vessel disease, stroke, or kidney disease .

losartan may be taken with or without food.

If you are unable to swallow tablets, ask your pharmacist about preparing an oral suspension for you.

Dosing

The dose of losartan will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of losartan. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage form (tablets): For high blood pressure: Adults—25 to 100 milligrams (mg) a day. The dose may be taken once a day or divided into two doses. Children 6 years of age and older—Use and dose must be determined by your doctor. Children younger than 6 years of age—Use and dose must be determined by your doctor. For high blood pressure with left ventricular hypertrophy: Adults—50 to 100 milligrams (mg) once a day. Your doctor may adjust your dose and add another medicine based on your blood pressure response. Children 6 years of age and older—Use and dose must be determined by your doctor. Children younger than 6 years of age—Use and dose must be determined by your doctor. For diabetic neuropathy: Adults—50 to 100 milligrams (mg) once a day. Your doctor may adjust your dose based on your blood pressure response. Children 6 years of age and older—Use and dose must be determined by your doctor. Children younger than 6 years of age—Use and dose must be determined by your doctor. Missed Dose

If you miss a dose of losartan, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using losartan

Check with your doctor immediately if you think that you may be pregnant. Losartan may cause birth defects or other problems in the baby if taken during pregnancy.

It is important that your doctor check your progress at regular visits to make sure that losartan is working properly and to check for unwanted effects.

Do not take other medicines unless they have been discussed with your doctor. This especially includes over-the-counter (nonprescription) medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems, since they may tend to increase your blood pressure.

Dizziness or lightheadedness may occur after the first dose of losartan, especially if you have been taking a diuretic (water pill). Make sure you know how you react to losartan before you drive, use machines, or do anything else that could be dangerous if you are dizzy.

Check with your doctor right away if you become sick while taking losartan, especially with severe or continuing nausea and vomiting or diarrhea. These conditions may cause you to lose too much water and lead to low blood pressure.

Dizziness, lightheadedness, or fainting may also occur if you exercise or if the weather is hot. Heavy sweating can cause loss of too much water and result in low blood pressure. Use extra care during exercise or hot weather.

Avoid alcoholic beverages until you have discussed their use with your doctor. Alcohol may make the low blood pressure effect worse and/or increase the possibility of dizziness or fainting.

losartan Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Rare Hoarseness swelling of face, mouth, hands, or feet trouble in swallowing or breathing (sudden) Incidence not known Abdominal pain black, tarry stools bleeding gums blood in urine or stools coma confusion convulsions decreased urine output difficult breathing fast or irregular breathing headache increased thirst irregular heartbeat large, flat, bluish patches on the skin muscle pain or cramps nausea or vomiting painful knees and ankles pinpoint red spots on skin unusual bleeding or bruising unusual tiredness or weakness upper right abdominal pain weakness or heaviness of legs yellow eyes and skin

Check with your doctor as soon as possible if any of the following side effects occur:

Less common Cough, fever or sore throat dizziness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common Headache Less common Back pain diarrhea fatigue nasal congestion Rare Cough, dry leg pain muscle cramps or pain sinus problems trouble in sleeping

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: losartan side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More losartan resources Losartan Side Effects (in more detail) Losartan Dosage Losartan Use in Pregnancy & Breastfeeding Drug Images Losartan Drug Interactions Losartan Support Group 47 Reviews for Losartan - Add your own review/rating Losartan Prescribing Information (FDA) Losartan MedFacts Consumer Leaflet (Wolters Kluwer) Cozaar Prescribing Information (FDA) Cozaar Monograph (AHFS DI) Cozaar Consumer Overview Compare losartan with other medications Diabetic Kidney Disease High Blood Pressure
read more / Download


Related Search:

Search


 

Best ED Pills

 

Erectile Dysfunction

 

RX Pharmacy Drugs List - Buy Pills Online

RSS | Site Map | Map | PageMap

Copyright © Online Pharmacy Drug Store. All rights reserved.