Praxilene 200Mg
 

Pills
 

ED Pills

ED Drugs
 

Praxilene


1. Name Of The Medicinal Product

Praxilene 100mg Capsules

2. Qualitative And Quantitative Composition

100mg naftidrofuryl oxalate equivalent to 81.0 mg naftidrofuryl and 19.0 mg oxalate.

3. Pharmaceutical Form

Capsule

4. Clinical Particulars 4.1 Therapeutic Indications

Peripheral vascular disorders - intermittent claudication, night cramps, rest pain, incipient gangrene, trophic ulcers, Raynaud's Syndrome, diabetic arteriopathy and acrocyanosis.

Cerebral vascular disorders - cerebral insufficiency and cerebral atherosclerosis, particularly where these manifest themselves as mental deterioration and confusion in the elderly.

4.2 Posology And Method Of Administration

Peripheral vascular disorders - one or two capsules three times daily for a minimum of three months, or at the discretion of the physician.

Cerebral vascular disorders - one 100mg capsule three times daily for a minimum of three months, or at the discretion of the physician.

There is no recommended use for children.

Administration:

For oral administration. The capsules should be swallowed whole during meals with a sufficient amount of water (minimum) of one glass.

4.3 Contraindications

Hypersensitivity to the drug. Patients with a history of hyperoxaluria or recurrent calcium-containing stones.

4.4 Special Warnings And Precautions For Use

A sufficient amount of liquid should be taken during treatment to maintain an adequate level of diuresis.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

None known.

4.6 Pregnancy And Lactation

Pregnancy: There is no, or inadequate, evidence of the safety of naftidrofuryl oxalate in human pregnancy, but it has been in wide use for many years without apparent ill consequence, animal studies having shown no hazard. If drug therapy is needed in pregnancy, this drug can be used if there is no safer alternative.

Lactation: No information is available.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Naftidrofuryl oxalate is normally well tolerated in the dosage recommended. Occasionally nausea, epigastric pain and rashes have been noted.

Rarely, hepatitis has been reported. Very rarely, calcium oxalate kidney stones have been reported.

4.9 Overdose

Signs and symptoms: Depression of cardiac conduction and convulsions may occur.

Treatment: The stomach should be emptied by gastric lavage and emesis. Activated charcoal may be employed if necessary. Cardiovascular function and respiration should be monitored and, in severe cases, electrical pacemaking or the use of isoprenaline should be considered. Convulsions may be managed by diazepam.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Naftidrofuryl oxalate has been shown to exert a direct effect on intracellular metabolism. Thus it has been shown in man and animals that it produces an increase of ATP levels and a decrease of lactic acid levels in ischaemic conditions, evidence for an enhancement of cellular oxidative capacity. Furthermore, naftidrofuryl oxalate is a powerful spasmolytic agent.

5.2 Pharmacokinetic Properties

Naftidrofuryl oxalate is well absorbed when given orally. Peak plasma levels occur about 30 minutes after dosing and the half life is about an hour, although inter subject variation is relatively high. Accumulation does not occur at a dose level of 200mg three times daily.

The drug becomes extensively bound to plasma proteins and is excreted principally via the urine, all in the form of metabolites.

5.3 Preclinical Safety Data

No toxic effects were seen in animal studies which provide additional information to that obtained in man. In repeated dose studies the no effect level was 25mg/kg/day or greater. There was no evidence of effects on reproduction below doses which caused maternal toxicity.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Talc

Magnesium Stearate

Purified Water*

Denatured Ethanol*

Capsule Shells:

Erythrosine (E127)

Titanium Dioxide (E171)

Gelatine

Printing ink:

Black iron oxide (E172)

*Not present in final product

6.2 Incompatibilities

None known.

6.3 Shelf Life

36 months.

6.4 Special Precautions For Storage

Store below 20°C in a dry place away from light.

6.5 Nature And Contents Of Container

Pack size 10 (medical sample), 21 and 84 capsules:-

Cardboard carton containing blister strips comprising heat-sealable PVC (250?m) and aluminium foil (30?m).

Pack size 100 and 500:

Polyethylene securitainers with tamper evident closures.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Merck Serono Ltd

Bedfont Cross

Stanwell Road

Feltham

Middlesex

TW14 8NX, UK

8. Marketing Authorisation Number(S)

PL 11648/0064

9. Date Of First Authorisation/Renewal Of The Authorisation

24 March 2009

10. Date Of Revision Of The Text

24 March 2009


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Urispas 200


Urispas 200mg Film-coated tablets

Flavoxate hydrochloride

Please read this leaflet carefully before you start to take your medicine. If you have any questions or are not sure about anything, ask your doctor or pharmacist.

What is Urispas 200mg Film-coated Tablets?

Urispas 200mg Film-coated Tablets contain the active ingredient flavoxate hydrochloride.

Flavoxate hydrochloride is one of a group of drugs called antispasmodics which relieve or prevent muscle spasms including spasms of the urinary tract. Urispas has also been shown to relieve pain.

Urispas 200mg Film-coated Tablets also contain the ingredients lactose, sodium starch glycollate, povidone, talc, cellulose microcrystalline, magnesium stearate, hypromellose, macrogol, macrogol stearate and titanium dioxide (E171).

Each white, film coated tablet is embossed with 'F 200' and contains 200mg flavoxate hydrochloride.

The pack contains 90 tablets, which is enough for about 4 weeks treatment at the normal dose of one tablet three times a day.

The Marketing Authorisation holder is

Recordati Pharmaceuticals
Isis House
43 Station Rd
Henley on Thames
OXON
RG9 1AT
Tel: 01491 576336
What is Urispas 200mg Film-coated Tablets used for?

Urispas is used to treat conditions which cause muscle spasms of the urinary tract. These muscle spasms may be due to inflammation of the bladder, prostate gland or urethra (tube from bladder to outside). In addition, Urispas can be used to treat the symptoms which may occur as a result of surgery, cystoscopy or catheterisation such as painful urination, excessive urination at night and the inability to control urine flow.

If you have a urine infection as well, your doctor will probably also prescribe medicine to treat this at the same time.

When must Urispas not be used?

If you have a condition which causes a blockage of the stomach, bowel or urinary tract or if you suffer from bleeding from the stomach or bowel.

If you are allergic to Urispas 200mg Film-coated Tablets or any of the ingredients they contain.

In children under 12 years of age.

When should you be extra careful while taking Urispas 200mg Film-coated Tablets?

Make sure your doctor knows if you have, or suspects you have, the eye condition glaucoma.

This medicine may cause drowsiness, blurred vision or dizziness. If it does you should not operate a motor vehicle or machinery.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

May Urispas be used during pregnancy or while breast feeding?

Before starting treatment, tell your doctor if you are pregnant, if you think you are pregnant or if you intend to become pregnant. Your doctor will then decide whether you should take the medicine.

Many drugs pass into breast milk, therefore, if you are breast feeding, this medicine should be avoided. Your doctor will be able to discuss this with you.

How should Urispas 200mg Film-coated Tablets be taken?

Always take the tablets as your doctor tells you to. A normal dose is one tablet three times a day for as long as is required.

If you take too many tablets or someone else accidentally takes your medicine, contact your doctor, pharmacist or nearest hospital straight away.

If you forget to take your tablets:

Take the normal dose when you remember unless it is almost time for your next dose.

DO NOT TAKE A DOUBLE DOSE OF TABLETS TO MAKE UP FOR A MISSED DOSE.

What are the possible unwanted effects of Urispas 200mg Film-coated Tablets?

In addition to the beneficial effects of Urispas, it is possible that unwanted effects will occur during treatment such as:

feeling or being sick, dry mouth or diarrhoea. indigestion or difficulty swallowing. vertigo, headache, confusion (especially in the elderly), drowsiness, tiredness, dizziness or nervousness. allergic reaction such as rash, itching, skin redness, sneezing, difficulty in breathing and swelling of the throat. if any of these occur stop taking the tablets and see your doctor immediately. heart beat irregularities. disturbances to your vision or eye pain. painful urination. low white blood cell count.

If you are concerned about these or any other unwanted effects, talk to your doctor.

How should Urispas 200mg Film-coated Tablets be stored?

Do not store above 30°C. In order to protect your medicine from light, keep the blister strips in the outer carton.

Keep this medicine out of the reach and sight of children.

This medicine must not be used after the expiry date printed on the pack. Return any left over medicine to your pharmacist. Only keep it if your doctor tells you to.

REMEMBER this medicine is for you. Only a doctor can prescribe it for you. Never give it to others. It may harm them even if their symptoms are the same as yours.

Further Information

You can get more information on Urispas 200mg Film-coated Tablets from your doctor or pharmacist.

Date of Preparation: April 2007

41894313 A


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Aciclovir 200mg / 5ml Oral Suspension


Aciclovir 200mg/5ml Oral Suspension

Read all of this leaflet carefully before you start taking this medicine. Keep this leaflet. You may need to read it again. If you have any further questions, ask your doctor or your pharmacist. This medicine has been prescribed only for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours. If any of these side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. In this leaflet 1. What is Aciclovir Oral Suspension and what is it used for 2. Before you take Aciclovir Oral Suspension 3. How to take Aciclovir Oral Suspension 4. Possible side effects 5. How to store Aciclovir Oral Suspension 6. Further information What is Aciclovir Oral Suspension and what is it used for

The name of your medicine is Aciclovir 200mg/5ml Oral Suspension (called aciclovir in this leaflet). This belongs to a group of medicines called anti-virals.

Aciclovir can be used:

to treat herpes and other viral infections caused by the herpes virus (varicella zoster) such as chickenpox and shingles to prevent recurrent attacks of herpes simplex to help prevent those who have low immune systems from getting herpes infections. Before you take Aciclovir Oral Suspension Do not take Aciclovir and tell your doctor if: you are allergic (hypersensitive) to aciclovir, valaciclovir or any other ingredients in this liquid (see section 6: Further Information). An allergic reaction can include a rash, itching or shortness of breath

Do not take this medicine if any of the above apply to you, talk to your doctor or pharmacist before taking aciclovir.

Take special care with Aciclovir

Before you take aciclovir tell your doctor if:

you have kidney problems you are over 65 years of age. Your doctor may adjust your dose to reduce the risk of side effects you are thirsty. You must make sure you drink plenty of 'liquids such as water' whilst taking this medicine.

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before using aciclovir.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines bought without a prescription, including herbal medicines.

In particular tell your doctor if you are taking any of the following medicines:

probenecid - used for gout cimetidine - used for stomach acid mycophenolate mofetil - used after transplant operations Tests

Tell your doctor you are taking this medicine if you are going to have any blood or urine tests.

Pregnancy and Breast-feeding

Talk to your doctor before taking this medicine if you are pregnant, planning to become pregnant or are breast-feeding.

Driving and using machines

This medicine does not usually affect you being able to drive or use any tools or machines.

Important information about what is in Aciclovir Oral Suspension:

This medicine contains:

Methyl and propyl parahydroxybenzoates. These may cause an allergic reaction. This allergy may happen some time after starting the medicine Liquid maltitol. If your doctor has told you that you cannot tolerate some sugars, talk to your doctor before taking this medicine Ethanol (alcohol). This product contains a small amount of alcohol, less than 100mg per dose How to take Aciclovir Oral Suspension

Take this medicine as your doctor or pharmacist has told you. Look on the label and ask the doctor or pharmacist if you are not sure.

Taking this medicine This medicine contains 200mg of aciclovir in each 5ml Take this medicine by mouth Drink plenty of ‘liquids such as water’ while taking this medicine Always shake the bottle before use If you feel that the effect of your medicine is too strong or too weak, do not change the dose yourself, but talk to your doctor or pharmacist

The usual doses are given below. These may be changed by your doctor:

Adults

Herpes Simplex

This medicine is the most appropriate treatment for Herpes Simplex

Take for at least 5 days One 5ml spoonful (200mg), five times each day Take every four hours while awake (for example, 6am, 10am, 2pm, 6pm, 10pm)

Shingles and Chickenpox

Take for 7 days Four 5ml spoonfuls (800mg), five times each day Take every four hours while awake (for example, 6am, 10am, 2pm, 6pm, 10pm)

Children

Herpes Simplex

Take for at least 5 days

Children over 2 years

One 5ml spoonful (200mg), five times each day Take every four hours while awake (for example, 6am, 10am, 2pm, 6pm, 10pm)

Children under 2 years

2.5ml of suspension (100mg), five times each day Take every four hours while awake (for example, 6am, 10am, 2pm, 6pm, 10pm)

Shingles

This medicine should not be used to treat shingles in children.

Chickenpox

Take for 5 days

Age 6 and above

Four 5ml spoonfuls (800mg), four times each day

Age 2 to 5 years

Two 5ml spoonfuls (400mg), four times each day

Under 2 years

One 5ml spoonful (200mg), four times each day

Elderly and people with kidney problems

Your doctor may decide to lower your dose if you are elderly or have kidney problems.

If you take more aciclovir than you should

Talk to your doctor or go to your nearest hospital straight away.

If you forget to take Aciclovir Oral Suspension

Do not take a double dose (two doses at the same time) to make up for a forgotten dose. Take your next dose as soon as you remember, then go on as before. However, if it is nearly time for the next dose, skip the missed dose.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Possible side effects

Like all medicines, Aciclovir Oral Suspension can cause side effects although not everybody gets them.

Allergic reactions (affects less than 1 in 1,000 people)

If you have an allergic reaction to aciclovir see a doctor straight away

An allergic reaction may include:

any kind of skin rash, flaking skin, boils or sore lips and mouth swelling of the face, lips, tongue or throat or difficulty breathing or swallowing sudden wheezing, fluttering or tightness of the chest or collapse If you get any of the following side effects, stop taking aciclovir and see your doctor as soon as possible:

Common (affects less than 1 in 10 people)

headaches feeling dizzy feeling or being sick diarrhoea stomach pains itching skin rash that happens in people who are oversensitive to sunlight feeling very tired fever

Uncommon (affects less than 1 in 100 people)

skin rashes (causing itchiness or redness) hair loss

Rare (affects less than 1 in 1,000 people)

shortness of breath this medicine may also cause changes in the results of blood tests such as a fall in the number of white blood cells changes in blood tests that check the way your liver or kidneys are working swelling of the face, lips, tongue or throat

Very rare (affects less than 1 in 10,000 people)

blood disorders such as nose bleeds, bruising more easily that usual, sore throat, high temperatures or chills, mouth ulcers and unusual tiredness. feeling weak. This could be caused by something called ‘anaemia’ feeling agitated shaking seeing or hearing things that are not there (hallucinations) fits feeling sleepy difficulty in controlling your movements or speech feeling confused loss of consciousness liver problems (hepatitis) yellowing of your skin or whites of the eyes (jaundice) kidney failure (which usually returns to normal) pain in your lower back, the kidney area of your back or above your hip (renal pain)

If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How to store Aciclovir Oral Suspension Keep out of the reach and sight of children Do not store above 25°C Take back to the pharmacy 1 month after you first open it Do not use after the expiry date (month, year) stated on the label and carton If it is out of date or you no longer want it, take it back to the pharmacy Do not use Aciclovir Oral Suspension if you notice anything wrong with the medicine. Talk to your pharmacist Medicines should not be disposed of via wastewater or household waste.
Ask your pharmacist how to dispose of medicine no longer required.
These measures will help to protect the environment. Further information What Aciclovir Oral Suspension contains The active ingredient is aciclovir The other ingredients are sodium methyl hydroxybenzoate (E219), sodium propyl hydroxybenzoate (E217), citric acid (E330), xanthan gum (E415), liquid maltitol (E965), compound orange spirit, vanillin and purified water. What Aciclovir Oral Suspension looks like and contents of the pack

A white to light beige suspension with an odour of orange and vanilla.

It comes in a brown glass bottle holding 125ml of suspension.

Marketing Authorisation Holder and Manufacturer Rosemont Pharmaceuticals Ltd Yorkdale Industrial Park Braithwaite Street Leeds LS11 9XE UK

This leaflet was last approved November 2009

P0479


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Vitamin E Suspension 100mg / ml (Cambridge Laboratories)


1. Name Of The Medicinal Product

Vitamin E Suspension 100mg/ml

2. Qualitative And Quantitative Composition

Each 5ml of suspension contains 500mg of DL-alpha-tocopheryl acetate.

3. Pharmaceutical Form

Oral Suspension

4. Clinical Particulars 4.1 Therapeutic Indications

For the correction of Vitamin E deficiency occurring in malabsorption disorders ie. cystic fibrosis, chronic cholestasis and abetalipoproteinaemia.

4.2 Posology And Method Of Administration

Route of administration: For oral use.

Adults (including the elderly)

For the treatment of malabsorption disorders the following doses should be administered:

Cystic fibrosis 100-200mg/day

Abetalipoproteinaemia 50-100mg/kg/day

Children

For the treatment of cystic fibrosis a dose of 50mg/day should be given to children less than 1 year and 100mg/day to children 1 year and over.

The adult dosage should be used for the treatment of abetalipoproteinaemia (50-100mg/kg/day).

Infants with vitamin E deficiency which is secondary to chronic cholestasis may be treated with doses of 150-200mg/kg/day.

4.3 Contraindications

Use in patients with a known hypersensitivity to Vitamin E.

4.4 Special Warnings And Precautions For Use

Vitamin E has been reported to increase the risk of thrombosis in patients predisposed to this condition, including patients taking oestrogens. This finding has not been confirmed but should be borne in mind when selecting patients for treatment, in particular women taking oral contraceptives containing oestrogens.

A higher incidence of necrotising enterocolitis has been noted in lower weight premature infants (less than 1.5kg) treated with vitamin E.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Vitamin E may increase the risk of thrombosis in patients taking oestrogens (see 4.4 above).

4.6 Pregnancy And Lactation

There is no evidence of the safety of high doses of vitamin E in pregnancy nor is there evidence from animal work that it is free from hazard, therefore do not use in pregnancy especially in the first trimester. No information is available on excretion in breast milk, therefore it is advisable not to use during lactation.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Diarrhoea and abdominal pain may occur with doses greater than 1g daily.

4.9 Overdose

Transient gastro-intestinal disturbances have been reported with doses greater than 1g daily and where necessary, general supportive measures should be employed.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

The exact role of vitamin E in the animal organism has not yet been established. Vitamin E is known to exert an important physiological function as an antioxidant for fats, with a sparing action on vitamin A, carotenoids and on unsaturated fatty acids. Other work has demonstrated that vitamin E is connected with the maintenance of certain factors essential for the normal metabolic cycle.

5.2 Pharmacokinetic Properties

Vitamin E is absorbed from the gastrointestinal tract. Most of the vitamin appears in the lymph and is then widely distributed to all tissues. Most of the dose is slowly excreted in the bile and the remainder is eliminated in the urine as glucuronides of tocopheronic acid or other metabolites.

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Castor oil polyethylene glycol ether

Benzoic acid

Sorbic acid

Glycerol

Syrup

Flavour raspberry

Purified Water

6.2 Incompatibilities

None.

6.3 Shelf Life

Unopened: Two years.

After first opening: One month (The product will be stable after opening for the normal duration of treatment providing the cap is replaced after use and the recommended storage conditions on the label are observed).

6.4 Special Precautions For Storage

Store below 25°C.

6.5 Nature And Contents Of Container

Amber glass bottles with aluminium screw caps or Vistop tamper-evident caps.

6.6 Special Precautions For Disposal And Other Handling

Vitamin E Suspension may be diluted with Syrup BP but should be used immediately and not stored.

7. Marketing Authorisation Holder

Cambridge Laboratories Limited

Deltic House

Kingfisher Way

Silverlink Business Park

Wallsend

Tyne & Wear

NE28 9NX

8. Marketing Authorisation Number(S)

PL 12070/0010

9. Date Of First Authorisation/Renewal Of The Authorisation

8 March 1993

10. Date Of Revision Of The Text

March 2000


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Sulpor 200mg / 5ml Oral Solution


Sulpor 200mg/5ml Oral Solution

Sulpiride

Read all of this leaflet carefully before you start taking this medicine. Keep this leaflet. You may need to read it again. If you have any further questions, ask your doctor or your pharmacist. This medicine has been prescribed only for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours. If any of these side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. In this leaflet 1. What Sulpor is and what it is used for 2. Before you take Sulpor 3. How to take Sulpor 4. Possible side effects 5. How to store Sulpor 6. Further information What Sulpor is and what it is used for

The name of your medicine is Sulpor. It contains sulpiride. This belongs to a group of medicines called benzamides. These act on the brain to reduce abnormal behaviour.

Sulpor is used for treating schizophrenia.

Before you take Sulpor Do not take Sulpor and tell your doctor if: you are allergic (hypersensitive) to sulpiride or any other ingredients in this liquid (listed in Section 6). The signs of an allergic reaction include a rash, itching or shortness of breath you have high blood pressure due to a growth on your adrenal glands (phaeochromocytoma) you have porphyria, a problem with your metabolism that can cause skin blisters, pain in and around your stomach (abdomen) and brain or nervous system problems severe kidney, blood or liver problems you have an alcohol-related illness or any other problems that affect your nervous system you have ever had breast cancer or a type of brain tumour called ‘pituitary prolactinoma’ you are taking levodopa (see section ‘Taking other medicines’).

Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking this medicine.

Take special care with Sulpor

Before you take Sulpor, tell your doctor if:

you have ‘hypomania’. These are mood swings that may show as excitability, anger, irritability and a lower need for sleep you have heart problems. If you or members of your family suffer from heart problems, your doctor may give you some tests on your heart and blood before giving you Sulpor you or someone else in your family has a history of blood clots, as medicines like these have been associated with formation of blood clots you have epilepsy you have Parkinson’s Disease you have had a stroke.

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking Sulpor.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines you buy without a prescription, including herbal medicines. This is because Sulpor can affect the way some other medicines work. Also, some medicines can affect the way Sulpor works.

In particular, tell your doctor if you are taking any of the following:

Levodopa, used to treat Parkinson’s Disease (sometimes this is called L-dopa). You must not take this at the same time as Sulpor medicines to treat high blood pressure or migraine such as beta-blockers, clonidine or diuretics (water tablets) medicines used to treat abnormal heart rhythms (quinidine, disopyramide, amiodarone, sotalol) or angina (diltiazem, verapamil) and other heart problems (digoxin) sucralfate, cisapride and antacids used to treat stomach problems or laxatives lithium used to treat depression medicines used to treat epilepsy steroids such as prednisolone, dexamethasone and tetracosactide medicines to treat infections such as erythromycin or amphotericin B that are injected into a vein or pentamidine that is breathed in or given by injection medicines used to treat Parkinson’s Disease, including ropinirole medicines used to treat mental or emotional problems such as pimozide, thioridazine, haloperidol or imipramine.

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking Sulpor.

Taking Sulpor with food and drink

Do not drink alcohol while taking Sulpor. This is because Sulpor can make you drowsy and alcohol will make you even more drowsy.

Pregnancy and breast-feeding

Talk to your doctor before taking this medicine if you are pregnant, planning to become pregnant or are breast-feeding.

Driving and using machines

Sulpor may make you drowsy or less alert to your surroundings. If this happens to you, do not drive or use machinery.

Important information about what is in Sulpor

This medicine contains:

methyl and propyl parahydroxybenzoates. These may cause an allergic reaction. This allergy may happen some time after starting the medicine liquid maltitol (a type of sugar). If your doctor has told you that you cannot tolerate some sugars, talk to your doctor before taking this medicine. How to take Sulpor

Take this medicine as your doctor or pharmacist has told you. Look on the label and ask the doctor or pharmacist if you are not sure.

Taking this medicine this medicine contains 200mg of sulpiride in each 5ml take this medicine by mouth. Adults:

The usual dose for adults is:

the doctor will start you on a dose of 200mg (5ml) to 400mg (10ml) two times a day (usually morning and early evening) the doctor may reduce the dose or increase it to a maximum of 1200mg (30ml) two times a day if you are an older person the dose will be the same as that for adults unless you have a kidney or liver problem. The doctor may lower the dose in this case. Children:

This medicine must not be given children under the age of 14.

If you take more Sulpor than you should

If you take more Sulpor than you should, talk to a doctor or go to a hospital straight away. Take the medicine pack with you so the doctor knows what you have taken.

If you forget to take Sulpor if you forget a dose, skip the missed dose then go on as before. do not take a double dose (two doses at the same time) to make up for a forgotten dose. If you stop taking Sulpor

Keep taking this medicine until your doctor tells you to stop, as it may be necessary to lower the dose gradually.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Possible side effects

Like all medicines, Sulpor can cause side effects although not everybody gets them.

Stop taking this medicine and see a doctor straight away if you have an allergic reaction to Sulpor.

Signs of an allergic reaction may include:

any kind of skin rash, flaking skin, boils or sore lips and mouth sudden wheezing, fluttering or tightness of the chest or collapse. Stop taking this medicine and see a doctor straight away if you have any of the following: early warning signs such as unusually fast heart beats and sweating over heating, muscle stiffness, change in consciousness leading to a coma. If you get any of the following side effects, see your doctor as soon as possible: blood clots in the veins especially in the legs (symptoms include swelling, pain and redness in the leg), which may travel through blood vessels to the lungs causing chest pain and difficulty in breathing. If you notice any of these symptoms seek medical advice immediately changes in the rhythm of your heart beat or heart attack muscle spasms, jerky movements of your hands or feet, unusual facial movements, shaking or a large amount of saliva in your mouth jaundice, which normally shows as yellowing of your skin and whites of the eyes inflammation of your liver (hepatitis). The signs of this include feeling sick (nausea), being sick (vomiting), swelling in your upper abdomen feeling more agitated and restless having fits feeling dizzy when standing up. This may be a sign of low blood pressure Tell your doctor if you get any of these side effects: feeling sleepy or drowsy unable to sleep swelling and breast pain (men or women) and secretion of breast milk in women irregular or absent periods changes in sexual function diarrhoea that may be caused by the liquid maltitol in the medicine weight gain

There have been reports of unexplained deaths, but it is not proven that they were due to sulpiride. In elderly people with dementia, a small increase in the number of deaths has been reported for patients taking antipsychotics compared with those not receiving antipsychotics.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How to store Sulpor keep out of the reach and sight of children do not store above 25°C. get rid of the medicine 3 months after opening do not use after the expiry date which is stated on the label and carton (Exp: month, year) the expiry date refers to the last day of that month do not use Sulpor if you notice a change in the appearance or smell of the medicine. Talk to your pharmacist medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment. Further information What Sulpor contains the active ingredient is sulpiride. the other ingredients are methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216), propylene glycol (E1520), citric acid monohydrate (E330), liquid maltitol (E965), lemon flavour, aniseed flavour and purified water. What Sulpor looks like and contents of the pack

A colourless to slightly yellow liquid with an odour of lemon and aniseed

It comes in a brown glass bottle holding 150ml of liquid.

Marketing Authorisation Holder and Manufacturer Rosemont Pharmaceuticals Ltd Yorkdale Industrial Park Braithwaite Street Leeds LS11 9XE UK

This leaflet was last revised in January 2010

P0497


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Zomorph capsules


1. Name Of The Medicinal Product

ZOMORPH capsules 10mg, 30mg, 60mg, 100mg, 200mg

2. Qualitative And Quantitative Composition

• Morphine sulphate BP 10mg

• Morphine sulphate BP 30mg

• Morphine sulphate BP 60mg

• Morphine sulphate BP 100mg

• Morphine sulphate BP 200mg

3. Pharmaceutical Form

Sustained-release capsules.

4. Clinical Particulars 4.1 Therapeutic Indications

Severe chronic pain and/or pain resistant to other analgesics, in particular pain associated with cancer.

4.2 Posology And Method Of Administration

Route of administration : orally.

As directed by a medical practitioner.

Recommended dosage

Adults: Recommended dosage is one capsule twice daily, at 12-hourly intervals.

Elderly: As with all narcotics, a reduction in dosage may be advisable in the elderly, as appropriate.

Children: Not recommended.

The capsules should not be chewed and should normally be swallowed whole.

The dosage varies according to the severity of pain and the previous analgesic treatments received by the patient.

If the pain persists, or if the patient develops tolerance to morphine, the dosage may be increased by prescribing the 10mg, 30mg, 60mg, 100mg and 200mg capsules in various combinations or alone to obtain the desired relief.

Patients previously treated with immediate-release oral morphine should receive the same daily dose of sustained-release capsules, but in two divided doses at 12-hourly intervals.

Patients previously treated with parenteral morphine should be given a sufficiently increased dosage to compensate for any reduction of the analgesic effect associated with oral administration. The dosage should be adjusted to meet the individual requirements of each patient.

For patients who cannot swallow the capsules, their contents can be administered directly in semi-solid food (puree, jam, yoghurt) or via gastric or gastrostomy tubes of a diameter of more than 16 F.G. with an open distal end or lateral pores. It is sufficient to rinse the tube with 30ml to 50ml of water.

4.3 Contraindications

Respiratory impairment, acute abdominal syndrome of unknown origin, severely impaired liver function, cranial trauma and raised intracranial pressure, convulsive state, acute alcoholic intoxication and delirium tremens, children, risk of paralytic ileus, known hypersensitivity to any of the ingredients contained in Zomorph, concurrent treatment with MAO (MAO = monoamine oxidase) inhibitors or within two weeks of their use.

4.4 Special Warnings And Precautions For Use

Caution should be exercised:

- in elderly subjects, in patients with impaired hepatic and/or renal functions, in patients with hypothyroidism or hypoadrenalism, in patients in a state of shock or with asthma. The dose of Zomorph should be reduced, or its use should be avoided in cases of hepatic or renal failure.

- in patients suffering from the following conditions: hypotension, convulsive disorders, dependence (severe withdrawal symptoms if withdrawn abruptly) and prostatic hypertrophy.

Urinary retention may occur in patients with urethral disease or prostatic hypertrophy.

Concomitant use of alcohol and Zomorph may increase the undesirable effects of Zomorph; concomitant use should be avoided.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

As serious and sometimes fatal reactions have occurred following administration of pethidine to patients receiving monoamine oxidase inhibitors, pethidine and related drugs are contra-indicated in patients taking monoamine oxidase inhibitors or within 14 days of stopping such treatment; morphine and other opioid analgesics should be given with extreme caution.

The depressant effects of opioid analgesics are enhanced by depressants of the central nervous system such as alcohol, anaesthetics, antipsychotics, anxyolitics, hypnotics and sedatives, tricyclic antidepressants and phenothiazines.

Cyclizine may counteract the haemodynamic benefits of opioids.

Opioid analgesics with some antagonist activity, such as buprenorphine, butorphanol, nalbuphine or pentazocine may precipitate withdrawal symptoms in patients who have recently used pure agonists such as morphine. The actions of opioids may in turn affect the activities of other compounds. For instance, their gastro-intestinal effects may delay absorption as with mexiletine or may be counteractive as with metoclopramide, domperidone and possibly cisapride.

Plasma concentrations of morphine are possibly increased by ritonavir.

Alcohol may enhance the pharmacodynamic effects of Zomorph; concomitant use should be avoided.

4.6 Pregnancy And Lactation

Since this product rapidly crosses the placental barrier, it should not be used during the second stage of labour or in premature delivery because of the risk of secondary respiratory depression in the newborn infant. If the mother is addicted, a withdrawal syndrome is observed in the newborn infant characterised by: convulsions, irritability, vomiting, increased mortality. As with all drugs, it is not advisable to administer morphine during pregnancy.

4.7 Effects On Ability To Drive And Use Machines

Because of the decrease in vigilance induced by this drug, attention is drawn to the possible dangers incurred by drivers of vehicles or machine operators.

4.8 Undesirable Effects

The most common side effects at usual doses are nausea, constipation, confusion and occasionally vomiting.

Other possible effects include: urticaria, pruritus, rashes, decreased libido or potency, mood changes, drowsiness, dry mouth, sweating, headache, facial flushing, vertigo, bradycardia, tachycardia, palpitations, postural hypotension, dysphoria, hypotension, hypothermia, miosis, dysuria, sedation or excitation (particularly in elderly subjects in whom delirium and hallucinations may occur), increased intracranial pressure which may aggravate existing cerebral disorders, increased pressure in the main bile duct and urinary retention in cases of prostatic adenoma or urethral stenosis. Mild respiratory depression occurs even at therapeutic doses. In the event of overdosage it may be severe, serious or even fatal. Physical and psychic dependence may appear after administration of therapeutic doses for periods of 1 to 2 weeks. Some cases of dependence have been observed after only 2 to 3 days.

Withdrawal syndrome: this may occur a few hours after withdrawal of a prolonged treatment, and is maximal between the 36th and 72nd hours.

4.9 Overdose

Symptoms include respiratory depression, extreme miosis, hypotension, hypothermia, coma. Treatment is by intravenous injection of naloxone 0.4mg, repeated every 2 to 3 minutes if necessary, or by an infusion of 2mg in 500ml of normal saline or 5% dextrose (0.004mg/ml).

In subjects dependent on morphine-like drugs, withdrawal symptoms may occur following injection of a high dose of naloxone. It should therefore be injected in gradually increasing doses to such subjects.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Morphine is an opioid analgesic. It acts mainly on the central nervous system and smooth muscle.

Morphine exerts an analgesic action, and affects psychomotor behaviour: depending on the dose administered, it induces sedation (> 1cg) or, in some cases, excitation (< 1cg). At high doses, greater than those required to produce analgesia, it induces somnolence and sleep.

5.2 Pharmacokinetic Properties

Absorption

This is a sustained-release form, which makes twice-daily oral administration possible. Morphine is immediately absorbed from the digestive tract following oral administration. The maximum serum concentrations of morphine are obtained in 2 to 4 hours.

Distribution

The percentage of binding to plasma proteins after absorption is low (about 34%). There is no clearly defined correlation between the plasma concentration of morphine and the analgesic effect.

Metabolism

A considerable quantity of morphine is metabolised by the liver to glucuronides, which undergo enterohepatic recirculation.

Excretion

The product is eliminated essentially in the urine, by glomerular filtration, mainly as glucuronides. A small amount (less than 10%) is eliminated in the faeces.

5.3 Preclinical Safety Data

None stated.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Sucrose, maize starch, polyethylene glycol 4000, ethyl-cellulose, cetyl alcohol, sodium lauryl sulphate, dibutyl sebacate, talc, gelatin, iron oxide ink (E172), titanium dioxide (E171) (for the 10mg, 30mg, 60mg and 100mg strengths), quinoline yellow (E104) (only for the 10mg strength), erythrosine (E127) (only for the 30mg strength), sunset yellow (E 110) (only for the 60mg strength).

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

36 months.

6.4 Special Precautions For Storage

Store below 25°C in a dry place protected from heat.

6.5 Nature And Contents Of Container

Blister packs (aluminium/PVC).

Boxes of 14, 30 and 60 capsules.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Archimedes Pharma UK Limited

250 South Oak Way

Green Park

Reading

Berkshire

RG2 6UG

UK

8. Marketing Authorisation Number(S)

10mg: PL 12406/0028

30mg: PL 12406/0029

60mg: PL 12406/0030

100mg: PL 12406/0031

200mg: PL 12406/0032

9. Date Of First Authorisation/Renewal Of The Authorisation

16 July 2010 (10mg, 30mg)

17 July 2010 (60mg, 100mg & 200mg)

10. Date Of Revision Of The Text

22 July 2011

ZomCapAll-SPC06

UK/ZC/11/006

OCT 2011


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Plaquenil


PLAQUENIL TABLETS

(Hydroxychloroquine Sulphate)

Please read this carefully before you start to take your medicine.

This leaflet provides a summary of the information about your medicine.

If you have any questions or are not sure about anything ask your doctor or pharmacist.

The name of this medicine is Plaquenil Tablets.

What Is In This Medicine?

Each tablet contains 200mg Hydroxychloroquine Sulphate BP.

It also contains lactose, maize starch, polyvidone, magnesium stearate, hypromellose, macrogol 4000 and titanium dioxide (E171).

Plaquenil tablets are round white tablets with HCQ on one side and 200 on the reverse.

They are supplied in boxes of 60.

Product Licence holder: Sanofi-Synthelabo PO Box 597 Guildford Surrey Manufactured by: Fawdon Manufacturing Centre Edgefield Avenue Fawdon Newcastle-upon-Tyne Tyne & Wear NE3 3TT What Is This Medicine For?

Plaquenil is used to treat rheumatoid arthritis, juvenile chronic arthritis, discoid and systemic lupus erythematosus and skin conditions caused or aggravated by sunlight.

Before Taking This Medicine

You should not take Plaquenil if you:

are allergic to hydroxychloroquine sulphate or similar substances or any of the other ingredients. are pregnant. have maculopathy (a type of visual disturbance).

Special care is needed (check with your doctor) if you:

have liver or kidney problems. have stomach, bowel, nerve or blood disorders. have the genetic condition G6PD deficiency. An inherited condition that results in a deficiency in glucose-6-phosphate dehydrogenase, which increases the risk of developing haemolytic anaemia. Particular drugs (such as Plaquenil) can exacerbate this problem. This mainly affects people of Mediterranean, African and Asian ancestry. have porphyria or psoriasis. are allergic to quinine. are breast feeding.

If you are going to be given a general anaesthetic, tell the doctor you are taking Plaquenil.

If taken with some other medicines the effects of Plaquenil or the effects of the other medicine may be changed. Please check with your doctor if you are taking any of the following:-

digoxin – used to treat heart rhythm problems cimetidine – used to treat stomach problems aminoglycoside antibiotics e.g. gentamicin, neomycin or tobramycin antacids – indigestion remedies. You should have a 4 hour gap between taking Plaquenil and antacids treatment for myasthenia gravis e.g. neostigmine or pyridostigmine insulin or other antidiabetic medicines including antidiabetic tablets; your doctor may need to reduce the dose that you are taking.

Plaquenil can cause serious eye problems, including abnormal colour vision. Your doctor should arrange for you to have an eye test before you start treatment and every twelve months whilst you are taking this medicine. Some people may need to have their eyes tested more often, for example if you are aged over 65 years, have kidney problems or poor eyesight, or if you are taking a daily dose of Plaquenil which is more than 6.5mg per kg of your body weight. If you experience any problems with your vision, including abnormal colour vision, stop taking this medicine and contact your doctor.

Rabies vaccination may be less effective in patients taking this medicine.

Plaquenil may cause blurred vision at the start of treatment, or abnormal colour vision during treatment If affected you should not drive or operate machinery. If the blurred vision does not get better, go back to your doctor. If you experience abnormal colour vision at any time you should stop taking this medicine immediately and contact your doctor.

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

Taking This Medicine

The usual dose of Plaquenil for adults is 200mg (one daily tablet) or 400mg (one tablet taken twice a day), depending upon your body weight. Your doctor may adjust the dose during the treatment. The dose of Plaquenil for children is based on their weight and should not be more than 6.5 mg for each kg of body weight per day.

In arthritis and lupus, treatment should be discontinued after 6 months if there has been no improvement in symptoms. In skin conditions due to sunlight, hydroxychloroquine sulphate should only be given when exposure to light is maximum.

Swallow the tablets with a drink of water either with a meal or a glass of milk.

If you forget a dose, take it as soon as you remember, but do not take two doses at once.

An overdose of this medicine may be dangerous. If you have taken an overdose tell your doctor or go to the nearest hospital casualty department immediately.

It may take several weeks before you start to feel the beneficial effects of this medicine but some of the problems which may occur do so within a few days of starting treatment. Keep taking your medicine until your doctor tells you to stop. Do not stop taking the tablets just because you feel better. If you stop them, your condition may get worse.

Whilst Taking This Medicine

Plaquenil may cause problems in some people. These include skin rashes (which are rarely severe and may be associated with fever and blistering), itching, changes in skin or hair colour, hair loss, nausea (feeling sick), diarrhoea, loss of appetite, stomach pain and vomiting. Less often it can cause muscle weakness, fits or convulsions, heart problems, dizziness, ringing in the ears, deafness, headache, nervousness and emotional upsets. If any of these problems become troublesome or if you experience any other problems, you should tell your doctor.

Plaquenil can also cause serious allergic reaction which causes swelling of the face or throat, nettle rash, difficulty in breathing, and wheezing. If you experience any of these problems you should stop taking this medicine and contact your doctor immediately.

Rarely Plaquenil has caused more serious problems with the blood, liver, skin, muscles or nerves.

If you develop any of the following symptoms you should stop taking this medicine and tell your doctor:

Unexplained bruising or bleeding Extreme pallor, shortness of breath and swelling of ankles and feet Frequent or severe infections – especially sore throats Yellowing of the eyes or skin (jaundice) Blistering of skin, mouth, eyes or genitals Weakness of the muscles (particularly shoulders and thighs) Changes in sensation such as tingling

Do not take this medicine after the month shown on the pack.

Store these tablets below 25°C. Keep out of reach and sight of children.

Date of revision of leaflet: May 2007.

This leaflet does not contain all the information about your medicine. If you have any questions or are not sure about anything, ask your doctor or pharmacist.

Plaquenil is a registered trade mark.

© Sanofi-Synthelabo, 1994-2007

31612303


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Bezalip 200mg tablets


1. Name Of The Medicinal Product

Bezalip

Bezafibrate 200mg Tablets

2. Qualitative And Quantitative Composition

Bezafibrate 200mg

3. Pharmaceutical Form

Tablet for oral use.

Bezalip is a round film-coated tablet with a white core and is imprinted G6.

4. Clinical Particulars 4.1 Therapeutic Indications

Bezalip is indicated for use in hyperlipidaemias of Type IIa, IIb, III, IV and V (Fredrickson classification).

Bezalip should be employed only in patients with a fully defined and diagnosed lipid abnormality which is inadequately controlled by dietary means, or by other changes in life-style such as physical exercise and weight reduction, and in whom the long-term risks associated with the condition warrant treatment.

The rationale for the use of Bezalip is to control abnormalities of serum lipids and lipoproteins to reduce or prevent the long term effects which have been shown by many epidemiological studies to be positively and strongly correlated with such hyperlipidaemias.

4.2 Posology And Method Of Administration

Adults

The recommended dosage for Bezalip tablets is three tablets daily, equivalent to 600mg bezafibrate. The tablets should be swallowed whole with a little fluid after each meal.

Elderly

No specific dosage reduction is necessary in elderly patients.

Children

At present there is inadequate information regarding an appropriate dosage in children.

Renal impairment

In patients with renal insufficiency the dose should be adjusted according to serum creatinine levels or creatinine clearance as shown in the following table;

Serum creatinine ( ?mol/l)

Creatinine clearance (ml/min)

Dosage (tablets/day)

Up to 135

Over 60

3

136 – 225

60 – 40

2

226 – 530

40 – 15

1 every 1 or 2 days

Over 530

Less than 15

Contra-indicated

In dialysis patients the dosage must be further reduced. As a general rule a dosage of one Bezalip tablet every third day is recommended, to avoid overdosage. The patient should be carefully monitored.

The response to therapy is normally rapid, although a progressive improvement may occur over a number of weeks. Treatment should be withdrawn if an adequate response has not been achieved within 3 to 4 months.

4.3 Contraindications

Significant hepatic disease (other than fatty infiltration of the liver associated with raised triglyceride values), severe renal insufficiency (serum creatinine> 530?mol/l; creatinine clearance <15ml/min), gall bladder disease with or without cholelithiasis, nephrotic syndrome, known photoallergic or phototoxic reactions to fibrates and hypersensitivity to bezafibrate or any component of the product or to other fibrates.

4.4 Special Warnings And Precautions For Use

See Preclinical safety data.

Bezafibrate could cause cholelithiasis, although there is no evidence of an increased frequency of gallstones in patients treated with Bezalip. Appropriate diagnostic procedures should be performed if cholelithic symptoms and signs occur (see section 4.8 Undesirable effects).

Muscle effects: Bezafibrate and other fibrates may cause myopathy, manifested as muscle weakness or pain, often accompanied by a considerable increase in creatine kinase (CPK). In isolated cases severe muscle damage (rhabdomyolysis) may occur. The risk of rhabdomyolysis may be increased in patients with predisposing factors for myopathy, (including renal impairment, hypothyroidism, severe infection, trauma, surgery, disturbances of hormone or electrolyte imbalance and a high alcohol intake).

Bezafibrate should be used with caution in combination with HMG CoA reductase inhibitors as the combination of HMG CoA inhibitors and fibrates has been shown to increase the incidence and severity of myopathy. Patients should be monitored for signs of myopathy and increased CPK activity and combination therapy discontinued if signs of myopathy develop. Combination therapy should not be used in patients with predisposing factors for myopathy (see section 4.5 Interaction with other medicaments and other forms of interaction).

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Care is required in administering Bezalip to patients taking coumarin-type anti-coagulants, the action of which may be potentiated. The dosage of anti-coagulant should be reduced by up to 50% and readjusted by monitoring blood coagulation.

As bezafibrate improves glucose utilisation the action of antidiabetic medication, including insulin, may be potentiated. Hypoglycaemia has not been observed although increased monitoring of the glycaemic status may be warranted for a brief period after introduction of Bezalip.

In isolated cases, a pronounced though reversible impairment of renal function (accompanied by a corresponding increase in serum creatinine level) has been reported in organ transplant patients receiving cyclosporin therapy and concomitant bezafibrate. Accordingly, renal function should be closely monitored in these patients and, in the event of relevant significant changes in laboratory parameters, bezafibrate, should if necessary, be discontinued.

Should combined therapy with an ion-exchange resin be considered necessary, there should be an interval of 2 hours between the intake of the resin and Bezalip as the absorption of bezafibrate otherwise may be impaired.

Concomitant therapy with HMG CoA reductase inhibitors and fibrates has been reported to increase the risk of myopathy (see section 4.4 Special warnings and precautions). The underlying mechanism for this remains unclear; the available data do not suggest a pharmacokinetic interaction between bezafibrate and HMG CoA reductase inhibitors.

MAO-inhibitors (with hepatotoxic potential) should not be administered together with bezafibrate.

Since oestrogens may lead to a rise in lipid levels, the necessity for treatment with Bezalip in patients receiving oestrogens or oestrogen containing preparations should be considered on an individual basis.

4.6 Pregnancy And Lactation

Although the drug substance has not been shown in animal studies to have any adverse effects on the foetus, it is recommended that Bezalip should not be administered to either pregnant women or to those who are breast feeding.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Gastro-intestinal system:

? occasionally gastro-intestinal symptoms such as loss of appetite, feelings of fullness in the stomach and nausea may occur. These side-effects are usually transient and generally do not require withdrawal of the drug. In susceptible patients a slowly increasing dosage over 5 to 7 days may help to avoid such symptoms.

Hepato-biliary system:

? in isolated cases, increase of transaminases, cholestasis and gallstones (see section 4.4 Special warnings and special precautions for use).

Hypersensitivity:

? occasionally allergic skin reactions such as pruritus or urticaria.

? in isolated cases, photosensitivity or generalised hypersensitivity reactions may occur.

Haematology:

Isolated cases of:

? decreases in haemoglobin and leucocytes.

? thrombocytopenia, which may cause bleeding (e.g. purpura).

? pancytopenia.

Renal system:

? frequently slight increases in serum creatinine. In patients with existing impairment of renal function, if dosage recommendations are not followed, myopathy may develop (in extreme cases rhabdomyolysis).

Muscular system:

? Muscular weakness, myalgia and muscle cramps, often accompanied by a considerable increase in creatine kinase may occur. In isolated cases, severe muscular damage (rhabdomyolysis) has been observed. In cases of rhabdomyolysis, bezafibrate must be stopped immediately and renal function closely monitored.

Others:

? in rare cases, headache and dizziness, alopecia.

? isolated cases of potency disorders have been reported.

In general, most of the adverse drug reactions disappear after withdrawal of Bezalip.

4.9 Overdose

No specific effects of acute overdose are known. Rhabdomyolysis has occurred. In cases of rhabdomyolysis, bezafibrate must be stopped immediately and renal function carefully monitored.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Bezafibrate lowers elevated levels of serum cholesterol and triglycerides (i.e. lowers elevated low density lipoprotein and very low density lipoprotein levels, and raises lowered high density lipoprotein levels) by stimulating lipoprotein lipase and hepatic lipase, and by suppressing the activity of 3 HMGCo-A reductase resulting in stimulation of low density lipoprotein receptors on the cell surface.

Studies have shown bezafibrate to be effective in treating hyperlipidaemia in patients with diabetes mellitus. Some cases showed a beneficial reduction in fasting blood glucose.

Significant reductions in serum fibrinogen levels have been observed in hyperfibrinogenaemic patients treated with bezafibrate.

5.2 Pharmacokinetic Properties

Maximum concentrations of bezafibrate appear around 2 hours after ingestion of Bezalip tablets. The protein-binding of bezafibrate in serum is approximately 95%. The elimination half-life is in the order of 2.1 hours although elimination is markedly slowed in the presence of limited renal function. Elimination may be increased in forced diuresis. The drug substance is non-dialysable (cuprophane filter).

5.3 Preclinical Safety Data

The chronic administration of a high dose of bezafibrate to rats was associated with hepatic tumour formation in females. This dosage was in the order of 30 to 40 times the human dosage. No such effect was apparent at reduced intake levels approximating more closely to the lipid-lowering dosage in humans.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Table core:

maize starch,

microcrystalline cellulose,

colloidal silicon dioxide,

sodium starch glycollate,

magnesium stearate.

Film-coating:

polyvinyl alcohol,

titanium dioxide (E171),

macrogol,

talc.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

5 years.

6.4 Special Precautions For Storage

Do not store above 25 °C.

6.5 Nature And Contents Of Container

Packs of 84 or 100 tablets in PVC/Aluminium blister strips.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Actavis Group PTC ehf

Reykjav?kurvegi 76-78

220 Hafnarfjordur

Iceland.

8. Marketing Authorisation Number(S)

PL 30306/0125

9. Date Of First Authorisation/Renewal Of The Authorisation

1 April 1999

10. Date Of Revision Of The Text

13/10/2009

11 DOSIMETRY (IF APPLICABLE) 12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS (IF APPLICABLE)
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Strong Pholcodine Linctus BP


1. Name Of The Medicinal Product

Strong Pholcodine Linctus BP

2. Qualitative And Quantitative Composition

Each 5ml contains Pholcodine BP 10mg

3. Pharmaceutical Form

Oral solution: Clear, colourless, raspberry and cola flavoured syrup.

4. Clinical Particulars 4.1 Therapeutic Indications

Suppression of non-productive cough.

4.2 Posology And Method Of Administration

Adults:

5ml spoonful 3-4 times daily

Children:

Not recommended.

4.3 Contraindications

Liver disease, ventilatory failure, asthma, bronchitis, bronchiectasis. Use in patients with hypersensitivity or idiosyncratic response to the active ingredient, use in children.

4.4 Special Warnings And Precautions For Use

Patients with rare hereditary problems of fructose intolerance should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Depressant effects may occur with concurrent alcohol ingestion; concurrent (or within 2 weeks) use of MAOIs may lead to excitation; the depressant effects might be increased by phenothiazines, MAOIs and tricyclic anti-depressants.

4.6 Pregnancy And Lactation

This product should not be used during pregnancy or lactation unless it is considered essential by the physician.

4.7 Effects On Ability To Drive And Use Machines

Pholcodine may induce drowsiness. Patients receiving this medication should not drive or operate machinery unless it has been shown not to affect mental or physical ability.

4.8 Undesirable Effects

Constipation, nausea and drowsiness occasionally occur.

Immune system disorders: hypersensitivity reactions, anaphylaxis.

4.9 Overdose

Restlessness, excitement and ataxia may occur after large doses. A toxic dose in children is reported to be about 200mg.

Treatment: Gastric lavage with supportive and symptomatic measures. In severe cases, and where respiratory depression occurs an opioid antagonist such as Naloxone – should be considered.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Morphine or codeine derivatives. By tradition used mainly as an antitussive. It suppresses the cough reflex by a direct central action, probably in the medulla or pons. It has little or no analgesic or euphorigenic activity.

5.2 Pharmacokinetic Properties

Metabolised in the liver.

5.3 Preclinical Safety Data

Not stated

6. Pharmaceutical Particulars 6.1 List Of Excipients

Citric Acid BP

Sodium Carboxymethylcellulose 7HOF BP

Glycerol BP

Sodium Benzoate BP

Saccharin Sodium BP

Lycasin 80/55 HSE

Ethanol 96% BP

Raspberry/Cola flavour

Purified Water BP to volume

6.2 Incompatibilities

None known

6.3 Shelf Life

Amber glass bottles – 2 years

High density polyethylene bottles – 2 years

6.4 Special Precautions For Storage

Store below 20°C. Protect from light.

6.5 Nature And Contents Of Container

Amber Grade III glass bottle with pilfer proof screw cap, 100ml, 125ml, 200ml and 500ml.

Virgin HDPE bottle with tamper evident screw cap, 500ml, 1 Litre, 2 Litres.

6.6 Special Precautions For Disposal And Other Handling

As for all medicines – no special requirements.

Administrative Data 7. Marketing Authorisation Holder

Pinewood Laboratories Ltd.,

Ballymacarbry, Clonmel,

Co. Tipperary, Ireland

8. Marketing Authorisation Number(S)

PL 04917/0005

9. Date Of First Authorisation/Renewal Of The Authorisation

15 August 1991

10. Date Of Revision Of The Text

February 2008


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Didronel 200mg Tablets


1. Name Of The Medicinal Product

Didronel 200mg Tablets.

2. Qualitative And Quantitative Composition

Each tablet contains 200mg of Etidronate Disodium, USP.

3. Pharmaceutical Form

White rectangular tablets marked with 'P&G' on one face and '402' on the other.

4. Clinical Particulars 4.1 Therapeutic Indications

Paget's disease of bone:

Effectiveness has been demonstrated primarily in patients with polyostotic Paget's disease with symptoms of pain and with clinically significant elevations of urinary hydroxyproline and serum alkaline phosphatase. In other circumstances in which there is extensive involvement of the skull or the spine with the prospect of irreversible neurological damage, or when a weight-bearing bone may be involved, the use of Didronel may also be considered.

4.2 Posology And Method Of Administration

5mg/kg/day to 20mg/kg/day as detailed below.

Didronel should be given on an empty stomach. It is recommended that patients take the therapy with water, at the mid point of a four hour fast (ie. two hours before and two after food).

The optimal duration of bisphosphonate treatment for osteoporosis has not been established. The need for continued treatment should be re-evaluated periodically based on the benefits and potential risks of risedronate on an individual patient basis, particularly after 5 or more years of use.

Adults and Elderly:

The recommended initial dose of Didronel for most patients is 5mg/kg body weight/day, for a period not exceeding six months. Doses above 10mg/kg should be reserved for use when there is an overriding requirement for suppression of increased bone turnover associated with Paget's disease or when the patient requires more prompt reduction of elevated cardiac output. Treatment with doses above 10mg/kg/day should be approached cautiously and should not exceed three months duration. Doses in excess of 20mg/kg/day are not recommended.

Re-treatment should be undertaken only after a drug-free period of at least three months and after it is evident that reactivation of the disease has occurred and biochemical indices of the disease have become substantially re-elevated or approach pretreatment values (approximately twice the upper limit of normal or 75% of pre-treatment value). In no case should duration of treatment exceed the maximum duration of the initial treatment. Premature re-treatment should be avoided. In clinical trials the biochemical improvements obtained during drug therapy have generally persisted for a period of three months to 2 years after drug withdrawal.

Daily Dosage Guide

Body Weight

Required Daily Regimen of 200mg Tablets

     

Kilogrames

Stones

5mg/kg*

10mg/kg*

20mg/kg+

50

8

1

3

5

60

9.5

2

3

6

70

11

2

4

7

80

12.5

2

4

8

90

14

2

5

9

*Course of therapy - 6 months

+Course of therapy - 3 months

Children:

Disorders of bone in children, referred to as juvenile Paget's disease, have been reported rarely. The relationship to adult Paget's disease has not been established. Didronel has not been studied in children for Paget's disease.

4.3 Contraindications

Known hypersensitivity to etidronate disodium or any of the other ingredients in the product (see Section 6.1 List of Excipients). Clinically overt osteomalacia.

4.4 Special Warnings And Precautions For Use

In Pagetic patients the physician should adhere to the recommended dose regimen in order to avoid over- treatment with Didronel. The response to therapy may be of slow onset and may continue even for months after treatment with the drug has been discontinued. Dosage should not be increased prematurely nor should treatment be resumed before there is clear evidence of reactivation of the disease process. Re-treatment should not be initiated until the patient has had at least a three-month drug-free interval.

Etidronate disodium is not metabolized and is excreted intact via the kidney. Due to the lack of clinical experience the treatment of patients with impaired renal function should be undertaken with due caution. The use of etidronate disodium is discouraged in patients with severely impaired kidney function.

Caution should be taken in patients with a history of renal stone formation. In patients with impaired renal function or a history of renal stone formation, serum and urinary calcium should be monitored regularly.

It is recommended that serum phosphate, serum alkaline phosphatase and urinary hydroxyproline be measured before commencing medication and at three month intervals during treatment. If after three months of medication the pre-treatment levels have not been reduced by at least 25%, the patient may be relatively resistant to therapy. If the serum phosphate level is unchanged in the "resistant" patient, consideration should be given to increasing the dose since the absorption of pharmacologically active amounts of Didronel is typically accompanied by a rise in serum phosphate. This rise usually correlates with reductions in the biochemical indices of disease activity. If after three or more months of medication elevations of serum phosphate above the upper limit of normal are not accompanied by clinical or biochemical evidence of reduced activity, resistance of the disease to the action of Didronel is probable and termination of Didronel medication should be considered. Etidronate disodium suppresses bone turnover and may retard mineralisation of osteoid laid down during the bone accretion process. These effects are dose and time dependent. Osteoid, which may accumulate noticeably at doses of 10-20 mg/kg/day, mineralises normally post-therapy. Patients in whom serum phosphate elevations are high and reductions of disease activity are low may be particularly prone to retarded mineralisation of new osteoid. In those cases where 200mg per day (a single tablet) may be excessive, doses may be administered less frequently.

Patients with Paget's disease of bone should maintain an adequate intake of calcium and vitamin D. Patients with low vitamin D and calcium intake may be particularly sensitive to drugs that affect calcium homeostasis and should be closely monitored during Didronel therapy.

Etidronate disodium does not adversely affect serum levels of parathyroid hormone or calcium.

Hyperphosphataemia has been observed in patients receiving etidronate disodium, usually in association with doses of 10-20mg/kg/day. No adverse effects have been traced to this, and it does not constitute grounds for discontinuing therapy. It is apparently due to a drug-related increase in renal tubular reabsorption of phosphate. Serum phosphate levels generally return to normal 2-4 weeks post therapy.

Patients with significant chronic diarrhoeal disease may experience increased frequency of bowel movements and diarrhoea, particularly at higher doses.

Increased or recurrent bone pain at existing Pagetic sites and/or the appearance of pain at sites previously asymptomatic have been reported at a dose of 5mg/kg/day.At higher doses, the incidence rises to approximately 20%. When therapy continues, pain resolves in some patients but persists in others.

Fractures are recognised as a common feature in patients with Paget's disease. There has been no evidence of increased risk of fractures at the recommended dose of 5mg/kg/day for six months. At doses of 20mg/kg/day in excess of three months' duration, mineralisation of newly formed osteoid may be impaired and the risk of fracture may be increased. The risk of fracture may also be greater in patients with extensive and severe disease, a history of multiple fractures, and/or rapidly advancing osteolytic lesions. It is therefore recommended that the drug is discontinued when fractures occur and therapy not reinstated until the fracture healing is complete.

Patients with predominantly lytic lesions should be monitored radiographically and biochemically to permit termination of etidronate disodium in those patients unresponsive to treatment.The incidence of osteogenic sarcoma is known to be increased in Paget's disease. Pagetic lesions, with or without therapy, may appear by X-ray to progress markedly, possibly with some loss of definition of periosteal margins. Such lesions should be evaluated carefully to differentiate these from osteogenic sarcoma.

Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis) has been reported in patients with cancer receiving treatment regimens including primarily intravenously administered bisphosphonates. Many of these patients were also receiving chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with osteoporosis receiving bisphosphonates.

A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patient with concominant risk factors (e.g. cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene).

While on treatment, these patients should avod invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces risk of osteonecrosis of the jaw.

Clinical judgement of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.

Atypical fractures of the femur

Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short oblique fractures can occur anywhere along the femur from just below the lesser trochanter to just above the supracondylar flare. These fractures occur after minimal or no trauma and some patients experience thigh or groin pain, often associated with imaging features of stress fractures, weeks to months before presenting with a completed femoral fracture. Fractures are often bilateral; therefore the contralateral femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft fracture. Poor healing of these fractures has also been reported. Discontinuation of bisphosphonate therapy in patients suspected to have an atypical femur fracture should be considered pending evaluation of the patient, based on an individual benefit risk assessment.

During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Food in the stomach or upper portions of the small intestine, particularly materials with a high calcium content such as milk, may reduce absorption of etidronate disodium. Vitamins with mineral supplements such as iron, calcium supplements, laxatives containing magnesium, or antacids containing calcium or aluminium should not be taken within two hours of dosing etidronate disodium.

The diagnostic utility of bone-imaging agents may be impaired by current or recent etidronate use.

There have been isolated reports of patients experiencing changes in their prothrombin times when etidronate was added to warfarin therapy. The majority of these reports concerned variable elevations in prothrombin times without clinically significant sequelae. Although the relevance of these reports and any mechanism of coagulation alterations is unclear, patients on warfarin should have their prothrombin time monitored.

4.6 Pregnancy And Lactation

The safety of this medicinal product for use in human pregnancy has not been established. Reproductive studies have shown skeletal abnormalities in rats. It is therefore recommended that Didronel should not be used in women of childbearing potential unless adequate contraceptive measures are taken.

It is not known whether this drug passes into breast milk. It should therefore not be used during lactation period.

4.7 Effects On Ability To Drive And Use Machines

Etidronate disodium does not interfere with the ability to drive or use machines.

4.8 Undesirable Effects

Gastro-intestinal

The most common effects reported are diarrhoea and nausea. Reports of exacerbation of peptic ulcer with complications in a few patients.

Dermatological/hypersensitivity

Hypersensitivity reactions, including angio-oedema/urticaria, rash and/or pruritus, have been reported rarely.

Nervous System

Paresthesia, peripheral neuropathy , confusion, have been reported rarely.

Haematological

In patients receiving etidronate disodium, there have been rare reports of leucopenia, agranulocytosis and pancytopenia.

Musculoskeletal and connective tissue disorders

osteonecrosis of the jaw (see section 4.4 special warnings and precautions of use)

Other

Less common effects believed to be related to therapy include arthropathies (arthralgia and arthritis), and rarely burning of the tongue, alopecia, erythema multiforme and exacerbation of asthma.

During post-marketing experience the following reactions have been reported (frequency rare):

Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction).

4.9 Overdose

Overdose would manifest as the signs and symptoms of hypocalcaemia. Treatment should involve cessation of therapy and correction of hypocalcaemia with administration of Ca2+ intravenously.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Etidronate acts primarily on bone. It can inhibit the formation, growth and dissolution of hydroxyapatite crystals and amorphous precursors by chemisorption to calcium phosphate surfaces. Inhibition of crystal resorption occurs at lower doses than are required for the inhibition of crystal growth. Both effects increase as dose increases.

5.2 Pharmacokinetic Properties

Etidronate is not metabolised. Absorption averages about 1% of an oral dose of 5mg/kg body weight/day. This increases to about 1.5% at 10mg/kg/day and 6% at 20mg/kg/day. Most of the drug is cleared from the blood within 6 hours. Within 24 hours about half of the absorbed dose is excreted in the urine. The remainder is chemically absorbed to bone, especially to areas of elevated osteogenesis, and is slowly eliminated. Unabsorbed drug is excreted in the faeces.

5.3 Preclinical Safety Data

In long term studies in mice and rats, there was no evidence of carcinogenicity with etidronate disodium. All in vitro and in vivo assays conducted to assess the mutagenic potential of etidronate disodium have been negative.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Starch, magnesium stearate and microcrystalline cellulose.

6.2 Incompatibilities

See section 4.5 Interactions with other medicaments and other forms of interaction.

6.3 Shelf Life

Four years.

6.4 Special Precautions For Storage

None.

6.5 Nature And Contents Of Container

Supplied in high density polypropylene bottles or blister packs of 60 tablets.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Warner Chilcott UK Limited

Old Belfast Road,

Millbrook,

Larne,

County Antrim,

BT40 2SH

8. Marketing Authorisation Number(S)

PL 10947/0018

9. Date Of First Authorisation/Renewal Of The Authorisation

26th November 1987

10. Date Of Revision Of The Text

September 2011


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Provera Tablets 100 mg, Provera Tablets 200 mg & Provera Tablets 400 mg


1. Name Of The Medicinal Product

Provera Tablets 100 mg or Medroxyprogesterone Acetate Tablets 100 mg.

Provera Tablets 200 mg or Medroxyprogesterone Acetate Tablets 200 mg.

Provera® Tablets 400 mg

2. Qualitative And Quantitative Composition

1 tablet contains 100mg medroxyprogesterone acetate.

1 tablet contains 200 mg medroxyprogesterone acetate.

1 tablet contains 400 mg medroxyprogesterone acetate.

For excipients, see 6.1.

3. Pharmaceutical Form

Tablet.

4. Clinical Particulars 4.1 Therapeutic Indications

Progestogen indicated for the treatment of certain hormone dependant neoplasms, such as:

1. Endometrial carcinoma.

2. Renal cell carcinoma.

3. Carcinoma of breast in post menopausal women.

4.2 Posology And Method Of Administration

Route of administration: Oral.

Adults

Endometrial and renal cell carcinoma

200 - 600 mg daily

Breast carcinoma

400 - 1500 mg daily

The incidence of minor side-effects, such as indigestion and weight gain, increase with the increase in dose.

Response to hormonal therapy may not be evident until after at least 8-10 weeks of therapy.

Elderly patients : This product has been used primarily in the older age group for the treatment of malignancies. There is no evidence to suggest that the older age group is any less prepared to handle the drug metabolically than is the younger patient. Therefore the same dosage, contra-indications, and precautions would apply to either age group.

Children:The product is not anticipated for paediatric use in the indications recommended.

4.3 Contraindications

Medroxyprogesterone acetate is contraindicated in the following conditions:

• thrombophlebitis, thrombo-embolic disorders, and where there is a high risk of developing such manifestations [presence or history of atrial fibrillation, valvular disorders, endocarditis, heart failure, pulmonary embolism; thrombo-embolic ischaemic attack (TIA), cerebral infarction; atherosclerosis; immediate post surgery period]

• hypercalcaemia in patients with osseous metastases

• known sensitivity to medroxyprogesterone acetate or any component of the drug.

• impaired liver function or active liver disease.

• missed abortion, metrorrhagia, known or suspected pregnancy.

• undiagnosed vaginal bleeding.

• previous idiopathic or current venous thromboembolism (deep vein thrombosis, pulmonary embolism).

• active or recent arterial thromboembolic disease (e.g., angina, myocardial infarction).

• suspected or early breast carcinoma

Progestogens are known to be porphyrogenic. Patients with a history of attacks or aged under 30 are at greatest risk of an acute attack while on progesterone treatment. A careful assessment of potential benefit should be made where this risk is present.

4.4 Special Warnings And Precautions For Use

Warnings:

In the treatment of carcinoma of breast occasional cases of hypercalcaemia have been reported.

Unexpected vaginal bleeding during therapy with medroxyprogesterone acetate should be investigated.

Medication should not be readministered pending examination if there is sudden partial or complete loss of vision or if there is a sudden onset of proptosis, diplopia or migraine. If examination reveals papilloedema or retinal vascular lesions, medication should not be readministered.

Medroxyprogesterone acetate may produce Cushingoid symptoms.

Some patients receiving medroxyprogesterone acetate may exhibit suppressed adrenal function. Medroxyprogesterone acetate may decrease ACTH and hydrocortisone blood levels.

Treatment with medroxyprogesterone acetate should be discontinued in the event of:

• jaundice or deterioration in liver function

• significant increase in blood pressure

• new onset of migraine-type headache

Precautions:

Animal studies show that Provera possesses adrenocorticoid activity. This has also been reported in man, therefore patients receiving large doses continuously and for long periods should be observed closely for signs normally associated with adrenocorticoid therapy, such as hypertension, sodium retention, oedema, etc. Care is needed in treating patients with diabetes and/or arterial hypertension.

Before using Provera the general medical condition of the patient should be carefully evaluated.

This product should be used under the supervision of a specialist and the patient kept under regular surveillance.

Patients with the following conditions should be carefully monitored while taking progestogens:

• Conditions which may be influenced by potential fluid retention

o Epilepsy

o Migraine

o Asthma

o Cardiac dysfunction

o Renal dysfunction

• History of mental depression

• Diabetes (a decrease in glucose tolerance has been observed in some patients).

• Hyperlipidaemia

The pathologist (laboratory) should be informed of the patient's use of medroxyprogesterone acetate if endometrial or endocervical tissue is submitted for examination.

The physician/laboratory should be informed that medroxyprogesterone acetate may decrease the levels of the following endocrine biomarkers:

• Plasma/urinary steroids (e.g., cortisol, oestrogen, pregnanediol, progesterone, testosterone)

• Plasma/urinary gonadotrophins (e.g., LH and FSH)

• Sex-hormone-binding-globulin

The use of medroxyprogesterone acetate in oncology indications may also cause partial adrenal insufficiency (decrease in pituitary-adrenal axis response) during Metyrapone testing. Thus the ability of adrenal cortex to respond to ACTH should be demonstrated before metyrapone is administered.

Although medroxyprogesterone acetate has not been causally associated with the induction of thromboembolic disorders, any patient with a history or who develops this kind of event while undergoing therapy with medroxyprogesterone acetate should have her status and need for treatment carefully assessed before continuing therapy.

Risk of venous thromboembolism (VTE)

The risk of VTE has not been assessed for progesterone alone. However, VTE is a known risk factor of oestrogen-only and combined hormone replacement therapy. When prescribing medroxyprogesterone acetate for oncology indications the following precautions and risk factors should be considered in the light of the patient's condition, the dose of medroxyprogesterone acetate and the duration of therapy:

• Generally recognised risk factors for VTE include a personal or family history of VTE or known thromboembolic states, severe obesity (BMI > 30 kg/m2) and systemic lupus erythematosus

• The risk of VTE may be temporarily increased with prolonged immobilisation, major trauma or major surgery.

• If VTE develops after initiating therapy, medroxyprogesterone acetate should be discontinued. Patients should be told to contact their doctor immediately if they become aware of a symptom suggestive of potential thromboembolism (e.g. painful swelling of a leg, sudden pain in the chest, dyspnoea).

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Interaction with other medicaments

The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes. These compounds include anticonvulsants (e.g., phenobarbital, phenytoin, carbamazepine) and anti-infectives (e.g., rifampicin, rifabutin, nevirapine, efavirenz,).

Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones. Herbal preparations containing St John's Wort (Hypericum Perforatum) may induce the metabolism of progestogens. Progestogen levels may therefore be reduced.

Aminoglutethimide has been reported to decrease plasma levels of some progestogens.

Concurrent administration of ciclosporin and MPA has been reported to lead to increased plasma ciclosporin levels and/or decreased plasma MPA levels.

Interactions with oral anti-coagulants have been reported rarely, but causality has not been established.

When used in combination with cytotoxic drugs, it is possible that progestogens may reduce the haematological toxicity of chemotherapy.

Special care should be taken when progestogens are administered with other drugs which also cause fluid retention, such as NSAIDs and vasodilators.

Other forms of interaction

Progestogens can influence certain laboratory tests (e.g., tests for hepatic function, thyroid function and coagulation).

4.6 Pregnancy And Lactation

Pregnancy

Medroxyprogesterone acetate is contraindicated in women who are pregnant. If medroxyprogesterone acetate is used during pregnancy, or if the patient becomes pregnant while using this drug, the patient should be apprised of the potential hazard to the foetus.

Some reports suggest an association between intrauterine exposure to progestational drugs in the first trimester of pregnancy and genital abnormalities in male and female foetuses.

Infants from unintentional pregnancies that occur 1 to 2 months after injection of medroxyprogesterone acetate injectable suspension may be at an increased risk of low birth weight, which, in turn, is associated with an increased risk of neonatal death. The attributable risk is low because pregnancies while on medroxyprogesterone acetate are uncommon.

Lactation

Medroxyprogesterone acetate and/or its metabolites are secreted in breast milk. Therefore, the use of Provera whilst breast-feeding is not recommended.

4.7 Effects On Ability To Drive And Use Machines

No adverse effect has been reported.

4.8 Undesirable Effects

Reactions occasionally associated with the use of progestogens, particularly in high doses, are:

Breast: Tenderness, mastodynia or galactorrhoea.

Genitourinary: Abnormal uterine bleeding (irregular, increase, decrease), amenorrhoea, alterations of cervical secretions, cervical erosions, prolonged anovulation.

Central nervous system: Confusion, euphoria, loss of concentration, nervousness, insomnia, somnolence, fatigue, dizziness, depression, vision disorders and headache.

Skin and mucous membranes: Sensitivity reactions ranging from pruritus, urticaria, angioneurotic oedema, to generalised rash and anaphylaxis have occasionally been reported. Acne, alopecia or hirsutism have been reported in a few cases.

Allergy: Hypersensitivity reactions (e.g., anaphylaxis or anaphylactoid reactions, angioedema).

Gastro-intestinal/hepatobiliary: Constipation, diarrhoea, dry mouth, disturbed liver function, jaundice, vomiting, nausea and indigestion .

Metabolic and nutritional: Adrenergic-like effects (e.g., fine hand tremors, sweating, tremors, cramps in calves at night), corticoid-like effects (e.g., Cushingoid Syndrome), decreased glucose tolerance, diabetic cataract, exacerbation of diabetes mellitus, glycosuria.

Cardiovascular: Cerebral and myocardial infarction, congestive heart failure, increased blood pressure, palpitations, pulmonary embolism, retinal thrombosis, tachycardia, thromboembolic disorders, thrombophlebitis.

Haematological: Elevation of white blood cells and platelet count.

Miscellaneous: Change in appetite, change in libido, oedema/fluid retention, hypercalcaemia, malaise, hyperpyrexia, weight gain, moon facies.

4.9 Overdose

No action required other than cessation of therapy.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Progestogens. ATC Code: L02A B

Medroxyprogesterone acetate has the pharmacological action of a progestogen.

5.2 Pharmacokinetic Properties

Medroxyprogesterone acetate is absorbed from the gastro intestinal tract with a single oral dose of 10-250 mg. The time taken to reach the peak serum concentration (Tmax) was 2-6 hours and the average peak serum concentration (Cmax) was 13-46.89 mg/ml.

Unmetabolised medroxyprogesterone acetate is highly plasma protein bound. Medroxyprogesterone acetate is metabolised in the liver.

Medroxyprogesterone acetate is primarily metabolised by faecal excretion as glucuronide conjugated metabolite.

Metabolised medroxyprogesterone acetate is excreted more rapidly and in a greater percentage following oral doses than after aqueous intramuscular injection

400 mg only:

The comparative bioavailability of medroxyprogesterone acetate (MPA) in sixteen healthy male volunteers was determined following the oral ingestion of 400 mg MPA as two Provera 200 mg tablets or as one Provera 400mg tablet. It is concluded that the bioavailability appeared to be equivalent in this group of volunteers.

5.3 Preclinical Safety Data

No further preclinical safety data available.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Microcrystalline cellulose

Maize Starch

Byco C

Macrogol 400

Sodium starch glycollate

Docusate sodium

Sodium benzoate

Magnesium stearate

Isopropyl alcohol

Purified water

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

Provera 100mg: 36 months if stored in glass/HDPE bottles, or 24 month in blister packs.

Provera 200mg: 36 months if stored in glass/HDPE bottles, or 24 month in blister packs.

Provera 400mg: The shelf-life for Provera Tablets 400 mg is 36 months

6.4 Special Precautions For Storage

Provera 100mg: Store below 25°C. Bottle packs only: keep in a well closed container.

Provera 200mg: Store below 25°C.Bottle packs only: keep in a well closed container.

Provera 400mg: Store at controlled room temperature (15 - 30?C).Bottle packs only: keep in a well closed container.

6.5 Nature And Contents Of Container

Provera 100mg: Amber glass bottle with screw cap containing 100 tablets. HDPE bottle with tamper evident cap containing 100 tablets. PVC/aluminium strip containing 30, 60 or 100 tablets.

Provera 200mg: Amber glass bottle with screw cap containing 100 tablets. HDPE bottle with tamper evident cap containing 100 tablets. PVC/aluminium strip containing 30, 60 or 100 tablets.

Provera 400mg: Glass/HDPE bottles of 60 tablets. PVC aluminium blisters of 30 tablets

6.6 Special Precautions For Disposal And Other Handling

None stated.

7. Marketing Authorisation Holder

Pharmacia Limited

Ramsgate Road

Sandwich

Kent

CT13 9NJ

UK

8. Marketing Authorisation Number(S)

Provera 100mg: PL 0032/0111

Provera 200mg: PL 0032/0112

Provera 400mg: PL 0032/0131

9. Date Of First Authorisation/Renewal Of The Authorisation

Provera 100mg: 7 November 1983/30 January 1996

Provera 200mg: 7 November 1983/30 January 1996

Provera 400mg: Date of first authorisation: 29 April 1986. Date of renewal of authorisation: 21 May 1998

10. Date Of Revision Of The Text

August 2007

LEGAL CATEGORY

POM

Company Reference: PVB1_0


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Orelox Paediatric Granules for Oral Suspension (sanofi-aventis)


1. Name Of The Medicinal Product

OreloxTM Paediatric Granules for Oral Suspension.

2. Qualitative And Quantitative Composition

When reconstituted each 5ml volume contains 52mg of cefpodoxime proxetil (equivalent to 40mg cefpodoxime).

3. Pharmaceutical Form

Granules for the preparation of an oral suspension.

4. Clinical Particulars 4.1 Therapeutic Indications

Orelox is a bactericidal cephalosporin antibiotic active against a wide range of Gram-negative and Gram-positive organisms. It is indicated for the treatment of the following infections either before the infecting organism has been identified or when caused by bacteria of established sensitivity.

Indications include:

Upper respiratory tract infections caused by organisms sensitive to cefpodoxime, including acute otitis media, sinusitis, tonsillitis and pharyngitis.

Orelox should be reserved for recurrent or chronic infections, or for infections where the causative organism is known or suspected to be resistant to commonly used antibiotics.

Lower respiratory tract infections caused by organisms sensitive to cefpodoxime. Including pneumonia, acute bronchitis and when bacterial super-infection complicates bronchiolitis.

Upper and lower urinary tract infections caused by organisms sensitive to cefpodoxime including cystitis and acute pyelonephritis.

Skin and soft tissue infections caused by organisms sensitive to cefpodoxime such as abscesses, cellulitis, infected wounds, furuncles, folliculitis, paronychia, carbuncles and ulcers.

4.2 Posology And Method Of Administration

Route of administration: oral.

Adults and Elderly:

Not applicable for this product.

Children:

The recommended mean dosage for children is 8mg/kg/day administered in two divided doses at 12 hour intervals.

The following dosage regimen is proposed as a guide to prescribing:-

Below 6 months: 8mg/kg/day in 2 divided doses

6 months-2 years: 5.0 ml twice daily

3-8 years : 10.0 ml twice daily

Above 9 years : 12.5ml twice daily or 100mg tablet twice daily

Orelox should not be used in infants less than 15 days old, as no experience yet exists in this age group.

A measuring spoon (5ml) is provided with the bottle to aid correct dosing. One measuring spoon (5ml) contains the equivalent of 40 mg cefpodoxime.

The product should be taken during meals for optimal absorption.

Renal Impairment:

The dosage of Orelox does not require modification if creatinine clearance exceeds 40 ml.min-1/1.73m2.

Below this value, pharmacokinetic studies indicate an increase in plasma elimination half-life and the maximum plasma concentrations, and hence the dosage should be adjusted appropriately.

CREATININE CLEARANCE

(ML/MIN)

 

39 – 10

Unit dose1 administered as a single dose every 24 hours (i.e half of the usual adult dose).

< 10

Unit dose1 administered as a single dose every 48 hours (i.e quarter of the usual adult dose).

Haemodialysis Patients

Unit dose1 administered after each dialysis session.

NOTE:

1The unit dose is either 100mg or 200mg, depending on the type of infection.

Hepatic Impairment:

The dosage does not require modification in cases of hepatic impairment.

Instructions for Reconstitution:

Before preparing the suspension the silica gel desiccant contained in a capsule inside the cap must be removed and disposed of. The suspension is prepared by adding water to the bottle up to the calibrated mark and shaking thoroughly to obtain an evenly dispersed suspension

4.3 Contraindications

Patients with hypersensitivity to cephalosporin antibiotics.

Patients with phenylketonuria since the product contains aspartame.

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

4.4 Special Warnings And Precautions For Use

Preliminary enquiry about allergy to penicillin is necessary before prescribing cephalosporins since cross allergy to penicillins occurs in 5-10% of cases.

Particular care will be needed in patients sensitive to penicillin: strict medical surveillance is necessary from the very first administration. Where there is doubt, medical assistance should be available at the initial administration, in order to treat any anaphylactic episode.

In patients who are allergic to other cephalosporins, the possibility of cross allergy to Orelox should be borne in mind. Orelox should not be given to those patients with a previous history of immediate type hypersensitivity to cephalosporins.

Hypersensitivity reactions (anaphylaxis) observed with beta-lactam antibiotics can be serious and occasionally fatal.

The onset of any manifestation of hypersensitivity indicates that treatment should be stopped.

Orelox is not the preferred antibiotic for the treatment of staphylococcal pneumonia and should not be used in the treatment of atypical pneumonia caused by organisms such as Legionella, Mycoplasma and Chlamydia.

In cases of severe renal insufficiency it may be necessary to reduce the dosage regimen dependent on the creatinine clearance.

Antibiotics should always be prescribed with caution in patients with a history of gastrointestinal disease, particularly colitis. Orelox may induce diarrhoea, antibiotic associated colitis and pseudomembranous colitis. These side-effects, which may occur more frequently in patients receiving higher doses for prolonged periods, should be considered as potentially serious. The presence of C. difficile should be investigated. In all potential cases of colitis, the treatment should be stopped immediately. The diagnosis should be confirmed by sigmoidoscopy and specific antibiotic therapy (vancomycin) substituted if considered clinically necessary. The administration of products which cause faecal stasis must be avoided. Although any antibiotic may cause pseudomembranous colitis, the risk may be higher with broad-spectrum drugs, such as the cephalosporins.

As with all beta-lactam antibiotics, neutropenia, and more rarely agranulocytosis may develop, particularly during extended treatment. For cases of treatment lasting longer than 10 days, blood count should therefore be monitored, and treatment discontinued if neutropenia is found.

Cephalosporins may be absorbed onto the surface of red cell membranes and react with antibiotics directed against the drug. This can produce a positive Coombs' test and very rarely, haemolytic anaemia. Cross-reactivity may occur with penicillin for this reaction.

The product should not be used in infants less than 15 days old as no clinical trial data in this age group yet exists.

Changes in renal function have been observed with antibiotics of the same class, particularly when given concurrently with potentially nephrotoxic drugs such as aminoglycosides and/or potent diuretics. In such cases, renal function should be monitored.

As with other antibiotics, the prolonged use of cefpodoxime proxetil may result in the overgrowth of non-susceptible organisms. With oral antibiotics the normal colonic flora may be altered, allowing overgrowth by clostridia with consequent pseudomembranous colitis. Repeated evaluation of the patient is essential and if superinfection occurs during therapy, appropriate measures should be taken.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No clinically significant drug interactions have been reported during the course of clinical studies.

Histamine H2-antagonists and antacids reduce the bioavailibility of cefpodoxime. Probenecid reduces the excretion of cephalosporins. Cephlasporins potentially enhance the anticoagulant effect of coumarins and reduce the contraceptive effect of oestrogens.

As with other cephalosporins, isolated cases showing development of a positive Coombs' test have been reported (see Precautions).

Studies have shown that bioavailability is decreased by approximately 30% when Orelox is administered with drugs which neutralise gastric pH or inhibit acid secretions. Therefore, such drugs as antacids of the mineral type and H2 blockers such as ranitidine, which cause an increase in gastric pH, should be taken 2 or 3 hours after Orelox administration.

In contrast, drugs which decrease gastric pH such as pentagastrine will increase bioavailability. The clinical consequences remain to be established.

The bioavailability increases if the product is administered during meals.

A false positive reaction for glucose in the urine may occur with Benedict's or Fehling's solutions or with copper sulphate test tablets, but not with tests based on enzymatic glucose oxidase reactions.

4.6 Pregnancy And Lactation

Not applicable.

4.7 Effects On Ability To Drive And Use Machines

Not applicable.

4.8 Undesirable Effects

Possible side effects include gastrointestinal disorders such as diarrhoea and rarely antibiotic-associated colitis, including pseudomembranous colitis (see Section 4.4: Special Warnings and Precautions for Use), nausea, vomiting and abdominal pain and rash, urticaria and itching. Changes in renal function have been observed with antibiotics from the same group as Cefpodoxime, particularly when co-prescribed with aminoglycosides and/or potent diuretics.

Occasional cases have been reported of headaches, dizziness, tinnitus, parethesia, asthenia and malaise. Rare cases of allergic reactions include hypersensitivity mucocutaneous reactions, skin rashes and pruritus. Occasional cases of bullous reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme have also been received. Transient moderate elevations of ASAT, ALAT and alkaline phosphatases and/or bilirubin have been reported. These laboratory abnormalities which may be explained by the infection, may rarely exceed twice the upper limit of the named range and elicit a pattern of liver injury, usually cholestatic and most often asymptomatic.Slight increases in blood urea and creatinine have also been reported. Exceptionally rare are the occurrence of liver damage and of haematological disorders such as reduction in haemoglobin, thrombocytosis, thrombocytopenia, leucopenia and eosinophilia. Haemolytic anaemia has extremely rarely been reported.

As with other ?-lactam antibiotics, neutropenia and, more rarely, agranulocytosis may develop during treatment with Cefpodoxime, particularly if given over long periods.

As with other cephalosporins, there have been rare reports of anaphylactic reactions, bronchospasm, purpura and angiodema, serum-sickness-like reactions with rashes, fever and arthralgia.

4.9 Overdose

In the event of overdosage with Orelox, supportive and symptomatic therapy is indicated.

In cases of overdosage, particularly in patients with renal insufficiency, encephalopathy may occur. The encephalopathy is usually reversible once cefpodoxime plasma levels have fallen.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Orelox (Cefpodoxime proxetil) is a beta-lactam antibiotic, a 3rd generation oral cephalosporin. It is the prodrug of cefpodoxime.

Following oral administration, Orelox is taken up by the gastro-intestinal wall where it is rapidly hydrolysed to cefpodoxime, a bactericidal antibiotic, which is then absorbed systemically.

BACTERIOLOGY:

The mechanism of action of cefpodoxime is based on inhibition of bacterial cell wall synthesis. It is stable to numerous beta-lactamases.

Cefpodoxime has been shown to possess in vitro bactericidal activity against numerous Gram-positive and Gram-negative bacteria.

ANTIBACTERIAL ACTIVITY:

It is highly active against the Gram-positive organisms:

• Streptococcus pneumoniae

Streptococci of Groups A (S. pyogenes), B (S. agalactiae), C, F and G

Other streptococci (S. mitis, S. sanguis and S. salivarius)

• Propionibacterium acnes

• Corynebacterium diphtheriae

It is highly active against the Gram-negative organisms:

• Haemophilus influenzae (beta-lactamase and non beta-lactamase producing strains)

• Haemophilus para-influenzae (beta-lactamase and non beta-lactamase producing strains)

• Moraxella catarrhalis (beta-lactamase and non beta-lactamase producing strains)

• Escherichia coli

• Klebsiella Spp. (K. pneumoniae)

• Proteus mirabilis

It is moderately active against:

Meticillin-sensitive staphylococci, penicillinase and non-penicillinase producing strains (S. aureus and S. epidermidis)

In addition, as with many cephalosporins, the following are resistant to cefpodoxime.

• Enterococci

Meticillin-resistant staphylococci (S. aureus and S. coagulase (negative))

• Staphylococcus saprophyticus

• Pseudomonas aeruginosa and Pseudomonas Spp.

• Clostridium difficile

• Bacteroides fragilis and related species

As with all antibiotics, whenever possible, sensitivity should be confirmed by in vitro testing.

5.2 Pharmacokinetic Properties

Orelox is taken up in the intestine and is hydrolysed to the active metabolite cefpodoxime. When cefpodoxime proxetil is administered orally to fasting subjects as a tablet corresponding to 100mg of cefpodoxime, 51.5% is absorbed and absorption is increased by food intake. The volume of distribution is 32.3 l and peak levels of cefpodoxime occur 2 to 3 hrs after dosing. The maximum plasma concentration is 1.2mg/l and 2.5mg/l after doses of 100mg and 200mg respectively. Following administration of 100mg and 200mg twice daily over 14.5 days, the plasma pharmacokinetic parameters of cefpodoxime remain unchanged.

Serum protein binding of cefpodoxime, 40% principally to albumin. This binding is non saturable in type.

Concentrations of cefpodoxime in excess of the minimum inhibitory levels (MIC) for common pathogens can be achieved in lung parenchyma, bronchial mucosa, pleural fluid, tonsils, interstitial fluid and prostate tissue.

As the majority of cefpodoxime is eliminated in the urine, the concentration is high. (Concentrations in 0-4, 4-8, 8-12 hr fractions after a single dose exceed MIC90 of common urinary pathogens). Good diffusion of cefpodoxime is also seen into renal tissue, with concentrations above MIC90 of the common urinary pathogens, 3-12hrs after an administration of a single 200mg dose (1.6-3.1µG/G). Concentrations of cefpodoxime in the medullary and cortical tissues is similar.

Studies in healthy volunteers show median concentrations of cefpodoxime in the total ejaculate 6-12hrs following administration of a single 200mg dose to be above the MIC90 of N. gonorrhoeae.

The main route of excretion is renal, 80% is excreted unchanged in the urine, with an elimination half life of approx 2.4 hours.

CHILDREN

In children, studies have shown the maximum plasma concentration occurs approximately 2-4 hours after dosing. A single 5mg/kg dose in 4-12 year olds produced a maximum concentration similar to that in adults given a 200mg dose.

In patients below 2 years receiving repeated doses of 5mg/kg 12 hourly, the average plasma concentrations, 2hrs post dose, are between 2.7mg/l (1-6 months) and 2.0mg/l (7 months-2 years).

In patients between 1 month and 12 years receiving repeated doses of 5mg/kg 12 hourly, the residual plasma concentrations at steady state are between 0.2-0.3mg/l (1 month-2 years) and 0.1mg/l (2-12 years).

5.3 Preclinical Safety Data

Not applicable.

6. Pharmaceutical Particulars 6.1 List Of Excipients

The product contains anhydrous colloidal silica, aspartame, banana flavour, carboxymethylcellulose calcium, carboxymethylcellulose sodium, citric acid monohydrate, hydroxypropylcellulose, yellow iron oxide, lactose monohydrate, monosodium glutamate, potassium sorbate, sodium chloride, sorbitan trioleate, sucrose and talc.

6.2 Incompatibilities

None reported during clinical studies.

6.3 Shelf Life

24 months.

Reconstituted suspension: can be stored for up to 10 days refrigerated (2-8°C).

6.4 Special Precautions For Storage

Bottles: unreconstituted product should be stored below 30°C.

6.5 Nature And Contents Of Container

Amber glass bottle with a calibration marking. This is fitted with a polyethylene dehydrating capsule containing silica gel, closed by a cardboard disc make up part of closure. There is a polyethylene pilfer and childproof screw cap fitted with tight triseal joint.

Pack sizes of 100ml of suspension.

A 5ml plastic spoon is supplied with the pack.

6.6 Special Precautions For Disposal And Other Handling

Before preparing the suspension the silica gel desiccant contained in a capsule inside the cap must be removed and disposed of. The suspension is prepared by adding water to the bottle up to the calibrated mark and shaking thoroughly to obtain an evenly dispersed suspension.

7. Marketing Authorisation Holder

Sanofi-aventis

One Onslow Street

Guildford

Surrey

GU1 4YS

UK

8. Marketing Authorisation Number(S)

PL 04425/0251

9. Date Of First Authorisation/Renewal Of The Authorisation

23rd July 2004

10. Date Of Revision Of The Text

8 October 2010

LEGAL CATEGORY

POM


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Comtan


Generic Name: Entacapone
Class: Catechol-O-Methyltransferase (COMT) Inhibitors
VA Class: CN500
Chemical Name: (E)-?-Cyano-N,N-diethyl-1,3,4-dihydroxy-5-nitrocinnamamide
Molecular Formula: C14H15N3O5
CAS Number: 130929-57-6

Introduction

Selective, reversible inhibitor of catechol-O-methyltransferase (COMT).1 2 3 7

Uses for Comtan Parkinsonian Syndrome

Adjunct to levodopa-carbidopa in the symptomatic treatment of idiopathic parkinsonian syndrome in patients with manifestations of end-of-dose “wearing-off.”1 4

Not evaluated systematically in patients without manifestations of end-of-dose “wearing-off.”1

Comtan Dosage and Administration Administration Oral Administration

Administer orally without regard to meals.1

Administer in conjunction with levodopa-carbidopa (conventional tablets, orally disintegrating tablets, or extended-release preparations) or as a fixed-combination preparation containing levodopa, carbidopa, and entacapone (Stalevo).1 8

Administer one tablet of the fixed-combination preparation (Stalevo) per dosing interval; do not divide the tablets.8

Dosage Adults Parkinsonian Syndrome Oral

200 mg with each levodopa-carbidopa dose.1

May need to reduce daily levodopa dosage or administration frequency to optimize patient response.1 In clinical studies, most patients receiving ?800 mg of levodopa daily or experiencing moderate or severe dyskinesias before initiating entacapone therapy required a reduction (average 25%) in levodopa dosage.1

Transferring to the Fixed-combination Preparation (Stalevo) Oral

Patients receiving levodopa-carbidopa conventional tablets containing a 1:4 ratio of carbidopa to levodopa: Switch to the corresponding strength of Stalevo.8

No information on transferring patients receiving extended-release levodopa-carbidopa preparation or levodopa-carbidopa preparations containing a 1:10 ratio of carbidopa to levodopa.8

Initiating Entacapone Using the Fixed-combination Preparation (Stalevo) Oral

Patients receiving levodopa >600 mg daily or with history of moderate or severe dyskinesias: Administer levodopa-carbidopa (1:4 ratio) and entacapone as separate preparations to determine optimum maintenance dosage and then switch to corresponding strength of Stalevo.8

Patients receiving levodopa <600 mg daily (conventional tablet, 1:4 ratio) with no dyskinesias: Switch to the strength of Stalevo that corresponds to the dosage of levodopa-carbidopa being taken.8 Further adjustment may be needed.8

Prescribing Limits Adults Parkinsonian Syndrome Oral

Entacapone: Maximum of 8 doses (1.6 g) daily; clinical experience with dosages >1.6 g daily is limited.1 8

Fixed-combination preparations containing levodopa 50–150 mg, carbidopa 12.5–37.5 mg, and entacapone 200 mg (Stalevo 50, 75, 100, 125, and 150): Maximum of 8 tablets daily; clinical experience with entacapone dosages >1.6 g daily is limited.8

Fixed-combination preparation containing levodopa 200 mg, carbidopa 50 mg, and entacapone 200 mg (Stalevo 200): Maximum of 6 tablets daily; clinical experience with carbidopa dosages >300 mg daily is limited.8

Cautions for Comtan Contraindications

Known hypersensitivity to entacapone or any ingredient in the formulation.1

When entacapone is used in fixed combination with levodopa-carbidopa, consider the contraindications associated with levodopa-carbidopa.8

Warnings/Precautions Warnings Concomitant Use with MAO Inhibitors

Possible inhibition of principal pathways involved in the metabolism of catecholamines if used concomitantly with a nonselective MAO inhibitor (e.g., phenelzine, tranylcypromine); concomitant use not recommended.1 (See Specific Drugs under Interactions.)

Concomitant Use with Drugs Metabolized by Catechol-O-methyltransferase

Possible increased heart rate, arrhythmias, and excessive changes in BP when used concomitantly with drugs metabolized by catechol-O-methyltransferase (COMT).1 (See Specific Drugs under Interactions.)

Potential Risk of Prostate Cancer

Higher incidence of prostate cancer was observed in one long-term, randomized, controlled study in patients initiating levodopa therapy with levodopa, carbidopa, and entacapone (Stalevo) compared with those initiating therapy with conventional levodopa-carbidopa formulation.11 13 Increased risk of prostate cancer not observed in other shorter-term controlled studies evaluating entacapone as an adjunct to levodopa-carbidopa.11 13 FDA is continuing to review available data related to this safety concern.11

FDA advises patients receiving entacapone as an adjunct to levodopa-carbidopa (either separately or as a fixed-combination preparation) to continue taking the drugs as prescribed unless otherwise instructed by a clinician.11 Men receiving such therapy should continue to be monitored for development of prostate cancer according to current prostate cancer screening guidelines.11

Major Toxicities Cardiovascular Effects

Enhances levodopa availability; possible increased occurrence of orthostatic hypotension or syncope when administered with levodopa-carbidopa.1

Findings from an FDA-conducted meta-analysis suggest that patients receiving combined therapy with levodopa, carbidopa, and entacapone may be at increased risk of adverse cardiovascular events (i.e., MI, stroke, cardiovascular death) compared with those receiving levodopa-carbidopa.12 However, several limitations of the meta-analysis preclude definite conclusions.12 FDA is continuing to review available data related to this safety concern.12 FDA advises patients receiving entacapone as an adjunct to levodopa-carbidopa (either separately or as a fixed-combination preparation) to continue taking the drugs as prescribed unless otherwise instructed by a clinician.12 Clinicians should monitor cardiac function regularly, particularly in patients with a history of cardiovascular disease.12

GI Effects

Possible mild to moderate diarrhea; rarely may be severe.1 Generally occurs during first 4–12 weeks of therapy; may occur as early as first week or as late as several months following initiation and resolves following discontinuance.1

Hallucinations

Possible hallucinations, sometimes resulting in hospitalization.1

Dyskinesia

May potentiate adverse dopaminergic effects of levodopa and may cause or exacerbate dyskinesias.1 3 4

Reduction of levodopa dosage may ameliorate dyskinesias; however, many patients in clinical studies continued to experience frequent dyskinesias.1 Discontinuance of therapy may be required.1

Rhabdomyolysis

Severe rhabdomyolysis reported rarely.1 4 7

Nervous System and Muscular Effects

Symptom complex resembling neuroleptic malignant syndrome (NMS) (elevated temperature, muscular rigidity, altered consciousness, elevated CPK) reported in association with abrupt withdrawal or dosage lowering of other dopaminergic agents.1 Similar episodes possible with entacapone.1 4 7 (See Withdrawal of Therapy under Cautions.)

Respiratory Effects

Retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, and thickening of the pleura reported with ergot-derivative dopamine receptor agonists (e.g., bromocriptine, pergolide); possibility exists that nonergot-derived drugs that increase dopaminergic activity (e.g., entacapone) may induce similar pulmonary changes.1

General Precautions Use of Fixed Combination

When the fixed combination containing levodopa, carbidopa, and entacapone (Stalevo) is used, observe the usual precautions and contraindications associated with all the drugs in the preparation.8

Withdrawal of Therapy

Slow withdrawal is recommended.1

If entacapone therapy is discontinued, closely monitor patient and adjust dosage of dopaminergic therapy accordingly.1

If hyperpyrexia or severe rigidity occurs, consider possibility of symptom complex resembling NMS.1

Melanoma

Epidemiologic studies indicate patients with parkinsonian syndrome have a twofold to approximately sixfold higher risk of developing melanoma than the general population.1 8 Unclear whether increased risk is due to parkinsonian syndrome or other factors (e.g., drugs used to treat the disease).1 8

Monitor for melanoma on a frequent and regular basis.1 8 Manufacturer recommends periodic skin examinations performed by appropriately qualified individuals (e.g., dermatologists).1 8

Intense Urges

Intense urges (e.g., urge to gamble, increased sexual urges, other intense urges) and inability to control these urges reported in some patients receiving antiparkinsonian agents that increase central dopaminergic tone (including entacapone).1 8 Although causal relationship not established, urges stopped in some cases when dosage was reduced or drug was discontinued.1 8

Consider reducing dosage or discontinuing entacapone if a patient develops such urges.1 8

Specific Populations Pregnancy

Category C.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Caution if used in nursing women.1

Pediatric Use

Not indicated.1

Geriatric Use

No substantial differences in safety or pharmacokinetics relative to younger adults.1 3 7

Hepatic Impairment

Use with caution.1 (See Special Populations under Pharmacokinetics.)

Biliary Obstruction

Use with caution.1

Common Adverse Effects

Dyskinesia, nausea, hyperkinesia, diarrhea, urine discoloration, hypokinesia, dizziness, abdominal pain, constipation, fatigue.1

Interactions for Comtan

Inhibits CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A only at very high concentrations.1 Inhibition of these isoenzymes not expected during clinical use.1

Drugs Metabolized by Catechol-O-methyltransferase

Possible increased heart rate, arrhythmias, and excessive changes in BP.1

Drugs Interfering with Biliary Excretion, Glucuronidation, and Intestinal ?-Glucuronidase

Decreased entacapone excretion.1 7

Protein-bound Drugs

No binding displacement between entacapone and other highly protein bound drugs (e.g., warfarin, salicylic acid, phenylbutazone, diazepam).1

Specific Drugs

Drug

Interaction

Comments

Anti-infective agents (e.g., ampicillin, chloramphenicol, erythromycin, rifampin)

Possible decreased entacapone excretion1 7

Use with caution1

Apomorphine

Possible increased heart rate, arrhythmias, and excessive changes in BP1

Cholestyramine

Possible decreased entacapone excretion1

Use with caution1

CNS depressants

Additive sedative effects1

Imipramine

Pharmacologic interaction unlikely1

Levodopa

Increased plasma levodopa concentrations, resulting in enhanced therapeutic effects1

Increased risk of levodopa-induced cardiovascular effects and dyskinesia1

MAO inhibitors

Potential inhibition of catecholamine metabolism when used concomitantly with nonselective MAO inhibitors (e.g., phenelzine, tranylcypromine)1

Pharmacologic interaction unlikely with selective MAO-B inhibitors (e.g., selegiline)1

Avoid concomitant use with nonselective MAO inhibitors1

Methyldopa

Possible increased heart rate, arrhythmias, and excessive changes in BP1

Probenecid

Possible decreased entacapone excretion1

Use with caution1

Sympathomimetic (adrenergic) agents (e.g., dobutamine, dopamine, epinephrine, isoetharine, isoproterenol, norepinephrine)

Possible increased heart rate, arrhythmias, and excessive changes in BP1

Comtan Pharmacokinetics Absorption Bioavailability

Rapidly absorbed following oral administration, with peak plasma concentrations attained within approximately 1 hour.1

Absolute bioavailability is 35%.1 a

Food

Food does not affect pharmacokinetics.1

Special Populations

Increased peak plasma concentrations and AUC in patients with mild to moderate hepatic impairment.1

Distribution Extent

Does not distribute widely into tissues.1

Distributed into milk in rats; not known whether distributed into human milk.1

Plasma Protein Binding

98% (mainly albumin).1

Elimination Metabolism

Almost completely metabolized, principally by isomerization followed by glucuronidation to an inactive conjugate.1

Elimination Route

Entacapone and its metabolites are eliminated principally in feces (90%) via biliary excretion and to a lesser extent in urine (10%).1 3 4

Half-life

Approximately 2.4 hours.1 a

Stability Storage Oral Tablets

25°C (may be exposed to 15–30°C).1

ActionsActions

Structurally and pharmacologically related to tolcapone;1 3 7 however, unlike tolcapone, not associated with hepatotoxicity (e.g., drug-induced hepatitis, fatal liver failure).1 3 4 7

Inhibits catechol-O-methyltransferase (COMT) enzyme in peripheral tissues;1 3 4 effects on central COMT activity in humans not studied.1

Concomitant administration with levodopa and a decarboxylase inhibitor (e.g., carbidopa) results in increased and more sustained plasma levodopa concentrations compared with administration of levodopa and a decarboxylase inhibitor.1 3 4

Lacks antiparkinsonian activity when administered alone.1

Advice to Patients

Importance of taking entacapone as prescribed and not discontinuing abruptly.1

Necessity of exercising caution when driving or operating machinery when entacapone is initiated.1 Caution when taking other CNS depressants.1

Advise that entacapone may cause brownish orange discoloration of urine; not clinically important.1

Advise that hallucinations, nausea, and increased dyskinesia can occur.1

Advise patients not to rise rapidly after prolonged sitting or lying down, especially during first few weeks of therapy.1

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

Importance of asking patients whether they have developed any new or increased gambling urges, sexual urges, or other urges while receiving entacapone and of advising them of the importance of reporting such urges.1 8

Importance of frequent monitoring for melanoma and periodic dermatologic examinations by a dermatologist.1 8

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Entacapone

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

200 mg

Comtan

Novartis

Entacapone Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

200 mg with Carbidopa 12.5 mg (of anhydrous carbidopa) and Levodopa 50 mg

Stalevo

Novartis

200 mg with Carbidopa 18.75 mg (of anhydrous carbidopa) and Levodopa 75 mg

Stalevo

Novartis

200 mg with Carbidopa 25 mg (of anhydrous carbidopa) and Levodopa 100 mg

Stalevo

Novartis

200 mg with Carbidopa 31.25 mg (of anhydrous carbidopa) and Levodopa 125 mg

Stalevo

Novartis

200 mg with Carbidopa 37.5 mg (of anhydrous carbidopa) and Levodopa 150 mg

Stalevo

Novartis

200 mg with Carbidopa 50 mg (of anhydrous carbidopa) and Levodopa 200 mg

Stalevo

Novartis

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Comtan 200MG Tablets (NOVARTIS): 30/$112.99 or 90/$310.97

Stalevo 100 25-100-200MG Tablets (NOVARTIS): 90/$318 or 270/$898.92

Stalevo 150 37.5-150-200MG Tablets (NOVARTIS): 30/$113.99 or 90/$334.97

Stalevo 200 50-200-200MG Tablets (NOVARTIS): 100/$363.99 or 300/$1043.97

Stalevo 50 12.5-50-200MG Tablets (NOVARTIS): 30/$110.98 or 90/$317.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions February 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Novartis Pharmaceuticals Corporation. Comtan (entacapone) tablets prescribing information. East Hanover, NJ; 2009 Mar.

2. LeWitt PA. New drugs for the treatment of Parkinson’s disease. Pharmacotherapy. 2000; 20:26S-32S.

3. Holm KJ, Spencer CM. Entacapone: a review of its use in Parkinson’s disease. Drugs. 1999; 58:159-77.

4. Anon. Entacapone for Parkinson’s disease. Med Lett Drugs Ther. 2000; 42:7-8.

5. Rinne UK, Larsen JP, Siden A et al. Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations. Neurology. 1998; 51:1309-14.

6. Parkinson Study Group. Entacapone improves motor fluctuations in levodopa-treated Parkinson’s disease patients. Ann Neurol. 1997; 42:747-55.

7. Novartis, East Hanover, NJ: Personal communication.

8. Novartis. Stalevo 50, Stalevo 75, Stalevo 100, Stalevo 125, Stalevo 150, Stalevo 200 (carbidopa, levodopa, and entacapone) tablets prescribing information. East Hanover, NJ; 2009 Mar.

9. Mylan Bertek Pharmaceuticals Inc. Apokyn (apomorphine hydrochloride) injection prescribing information. Research Triangle Park, NC; 2004 Apr.

10. van der Geest R, van Laar T, Kruger PP et al. Pharmacokinetics, enantiomer interconversion, and metabolism of R-apomorphine in patients with idiopathic Parkinson’s disease. Clin Neuropharmacol. 1998; 21:159-68. [PubMed 9617507]

11. Food and Drug Administration. FDA drug safety communication: ongoing safety review of Stalevo (entacapone/carbidopa/levodopa) and possible development of prostate cancer. Rockville, MD; 2010 Mar 31. From FDA website ().

12. Food and Drug Administration. FDA drug safety communication: ongoing safety review of Stalevo and possible increased cardiovascular risk. Rockville, MD; 2010 Aug 20. From FDA website ().

13. Stocchi F, Rascol O, Kieburtz K et al. Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE-PD study. Ann Neurol. 2010; 68:18-27. [PubMed 20582993]

a. Heikkinen H, Saraheimo M, Antila S et al. Pharmacokinetics of entacapone, a peripherally acting catechol-O-methyltransferase inhibitor, in man. A study using a stable isotope technique. Eur J Clin Pharmacol. 2001; 56: 821-6. [PubMed 11294372]

More Comtan resources Comtan Side Effects (in more detail) Comtan Dosage Comtan Use in Pregnancy & Breastfeeding Drug Images Comtan Drug Interactions Comtan Support Group 2 Reviews for Comtan - Add your own review/rating Comtan Prescribing Information (FDA) Comtan MedFacts Consumer Leaflet (Wolters Kluwer) Comtan Concise Consumer Information (Cerner Multum) Comtan Advanced Consumer (Micromedex) - Includes Dosage Information Entacapone Professional Patient Advice (Wolters Kluwer) Compare Comtan with other medications Parkinson's Disease
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J Collis Browne's Tablets


1. Name Of The Medicinal Product

J Collis Browne's Tablets

2. Qualitative And Quantitative Composition

Morphine hydrochloride Ph. Eur.

0.35mg/tablet

Light kaolin BP1980

750mg/tablet

Calcium carbonate, heavy Ph. Eur

200mg/tablet

3. Pharmaceutical Form

Uncoated tablet

4. Clinical Particulars 4.1 Therapeutic Indications

For the symptomatic relief of occasional diarrhoea.

4.2 Posology And Method Of Administration

Oral.

Adults and the Elderly:

Two or three tablets at once, then two or three tablets every four hours.

Children aged 6 to 10 years

One tablet at once, then one tablet every four hours.

Children under 6 years

Not recommended

4.3 Contraindications

Contraindicated in acute respiratory depression (asthma), acute alcoholism, paralytic ileus, acute ulcerative colitis, raised intra-cranial pressure and head injury. Hypersensitivity to any of the ingredients.

4.4 Special Warnings And Precautions For Use

If symptoms persist for more than 48 hours, consult the doctor.

Keep out of the reach of children. Do not exceed the stated dose.

Do not take more than 6 doses in 24 hours. In addition to taking these tablets, it is important to replace body fluids lost during diarrhoea.

Not recommended for children under 6 years of age.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

This product should be given with caution to patients exhibiting the following clinical conditions: hypotension, hypothyroidism, prostatic hypertrophy, renal or hepatic impairment, convulsive disorders, dependence, also if elderly or debilitated.

The depressant effects of opioid analgesics are enhanced by other CNS depressants such as alcohol, anxiolytics, hypnotics, antidepressants including tricyclic antidepressants, anticoagulants such as warfarin, antiepileptics and antipsychotics.

Morphine may interact with monoamine oxidase inhibitors (MAOI's) or within 14 days of stopping such treatment. If opioid analgesics are required they should be given with extreme caution. The effects of morphine in reducing gastrointestinal motility may interfere with the absorption of antiarrhythmics such as mexiletine, and may counteract the stimulatory effect of metoclopramide, domperidone and cisapride.

Cimetidine inhibits the metabolism of some opioids.

4.6 Pregnancy And Lactation

No known effects in pregnancy and lactation. However, as with all medicines, use with caution.

4.7 Effects On Ability To Drive And Use Machines

No known effects.

4.8 Undesirable Effects

Side effects are nausea, vomiting, constipation, drowsiness, difficulty in micturition, ureteric or biliary spasm, dry mouth, sweating, headache, facial flushing, vertigo, bradycardia, tachycardia, palpitations, postural hypotension, hypothermia, hallucinations, dysphoria, mood changes, dependence, miosis, decreased libido or potency, rashes, urticaria and pruritus.

4.9 Overdose

Gastric lavage and symptomatic treatment as for morphine hydrochloride is recommended.

Naloxone may be used to counteract central nervous system depression.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Light kaolin is absorbent and, when given by mouth, absorbs toxic and other substances from the alimentary tract.

Morphine, among other actions, diminishes propulsive peristalsis in the intestinal tract.

It is an effective agent for treating diarrhoea.

Calcium carbonate is an antacid that also has a constipating effect.

5.2 Pharmacokinetic Properties

No pharmacokinetic studies have been carried out.

5.3 Preclinical Safety Data

None stated.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Magnesium stearate, sodium polymetaphosphate, sucrose (icing sugar), talc, dispersed pink 11150 (contains E127), liquorice powder 07123937, peppermint flavour extra

6.2 Incompatibilities

None stated.

6.3 Shelf Life

Three years unopened.

6.4 Special Precautions For Storage

None

6.5 Nature And Contents Of Container

250 micron rigid uPVC 25µ aluminium foil blisters in cardboard cartons in packs of 18 or 36 tablets

6.6 Special Precautions For Disposal And Other Handling

None stated.

7. Marketing Authorisation Holder

Thornton & Ross Limited

Linthwaite

Huddersfield

West Yorkshire

HD7 5QH

United Kingdom

8. Marketing Authorisation Number(S)

PL 00240/0092

9. Date Of First Authorisation/Renewal Of The Authorisation

15 January 2003

10. Date Of Revision Of The Text 11 DOSIMETRY

Not Applicable

12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS

Not Applicable


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Sectral 400mg tablets


1. Name Of The Medicinal Product

Sectral 400mg Tablets

2. Qualitative And Quantitative Composition

Each tablet contains 443.40mg of the active substance Acebutolol hydrochloride (equivalent to 400mg of base).

Also contains 21.20mg of lactose monohydrate.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Tablet

White to off-white, circular, biconvex, film-coated tablets with bevel edges, one face impressed 'SECTRAL 400 or ACB 400. Plain reverse.

4. Clinical Particulars 4.1 Therapeutic Indications

The management of hypertension, angina pectoris and the control of tachyarrhythmias.

4.2 Posology And Method Of Administration

Hypertension: Initial dosage of 400mg orally once daily at breakfast or 200mg orally twice daily. If response is not adequate within two weeks, dosage may be increased up to 400mg orally twice daily; in some patients 1200mg orally daily, given as 800mg at breakfast and 400mg in the evening may be required. A further reduction in blood pressure may be obtained by the concurrent administration of a thiazide diuretic or other anti-hypertensive agent (except Rauwolfia and its alkaloids).

Angina pectoris: Initial dosage of 400mg orally once daily at breakfast or 200mg twice daily. In severe forms up to 300mg three times daily may be required. Up to 1200mg daily has been used.

Cardiac Arrhythmias: When given orally, an initial dose of 200mg is recommended. The daily dose requirement for long term anti arrhythmic activity should lie between 400 and 1200mg daily. The dose can be gauged by response, and better control may be achieved by divided doses rather than single doses. It may take up to three hours for maximal anti-arrhythmic effect to become apparent.

Elderly: There are no specific dosage recommendations for the elderly with normal glomerular filtration rate. Dose reduction is necessary if moderate to severe renal impairment is present (see Section 4.4)

Children: Paediatric dose has not been established.

For all indications, it is advised that the lowest recommended dosage be used initially.

4.3 Contraindications

Cardiogenic shock is an absolute contraindication. Extreme caution is required in patients with blood pressures of the order of 100/60 mmHg or below.

Sectral is also contraindicated in patients with second and third degree heart block, sick sinus syndrome, marked bradycardia (< 45 – 50 bpm) and uncontrolled heart failure, metabolic acidosis, severe peripheral circulatory disorders, hypersensitivity to Acebutolol, any of the excipients or to beta blockers, and untreated phaeochromocytoma.

4.4 Special Warnings And Precautions For Use

Renal impairment is not contraindicated to the use of Sectral which has both renal and non-renal excretory pathways. Some caution should be exercised when administering high doses to patients with severe renal failure as accumulation could possibly occur in these circumstances.

The dosage frequency should not exceed once daily in patients with renal impairment. As a guide, the dosage should be reduced by 50% when glomerular filtration rates are between 25-50ml/min and by 75% when they are below 25ml/min (see section 4.2).

Drug-induced bronchospasm is usually at least partially reversible by the use of a suitable agonist.

Although cardio-selective beta blockers may have less effect on lung function than non-selective beta blockers as with all beta blockers these should be avoided in patients with obstructive airways disease unless there are compelling clinical reasons for their use. Where such reasons exist, cardio-selective ?-blockers should be used with the utmost care. (see section 4.3)

Beta-blockers may induce bradycardia. In such cases, the dosage should be reduced. They may be used with patients with controlled heart failure. (see Section 4.3)

Use with caution in patients with Prinzmetal's angina.

Beta-blockers may aggravate peripheral circulatory disorders. They may mask signs of thyrotoxicosis and hypoglycaemia. They should only be used in patients with phaeochromocytoma with concomitant alpha-adrenoreceptor therapy.

Patients with known psoriasis should take beta-blockers only after careful consideration.

Beta-blockers may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions.

Withdrawal of treatment by beta-blockers should be achieved by gradual dosage reduction: this is especially important in patients with ischaemic heart disease.

When it has been decided to interrupt beta-blockade prior to surgery, therapy should be discontinued for at least 24 hours. Continuation of the therapy reduces the risk of arrhythmias but the risk of hypotension may be increased. If treatment is continued, caution should be observed with certain anaesthetic drugs. The patient may be protected against vagal reactions by intravenous administration of atropine

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

Sectral should not be used with Verapamil or within several days of Verapamil therapy (and vice versa). Use with great care with any other calcium antagonists, particularly Diltiazem

Class 1 anti-arrthythmic drugs (such as disopyramide) and amiodarone may increase atrial conduction time and induce negative inotropic effects when used concomitantly with beta-blockers.

In patients with labile and insulin-dependent diabetes, the dosage of the hypoglycaemic agent may need to be reduced. However beta-blockers have also been known to blunt the effect of glibenclamide. Beta-adrenergic blockade may also prevent the appearance of signs of hypoglycaemia (tachycardia, see section 4.4)

Cross reactions due to displacement of other drugs from plasma protein binding sites are unlikely due to the low degree of plasma protein binding exhibited by Acebutolol and Diacetolol.

If a beta-blocker is used concurrently with clonidine the latter should not be withdrawn until several days after the former is discontinued.

Acebutolol may antagonize the effect of sympathomimetic and xanthine bronchodilators.

Concurrent use of digoxin and beta-blockers may occasionally induce serious bradycardia. The anti-hypertensive effects of beta-blockers may be attenuated by non-steroidal anti-inflammatory agents.

Concomitant administration of tricyclic antidepressants, barbiturates and phenothiazines as well as other anti-hypertensive agents may increase the blood pressure lowering effects of beta-blockers.

There is a theoretical risk that concurrent administration of monoamine oxidase inhibitors and high doses of beta-blockers, even if they are cardio-selective can produce hypertension. Sectral therapy should be brought to the attention of the anaesthetist prior to general anaesthesia. (see Section 4.4). If treatment is continued, special care should be taken when using anaesthetic agents such as ether, cyclopropane and trichlorethylene.

4.6 Pregnancy And Lactation

Pregnancy: Acebutolol should not be administered to female patients during the first trimester of pregnancy unless the physician considers it essential. In such cases the lowest possible dose should be used.

Beta blockers administered in late pregnancy may give rise to bradycardia, hypoglycaemia and cardiac or pulmonary complications in the foetus/neonate.

Beta-blockers can reduce placental perfusion, which may result in intrauterine foetal death, immature and premature deliveries

Animal studies have shown no teratogenic hazard.

Lactation: Acebutolol and its active metabolites are excreted in human milk and effects have been shown in breastfed newborns/infants of treated mothers. Acebutolol should not be used during breast-feeding.

4.7 Effects On Ability To Drive And Use Machines

No studies on the effects on the ability to drive and use machines have been performed. As with all beta-blockers, dizziness or fatigue may occur occasionally. This should be taken into account when driving or operating machinery.

4.8 Undesirable Effects

Adverse reactions associated with acebutolol during controlled clinical trials in patients with hypertension, angina pectoris or arrhythmia (1002 patients exposed to acebutolol) are presented by system organ class and by decreasing order of frequency.

The frequency of the events “anti-nuclear antibody” and “lupus like syndrome” was found from 1440 patients suffering from hypertension, angina pectoris or arrhythmia and exposed to acebutolol in open or double blind studies performed in the United States.

Frequencies are defined as: very common (

When the exact frequency of the event was not reported, the frequency category assigned is “not known” (ADRs with *).

Adverse reactions reported from post-marketing experience are also listed. These adverse reactions are derived from spontaneous reports and therefore, the frequency of these adverse reactions is “not known” (cannot be estimated from the available data).

The most frequent and serious adverse reactions of acebutolol are related to the beta-adrenergic blocking activity. The most frequent reported clinical adverse reactions are fatigue and gastrointestinal disorders. Among the most serious adverse reactions are cardiac failure, atrioventricular block and bronchospasm. Abrupt withdrawal as for all beta-blockers may exacerbate angina pectoris and precaution is especially required in patients with ischaemic heart disease (see Section 4.4).

Immune system disorders

Very common

Antinuclear antibody

Uncommon

Lupus like syndrome

 

Psychiatric disorders

Common

Depression, nightmare

Not known

Pychoses, hallucinations, confusion, loss of libido*, sleep disorder

 

Nervous system disorders

Very common

Fatigue

Common

Dizziness, headache

 

Not known

Paraesthesia*, central nervous system disorder

 

Eye disorders

Common

Visual impairment

Not known

Dry eye*

 

Cardiac disorders

Not known

Cardiac failure*, atrioventricular block first degree, increase of an existing atrioventricular block, bradycardia*

Vascular disorders

Not known

Intermittent claudication, Raynaud's syndrome, cyanosis peripheral and peripheral coldness, hypotension*

Respiratory, thoracic and mediastinal disorders

Common

Dyspnoea

Not known

Pneumonitis, lung infiltration, bronchospasm

 

Gastrointestinal disorders

Very common

Gastrointestinal disorders

Common

Nausea, diarrhoea

 

Not known

Vomiting*

 

Skin and subcutaneous tissue disorders

Common

Rash

General disorders and administration site condition

Not known

Withdrawal syndrome (see Section 4.4)

4.9 Overdose

In the event of excessive bradycardia or hypotension, 1mg atropine sulphate administered intravenously should be given without delay. If this is insufficient it should be followed by a slow intravenous injection of isoprenaline (5mcg per minute) with constant monitoring until a response occurs. In severe cases of self-poisoning with circulatory collapse unresponsive to atropine and catecholamines the intravenous injection of glucagon 10-20mg may produce a dramatic improvement. Cardiac pacing may be employed if bradycardia becomes severe.

Judicious use of vasopressors, diazepam, phenytoin, lidocaine, digoxin and bronchodilators should be considered depending on the presentation of the patient. Acebutolol can be removed from blood by haemodialysis. Other symptoms and signs of over dosage include cardiogenic shock, AV block, conduction defects, pulmonary oedema, depressed level of consciousness, bronchospasm, hypoglycaemia and rarely hyperkalaemia.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Beta Blocker agents; Beta blocker agents, selective, ATC code: C07AB04.

Mode of action: Sectral is a beta adrenoceptor antagonist which is cardio selective, i.e. acts preferentially on beta-1 adrenergic receptors in the heart. Its principal effects are to reduce heart rate especially on exercise and to lower blood pressure in hypertensive subjects. Sectral and its active metabolite, diacetolol have anti-arrhythmic activity, the combined plasma half-life of the active drug and metabolite being 7-10 hours. Both have partial agonist activity (PAA) also known as intrinsic sympathomimetic activity (ISA). This property ensures that some degree of stimulation of beta-receptors is maintained. Under conditions of rest, this tends to balance the negative chronotropic and negative inotropic effects. Sectral blocks the effects of excessive catecholamine stimulation resulting from stress.

5.2 Pharmacokinetic Properties

After oral administration, Acebutolol is rapidly and almost completely absorbed. Absorption appears to be unaffected by the presence of food in the gut. There is rapid formation of a major equiactive metabolite, diacetolol, which possesses a similar pharmacological profile to Acebutolol. Peak plasma concentrations of active material (i.e. Acebutolol plus diacetolol) are achieved within 2-4 hours and the terminal plasma elimination half-life is around 8-10 hours. Because of biliary excretion and direct transfer across the gut wall from the systemic circulation to the gut lumen, more than 50% of an oral dose of Sectral is recovered in the faeces with Acebutolol and diacetolol in equal proportions; the rest of the dose is recovered in the urine, mainly as diacetolol. Both Acebutolol and diacetolol are hydrophilic and exhibit poor penetration of the CNS.

5.3 Preclinical Safety Data

No particulars.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Lactose monohydrate

Starch Maize

Talc (E553b)

Silica colloidal anhydrous (E551)

Povidone K30

Magnesium Stearate (E572)

Tablet coat:

Opadry OY-L-28900 containing

Titanium dioxide (E171)

Lactose monohydrate

Hypromellose (E464)

Macrogol

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

3 years

6.4 Special Precautions For Storage

None

6.5 Nature And Contents Of Container

Sectral is packed in aluminium foil/PVC blister strip packs of 28 tablets

6.6 Special Precautions For Disposal And Other Handling

No special requirements

7. Marketing Authorisation Holder

Sanofi-aventis

One Onslow Street

Guildford

Surrey, GU1 4YS, UK

8. Marketing Authorisation Number(S)

PL 4425/0264

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of first authorisation: 16 December 1974

Date of latest renewal: 10 May 2004

10. Date Of Revision Of The Text

6th July 2011

LEGAL CLASSIFICATION

POM


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Hydralazine Tablets BP 25mg


1. Name Of The Medicinal Product

HYDRALAZINE TABLETS BP 25mg

2. Qualitative And Quantitative Composition

Each tablet contains 25mg Hydralazine Hydrochloride.

For excipients, see 6.1.

3. Pharmaceutical Form

Film-coated tablet.

Ivory, circular, biconvex film-coated tablets impressed “C” on one face and the identifying letters “HY” on the reverse.

4. Clinical Particulars 4.1 Therapeutic Indications

Hydralazine is indicated for:

1) Moderate to severe hypertension (in conjunction with a beta-adrenoceptor blocking agent or diuretic) and hypertensive crisis.

2) The management of moderate to severe congestive cardiac failure (reduces afterload), where optimal doses of diuretics and cardiac glycosides prove insufficient. In patients with high left ventricular filling pressure, it is recommended to combine hydralazine with a nitrate.

4.2 Posology And Method Of Administration

For oral administration.

Adults: Dosage should not be increased beyond 100mg daily without first checking the patient's acetylator status.

Hypertension: The dose should be adjusted to the individual requirements of the patient. Treatment should begin with low doses of hydralazine which, depending on the patient's response, should be increased stepwise to achieve optimal therapeutic effect whilst keeping unwanted effects to a minimum. Initially 25mg twice daily. This can be increased gradually to a dose not exceeding 200mg daily.

Chronic congestive heart failure: Treatment with hydralazine should always be initiated in hospital, where the patient's individual haemodynamic values can be reliably determined with the help of invasive monitoring. It should then be continued in hospital until the patient has become stabilised on the requisite maintenance dose. Doses vary greatly between individual patients and are generally higher than those used for treating hypertension. After progressive titration (initially 25mg 3-4 times daily) the maintenance dosage averages 75mg four times daily.

Children: Not recommended for this age group.

Elderly: Clinical evidence indicates that no special dosage regime is necessary. Advancing age does not affect either blood concentration or systemic clearance. Renal elimination may however be affected in so far as kidney function diminishes with age.

4.3 Contraindications

Hydralazine should not be given to patients with tachycardia and also in cases of left ventricular failure due to severe aortic or mitral stenosis or in constrictive pericarditis; in heart failure associated with high output (ie in thyrotoxicosis); isolated right ventricular failure due to pulmonary hypertension (ie cor pulmonale); hypersensitivity to hydralazine and dihydralazine or to any of the excipients. Idiopathic system lupus erythematosus (SLE) and related diseases. Dissecting aortic aneurism. Porphyria.

4.4 Special Warnings And Precautions For Use

Use with caution in patients with coronary disease (may provoke angina), in those undergoing anaesthesia (which may precipitate severe hypotension) or in patients with cerebrovascular disease.

Avoid after myocardial infarction until stabilised.

During long-term therapy with hydralazine, it is advisable to determine the antinuclear factors and conduct urinalysis (for microhaematuria and proteinuria) at intervals of approximately 6 months. In the event of positive findings for antinucuclear factors, the titres should be monitored more frequently. At the first signs or symptoms suggestive of SLE or renal disease, hydralazine should be withdrawn, (see also under “other undesirable effects”).

In severe renal failure the interval between doses should be prolonged to avoid accumulation; also in hepatic dysfunction a reduction in dosage or prolonged dosage interval may be indicated.

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

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Potentiation of effects: Concurrent treatment with other antihypertensives, muscle relaxants (baclofen and tizonidine), nitrates, anaesthetics, minor tranquillisers, antidepressants, levodopa or drugs exerting a central depressant action (including alcohol).

Reduction in effects: Concomitant treatment with sympathomimetics, tricyclic antidepressants or MAOI's, NSAIDs, corticosteroids.

4.6 Pregnancy And Lactation

Due to the discovery that hydralazine has a teratogenic effect in mice, causing a small incidence of cleft palate and certain other minor bone malformations in doses ranging from 20-120mg/kg; its use should be avoided in pregnancy during the period of organogenesis, that is the first half of pregnancy. Hydralazine crosses the placental barrier and is excreted in breast milk. Mothers who are receiving hydralazine should not therefore breast feed their infants.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Tachycardia, palpitations, headache, flushing, dizziness, anorexia, angina, nasal congestion, nausea and vomiting can occur, but may be minimised by the prior administration of a beta blocker. Fluid retention.

Patients may occasionally develop symptoms suggestive of rheumatoid arthritis. Skin reactions and fever may occur producing a syndrome similar to systemic lupus erythematosus. This is more likely to occur with high dosage regimes (more than 200mg daily). If such symptoms develop the drug should be gradually withdrawn, when remission will usually occur.

Rarely: Anaemia, leucopenia, neutropenia, thrombocytopenia with or without purpura, proteinuria, increased plasma creatinine, haematuria, dyspnoea and pleural pain.

Isolated cases: Haemolytic anaemia, leucocytosis, lymphadenopathy, pancytopenia, splenomegaly, agranulocytosis.

Occasionally liver damage may occur resembling an hepatitis-like syndrome which is reversible on withdrawal of the drug. Isolated cases of glomerulonephritis have been reported. Hydralazine should be withdrawn if anxiety, depression, febrile reactions, change in blood count or skin rash occur. Rare cases of peripheral neuritis, causing paraesthesia, may be reversed by the administration of pyridoxine, or by withdrawal of hydralazine.

4.9 Overdose

Symptoms including hypotension, tachycardia, myocardial ischaemia, dysrrhythmias and coma.

Gastric lavage or, in the absence of coma, emetic treatment should be given as soon as possible. If hypotension is present, an attempt should be made to raise blood pressure without increasing tachycardia, hence adrenaline (epinephrine) should be avoided. Supportive measures such as intravenous fluids and elevation of foot of bed are also indicated. Cautious administration of angiotensin or noradrenaline (norepinephrine) intravenously may be of use.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Hydralazine hydrochloride is a vasodilator and antihypertensive agent.

Hydralazine is a direct acting vasodilator which exerts a moderate but significant antihypertensive effect (diastolic more than systolic) principally on the arterioles. It tends to improve the renal, uterine and cerebral blood flow. The effect results in a decrease in arterial blood pressure and peripheral vascular resistance, and an increase in heart rate, reflex tachycardia, stroke volume and cardiac output. The rise in cardiac output accompanies the fall in blood pressure, probably as a reflex response; (hydralazine also serves to improve renal blood flow and renal function). Hydralazine lowers blood pressure seemingly by exerting an arteriolar dilating effect through a direct relaxation of vascular smooth muscle.

In heart failure cardiac output is improved as a result of the afterload reduction which is induced by hydralazine; tachycardia or hypotension are seldom seen in this group.

5.2 Pharmacokinetic Properties

Hydralazine is rapidly absorbed from the gastrointestinal tract and peak plasma concentrations have been reported to occur in the plasma after about one hour. It is metabolised by hydroxylation of the ring system and conjugation with glucuronic acid, and by N-acetylation.

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars 6.1 List Of Excipients

The tablet core contains: polyvidone, disodium edetate, microcrystalline cellulose (E460), magnesium stearate.

The coating contains: hypromellose (E464), titanium dioxide (E171), lactose monohydrate, macrogol, glycerol triacetate (E1518), iron oxide (E172).

6.2 Incompatibilities

None known.

6.3 Shelf Life

Three years.

6.4 Special Precautions For Storage

Polypropylene and polyethylene containers

Do not store above 25°C. Store in the original container.

Blister packs

Do not store above 25°C. Keep container in the outer carton.

6.5 Nature And Contents Of Container

The product containers are rigid injection moulded polypropylene containers and snap-on polyethylene lids.

The product may also be supplied in blister packs and cartons:

a) Carton: Printed carton manufactured from white folding box board.

b) Blister pack: 250µm white rigid PVC. Surface printed 20µm hard temper aluminium foil with 5-6g/M? PVC and PVdC compatible heat seal lacquer on the reverse side.

Pack sizes: 28s, 30s, 56s, 60s, 84s, 90s, 100s, 112s, 120s, 168s, 180s, 250s, 500s, 1000s.

Polyethylene container with a polypropylene lid.

Pack size: 56s

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Actaivs UK Limited (Trading style: Actavis)

Whiddon Valley

BARNSTAPLE

N Devon EX32 8NS

8. Marketing Authorisation Number(S)

PL 00142/ 0499

9. Date Of First Authorisation/Renewal Of The Authorisation

6 March 2001

Renewed – 19.03.09

10. Date Of Revision Of The Text

08/07/2009


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Kolanticon Gel


1. Name Of The Medicinal Product

Kolanticon Gel

2. Qualitative And Quantitative Composition

Kolanticon Gel is a white viscous suspension containing 2.5mg dicycloverine hydrochloride, 200mg aluminium hydroxide, 100mg light magnesium oxide, 20mg simethicone per 5ml.

3. Pharmaceutical Form

Suspension for oral administration.

4. Clinical Particulars 4.1 Therapeutic Indications

Treatment and prophylaxis of symptoms of peptic ulcer and functional dyspepsia especially in patients in whom gastric distress results from hyperacidity, smooth muscle spasm, including irritable bowel syndrome (IBS), and flatulence. Also indicated for symptomatic relief in oesophagitis, hiatus hernia, gastritis and iatrogenic gastritis.

4.2 Posology And Method Of Administration

Two to four 5ml spoonfuls every four hours as required.

4.3 Contraindications

Known idiosyncrasy to any of the ingredients. Should not be used in patients with prostatic enlargement, glaucoma, obstructive uropathy, obstructive disease of the gastro-intestinal tract, paralytic ileus and intestinal atony, severe ulcerative colitis, and myasthenia gravis.

4.4 Special Warnings And Precautions For Use

In the presence of renal insufficiency magnesium salts may cause central nervous system depression. Aluminium hydroxide in the presence of low phosphorous diets may cause phosphorous deficiency. Aluminium hydroxide may reduce absorption of tetrayclines when given concomitantly. Use with care in patients with hiatus hernia associated with reflux oesophagitis because anticholinergic drugs may aggravate this condition.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Antacids may interfere with the absorption of tetracyclines, ACE inhibitors, digoxin, rifampicin, ketoconazole, penicillamine, ciprofloxacin (and other quinolones), anticoagulants and biphosphonates, if given concurrently. Because of the large number of possible interactions they should not be given at the same time as any other drugs.

4.6 Pregnancy And Lactation

Epidemiological studies in pregnant women with products containing dicycloverine hydrochloride (at doses up to 40mg/day) have not shown that dicycloverine increases the risk of foetal abnormalities if administered during the first trimester of pregnancy. Reproduction studies have been performed in rats and rabbits at doses of up to 100 times the maximum recommended dose (based on 60mg per day for an adult person) and have revealed no evidence of impaired fertility or harm to the foetus due to dicycloverine.

For aluminium hydroxide, magnesium oxide and simethicone no clinical data on exposed pregnancies are available.

Caution should be exercised when prescribing to pregnant women.

Since the risk of teratogenicity cannot be excluded with absolute certainty for any product, the drug should be used during pregnancy only if clearly needed.

It is not known whether dicycloverine is secreted into human milk. Because many drugs are excreted in human milk, caution should be exercised when dicycloverine is administered to a nursing woman.

4.7 Effects On Ability To Drive And Use Machines

None known

4.8 Undesirable Effects

In particularly sensitive patients dicycloverine hydrochloride may cause atropine-like

side-effects such as dry mouth, blurred vision, urinary retention or constipation.

4.9 Overdose

Signs and symptoms of dicycloverine hydrochloride overdose include: headache, nausea and vomiting, blurred vision, dilated pupils, hot dry skin, dizziness, vertigo, dryness of mouth, difficulty in swallowing and CNS stimulation.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Dicycloverine hydrochloride:

anticholinergic agent used as an antispasmodic; also has direct antispasmodic activity.

Aluminium hydroxide dried gel, magnesium hydroxide are antacids.

 

Simethicone:

antiflatulent

5.2 Pharmacokinetic Properties

Dicycloverine hydrochloride:

Dicycloverine hydrochloride when given orally was rapidly and completely absorbed and the drug and/or its metabolites were found in the urine (dominant route of elimination) within 1 hour after drug ingestion. Plasma half-life of 4-6 hours was found for dicycloverine and/or its metabolites.

Antacids:

Act by local action in the stomach by neutralising stomach acid and are largely unabsorbed.

5.3 Preclinical Safety Data

None applicable.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Kolanticon Gel contains magnesium sulphate, methylcellulose 450, benzyl alcohol, sodium lauryl sulphate, saccharin sodium, alcohol 95%, methylparaben, propylparaben, butylparaben., citric acid, oil of cinnamon, oil of peppermint, oil of spearmint, oil of cedar leaf, oil of nutmeg, menthol and eucalyptol.

6.2 Incompatibilities

None known

6.3 Shelf Life

36 Months

6.4 Special Precautions For Storage

Store below 25°C

6.5 Nature And Contents Of Container

Amber glass bottles of 200 and 500ml

6.6 Special Precautions For Disposal And Other Handling

Shake well before use.

Administrative Data 7. Marketing Authorisation Holder

Peckforton Pharmaceuticals Ltd,

Crewe Hall,

Crewe,

Cheshire,

CW1 6UL.

United Kingdom

8. Marketing Authorisation Number(S)

PL 15760/0004

9. Date Of First Authorisation/Renewal Of The Authorisation

15 October 1999

10. Date Of Revision Of The Text

June 2007

11. Legal Category

P


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Stalevo 125 / 31.25 / 200mg


Stalevo 125 mg/31.25 mg/200 mg film-coated tablets

Levodopa/carbidopa/entacapone

Read all of this leaflet carefully before you start taking this medicine. Keep this leaflet. You may need to read it again. If you have any further questions, ask your doctor or pharmacist. This medicine has been prescribed for you. Do not pass it to others. It may harm them, even if their symptoms are the same as yours. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. In this leaflet:

1. What Stalevo is and what it is used for
2. Before you take Stalevo
3. How to take Stalevo
4. Possible side effects
5 How to store Stalevo
6. Further information

What Stalevo Is And What It Is Used For

Stalevo contains three active substances (levodopa, carbidopa and entacapone) in one film-coated tablet. Stalevo is used for the treatment of Parkinson’s disease.

Parkinson’s disease is caused by low levels of a substance called dopamine in the brain.

Levodopa increases the amount of dopamine and hence reduces the symptoms of Parkinson’s disease. Carbidopa and entacapone improve the antiparkinson effects of levodopa.

Before You Take Stalevo Do not take Stalevo if you are allergic (hypersensitive) to levodopa, carbidopa or entacapone, or any of the other ingredients of Stalevo have narrow-angle glaucoma (an eye disorder) have a tumour of the adrenal gland are taking certain medicines for treating depression (combinations of selective MAO-A and MAO-B inhibitors, or non-selective MAO-inhibitors) have ever had neuroleptic malignant syndrome (NMS – this is a rare reaction to medicines used to treat severe mental disorders) have ever had non-traumatic rhabdomyolysis (a rare muscle disorder) have a severe liver disease. Take special care with Stalevo

Consult your doctor if you have or have ever had:

a heart attack or any other diseases of the heart including cardiac arrythmias, or of the blood vessels asthma or any other disease of the lungs a liver problem, because your dose may need to be adjusted kidney or hormone-related diseases stomach ulcers or convulsions if you experience prolonged diarrhoea consult your doctor as it may be a sign of inflammation of the colon any form of severe mental disorder like psychosis chronic wide-angle glaucoma, because your dose may need to be adjusted and the pressure in your eyes may need to be monitored.

Consult your doctor if you are currently taking:

antipsychotics (medicines used to treat psychosis) a medicine which may cause low blood pressure when rising from a chair or bed. You should be aware that Stalevo may make these reactions worse.

Consult your doctor if during the treatment with Stalevo you:

notice that your muscles get very rigid or jerk violently, or if you get tremors, agitation, confusion, fever, rapid pulse, or wide fluctuations in your blood pressure. If any of this happens, contact your doctor immediately feel depressed, have suicidal thoughts, or notice unusual changes in your behaviour find yourself suddenly falling asleep, or if you feel very drowsy. If this happens, you should not drive or use any tools or machines (see also section 'Driving and using machines') notice that uncontrolled movements begin or get worse after you started to take Stalevo. If this happens, your doctor may need to change the dose of your antiparkinson medicine experience diarrhoea: monitoring of your weight is recommended in order to avoid potentially excessive weight loss experience progressive anorexia, asthenia (weakness, exhaustion) and weight decrease within a relatively short period of time. If this happens, a general medical evaluation including liver function should be considered experience excessive gambling or excessive sexual activity feel the need to stop using Stalevo, see section 'If you stop taking Stalevo'.

Your doctor may take some regular laboratory tests during a long term treatment with Stalevo.

If you must undergo surgery, please tell your doctor that you are using Stalevo. Stalevo is not recommended to be used for treatment of extrapyramidal symptoms (e.g. involuntary movements, shaking, muscle rigidity and muscle contractions) caused by other medicines.

Children

Experience with Stalevo in patients under 18 years is limited. Therefore, the use of Stalevo in children is not recommended.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription and herbal medicines.

Do not take Stalevo if you are taking certain medicines for treating depression (combinations of selective MAO-A and MAO-B inhibitors, or non-selective MAO inhibitors).

Stalevo may increase the effects and side effects of certain medicines. These include:

medicines used to treat depression such as moclobemide, amitryptiline, desipramine, maprotiline, venlafaxine and paroxetine rimiterole and isoprenaline, used to treat respiratory diseases adrenaline, used for severe allergic reactions noradrenaline, dopamine and dobutamine, used to treat heart diseases and low blood pressure alpha-methyldopa, used to treat high blood pressure apomorphine, which is used to treat Parkinson’s disease.

The effects of Stalevo may be weakened by certain medicines. These include:

dopamine antagonists used to treat mental disorders, nausea and vomiting phenytoin, used to prevent convulsions papaverine used to relax the muscles.

Stalevo may make it harder for you to digest iron. Therefore, do not take Stalevo and iron supplements at the same time. After taking one of them, wait at least 2 to 3 hours before taking the other.

Taking Stalevo with food and drink

Stalevo may be taken with or without food. For some patients, Stalevo may not be well absorbed if it is taken with, or shortly after eating protein-rich food (such as meats, fish, dairy products, seeds and nuts). Consult your doctor if you think this applies to you.

Pregnancy and breast-feeding

If you are pregnant or think you may be pregnant, consult your doctor before taking Stalevo.

You should not breast-feed during treatment with Stalevo.

Driving and using machines

Stalevo may lower your blood pressure, which may make you feel light-headed or dizzy. Therefore, be particularly careful when you drive or when you use any tools or machines.

If you feel very drowsy, or if you sometimes find yourself suddenly falling asleep, wait until you feel fully awake again before driving or doing anything else that requires you to be alert. Otherwise, you may put yourself and others at risk of serious injury or death.

Important information about some of the ingredients of Stalevo

Stalevo contains sucrose (1.6 mg/tablet). If you have been told by your doctor that you have intolerance to some sugars, contact your doctor before taking this medicinal product.

How To Take Stalevo

4.

Always take Stalevo exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

For adults and elderly:

Your doctor will tell you exactly how many tablets of Stalevo to take each day. The tablets are not intended to be split or broken into smaller pieces. You should take only one tablet each time. Depending on how you respond to treatment, your doctor may suggest a higher or lower dose. If you are taking Stalevo 50 mg/12.5 mg/200 mg, 75 mg/18.75 mg/200 mg, 100 mg/25 mg/200 mg, 125 mg/31.25 mg/200 mg or 150 mg/37.5 mg/200 mg tablets, do not take more than 10 tablets per day.

Talk to your doctor or pharmacist if you think the effect of Stalevo is too strong or too weak, or if you experience possible side effects

If you take more Stalevo than you should

If you have accidentally taken more Stalevo tablets than you should, talk to your doctor or pharmacist immediately.

If you forget to take Stalevo

Do not take a double dose to make up for a forgotten tablet.

If it is more than 1 hour until your next dose:

Take one tablet as soon as you remember, and the next tablet at the normal time.

If it is less than 1 hour until your next dose:

Take a tablet as soon as you remember, wait 1 hour, then take another tablet. After that carry on as normal.

Always leave at least an hour between Stalevo tablets, to avoid possible side effects.

If you stop taking Stalevo

Do not stop taking Stalevo unless your doctor tells you to. In such a case your doctor may need to adjust your other antiparkinson medicines, especially levodopa, to give sufficient control of your symptoms. If you suddenly stop taking Stalevo and other antiparkinsonian medicines it may result in unwanted side effects.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Stalevo 125/31.25/200mg Side Effects

Like all medicines, Stalevo can cause side effects, although not everybody gets them. If you experience any of these side effects, talk to your doctor as soon as possible. Many of the side effects can be relieved by adjusting the dose.

The frequencies are defined as:

Very common (affects more than 1 user in 10)

Common (affects 1 to 10 users in 100)

Uncommon (affects 1 to 10 users in 1,000)

Rare (affects 1 to 10 users in 10,000)

Very rare (affects less than 1 user in 10,000)

Not known (frequency cannot be estimated from the available data).

Very common

uncontrolled movements (dyskinesias), worsening of Parkinson’s symptoms feeling sick (nausea) harmless reddish-brown discoloration of urine

Common

light-headedness or fainting due to low blood pressure dizziness, drowsiness, tingling or numbness vomiting, abdominal pain, dry mouth, constipation, diarrhoea inability to sleep, hallucinations, confusion, nightmares, feeling agitated, tiredness – including paranoid and psychotic symptoms, depression (possibly with thoughts of suicide) and problems with memory or thinking heart or artery disease events (e.g. chest pain), irregular heart rate or rhythm more frequent falling shortness of breath increased sweating, itching and rashes muscle cramps vision disturbances

Uncommon

heart attack loss of appetite, weight loss or gain, bleeding in the gut, duodenal ulcers high blood pressure changes in the blood cell count (which may result in symptoms such as tiredness, fainting,infections, bleeding) inflammation of the veins in the legs convulsions

The following side effects have also been reported:

colitis (inflammation of the colon) hepatitis (inflammation of the liver) skin, hair, beard and nail discolorations

If you during the treatment with Stalevo experience the following symptoms, contact your doctor immediately:

Your muscles get very rigid or jerk violently, you get tremors, agitation, confusion, fever, rapid pulse, or wide fluctuations in your blood pressure. These can be symptoms of neuroleptic malignant syndrome (NMS, a rare severe reaction to medicines used to treat disorders of the central nervous system) or rhabdomyolysis (a rare severe muscle disorder). Allergic reaction, the signs may include hives (nettle rash), itching, rash, swelling of your face,lips, tongue or throat. This may cause difficulties in breathing or swallowing.

Behavioural changes such as urge to gamble (pathological gambling) or increased sexual desire and urges (increased libido and hypersexuality) have been reported in patients receiving dopamine replacement therapy including Stalevo.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How To Store Stalevo

Keep out of the reach and sight of children.

Do not use after the expiry date which is stated on the bottle and the carton after EXP. The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Further Information What Stalevo contains The active substances of Stalevo are levodopa, carbidopa and entacapone. Each Stalevo 125 mg/31.25 mg/200 mg tablet contains 125 mg of levodopa, 31.25 mg of carbidopa and 200 mg of entacapone. The other ingredients in the tablet core are croscarmellose sodium, magnesium stearate, maize starch, mannitol (E421) and povidone (E1201) The ingredients in the film-coating are glycerol (85 per cent) (E422), hypromellose, magnesium stearate, polysorbate 80, red iron oxide (E172), sucrose, and titanium dioxide (E171). What Stalevo looks like and contents of the pack

Stalevo 125 mg/31.25 mg/200 mg: light brownish red, oval film-coated tablets marked with ‘LCE 125’on one side.

Stalevo 125 mg/31.25 mg/200 mg tablet comes in five different pack sizes (10, 30, 100, 130 or 175tablets). Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer Orion Corporation Orionintie 1 FI-02200 Espoo Finland

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

United Kingdom Orion Pharma (UK) Ltd. Tel:+44 1635 520 300

This leaflet was last approved on 2 June 2010

Detailed information on this medicine is available on the European Medicine’s Agency (EMA) website: http://www.ema.europa.eu


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Ibuprofen Caplets 200mg (100 pack) (Boots Company plc)


Boots Ibuprofen Caplets 200 mg

Read all of this leaflet carefully. It contains important information for you.

What this medicine is for

This medicine contains Ibuprofen which belongs to a group called non-steroidal anti-inflammatory medicines, which act to relieve pain and reduce swelling.

It can be used to relieve headaches, rheumatic and muscular pain, pain from non-serious arthritic conditions, backache, migraine, period pain, dental pain and neuralgia. It can also be used to reduce fever and relieve the symptoms of colds and flu.

Before you take this medicine

This medicine can be taken by adults and children aged 12 years and over. However, some people should not take this medicine or should seek the advice of their pharmacist or doctor first.

Do not take: If you have a stomach ulcer, perforation or bleeding, or have had one twice or more in the past If you have had perforation or a bleeding stomach after taking a non-steroidal anti-inflammatory medicine (you may have been sick and it contained blood or dark particles that look like coffee grounds, passed blood in your stools or passed black tarry stools) If you are allergic to ibuprofen or any other ingredients of the product, aspirin or other non-steroidal anti-inflammatory medicines (you have ever had asthma, runny nose, itchy skin or swelling of the lips, face or throat after taking these medicines) If you are taking aspirin with a daily dose above 75 mg, or other non-steroidal anti-inflammatory medicines If you have severe heart, kidney or liver failure If you have an intolerance to some sugars, unless your doctor tells you to (this medicine contains lactose) If you are pregnant, and in the last 3 months of pregnancy Talk to your pharmacist or doctor: If you have asthma, a history of asthma or other allergic disease, bowel problems, Crohn's disease, connective tissue disorder (e.g. SLE) If you have other kidney, heart or liver problems (see "Do not take") If you are receiving regular treatment from your doctor If you take other medicines – other painkillers, Aspirin 75 mg, blood thinners (e.g. warfarin), water tablets (diuretics), medicines to treat high blood pressure or heart problems, corticosteroids, lithium, methotrexate, zidovudine, quinolone antibiotics, anti-depressants, ciclosporin or tacrolimus, mifepristone (within the last 12 days) If you are elderly – you may get more side effects If you have had a stroke, or have heart problems, high blood pressure, diabetes, high cholesterol, or you smoke – see 'Risk of heart attack or stroke' below If you are pregnant, and in the first 6 months of pregnancy If you are breastfeeding Other important information

Risk of heart attack or stroke: Ibuprofen may increase the risk if you take large amounts for a long time. The risk is small. Take the lowest amount for the shortest possible time to reduce this risk.

Women of childbearing age: If you take this medicine, it may reduce your ability to become pregnant. This effect will be reversed when you stop the medicine.

How to take this medicine

Check the seal is not broken before first use. If it is, do not take the caplets.

Adults and children of 12 years and over

Take one or two caplets

Every 4 hours, if you need to.

Don't take more than 6 caplets in 24 hours.

Take the lowest amount for the shortest possible time to relieve your symptoms.

Swallow each caplet with water.

Do not give to children under 12 years.

Do not take more than the amount recommended.

If your symptoms worsen at any time, talk to your doctor.

If your symptoms do not go away within 10 days, talk to your doctor.

If you take too many caplets: Talk to a doctor straight away. Take your medicine and this leaflet with you.

Possible side effects

Most people will not have problems, but some may get some.

If you are elderly you may be more likely to have some of these side effects.

If you get any of these serious side effects, stop taking the caplets. See a doctor at once: You are sick and it contains blood or dark particles that look like coffee grounds Pass blood in your stools or pass black tarry stools Stomach problems including pain, indigestion or heartburn Allergic reactions such as skin rash (which can sometimes be severe and include peeling and blistering of the skin), swelling of the face, neck or throat, worsening of asthma, difficulty in breathing Meningitis (e.g. stiff neck, fever, disorientation) The following effects are less serious. If they bother you talk to a pharmacist: Kidney problems, which may lead to kidney failure Feeling sick or being sick, headache High blood pressure, heart failure Fluid retention, which may cause swelling of the limbs Rarely, liver problems, diarrhoea, wind, constipation, worsening of colitis or Crohn’s disease Very rarely, tiredness or severe exhaustion, changes in the blood which may cause unusual bruising and an increase in the number of infections that you get (e.g. sore throats, mouth ulcers, flu-like symptoms) A small increased risk of heart attack or stroke if you take large amounts for a long time

If any side effect becomes severe, or you notice any side effect not listed here, please tell your pharmacist or doctor.

How to store this medicine

Keep this medicine in a safe place out of the sight and reach of children, preferably in a locked cupboard.

Use by the date on the label edge.

What is in this medicine

Each tablet contains Ibuprofen 200 mg, which is the active ingredient.

As well as the active ingredient, the tablets also contain microcrystalline cellulose, lactose, hypromellose, croscarmellose sodium, sodium laurilsulfate, magnesium stearate, french chalk, colloidal silicon dioxide, titanium dioxide (E171).

The pack contains 100 white capsule shaped tablets.

Who makes this medicine

Manufactured for the Marketing Authorisation holder

The Boots Company PLC Nottingham NG2 3AA

by

Hamol Limited Nottingham NG90 2DB

Leaflet prepared October 2008

If you would like any further information about this medicine, please contact

The Boots Company PLC Nottingham NG2 3AA

BTC13263 vR 02/12/08


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Levodopa/Carbidopa


Class: Dopamine Precursors
VA Class: CN500
CAS Number: 59-92-7
Brands: Lodosyn, Parcopa, Sinemet, Sinemet CR, Stalevo

Introduction

Antiparkinsonian; levodopa is the levorotatory isomer of dihydroxyphenylalanine and the metabolic precursor of dopamine, and carbidopa is a decarboxylase inhibitor that inhibits the peripheral decarboxylation of levodopa to dopamine.104 105 106 107 108

Uses for Levodopa/Carbidopa Parkinsonian Syndrome

Symptomatic treatment of idiopathic Parkinson’s disease (paralysis agitans), parkinsonian syndrome (postencephalitic parkinsonism), and symptomatic parkinsonism resulting from carbon monoxide intoxication and/or manganese intoxication.104 105 106 107 108

Levodopa is the most effective drug for relieving the symptoms of parkinsonian syndrome.d

Levodopa provides symptomatic relief (e.g., akinesia, rigidity, tremor); does not alter the disease course.d

Drug of choice in the management of idiopathic parkinsonian syndrome, especially in patients >70 years of age, those with cognitive impairment, and those with severe disease.101 103 d

Levodopa is used in conjunction with a decarboxylase inhibitor, carbidopa.104 105 106 107 108 Levodopa-carbidopa can be used alone or in conjunction with other antiparkinsonian drugs (e.g. ergot- and nonergot-derivative dopamine receptor agonists, catechol-O-methyltransferase [COMT] inhibitor, and/or selegiline).d 106

Drug-induced Extrapyramidal Effects

Not effective in the management of extrapyramidal effects† induced by antipsychotic agents (e.g., phenothiazines).d

Levodopa/Carbidopa Dosage and Administration Administration Oral Administration

Administer extended-release tablets as whole or half tablets; do not chew or crush.105

Just prior to administration of the orally disintegrating tablet, gently remove the tablet from the bottle with dry hands.104 Place tablet on tongue to dissolve (usually within seconds) and swallow with saliva.104

Administration of orally disintegrating tablet with water is not necessary.104

Do not divide the fixed-combination preparation containing levodopa, carbidopa, and entacapone (Stalevo); administer only one tablet per dosing interval.106

Dosage

Dosage expressed in terms of levodopa and carbidopa.104 105 106 107 108

Available in combination products containing a 1:4 or 1:10 ratio of carbidopa to levodopa.104 105 106 107 Additional carbidopa can be administered separately if a higher carbidopa dosage than is available in the combination preparations is needed.108 The treatment regimen can include levodopa-carbidopa extended-release tablets, conventional tablets, and orally disintegrating tablets and carbidopa tablets based on individual requirements.104 105 107 108 Levodopa no longer is commercially available in the US as a single-entity preparation.d

Also available as a fixed-combination preparation containing levodopa, carbidopa, and entacapone (Stalevo); available in a 1:4 ratio of carbidopa to levodopa.106 Used if optimum maintenance dosage of the 3 drugs corresponds to the dosage in the combination preparation.106 No experience transferring patients receiving levodopa-carbidopa extended-release tablets or levodopa-carbidopa preparations containing the 1:10 ratio.106

For some patients (maintenance levodopa dosage ?600 mg daily, no dyskinesias), the fixed combination containing levodopa, carbidopa, and entacapone (Stalevo) can be used when initiating entacapone therapy if optimum maintenance dosage of levodopa-carbidopa corresponds to dosage in the combination preparation.106

Adjust levodopa-carbidopa dosage carefully according to individual requirements, response, and tolerance.104 105 106 107 108

Dosage adjustment may be needed when other antiparkinsonian drugs are added to or discontinued from the regimen.104 105 106 107 108

Daily dosage of carbidopa should be at least 70–100 mg daily; patients receiving <70–100 mg daily are likely to experience nausea and vomiting.104 105 107 108 d

Observe patient closely if dosage is reduced abruptly or the drug is discontinued; risk of precipitating a symptom complex resembling neuroleptic malignant syndrome (NMS).104 105 106 107 (See Neuroleptic Malignant Syndrome under Cautions.)

If general anesthesia required, continue therapy as long as patient permitted to take oral medications; resume as soon as patient is able to take oral medication.104 105 106 107 If therapy interrupted, observe for NMS.104 105 106 107 (See Neuroleptic Malignant Syndrome under Cautions.)

Adults Parkinsonian Syndrome Levodopa-Carbidopa Conventional Tablets or Orally Disintegrating Tablets Oral

Initially, levodopa 100 mg/carbidopa 25 mg (as 1 tablet) 3 times daily.104 107 109

Increase dosage by levodopa 100 mg/carbidopa 25 mg (1 tablet) daily or every other day until a daily dosage of levodopa 800 mg/carbidopa 200 mg is reached or adverse effects prevent further increases or necessitate discontinuance.104 107 109 d

Alternatively, initiate with levodopa 100 mg/carbidopa 10 mg (as 1 tablet) 3 or 4 times daily; this dosage will not provide an adequate dose of carbidopa for most patients.104 107 109 Increase dosage by levodopa 100 mg/carbidopa 10 mg (1 tablet) daily or every other day until a daily dosage of levodopa 800 mg/carbidopa 80 mg is reached.104 107 109

Levodopa-Carbidopa Extended-release Tablets Oral

Initially, levodopa 200 mg/carbidopa 50 mg (as 1 extended-release tablet) twice daily; initial dosage should not be given at intervals <6 hours.105 Adjust dosage based on response and tolerance at intervals ?3 days.105 Most patients are treated adequately with levodopa 400 mg to 1.6 g daily and carbidopa 100–400 mg daily, administered in divided doses at intervals ranging from 4–8 hours while awake.105 Higher dosages (levodopa 2.4 g/carbidopa 600 mg) and shorter intervals (<4 hours) have been used but usually are not recommended.105 If the dosing interval is <4 hours and/or the divided doses are not equal, the smaller doses can be given at the end of the day.105

Dosage may be initiated, titrated, and stabilized initially with conventional (immediate-release) tablets.105 107

Transfer to extended-release tablets: initial dosage should provide 10% more levodopa daily than dosage previously received as conventional tablets; levodopa dosage may need to be increased up to 30% more daily, depending on response.105 (See Bioavailability under Pharmacokinetics.)

Carbidopa

Carbidopa: 25 mg with first dose of levodopa/carbidopa each day for patients who need additional carbidopa; additional 12.5- or 25-mg doses may given during the day with each dose of levodopa/carbidopa.108

Prescribing Limits Adults Parkinsonian Syndrome Oral

Experience with carbidopa dosages >200 mg daily limited.104 105 107 108

If fixed-combination preparations containing levodopa 50–150 mg, carbidopa 12.5–37.5 mg, and entacapone 200 mg (Stalevo 50, 75, 100, 125, and 150) are used, maximum of 8 tablets daily.106

If fixed-combination preparation containing levodopa 200 mg, carbidopa 50 mg, and entacapone 200 mg (Stalevo 200) is used, maximum of 6 tablets daily.106

Cautions for Levodopa/Carbidopa Contraindications

Concomitant use with a nonselective MAO inhibitor.104 105 106 107 (See Specific Drugs and Foods under Interactions.)

Angle-closure glaucoma.104 105 106 107 d

Known hypersensitivity to levodopa, carbidopa, or any ingredient in the formulation.104 105 106 107

Malignant melanoma, history of melanoma, or suspicious undiagnosed skin lesions.104 105 106 107

Warnings/Precautions Warnings Nervous System and Muscular Effects

Therapy associated with dyskinesias; dosage reduction may be needed.104 105 106 107

Mental disturbances reported.104 105 106 107 d Observe patients for depression with concomitant suicidal tendencies.104 105 106 107 d Use with caution in patients with current or past psychoses.104 105 106 107 d

Bradykinetic Episodes

“On-off” phenomenon: Sudden loss of effectiveness with abrupt onset of akinesia (“off” effect; persists 1–60 minutes) followed by sudden return of effectiveness (“on” effect); may recur many times daily and respond to increased dosing frequency.d

Akinesia Paradoxica (“start hesitation”): Sudden hypotonic freezing (patient falls frequently while attempting to walk); may respond to decreased dosage.d

Cardiovascular Effects

Risk of orthostatic hypotension; usually asymptomatic and tolerance usually develops within a few months.d

Use with care in patients with a history of MI who have residual atrial, nodal, or ventricular arrhythmias; monitor cardiac function in a facility with intensive cardiac care immediately available during the initial dosage adjustment.104 105 106 107 d

Use with caution in patients with severe cardiovascular disease.104 105 106 107 d

Respiratory Effects

Caution in patients with pulmonary disease (e.g., emphysema) or asthma who may require use of sympathomimetics.104 105 106 107 d

GI Effects

Use with caution in patients with a history of peptic ulcers; possibility of upper GI hemorrhage in these patients.d 104 105 106 107

Neuroleptic Malignant Syndrome (NMS)

Symptom complex resembling NMS reported following dosage reduction or abrupt withdrawal of levodopa.104 105 106 107 d

Observe closely when dosage is reduced or the drug discontinued; especially important in patients receiving concomitant therapy with an antipsychotic agent.d 104 105 106 107

General Precautions

Evaluate hepatic, hematopoietic, cardiovascular, and renal function periodically.d 104 105 106 107

Use of Fixed Combinations

When the fixed-combination preparation containing levodopa, carbidopa, and entacapone (Stalevo) is used, observe the usual precautions and contraindications associated with all drugs in the preparation.106

Glaucoma

Can be used with caution in patients with well-controlled open-angle glaucoma; monitor IOP.104 105 106 107 d (See Contraindications under Cautions.)

Endocrine Disorders

Use with caution.104 105 106 107

Closely monitor diabetic patients; levodopa may affect glycemic control.d

Somnolence

Possible somnolence and, very rarely, episodes of sudden onset of sleep, sometimes occurring without the patient’s awareness or without warning during daily activities.105 107

Patients must be informed of this risk; advise patients that they should exercise caution while driving or operating machinery and that they must refrain from such activities if they experience somnolence and/or an episode of sudden sleep onset.105 107

Melanoma

Epidemiologic studies indicate patients with parkinsonian syndrome have a twofold to approximately sixfold higher risk of developing melanoma than the general population.105 106 107 Unclear whether increased risk is due to parkinsonian syndrome or other factors (e.g., drugs used to treat the disease).105 106 107

Monitor for melanoma on a frequent and regular basis.105 106 107 Manufacturer recommends periodic skin examinations performed by appropriately qualified individuals (e.g., dermatologists).105 106 107

Intense Urges

Intense urges (e.g., urge to gamble, increased sexual urges, other intense urges) and inability to control these urges reported in some patients receiving antiparkinsonian agents that increase central dopaminergic tone (including levodopa-carbidopa).105 106 107 Although causal relationship not established, urges stopped in some cases when dosage was reduced or drug was discontinued.105 106 107

Consider reducing dosage or discontinuing levodopa-carbidopa if a patient develops such urges.105 106 107

Phenylketonuria

Levodopa-carbidopa orally disintegrating tablets contain aspartame (NutraSweet), which is metabolized in the GI tract to phenylalanine.104 110 111 112 113 114

Specific Populations Pregnancy

Category C.104 105 106 107

Lactation

Carbidopa is distributed into milk in rats;106 not known whether carbidopa distributes into human milk.108 Distribution of levodopa into human milk reported in at least one nursing woman.105 107 Caution advised.104 105 106 107

Pediatric Use

Safety and efficacy not established in children <18 years of age.104 105 106 107

Common Adverse Effects

Dyskinesias (choreiform, dystonic, other adventitious movements), nausea.104 105 106 107

Interactions for Levodopa/Carbidopa Specific Drugs and Foods

Drug or Food

Interaction

Comments

Anesthetics, general (cyclopropane, halogenated hydrocarbon general anesthetics)

Potential for cardiac arrhythmias with these anesthetic agentsd

Use alternative anesthetic agentsd

Anticholinergic agents

Potential for decreased tremor and/or exacerbation of abnormal involuntary movements104 105 106 107 d

Possible delay in levodopa absorption and increase in gastric metabolism of levodopad

Antidepressants, tricyclic

Potential for hypertension and dyskinesia104 105 106 107

Use concomitantly with cautiond

Antipsychotic agents (phenothiazines, butyrophenones, risperidone)

Possible reduction in the therapeutic effects of levodopa104 105 106 107

Possible increased risk of NMS104 105 106 107 (see Neuroleptic Malignant Syndrome under Cautions)

Observe patient for loss of therapeutic effect104 105 106 107

Benzodiazepines

Possible reduction in the therapeutic effects of levodopa with chlordiazepoxide or diazepamd

Use concomitantly with cautiond

Hypotensive agents

Potential for symptomatic postural hypotension104 105 106 107

Potential for toxic CNS effects such as psychosis with methyldopad

Dosage adjustment of the hypotensive agent may be needed104 105 106 107

Iron preparations

Decreased absorption of levodopa and carbidopa104 105 106 107

Clinical importance unknown104 105 106 107

Isoniazid

Possible reduction in the therapeutic effects of levodopa104 105 106 107

Observe patient for loss of therapeutic effect104 105 106 107

MAO inhibitors

Potential for hypertension, headache, hyperexcitability with nonselective MAO inhibitorse

Possible severe orthostatic hypotension with selegiline104 105 106 107

Contraindicated with nonselective MAO inhibitors;104 105 106 107 discontinue nonselective MAO inhibitor at least 2 weeks prior to initiation of levodopa104 105 106 107

May be administered concomitantly with a selective MAO inhibitor (e.g., selegiline) with caution104 105 106 107

Metoclopramide

Possible increase in bioavailability of levodopa104 105 106 107

Possible reduction in the therapeutic effects of levodopa104 105 106 107

Papaverine

Possible reduction in the therapeutic effects of levodopa104 105 106 107

Observe patient for loss of therapeutic effect104 105 106 107

Phenytoin

Possible reduction in the therapeutic effects of levodopa104 105 106 107

Observe patient for loss of therapeutic effect104 105 106 107

Protein

High protein diet may impair absorption104 105 106 107

Levodopa/Carbidopa Pharmacokinetics Absorption Bioavailability

Well absorbed from the GI tract; peak plasma levodopa concentrations achieved within 0.5 or 2 hours following administration of conventional tablets or extended-release tablets, respectively.105

Bioavailability of levodopa from extended-release tablets 70–75% of that from conventional tablets.105

Extended-release tablets result in less fluctuation in plasma concentrations between doses than conventional tablets.105

Levodopa-carbodopa conventional tablets and orally disintegrating tablets begin to release the drugs within 30 minutes of administration.104 107 109 Pharmacokinetic values for orally disintegrating tablet are similar to those for the conventional tablet.109

Food

High protein diet may interfere with absorption of levodopa.104 105 106 107

Extended-release tablets: Food increases bioavailability and peak plasma concentrations of levodopa.105

Distribution Extent

Widely distributed.d

<1% of levodopa penetrates the CNS;d carbidopa does not cross the blood-brain barrier.104 105 106 107

Plasma Protein Binding

Levodopa: 10–30%.106

Carbidopa: About 36%.106 d

Elimination Metabolism

Levodopa is metabolized in the stomach and intestine and on first pass through the liver; absorbed levodopa decarboxylated to dopamine.d

Carbidopa inhibits peripheral decarboxylation of levodopa, thus increasing availability of levodopa for distribution into the CNS.104 105 106 107

Elimination Route

Levodopa is excreted in urine as metabolites.d

Half-life

Levodopa: 1.5 hours when administered with carbidopa.104 105

Stability Storage Oral Conventional Tablets

25°C (may be exposed to 15–30°C).106 107 108 Protect from light.107

Extended-release Tablets

Tight container; <30°C.105

Orally Disintegrating Tablets

Tight, light-resistant container; 20–25°C (may be exposed to 15–30°C).104

ActionsActions

Manifestations of parkinsonian syndrome related to depletion of dopamine in the corpus striatum.104 105 106 107

Levodopa relieves symptoms of parkinsonism presumably by increasing dopamine concentrations in the brain.104 105 106 107

Advice to Patients

Importance of taking levodopa/carbidopa at regular intervals as scheduled by the clinician.104 105 106 107 Importance of not altering the prescribed dosage regimen or adding other antiparkinsonian drugs.104 105 106 107

Advise patient not to chew or crush extended-release tablets; however, tablets may be halved.105

For patients taking orally disintegrating tablets, advise to gently remove the tablet from the bottle with dry hands just before administering a dose and then placing the tablet on the tongue to dissolve and be swallowed with saliva.104

Importance of informing patients with phenylketonuria that the orally disintegrating tablets contain aspartame.104

Advise patient to notify clinician if abnormal involuntary movements appear or get worse; dosage adjustment may be needed.104 105 106 107

Advise patient of expected onset and duration of effect.104 105 106 107

Possibility that dark color (red, brown, black) may appear in saliva, urine, or sweat; garments may be discolored.104 105 106 107

Advise patient that a change in diet to food high in protein may delay absorption of levodopa and reduce systemic availability.104 105 106 107 Excess acidity may delay absorption.104 105 106 107

Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products.104 105 106 107

Risk of somnolence and episodes of sudden sleep onset; importance of exercising caution when driving or operating machinery and of refraining from such activities if somnolence and/or an episode of sudden sleep onset occurs.105 107

Importance of asking patients whether they have developed any new or increased gambling urges, sexual urges, or other urges while receiving levodopa-carbidopa and of advising them of the importance of reporting such urges.105 106 107

Importance of frequent monitoring for melanoma and periodic dermatologic examinations by a dermatologist.105 106 107

Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.104 105 106 107

Importance of advising patients of other important precautionary information.104 105 106 107 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Carbidopa

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

25 mg (of anhydrous carbidopa)

Lodosyn (scored)

Bristol-Myers Squibb

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Carbidopa-Levodopa (Co-careldopa)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

Carbidopa 10 mg (of anhydrous carbidopa) and Levodopa 100 mg*

Carbidopa and Levodopa Tablets

Sinemet (scored)

Bristol-Myers Squibb

Carbidopa 25 mg (of anhydours carbidopa) and Levodopa 100 mg*

Carbidopa and Levodopa Tablets

Sinemet (scored)

Bristol-Myers Squibb

Carbidopa 25 mg (of anhydrous carbidopa) and Levodopa 250 mg*

Carbidopa and Levodopa Tablets

Sinemet (scored)

Bristol-Myers Squibb

Tablets, extended-release

Carbidopa 50 mg (of anhydrous carbidopa) and Levodopa 200 mg*

Carbidopa and Levodopa Extended-release Tablets

Sinemet CR (scored)

Bristol-Myers Squibb

Carbidopa 25 mg (of anhydrous carbidopa) and Levodopa 100 mg*

Carbidopa and Levodopa Extended-release Tablets (scored)

Sinemet CR

Bristol-Myers Squibb

Tablets, orally disintegrating

Carbidopa 10 mg (of anhydrous carbidopa) and Levodopa 100 mg

Parcopa (scored)

Azur

Carbidopa 25 mg (of anhydrous carbidopa) and Levodopa 100 mg

Parcopa (scored)

Azur

Carbidopa 25 mg (of anhydrous carbidopa) and Levodopa 250 mg

Parcopa (scored)

Azur

Other Carbidopa Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

Carbidopa 12.5 mg (of anhydrous carbidopa) with Entacapone 200 mg and Levodopa 50 mg

Stalevo

Novartis

Carbidopa 18.75 mg (of anhydrous carbidopa) Entacapone 200 mg and Levodopa 75 mg

Stalevo

Novartis

Carbidopa 25 mg (of anhydrous carbidopa) with Entacapone 200 mg and Levodopa 100 mg

Stalevo

Novartis

Carbidopa 31.25 mg (of anhydrous carbidopa) Entacapone 200 mg and Levodopa 125 mg

Stalevo

Novartis

Carbidopa 37.5 mg (of anhydrous carbidopa) with Entacapone 200 mg and Levodopa 150 mg

Stalevo

Novartis

Carbidopa 50 mg (of anhydrous carbidopa) Entacapone 200 mg and Levodopa 200 mg

Stalevo

Novartis

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 04/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Carbidopa-Levodopa 10-100MG Tablets (TEVA PHARMACEUTICALS USA): 90/$34.99 or 180/$65.97

Carbidopa-Levodopa 25-100MG Tablets (ACTAVIS ELIZABETH): 90/$39.98 or 270/$101.98

Carbidopa-Levodopa 25-250MG Tablets (TEVA PHARMACEUTICALS USA): 60/$33.99 or 180/$82.98

Carbidopa-Levodopa CR 25-100MG Controlled-release Tablets (MYLAN): 60/$40.99 or 180/$116.98

Carbidopa-Levodopa CR 50-200MG Controlled-release Tablets (MYLAN): 60/$80.99 or 180/$221.98

Parcopa 25-100MG Dispersible Tablets (AZUR PHARMA): 30/$97.64 or 90/$234.33

Sinemet 10-100MG Tablets (MERCK SHARP &amp; DOHME): 90/$91.16 or 270/$256.57

Sinemet 25-100MG Tablets (MERCK SHARP &amp; DOHME): 90/$113.41 or 270/$305.96

Sinemet 25-250MG Tablets (MERCK SHARP &amp; DOHME): 60/$88.99 or 180/$255.97

Sinemet CR 25-100MG Controlled-release Tablets (MERCK SHARP &amp; DOHME): 60/$78.99 or 180/$225.96

Sinemet CR 50-200MG Controlled-release Tablets (MERCK SHARP &amp; DOHME): 60/$145.5 or 180/$417.26

Stalevo 100 25-100-200MG Tablets (NOVARTIS): 90/$318 or 270/$898.92

Stalevo 150 37.5-150-200MG Tablets (NOVARTIS): 30/$113.99 or 90/$334.97

Stalevo 200 50-200-200MG Tablets (NOVARTIS): 100/$363.99 or 300/$1043.97

Stalevo 50 12.5-50-200MG Tablets (NOVARTIS): 30/$110.98 or 90/$317.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions February 01, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

101. Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease (2001): treatment guidelines. Neurology. 2001; 56:S1-S88.

102. Chong BS, Mersfelder TL. Entacapone. Ann Pharmacother. 2000; 34:1056-65. [IDIS 452302] [PubMed 10981253]

103. Anon. Initial treatment of Parkinson’s disease: wait just a minute. Med Lett Drugs Ther. 2001; 43:59-60. [PubMed 11445778]

104. Azur Pharma. Parcopa (carbidopa-levodopa) orally disintegrating tablets prescribing information. Philadelphia, PA; 2009 Sep.

105. Bristol-Myers Squibb. Sinemet CR (carbidopa-levodopa) sustained-release tablets prescribing information. Princeton, NJ; 2009 Jan.

106. Novartis. Stalevo 50, Stalevo 75, Stalevo 100, Stalevo 125, Stalevo 150, Stalevo 200 (carbidopa, levodopa and entacapone) tablets prescribing information. East Hanover, NJ; 2009 Mar.

107. Bristol-Myers Squibb. Sinemet (carbidopa-levodopa) tablets prescribing information. Princeton, NJ; 2009 Jan.

108. Bristol-Myers Squibb. Lodosyn (carbidopa) tablets prescribing information. Princeton, NJ; 2006 Sep.

109. Anon. Parcopa: a rapidly dissolving formulation of carbidopa/levodopa. Med Lett Drugs Ther. 2005; 47:12.

110. American Medical Association Council on Scientific Affairs. Aspartame: review of safety issues. JAMA. 1985; 254:400 2. [IDIS 202002] [PubMed 2861297]

111. Gossel TA. A review of aspartame: characteristics, safety and uses. US Pharm. 1984; 9:26,28 30.

112. Food and Drug Administration. Aspartame as an inactive ingredient in human drug products; labeling requirements. Proposed rule. [21 CFR Part 201] Fed Regist. 1983; 48:54993 5. (lDIS 178728)

113. Food and Drug Administration. Food additives permitted for direct addition to food for human consumption; aspartame. Final rule. [21 CFR Part 172] Fed Regist. 1983; 48:31376 82. (IDIS 172957)

114. Anon. Aspartame and other sweeteners. Med Lett Drugs Ther. 1982; 24:1 2. [PubMed 7054648]

d. AHFS drug information 2004. McEvoy GK, ed. Levodopa/carbidopa. Bethesda, MD: American Society of Health-System Pharmacists; 2005:2485-90.

e. AHFS drug information 2004. McEvoy GK, ed. Monoamine Oxidase Inhibitors General Statement. Bethesda, MD: American Society of Health-System Pharmacists; 2005:2174-80.

More Levodopa/Carbidopa resources Levodopa/Carbidopa Side Effects (in more detail) Levodopa/Carbidopa Use in Pregnancy & Breastfeeding Drug Images Levodopa/Carbidopa Drug Interactions Levodopa/Carbidopa Support Group 12 Reviews for Levodopa/Carbidopa - Add your own review/rating Compare Levodopa/Carbidopa with other medications GTP-CH Deficiency Neuroleptic Malignant Syndrome Parkinson's Disease Restless Legs Syndrome
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