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Milrinone Lactate Injection

Milrinone Lactate Injection

Rx only

Revised 04/2011

Milrinone Description

Milrinone Lactate Injection is a member of a new class of bipyridine inotropic/vasodilator agents with phosphodiesterase inhibitor activity, distinct from digitalis glycosides or catecholamines. Milrinone lactate is designated chemically as 1,6-dihydro-2-methyl-6-oxo-[3,4?-bipyridine]-5-carbonitrile lactate and has the following structure:

CH3CHOHCOOH

Milrinone is an off-white to tan crystalline compound with a molecular weight of 211.22 and a molecular formula of C12H9N3O. It is slightly soluble in methanol, and very slightly soluble in chloroform and in water. As the lactate salt, it is stable and colorless to pale yellow in solution. Milrinone Lactate is available as sterile aqueous solutions of the lactate salt of Milrinone for injection or infusion intravenously.

Sterile, single dose vials: Single dose vials of 10, 20 and 50 mL contain in each mL Milrinone lactate equivalent to 1 mg Milrinone and 47 mg Dextrose, Anhydrous, USP, in Water for Injection, USP. The pH is adjusted to between 3.2 and 4.0 with lactic acid or sodium hydroxide. The total concentration of lactic acid can vary between 0.95 mg/mL and 1.29 mg/mL. These vials require preparation of dilutions prior to administration to patients intravenously.

Pre-Mix Flexible Containers: The Flexible Containers provide two ready-to-use dilutions of Milrinone in volumes of 100 mL and 200 mL of 5% Dextrose Injection. Each mL contains Milrinone lactate equivalent to 200 mcg (0.2 mg) Milrinone. The nominal concentration of lactic acid is 0.282 mg/mL. Each mL also contains 49.4 mg Dextrose Anhydrous, USP. The pH is adjusted to between 3.2 and 4.0 with lactic acid or sodium hydroxide. The flexible plastic container is comprised of polypropylene with a foil overwrap. Water can permeate the plastic into the overwrap, but the amount is insufficient to significantly affect the pre-mix solution.

Milrinone - Clinical Pharmacology

Milrinone is a positive inotrope and vasodilator, with little chronotropic activity different in structure and mode of action from either the digitalis glycosides or catecholamines.

Milrinone, at relevant inotropic and vasorelaxant concentrations, is a selective inhibitor of peak III cAMP phosphodiesterase isozyme in cardiac and vascular muscle. This inhibitory action is consistent with cAMP mediated increases in intracellular ionized calcium and contractile force in cardiac muscle, as well as with cAMP dependent contractile protein phosphorylation and relaxation in vascular muscle. Additional experimental evidence also indicates that Milrinone is not a beta-adrenergic agonist nor does it inhibit sodium-potassium adenosine triphosphatase activity as do the digitalis glycosides.

Clinical studies in patients with congestive heart failure have shown that Milrinone produces dose-related and plasma drug concentration-related increases in the maximum rate of increase of left ventricular pressure. Studies in normal subjects have shown that Milrinone produces increases in the slope of the left ventricular pressure-dimension relationship, indicating a direct inotropic effect of the drug. Milrinone also produces dose-related and plasma concentration-related increases in forearm blood flow in patients with congestive heart failure, indicating a direct arterial vasodilator activity of the drug.

Both the inotropic and vasodilatory effects have been observed over the therapeutic range of plasma Milrinone concentrations of 100 ng/mL to 300 ng/mL.

In addition to increasing myocardial contractility, Milrinone improves diastolic function as evidenced by improvements in left ventricular diastolic relaxation.

The acute administration of intravenous Milrinone has also been evaluated in clinical trials in excess of 1600 patients with chronic heart failure, heart failure associated with cardiac surgery, and heart failure associated with myocardial infarction. The total number of deaths, either on therapy or shortly thereafter (24 hours) was 15, less than 0.9%, few of which were thought to be drug-related.

Pharmacokinetics

Following intravenous injections of 12.5 mcg/kg to 125 mcg/kg to congestive heart failure patients, Milrinone had a volume of distribution of 0.38 liters/kg, a mean terminal elimination half-life of 2.3 hours, and a clearance of 0.13 liters/kg/hr. Following intravenous infusions of 0.2 mcg/kg/min to 0.7 mcg/kg/min to congestive heart failure patients, the drug had a volume of distribution of about 0.45 liters/kg, a mean terminal elimination half-life of 2.4 hours, and a clearance of 0.14 liters/kg/hr. These pharmacokinetic parameters were not dose-dependent, and the area under the plasma concentration versus time curve following injections was significantly dose-dependent.

Milrinone has been shown (by equilibrium dialysis) to be approximately 70% bound to human plasma protein.

The primary route of excretion of Milrinone in man is via the urine. The major urinary excretions of orally administered Milrinone in man are Milrinone (83%) and its 0-glucuronide metabolite (12%). Elimination in normal subjects via the urine is rapid, with approximately 60% recovered within the first two hours following dosing and approximately 90% recovered within the first eight hours following dosing. The mean renal clearance of Milrinone is approximately 0.3 liters/min, indicative of active secretion.

Pharmacodynamics

In patients with heart failure due to depressed myocardial function, Milrinone produced a prompt dose and plasma concentration related increase in cardiac output and decreases in pulmonary capillary wedge pressure and vascular resistance, which were accompanied by mild-to-moderate increases in heart rate. Additionally, there is no increased effect on myocardial oxygen consumption. In uncontrolled studies, hemodynamic improvement during intravenous therapy with Milrinone was accompanied by clinical symptomatic improvement, but the ability of Milrinone to relieve symptoms has not been evaluated in controlled clinical trials. The great majority of patients experience improvements in hemodynamic function within 5 to 15 minutes of initiation of therapy.

In studies in congestive heart failure patients, Milrinone when administered as a loading injection followed by a maintenance infusion produced significant mean initial increases in cardiac index of 25 percent, 38 percent, and 42 percent at dose regimens of 37.5 mcg/kg/0.375 mcg/kg/min, 50 mcg/kg/0.5 mcg/kg/min, and 75 mcg/kg/0.75 mcg/kg/min, respectively. Over the same range of loading injections and maintenance infusions, pulmonary capillary wedge pressure significantly decreased by 20 percent, 23 percent, and 36 percent, respectively, while systemic vascular resistance significantly decreased by 17 percent, 21 percent, and 37 percent. Mean arterial pressure fell by up to 5 percent at the two lower dose regimens, but by 17 percent at the highest dose. Patients evaluated for 48 hours maintained improvements in hemodynamic function, with no evidence of diminished response (tachyphylaxis). A smaller number of patients have received infusions of Milrinone for periods up to 72 hours without evidence of tachyphylaxis.

The duration of therapy should depend upon patient responsiveness.

Milrinone has a favorable inotropic effect in fully digitalized patients without causing signs of glycoside toxicity. Theoretically, in cases of atrial flutter/fibrillation, it is possible that Milrinone may increase ventricular response rate because of its slight enhancement of AV node conduction. In these cases, digitalis should be considered prior to the institution of therapy with Milrinone.

Improvement in left ventricular function in patients with ischemic heart disease has been observed. The improvement has occurred without inducing symptoms or electrocardiographic signs of myocardial ischemia.

The steady-state plasma Milrinone concentrations after approximately 6 to 12 hours of unchanging maintenance infusion of 0.5 mcg/kg/min are approximately 200 ng/mL. Near maximum favorable effects of Milrinone on cardiac output and pulmonary capillary wedge pressure are seen at plasma Milrinone concentrations in the 150 ng/mL to 250 ng/mL range.

Indications and Usage for Milrinone

Milrinone lactate injection is indicated for the short-term intravenous treatment of patients with acute decompensated heart failure. Patients receiving Milrinone should be observed closely with appropriate electrocardiographic equipment. The facility for immediate treatment of potential cardiac events, which may include life threatening ventricular arrhythmias, must be available. The majority of experience with intravenous Milrinone has been in patients receiving digoxin and diuretics. There is no experience in controlled trials with infusions of Milrinone for periods exceeding 48 hours.

Contraindications

Milrinone lactate injection is contraindicated in patients who are hypersensitive to it.

Warnings

Whether given orally or by continuous or intermittent intravenous infusion, Milrinone has not been shown to be safe or effective in the longer (greater than 48 hours) treatment of patients with heart failure. In a multicenter trial of 1088 patients with Class III and IV heart failure, long-term oral treatment with Milrinone was associated with no improvement in symptoms and an increased risk of hospitalization and death. In this study, patients with Class IV symptoms appeared to be at particular risk of life-threatening cardiovascular reactions. There is no evidence that Milrinone given by long-term continuous or intermittent infusion does not carry a similar risk.

The use of Milrinone both intravenously and orally has been associated with increased frequency of ventricular arrhythmias, including nonsustained ventricular tachycardia. Long-term oral use has been associated with an increased risk of sudden death. Hence, patients receiving Milrinone should be observed closely with the use of continuous electrocardiographic monitoring to allow the prompt detection and management of ventricular arrhythmias.

Precautions General

Milrinone should not be used in patients with severe obstructive aortic or pulmonic valvular disease in lieu of surgical relief of the obstruction. Like other inotropic agents, it may aggravate outflow tract obstruction in hypertrophic subaortic stenosis.

Supraventricular and ventricular arrhythmias have been observed in the high-risk population treated. In some patients, injections of Milrinone and oral Milrinone have been shown to increase ventricular ectopy, including nonsustained ventricular tachycardia. The potential for arrhythmia, present in congestive heart failure itself, may be increased by many drugs or combinations of drugs. Patients receiving Milrinone should be closely monitored during infusion.

Milrinone produces a slight shortening of AV node conduction time, indicating a potential for an increased ventricular response rate in patients with atrial flutter/fibrillation which is not controlled with digitalis therapy.

During therapy with Milrinone, blood pressure and heart rate should be monitored and the rate of infusion slowed or stopped in patients showing excessive decreases in blood pressure.

If prior vigorous diuretic therapy is suspected to have caused significant decreases in cardiac filling pressure, Milrinone should be cautiously administered with monitoring of blood pressure, heart rate, and clinical symptomatology.

There is no experience in controlled trials with infusions of Milrinone for periods exceeding 48 hours. Cases of infusion site reaction have been reported with intravenous Milrinone therapy (see ADVERSE REACTIONS). Consequently, careful monitoring of the infusion site should be maintained to avoid possible extravasation.

Use in Acute Myocardial Infarction

No clinical studies have been conducted in patients in the acute phase of post myocardial infarction. Until further clinical experience with this class of drugs is gained, Milrinone is not recommended in these patients.

Laboratory Tests Fluid And Electrolytes

Fluid and electrolyte changes and renal function should be carefully monitored during therapy with Milrinone. Improvement in cardiac output with resultant diuresis may necessitate a reduction in the dose of diuretic. Potassium loss due to excessive diuresis may predispose digitalized patients to arrhythmias. Therefore, hypokalemia should be corrected by potassium supplementation in advance of or during use of Milrinone.

Drug Interactions

No untoward clinical manifestations have been observed in limited experience with patients in whom Milrinone was used concurrently with the following drugs: digitalis glycosides; lidocaine, quinidine; hydralazine, prazosin; isosorbide dinitrate, nitroglycerin; chlorthalidone, furosemide, hydrochlorothiazide, spironolactone; captopril; heparin, warfarin, diazepam, insulin; and potassium supplements.

Chemical Interactions

There is an immediate chemical interaction which is evidenced by the formation of a precipitate when furosemide is injected into an intravenous line of an infusion of Milrinone. Therefore, furosemide should not be administered in intravenous lines containing Milrinone.

Carcinogenesis and Mutagenesis and Impairment of Fertility

Twenty-four months of oral administration of Milrinone to mice at doses up to 40 mg/kg/day (about 50 times the human oral therapeutic dose in a 50 kg patient) was unassociated with evidence of carcinogenic potential. Neither was there evidence of carcinogenic potential when Milrinone was orally administered to rats at doses up to 5 mg/kg/day (about 6 times the human oral therapeutic dose) for twenty-four months or at 25 mg/kg/day (about 30 times the human oral therapeutic dose) for up to 18 months in males and 20 months in females. Whereas the Chinese Hamster Ovary Chromosome Aberration Assay was positive in the presence of a metabolic activation system, results from the Ames Test, the Mouse Lymphoma Assay, the Micronucleus Test, and the in vivo Rat Bone Marrow Metaphase Analysis indicated an absence of mutagenic potential. In reproductive performance studies in rats, Milrinone had no effect on male or female fertility at oral doses up to 32 mg/kg/day.

Animal Toxicity

Oral and intravenous administration of toxic dosages of Milrinone to rats and dogs resulted in myocardial degeneration/fibrosis and endocardial hemorrhage, principally affecting the left ventricular papillary muscles. Coronary vascular lesions characterized by periarterial edema and inflammation have been observed in dogs only. The myocardial/endocardial changes are similar to those produced by beta-adrenergic receptor agonists such as isoproterenol, while the vascular changes are similar to those produced by minoxidil and hydralazine. Doses within the recommended clinical dose range (up to 1.13 mg/kg/day) for congestive heart failure patients have not produced significant adverse effects in animals.

Pregnancy Pregnancy Category C

Oral administration of Milrinone to pregnant rats and rabbits during organogenesis produced no evidence of teratogenicity at dose levels up to 40 mg/kg/day and 12 mg/kg/day, respectively. Milrinone lactate did not appear to be teratogenic when administered intravenously to pregnant rats at doses up to 3 mg/kg/day (about 2.5 times the maximum recommended clinical intravenous dose) or pregnant rabbits at doses up to 12 mg/kg/day, although an increased resorption rate was apparent at both
8 mg/kg/day and 12 mg/kg/day (intravenous) in the latter species. There are no adequate and well-controlled studies in pregnant women. Milrinone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Caution should be exercised when Milrinone lactate is administered to nursing women, since it is not known whether it is excreted in human milk.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Use in Elderly Patients

There are no special dosage recommendations for the elderly patient. Ninety percent of all patients administered Milrinone in clinical studies were within the age range of 45 to 70 years, with a mean age of 61 years. Patients in all age groups demonstrated clinically and statistically significant responses. No age-related effects on the incidence of adverse reactions have been observed. Controlled pharmacokinetic studies have not disclosed any age-related effects on the distribution and elimination of Milrinone.

ADVERSE REACTIONS Cardiovascular Effects

In patients receiving Milrinone in Phase II and III clinical trials, ventricular arrhythmias were reported in 12.1%: Ventricular ectopic activity, 8.5%; nonsustained ventricular tachycardia, 2.8%; sustained ventricular tachycardia, 1% and ventricular fibrillation, 0.2% (2 patients experienced more than one type of arrhythmia). Holter recordings demonstrated that in some patients injection of Milrinone increased ventricular ectopy, including nonsustained ventricular tachycardia. Life-threatening arrhythmias were infrequent and when present have been associated with certain underlying factors such as preexisting arrhythmias, metabolic abnormalities (e.g. hypokalemia), abnormal digoxin levels and catheter insertion. Milrinone was not shown to be arrhythmogenic in an electrophysiology study. Supraventricular arrhythmias were reported in 3.8% of the patients receiving Milrinone. The incidence of both supraventricular and ventricular arrhythmias has not been related to the dose or plasma Milrinone concentration.

Other cardiovascular adverse reactions include hypotension, 2.9% and angina/chest pain, 1.2%.

In the post-marketing experience, there have been rare cases of “torsades de pointes” reported.

CNS Effects

Headaches, usually mild to moderate in severity, have been reported in 2.9% of patients receiving Milrinone.

Other Effects

Other adverse reactions reported, but not definitely related to the administration of Milrinone include hypokalemia, 0.6%; tremor, 0.4%; and thrombocytopenia, 0.4%.

Isolated spontaneous reports of bronchospasm and anaphylactic shock have been received; and in the post-marketing experience, liver function test abnormalities and skin reactions such as rash have been reported.

Post-Marketing Adverse Event Reports

In addition to adverse events reported from clinical trials, the following events have been reported from worldwide post-marketing experience with Milrinone:

Isolated spontaneous reports of bronchospasm and anaphylactic shock.

Liver function test abnormalities and skin reactions such as rash.

Administration site conditions: Infusion site reaction.

Overdosage

Doses of Milrinone may produce hypotension because of its vasodilator effect. If this occurs, administration of Milrinone should be reduced or temporarily discontinued until the patient's condition stabilizes. No specific antidote is known, but general measures for circulatory support should be taken.

Milrinone Dosage and Administration

Milrinone Lactate in 5% Dextrose Injection should not be used for administering a loading dose. The information regarding loading dose for Milrinone is for 1 mg/mL vial only. A loading dose of Milrinone lactate injection (1 mg [base]/mL) should be administered followed by a continuous infusion (maintenance dose) according to the following guidelines:

  LOADING DOSE — 50 mcg/kg: Administer slowly over 10 minutes   The table below shows the loading dose in milliliters (mL) of Milrinone (1 mg/mL) by patient body weight (kg).   Loading Dose (mL) Using 1 mg/mL Concentration   Patient Body Weight kg)   kg   30   40   50   60   70   80   90   100   110   120   mL   1.5   2.0   2.5   3.0   3.5   4.0   4.5   5.0   5.5   6.0

The loading dose may be given undiluted, but diluting to a rounded total volume of 10 or 20 mL (see Maintenance Dose for diluents) may simplify the visualization of the injection rate.

  MAINTENANCE DOSE      Infusion Rate   Total Daily Dose
(24 hours)      Minimum   0.375 mcg/kg/min   0.59 mg/kg   Administer as a continuous intravenous infusion   Standard   0.50 mcg/kg/min   0.77 mg/kg     Maximum   0.75 mcg/kg/min   1.13 mg/kg  

Milrinone drawn from vials should be diluted prior to maintenance dose administration. The diluents that may be used are 0.45% Sodium Chloride Injection, USP; 0.9% Sodium Chloride Injection, USP; or 5% Dextrose Injection, USP. The table below shows the volume of diluent in milliliters (mL) that must be used to achieve 200 mcg/mL concentration for infusion, and the resultant total volumes.

  Desired Infusion Concentration mcg/mL   Milrinone
1 mg/mL
(mL)   Diluent
(mL)   Total Volume
(mL)   200   10   40   50   200   20   80   100

The infusion rate should be adjusted according to hemodynamic and clinical response. Patients should be closely monitored. In controlled clinical studies, most patients showed an improvement in hemodynamic status as evidenced by increases in cardiac output and reductions in pulmonary capillary wedge pressure.

Note: See "Dosage Adjustment in Renally Impaired Patients." Dosage may be titrated to the maximum hemodynamic effect and should not exceed 1.13 mg/kg/day. Duration of therapy should depend upon patient responsiveness.

The maintenance dose in mL/hr by patient body weight (kg) may be determined by reference to the following table.

Note: Milrinone Lactate in 5% Dextrose Injection supplied in 100 mL and 200 mL Flexible Containers (200 mcg/mL in 5% Dextrose Injection) need not be diluted prior to use.

  Milrinone Infusion Rate(mL/hr) Using 200 mcg/mL Concentration   Maintenance Dose (mcg/kg/min)   Patient Body Weight (kg)      30   40   50   60   70   80   90   100   110   120   0.375   3.4   4.5   5.6   6.8   7.9   9.0   10.1   11.3   12.4   13.5   0.400   3.6   4.8   6.0   7.2   8.4   9.6   10.8   12.0   13.2   14.4   0.500   4.5   6.0   7.5   9.0   10.5   12.0   13.5   15.0   16.5   18.0   0.600   5.4   7.2   9.0   10.8   12.6   14.4   16.2   18.0   19.8   21.6   0.700   6.3   8.4   10.5   12.6   14.7   16.8   18.9   21.0   23.1   25.2   0.750   6.8   9.0   11.3   13.5   15.8   18.0   20.3   22.5   24.8   27.0

When administering Milrinone lactate by continuous infusion, it is advisable to use a calibrated electronic infusion device.

The Flexible Container has a concentration of Milrinone equivalent to 200 mcg/mL in 5% Dextrose Injection and is more convenient to use than dilutions prepared from the vials. To use the Flexible Container, tear the overwrap at the notch and remove the Pre-Mix solution container. Squeeze the container firmly to check for leaks. Discard the container if leaks are found since the sterility of the product could be affected. Do not add supplementary medication.

To prepare the container for administration of Milrinone intravenously, use aseptic techniques.
1. The flow control clamp of the administration set is closed.
2. The cover of the outlet port at the bottom of the container is removed.
3. Noting the full directions on the administration set carton, the piercing pin of the set is inserted into the port with a twisting motion until it is firmly sealed.
4. The container is suspended on the hanger.
5. The drop chamber is squeezed and released to establish the fill level.
6. The flow control clamp is opened to expel air from the set and then closed.
7. The set is attached to the venipuncture device, primed, and if not indwelling, the venipuncture is performed.
8. The rate of administration is controlled with the flow control clamp. WARNING - DO NOT USE IN SERIES CONNECTIONS. Caution: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

Intravenous drug products should be inspected visually and should not be used if particulate matter or discoloration is present.

Dosage Adjustment in Renally Impaired Patients

Data obtained from patients with severe renal impairment (creatinine clearance = 0 to 30 mL/min) but without congestive heart failure have demonstrated that the presence of renal impairment significantly increases the terminal elimination half-life of Milrinone lactate. Reductions in infusion rate may be necessary in patients with renal impairment. For patients with clinical evidence of renal impairment, the recommended infusion rate can be obtained from the following table:

  Creatinine Clearance
(mL/min/1.73 m2)   Infusion Rate
(mcg/kg/min)   5   0.20   10   0.23   20   0.28   30   0.33   40   0.38   50   0.43 How is Milrinone Supplied

Milrinone Lactate Injection is supplied as 10 mL single dose vials in a box of 10, NDC 0143-9710-10, or box of 25, NDC 0143-9710-25; as 20 mL single dose vials in a box of 10, NDC 0143-9709-10; as a 50 mL single dose vial in a box of 1, NDC 0143-9708-01, or box of 10, NDC 0143-9708-10, containing a sterile, clear, colorless to pale yellow solution. Each mL contains Milrinone lactate equivalent to 1 mg Milrinone.

Milrinone Lactate Injection in 5% Dextrose in Flexible Containers are supplied as 100 mL (200 mcg/mL) in 5% Dextrose Injection single units, NDC 0143-9719-10; as 200 mL (200 mcg/mL) in 5% Dextrose Injection single units, NDC 0143-9718-10.

Storage

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Avoid freezing.

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. 

Brief exposure of Flexible Containers up to 40?C (104?F) does not adversely affect the product. 

Manufactured by:                                                    
HIKMA FARMAC?UTICA (PORTUGAL), S.A.
Estrada do Rio da M?, n? 8, 8A e 8B - Ferven?a,
2705 – 906 Terrugem SNT
PORTUGAL

Distributed by:
WEST-WARD PHARMACEUTICAL CORP.
Eatontown NJ 07724 USA

Revised: 04/2011

PRINCIPAL DISPLAY PANEL

Milrinone Lactate Injection
10 mg/ 10 mL (1 mg/mL)
NDC 0143-9710-10

PRINCIPAL DISPLAY PANEL

Milrinone Lactate Injection
20 mg / 20 mL (1 mg /1 mL)
NDC 0143-9709-10

PRINCIPAL DISPLAY PANEL

Milrinone Lactate Injection
50 mg /50 mL (1 mg /1 mL)
NDC 0143-9708-10


Milrinone LACTATE 
Milrinone lactate  injection, solution Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0143-9710 Route of Administration INTRAVENOUS DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Milrinone LACTATE (Milrinone) Milrinone LACTATE 1 mg  in 1 mL Inactive Ingredients Ingredient Name Strength ANHYDROUS DEXTROSE 47 mg  in 1 mL LACTIC ACID 1 mg  in 1 mL SODIUM HYDROXIDE   WATER   Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 0143-9710-10 10 mL In 1 VIAL None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA077966 12/03/2010
Milrinone LACTATE 
Milrinone lactate  injection, solution Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0143-9709 Route of Administration INTRAVENOUS DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Milrinone LACTATE (Milrinone) Milrinone LACTATE 1 mg  in 1 mL Inactive Ingredients Ingredient Name Strength ANHYDROUS DEXTROSE 47 mg  in 1 mL WATER   LACTIC ACID 1 mg  in 1 mL SODIUM HYDROXIDE   Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 0143-9709-01 10 mL In 1 VIAL None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA077966 12/03/2010
Milrinone LACTATE 
Milrinone lactate  injection, solution Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0143-9708 Route of Administration INTRAVENOUS DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Milrinone LACTATE (Milrinone) Milrinone LACTATE 1 mg  in 1 mL Inactive Ingredients Ingredient Name Strength ANHYDROUS DEXTROSE 47 mg  in 1 mL WATER   LACTIC ACID 1 mg  in 1 mL SODIUM HYDROXIDE   Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 0143-9708-01 50 mL In 1 VIAL None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA077966 12/03/2010
Labeler - West-ward Pharmaceutical Corp (001230762) Establishment Name Address ID/FEI Operations Hikma Farmaceutica 452742943 MANUFACTURE Revised: 05/2011West-ward Pharmaceutical Corp More Milrinone resources Milrinone Side Effects (in more detail) Milrinone Dosage Milrinone Use in Pregnancy & Breastfeeding Milrinone Drug Interactions Milrinone Support Group 0 Reviews for Milrinone - Add your own review/rating Milrinone MedFacts Consumer Leaflet (Wolters Kluwer) milrinone Concise Consumer Information (Cerner Multum) Milrinone Lactate Monograph (AHFS DI) Primacor I.V. Concise Consumer Information (Cerner Multum) Compare Milrinone with other medications Heart Failure
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Milrinone Lactate in Dextrose Injection



Dosage Form: injection
Milrinone Lactate in 5% Dextrose Injection

in INTRAVIA Plastic Container

Milrinone Lactate in Dextrose Injection Description

Milrinone lactate is a member of a new class of bipyridine inotropic/vasodilator agents with phosphodiesterase inhibitor activity, distinct from digitalis glycosides or catecholamines. Milrinone lactate is designated chemically as 1,6-dihydro-2-methyl-6-oxo-[3,4’-bipyridine]-5-carbonitrile lactate and has the following structure:

Milrinone is an off-white to tan crystalline compound with a molecular weight of 211.2 and a molecular formula of C12H9N3O. It is slightly soluble in methanol, and very slightly soluble in chloroform and in water. As the lactate salt, it is stable and colorless to pale yellow in solution. Milrinone is available as sterile aqueous solutions of the lactate salt of milrinone for infusion intravenously. The flexible containers provide two ready-to-use dilutions of milrinone in volumes of 100 mL and 200 mL of 5% Dextrose Injection. Each mL contains milrinone lactate equivalent to 200 mcg milrinone. The nominal concentration of lactic acid is 0.282 mg/mL. Each mL also contains 54.3 mg Dextrose Hydrous, USP. The pH is adjusted with lactic acid and/or sodium hydroxide pH 3.5 (3.2 - 4.0). The flexible container is manufactured from a specially designed multilayer plastic (PL 2408). Solutions in contact with the plastic container leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the plastic container materials. The flexible container has a foil overwrap. Water can permeate the plastic into the overwrap, but the amount is insufficient to significantly affect the premixed solution.

Milrinone Lactate in Dextrose Injection - Clinical Pharmacology

Milrinone is a positive inotrope and vasodilator, with little chronotropic activity different in structure and mode of action from either the digitalis glycosides or catecholamines. Milrinone, at relevant inotropic and vasorelaxant concentrations, is a selective inhibitor of peak III cAMP phosphodiesterase isozyme in cardiac and vascular muscle. This inhibitory action is consistent with cAMP mediated increases in intracellular ionized calcium and contractile force in cardiac muscle, as well as with cAMP dependent contractile protein phosphorylation and relaxation in vascular muscle. Additional experimental evidence also indicates that milrinone is not a beta-adrenergic agonist nor does it inhibit sodium-potassium adenosine triphosphatase activity as do the digitalis glycosides.

Clinical studies in patients with congestive heart failure have shown that milrinone produces dose-related and plasma drug concentration-related increases in the maximum rate of increase of left ventricular pressure. Studies in normal subjects have shown that milrinone produces increases in the slope of the left ventricular pressure-dimension relationship, indicating a direct inotropic effect of the drug. Milrinone also produces dose-related and plasma concentration-related increases in forearm blood flow in patients with congestive heart failure, indicating a direct arterial vasodilator activity of the drug.

Both the inotropic and vasodilatory effects have been observed over the therapeutic range of plasma milrinone concentrations of 100 ng/mL to 300 ng/mL.

In addition to increasing myocardial contractility, milrinone improves diastolic function as evidenced by improvements in left ventricular diastolic relaxation.

The acute administration of intravenous milrinone has also been evaluated in clinical trials in excess of 1600 patients, with chronic heart failure, heart failure associated with cardiac surgery, and heart failure associated with myocardial infarction. The total number of deaths, either on therapy or shortly thereafter (24 hours) was 15, less than 0.9%, few of which were thought to be drug-related.

PHARMACOKINETICS

Following intravenous injections of 12.5 mcg/kg to 125 mcg/kg to congestive heart failure patients, milrinone had a volume of distribution of 0.38 liters/kg, a mean terminal elimination half-life of 2.3 hours, and a clearance of 0.13 liters/kg/hr. Following intravenous infusions of 0.20 mcg/kg/min to 0.70 mcg/kg/min to congestive heart failure patients, the drug had a volume of distribution of about 0.45 liters/kg, a mean terminal elimination half-life of 2.4 hours, and a clearance of 0.14 liters/kg/hr. These pharmacokinetic parameters were not dose-dependent, and the area under the plasma concentration versus time curve following injections was significantly dose-dependent.

Milrinone has been shown (by equilibrium dialysis) to be approximately 70% bound to human plasma protein.

The primary route of excretion of milrinone in man is via the urine. The major urinary excretions of orally administered milrinone in man are milrinone (83%) and its O-glucuronide metabolite (12%). Elimination in normal subjects via the urine is rapid, with approximately 60% recovered within the first two hours following dosing and approximately 90% recovered within the first eight hours following dosing. The mean renal clearance of milrinone is approximately 0.3 liters/min, indicative of active secretion.

PHARMACODYNAMICS

In patients with heart failure due to depressed myocardial function, milrinone produced a prompt dose and plasma concentration related increase in cardiac output and decreases in pulmonary capillary wedge pressure and vascular resistance, which were accompanied by mild-to-moderate increases in heart rate. Additionally, there is no increased effect on myocardial oxygen consumption. In uncontrolled studies, hemodynamic improvement during intravenous therapy with milrinone was accompanied by clinical symptomatic improvement, but the ability of milrinone to relieve symptoms has not been evaluated in controlled clinical trials. The great majority of patients experience improvements in hemodynamic function within 5 to 15 minutes of initiation of therapy.

In studies in congestive heart failure patients, milrinone when administered as a loading injection followed by a maintenance infusion produced significant mean initial increases in cardiac index of 25 percent, 38 percent, and 42 percent at dose regimens of 37.5 mcg/kg/0.375 mcg/kg/min, 50 mcg/kg/0.50 mcg/kg/min, and 75 mcg/kg/ 0.75 mcg/kg/min, respectively. Over the same range of loading injections and maintenance infusions, pulmonary capillary wedge pressure significantly decreased by 20 percent, 23 percent, and 36 percent, respectively, while systemic vascular resistance significantly decreased by 17 percent, 21 percent, and 37 percent. Mean arterial pressure fell by up to 5 percent at the two lower dose regimens, but by 17 percent at the highest dose. Patients evaluated for 48 hours maintained improvements in hemodynamic function, with no evidence of diminished response (tachyphylaxis). A smaller number of patients have received infusions of milrinone for periods up to 72 hours without evidence of tachyphylaxis.

The duration of therapy should depend upon patient responsiveness.

Milrinone has a favorable inotropic effect in fully digitalized patients without causing signs of glycoside toxicity. Theoretically, in cases of atrial flutter/fibrillation, it is possible that milrinone may increase ventricular response rate because of its slight enhancement of AV node conduction. In these cases, digitalis should be considered prior to the institution of therapy with milrinone.

Improvement in left ventricular function in patients with ischemic heart disease has been observed. The improvement has occurred without inducing symptoms or electrocardiographic signs of myocardial ischemia.

The steady-state plasma milrinone concentrations after approximately 6 to 12 hours of unchanging maintenance infusion of 0.50 mcg/kg/min are approximately 200 ng/mL. Near maximum favorable effects of milrinone on cardiac output and pulmonary capillary wedge pressure are seen at plasma milrinone concentrations in the 150 ng/mL to 250 ng/mL range.

Indications and Usage for Milrinone Lactate in Dextrose Injection

Milrinone is indicated for the short-term intravenous treatment of patients with acute decompensated heart failure. Patients receiving milrinone should be observed closely with appropriate electrocardiographic equipment. The facility for immediate treatment of potential cardiac events, which may include life-threatening ventricular arrythmias, must be available. The majority of experience with intravenous milrinone has been in patients receiving digoxin and diuretics. There is no experience in controlled trials with infusions of milrinone for periods exceeding 48 hours.

Contraindications

Milrinone is contraindicated in patients who are hypersensitive to it.

Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

Warnings

Whether given orally or by continuous or intermittent intravenous infusion, milrinone has not been shown to be safe or effective in the longer (greater than 48 hours) treatment of patients with heart failure. In a multicenter trial of 1088 patients with Class III and IV heart failure, long-term oral treatment with milrinone was associated with no improvement in symptoms and an increased risk of hospitalization and death. In this study, patients with Class IV symptoms appeared to be at particular risk of life-threatening cardiovascular reactions. There is no evidence that milrinone given by long-term continuous or intermittent infusion does not carry a similar risk.

The use of milrinone both intravenously and orally has been associated with increased frequency of ventricular arrhythmias, including nonsustained ventricular tachycardia. Long-term oral use has been associated with an increased risk of sudden death. Hence, patients receiving milrinone should be observed closely with the use of continuous electrocardiographic monitoring to allow the prompt detection and management of ventricular arrhythmias.

Precautions General

Milrinone should not be used in patients with severe obstructive aortic or pulmonic valvular disease in lieu of surgical relief of the obstruction. Like other inotropic agents, it may aggravate outflow tract obstruction in hypertrophic subaortic stenosis.

Supraventricular and ventricular arrhythmias have been observed in the high-risk population treated. In some patients, injections of milrinone and oral milrinone have been shown to increase ventricular ectopy, including nonsustained ventricular tachycardia. The potential for arrhythmia, present in congestive heart failure itself, may be increased by many drugs or combinations of drugs. Patients receiving milrinone should be closely monitored during infusion.

Milrinone produces a slight shortening of AV node conduction time, indicating a potential for an increased ventricular response rate in patients with atrial flutter/fibrillation which is not controlled with digitalis therapy.

During therapy with milrinone, blood pressure and heart rate should be monitored and the rate of infusion slowed or stopped in patients showing excessive decreases in blood pressure. If prior vigorous diuretic therapy is suspected to have caused significant decreases in cardiac filling pressure, milrinone should be cautiously administered with monitoring of blood pressure, heart rate, and clinical symptomatology.

There is no experience in controlled trials with infusions of milrinone for periods exceeding 48 hours. Cases of infusion site reaction have been reported with intravenous milrinone therapy (see ADVERSE REACTIONS). Consequently, careful monitoring of the infusion site should be maintained to avoid possible extravasation.

Use in Acute Myocardial Infarction

No clinical studies have been conducted in patients in the acute phase of post myocardial infarction. Until further clinical experience with this class of drugs is gained, milrinone is not recommended in these patients.

Laboratory Tests

Fluid and electrolytes: Fluid and electrolyte changes and renal function should be carefully monitored during therapy with milrinone. Improvement in cardiac output with resultant diuresis may necessitate a reduction in the dose of diuretic. Potassium loss due to excessive diuresis may predispose digitalized patients to arrhythmias. Therefore, hypokalemia should be corrected by potassium supplementation in advance of or during use of milrinone.

Drug Interactions

No untoward clinical manifestations have been observed in limited experience with patients in whom milrinone was used concurrently with the following drugs: digitalis glycosides; lidocaine, quinidine; hydralazine, prazosin; isosorbide dinitrate, nitroglycerin; chlorthalidone, furosemide, hydrochlorothiazide, spironolactone; captopril; heparin, warfarin, diazepam, insulin; and potassium supplements.

Chemical Interactions

There is an immediate chemical interaction which is evidenced by the formation of a precipitate when furosemide is injected into an intravenous line of an infusion of milrinone. Therefore, furosemide should not be administered in intravenous lines containing milrinone.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Twenty-four months of oral administration of milrinone to mice at doses up to 40 mg/kg/day (about 50 times the human oral therapeutic dose in a 50 kg patient) was unassociated with evidence of carcinogenic potential. Neither was there evidence of carcinogenic potential when milrinone was orally administered to rats at doses up to 5 mg/kg/day (about 6 times the human oral therapeutic dose) for twenty-four months or at 25 mg/kg/day (about 30 times the human oral therapeutic dose) for up to 18 months in males and 20 months in females. Whereas the Chinese Hamster Ovary Chromosome Aberration Assay was positive in the presence of a metabolic activation system, results from the Ames Test, the Mouse Lymphoma Assay, the Micronucleus Test, and the in vivo Rat Bone Marrow Metaphase Analysis indicated an absence of mutagenic potential. In reproductive performance studies in rats, milrinone had no effect on male or female fertility at oral doses up to 32 mg/kg/day.

Animal Toxicity

Oral and intravenous administration of toxic dosages of milrinone to rats and dogs resulted in myocardial degeneration/fibrosis and endocardial hemorrhage, principally affecting the left ventricular papillary muscles. Coronary vascular lesions characterized by periarterial edema and inflammation have been observed in dogs only. The myocardial/endocardial changes are similar to those produced by beta-adrenergic receptor agonists such as isoproterenol, while the vascular changes are similar to those produced by minoxidil and hydralazine. Doses within the recommended clinical dose range (up to 1.13 mg/kg/day) for congestive heart failure patients have not produced significant adverse effects in animals.

Pregnancy Category C

Oral administration of milrinone to pregnant rats and rabbits during organogenesis produced no evidence of teratogenicity at dose levels up to 40 mg/kg/day and 12 mg/kg/day, respectively. Milrinone did not appear to be teratogenic when administered intravenously to pregnant rats at doses up to 3 mg/kg/day (about 2.5 times the maximum recommended clinical intravenous dose) or pregnant rabbits at doses up to 12 mg/kg/day, although an increased resorption rate was apparent at both 8 mg/kg/day and 12 mg/kg/day (intravenous) in the latter species. There are no adequate and well-controlled studies in pregnant women. Milrinone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Caution should be exercised when milrinone is administered to nursing women, since it is not known whether it is excreted in human milk.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Use in Elderly Patients

There are no special dosage recommendations for the elderly patient. Ninety percent of all patients administered milrinone in clinical studies were within the age range of 45 to 70 years, with a mean age of 61 years. Patients in all age groups demonstrated clinically and statistically significant responses. No age-related effects on the incidence of adverse reactions have been observed. Controlled pharmacokinetic studies have not disclosed any age-related effects on the distribution and elimination of milrinone.

Adverse Reactions Cardiovascular Effects

In patients receiving milrinone in Phase II and III clinical trials, ventricular arrhythmias were reported in 12.1%: Ventricular ectopic activity, 8.5%; nonsustained ventricular tachycardia, 2.8%; sustained ventricular tachycardia, 1% and ventricular fibrillation, 0.2% (2 patients experienced more than one type of arrhythmia). Holter recordings demonstrated that in some patients injection of milrinone increased ventricular ectopy, including nonsustained ventricular tachycardia. Life-threatening arrhythmias were infrequent and when present have been associated with certain underlying factors such as preexisting arrhythmias, metabolic abnormalities (e.g. hypokalemia), abnormal digoxin levels and catheter insertion. Milrinone was not shown to be arrhythmogenic in an electrophysiology study. Supraventricular arrhythmias were reported in 3.8% of the patients receiving milrinone. The incidence of both supraventricular and ventricular arrhythmias has not been related to the dose or plasma milrinone concentration.

Other cardiovascular adverse reactions include hypotension, 2.9% and angina/chest pain, 1.2%.

In the post-marketing experience, there have been rare cases of “torsades de pointes” reported.

CNS Effects

Headaches, usually mild to moderate in severity, have been reported in 2.9% of patients receiving milrinone.

Other Effects

Other adverse reactions reported, but not definitely related to the administration of milrinone include hypokalemia, 0.6%; tremor, 0.4%; and thrombocytopenia, 0.4%.

Post-Marketing Adverse Event Reports

In addition to adverse events reported from clinical trials, the following events have been reported from worldwide post-marketing experience with Milrinone:

Isolated spontaneous reports of bronchospasm and anaphylactic shock.

Liver function test abnormalities and skin reactions such as rash.

Administration site conditions: Infusion site reaction.

Overdosage

Doses of milrinone may produce hypotension because of its vasodilator effect. If this occurs, administration of milrinone should be reduced or temporarily discontinued until the patient's condition stabilizes. No specific antidote is known, but general measures for circulatory support should be taken.

Milrinone Lactate in Dextrose Injection Dosage and Administration

Milrinone should be administered with a loading dose followed by a continuous infusion (maintenance dose) according to the following guidelines:

Loading Dose

50 mcg/kg: Administer slowly over 10 minutes

Note: Milrinone (200 mcg/mL) in INTRAVIA Plastic Container is for intravenous infusion only.

Dosage recommendations using a 1 mg/mL concentration of milrinone are included for informational purposes only.

The table below shows the loading dose in milliliters (mL) of milrinone (1mg/mL) by patient body weight (kg).

Loading Dose (mL) Using 1 mg/mL Concentration Patient Body Weight (kg) kg 30 40 50 60 70 80 90 100 110 120 mL 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0

The loading dose may be given undiluted, but diluting to a rounded total volume of 10 or 20 mL (see appropriate package insert for diluents) may simplify the visualization of the injection rate.

Maintenance Dose   Infusion Rate Total Daily Dose
(24 Hours)   Minimum 0.375 mcg/kg/min 0.59 mg/kg Administer as a continuous intravenous infusion Standard 0.50 mcg/kg/min 0.77 mg/kg   Maximum 0.75 mcg/kg/min 1.13 mg/kg  

The infusion rate should be adjusted according to hemodynamic and clinical response. Patients should be closely monitored. In controlled clinical studies, most patients showed an improvement in hemodynamic status as evidenced by increases in cardiac output and reductions in pulmonary capillary wedge pressure.

Note: See "Dosage Adjustment in Renally Impaired Patients." Dosage may be titrated to the maximum hemodynamic effect and should not exceed 1.13 mg/kg/day. Duration of therapy should depend upon patient responsiveness.

The maintenance dose in mL/hr by patient body weight (kg) may be determined by reference to the following table.

Milrinone Infusion Rate (mL/hr) Using 200 mcg/mL Concentration Maintenance Dose (mcg/kg/min) Patient Body Weight (kg) 30 40 50 60 70 80 90 100 110 120   0.375 3.4 4.5 5.6 6.8 7.9 9.0 10.1 11.3 12.4 13.5 0.400 3.6 4.8 6.0 7.2 8.4 9.6 10.8 12.0 13.2 14.4 0.500 4.5 6.0 7.5 9.0 10.5 12.0 13.5 15.0 16.5 18.0 0.600 5.4 7.2 9.0 10.8 12.6 14.4 16.2 18.0 19.8 21.6 0.700 6.3 8.4 10.5 12.6 14.7 16.8 18.9 21.0 23.1 25.2 0.750 6.8 9.0 11.3 13.5 15.8 18.0 20.3 22.5 24.8 27.0 Dosage Adjustment in Renally Impaired Patients

Data obtained from patients with severe renal impairment (creatinine clearance = 0 to 30 mL/min) but without congestive heart failure have demonstrated that the presence of renal impairment significantly increases the terminal elimination half-life of milrinone. Reductions in infusion rate may be necessary in patients with renal impairment. For patients with clinical evidence of renal impairment, the recommended infusion rate can be obtained from the following table:

Creatinine Clearance
(mL/min/1.73 m2) Infusion Rate
(mcg/kg/min) 5 0.20 10 0.23 20 0.28 30 0.33 40 0.38 50 0.43

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Milrinone Lactate in 5% Dextrose Injection is a clear, colorless to pale yellow solution.

DIRECTIONS FOR USE

When administering Milrinone Lactate in 5% Dextrose Injection by continuous infusion, it is advisable to use a calibrated electronic infusion device.

To open

Tear overwrap down side at slit and remove solution container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. After removing overwrap, check for minute leaks by squeezing inner bag firmly. If leaks are found, discard solution as sterility may be impaired.

Preparation for Administration

(Use aseptic technique)

Suspend container from eyelet support. Remove protector from outlet port at bottom of container. Attach administration set. Refer to complete directions accompanying set.

WARNING: DO NOT USE IN SERIES CONNECTIONS. Do not administer simultaneously with blood. Caution: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

How is Milrinone Lactate in Dextrose Injection Supplied

Baxter’s Milrinone Lactate in 5% Dextrose Injection is supplied in INTRAVIA Plastic Container as follows:

2J0900 NDC 0338-6010-48 100 mL (200 mcg/mL) 2J0901 NDC 0338-6011-37 200 mL (200 mcg/mL)

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. It is recommended that the product be stored at room temperature, 25° C (77° F); however, brief exposure up to 40° C (104° F) does not adversely affect the product.

Baxter Healthcare Corporation
Deerfield, IL 60015 USA

Printed in USA

BAXTER and INTRAVIA are trademarks of Baxter International Inc.

07-19-54-485

Revised, September 2007

PACKAGE LABELING - PRINCIPAL DISPLAY PANEL

 

Container Label

LOT

EXP

2J0901
NDC 0338-6011-37

200 mL
MILRINONE
LACTATE

40 mg/200 mL
200 mcg (0.2 mg) per mL*
in 5% Dextrose Injection

*Each mL contains milrinone lactate
equivalent to 0.2 mg milrinone 0.282 mg
lactic acid 54.3 mg Dextrose Hydrous
USP in Water for Injection USP The pH
is adjusted with lactic acid and/or sodium
hydroxide pH 3.5 (3.2 - 4.0)

Sterile Nonpyrogenic Single dose No preservative is added
Usual Dosage intravenously as directed by a physician See
package insert

Cautions Check for minute leaks by squeezing bag firmly If
leaks are found discard bag as sterility may be impaired MUST
NOT BE USED IN SERIES CONECTIONS Do not administer
simultaneously with blood Use only if solution is clear
colorless to pale yellow

RX ONLY

Recommended storage Store at room temperature 25°C (77°F)
However brief exposure up to 40°C (104°F) does not adversely
affect the product Protect from freezing Avoid excessive heat

INTRAVIA container
Baxter and INTRAVIA are trademarks
of Baxter International Inc
US Pat Nos 5 849 843 5 998 019 Pat Pending


Baxter Logo
Baxter Healthcare Corporation
Deerfield IL 60015 USA
Made in USA

Carton Label

LOT
EXP

10 x 200 mL Single Dose IntraVia Containers

NDC 0338-6011-37

Code 2J0901

Milrinone Lactate
in 5% Dextrose Injection
40 mg/200 mL

Recommended storage: Store at room temperature (25°C/77°F); however brief exposure to
40°C (104°F) does not adversely affect the product. Protect from freezing. Avoid excessive heat.

GS1 128 BARCODE PLACEMENT ONLY
(01)50303386011376


MILRINONE LACTATE IN DEXTROSE 
milrinone lactate  injection Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0338-6010 Route of Administration INTRAVENOUS DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength MILRINONE LACTATE (MILRINONE) MILRINONE LACTATE 200 ug  in 1 mL Inactive Ingredients Ingredient Name Strength LACTIC ACID 0.282 mg  in 1 mL DEXTROSE MONOHYDRATE 54.3 mg  in 1 mL Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 0338-6010-48 100 mL In 1 BAG None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA075834 06/02/2008
MILRINONE LACTATE IN DEXTROSE 
milrinone lactate  injection Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0338-6011 Route of Administration INTRAVENOUS DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength MILRINONE LACTATE (MILRINONE) MILRINONE LACTATE 200 ug  in 1 mL Inactive Ingredients Ingredient Name Strength LACTIC ACID 0.282 mg  in 1 mL DEXTROSE MONOHYDRATE 54.3 mg  in 1 mL Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 0338-6011-37 200 mL In 1 BAG None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA075834 06/02/2008
Labeler - Baxter Healthcare Corporation (005083209) Establishment Name Address ID/FEI Operations Baxter Healthcare SA dba Baxter Healthcare of Puerto Rico 189326168 MANUFACTURE Revised: 10/2010Baxter Healthcare Corporation More Milrinone Lactate in Dextrose Injection resources Milrinone Lactate in Dextrose Injection Side Effects (in more detail)Milrinone Lactate in Dextrose Injection Use in Pregnancy & BreastfeedingMilrinone Lactate in Dextrose Injection Drug InteractionsMilrinone Lactate in Dextrose Injection Support Group0 Reviews for Milrinone Lactate in Dextrose Injection - Add your own review/rating Compare Milrinone Lactate in Dextrose Injection with other medications Heart Failure
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Heparin sodium 100 IU / ml I.V. flush solution (Leo Laboratories Ltd)


1. Name Of The Medicinal Product

HEPARIN SODIUM 100 IU/ml I.V. FLUSH SOLUTION

2. Qualitative And Quantitative Composition

Heparin sodium Ph. Eur. 100 IU/ml

3. Pharmaceutical Form

Solution for Injection.

4. Clinical Particulars 4.1 Therapeutic Indications

To maintain the patency of in-dwelling intravenous lines. It is not recommended for therapeutic use.

4.2 Posology And Method Of Administration

For routine use, 2 ml containing 200 IU of heparin should be administered into the catheter/cannula every 4-8 hours or as required.

4.3 Contraindications

Known hypersensitivity to constituents.

Current or history of heparin induced thrombocytopenia.

Heparin Sodium 100 IU/ml i.v. flush solution contains 10 mg/ml of the preservative benzyl alcohol. This formulation must not be given to premature babies or neonates.

4.4 Special Warnings And Precautions For Use

As there is a risk of antibody-mediated heparin-induced thrombocytopenia, platelet counts should be measured in patients receiving regular and repeated use of heparin flush solutions for longer than 5 days and the treatment should be stopped immediately in those who develop thrombocytopenia.

Heparin induced thrombocytopenia and heparin induced thrombocytopenia with thrombosis can occur up to several weeks after discontinuation of heparin therapy. Patients presenting with thrombocytopenia or thrombosis after discontinuation of heparin should be evaluated for HIT and HITT.

Heparin Sodium 100 IU/ml i.v. flush solution should be used with caution in patients with hypersensitivity to low molecular weight heparin.

Heparin Sodium 100 IU/ml i.v. flush solution contains the preservative benzyl alcohol 10mg/ml. This product should be administered with caution to infants and children up to 3 years old, as there is a risk that benzyl alcohol may cause toxic and allergic reactions (anaphylactoid) in this age group (see also section 4.3 for premature babies or neonates).

Heparin Sodium 100 IU/ml i.v. flush solution contains esters of parahydroxybenzoates as a preservative system. These may cause allergic reactions (possibly delayed), and exceptionally, bronchospasm.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

For incompatibilities with other medicinal products see Section 6.2.

When an indwelling device is used for repeated withdrawal of blood samples for laboratory analyses and the presence of heparin or saline is likely to interfere with or alter the results of the tests, the in situ heparin flush solution should be cleared from the device by aspirating and discarding a volume of solution equivalent to that of the indwelling venipuncture device before the desired blood sample is taken.

4.6 Pregnancy And Lactation

The dose of heparin used would not be expected to constitute a hazard. However, as benzyl alcohol may cross the placenta, the use of Heparin Sodium 100 IU/ml i.v. flush solution containing benzyl alcohol should be avoided during pregnancy.

Heparin does not cross the placental barrier and is not excreted in breast milk.

4.7 Effects On Ability To Drive And Use Machines

Heparin has no or negligible influence on the ability to drive or use machines.

4.8 Undesirable Effects

When used as recommended, the low dose of heparin reaching the blood is unlikely to have any systemic effects. However, heparin may cause thrombocytopenia and hypersensitivity reactions.

Local irritation may occur if inadvertently injected subcutaneously.

4.9 Overdose

An overdose is unlikely to occur. Bleeding is the main sign of overdose with heparin. As heparin is eliminated quickly, a discontinuation of treatment is sufficient in case of minor haemorrhages. In case of severe haemorrhages heparin may be neutralised with protamine sulphate injected slowly intravenously. One mg of protamine sulphate neutralises approximately 100 IU of heparin. Nevertheless, the required protamine sulphate dose varies according to the time of heparin administration and the dose administered.

It is important to avoid overdosage of protamine sulphate because protamine sulphate itself has anticoagulant properties. A single dose of protamine sulphate should never exceed 50 mg. Intravenous injection of protamine sulphate may cause a sudden fall in blood pressure, bradycardia, dyspnoea and transitory flushing, but these may be avoided or diminished by slow and careful administration.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Heparin is a naturally occurring anticoagulant which prevents the coagulation of blood in-vivo and in-vitro. It potentiates the inhibition of several activated coagulation factors, including thrombin and factor X.

5.2 Pharmacokinetic Properties

Not applicable

5.3 Preclinical Safety Data

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the Summary Product Characteristics.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Benzyl alcohol,

Methylparahydroxybenzoate,

Propylparahydroxybenzoate,

Sodium citrate,

Sodium chloride,

Water for Injections.

6.2 Incompatibilities

This product is compatible with normal saline. Heparin has been reported to be incompatible in aqueous solution with certain substances, e.g. some antibiotics, hydrocortisone, phenothiazines, narcotic analgesics and antihistamines.

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Do not store above 25?C.

6.5 Nature And Contents Of Container

10 x 2 ml ampoules.

6.6 Special Precautions For Disposal And Other Handling

None

7. Marketing Authorisation Holder

LEO Laboratories Limited

Longwick Road

Princes Risborough

Bucks HP27 9RR

8. Marketing Authorisation Number(S)

PL 0043/0057

9. Date Of First Authorisation/Renewal Of The Authorisation

23 October 1978/16 January 1995

10. Date Of Revision Of The Text

November 2007

LEGAL CATEGORY

POM


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Heparins


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

Heparin is an injectable anticoagulant that activates antithrombin III, which inhibits thrombin and factor Xa, factors necessary in the final stages of blood clotting cascade.

There are two types of heparins: high molecular weight heparins and low molecular weight heparins.

High molecular weight heparins require daily blood monitoring to check the aPTT. Low molecular weight heparins give a better anticoagulant response and do not need daily blood monitoring.

Heparin is used to treat or prevent clots in conditions where there is a high risk of clot formation and thromboembolism, such as in atrial fibrillation, myocardial infarction, deep vein thrombosis, knee and hip surgery and so on.

See also

Medical conditions associated with heparins:

Acute Coronary Syndrome Angina Anticoagulation During Pregnancy Antiphospholipid Syndrome Deep Vein Thrombosis Deep Vein Thrombosis Prophylaxis after Abdominal Surgery Deep Vein Thrombosis Prophylaxis after Hip Replacement Surgery Deep Vein Thrombosis Prophylaxis after Knee Replacement Surgery Deep Vein Thrombosis Prophylaxis after Orthopedic Surgery Deep Vein Thrombosis, Prophylaxis Heart Attack Patency Maintenance of Indwelling Intravenous Devices Pulmonary Embolism Thrombotic/Thromboembolic Disorder Venous Thromboembolism Drug List: Fragmin Innohep Lovenox Normiflo Heparin-Lock-Flush Heparin-Sodium Orgaran
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Sentry AQ Mardel Maracyn-Oxy



Dosage Form: FOR ANIMAL USE ONLY
Medication for Fresh and Saltwater Fish Indications and Usage for Sentry AQ Mardel Maracyn-Oxy

For the treatment and control of the symptoms associated with common bacterial, fungal and viral infections of fresh and saltwater fish.

For true fungal infections of fish and eggs
Effective against common forms of bacterial fin and tail rot. NOTE

Consult a veterinarian or fish expert for assistance in diagnosis of disease causing organisms and treatment options.

DIRECTIONS Use of a hospital tank is recommended.  It is always wise to check your water quality levels to ensure they are within their acceptable ranges before administering any water treatment.  No water changes, pH or temperature adjustments necessary if readings are in ideal range.  Maintain normal filtration and air.  Use 1/2 capfull (2.5 mL) per 10 gallons of water.  Repeat as needed for not more than 5 days.  It is suggested to always increase tank aeration during treatment to ensure an adequate oxygen supply for sick fish.  Switch off UV sterilizers during treatment.  Should fish exhibit signs of distress neutralize the medication by using an aquarium dechlorinator.  Follow the manufacturers directions for dosing. KEEP OUT OF REACH OF CHILDREN
Precautions For aquarium use only.
Warnings Causes irritation.  Avoid contact with eyes, skin and clothing.  If in eyes: Flush eyes with water for 15 minutes.  Call a physician.  If on Skin: Flush skin with water.  (Wash clothing before reuse.)  Wash thoroughly after handling.  THIS PRODUCT IS INTENDED FOR THE EXCLUSIVE USE WITH THE ORNAMENTAL ORGANISMS INDICATED AND IS NOT INTENDED FOR USE WITH HUMANS OR FISH FOR HUMAN CONSUMPTION.  
ACTIVE INGREDIENT Stabilized chlorine oxides
How is Sentry AQ Mardel Maracyn-Oxy Supplied Net Contents 2 fl oz (59 mL)
Net Contents 4 fl oz (118 mL) PACKAGING COMPONENT Sentry AQ Mardel Maracyn-Oxy
Distributed by:
Sergeant's Pet Care Products, Inc., Omaha NE 68130
www.sentrypetcare.com
Sentry AQ Mardel Maracyn-Oxy 
stabilized chlorine oxides  liquid Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 21091-183 Route of Administration EXTRACORPOREAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Sodium Chlorite (Chlorous Acid) Sodium Chlorite 43 mg  in 1 mL Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found Product Characteristics Color yellow (slight yellow tint) Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 21091-183-04 1 BOTTLE In 1 CARTON contains a BOTTLE, PLASTIC 1 118 mL In 1 BOTTLE, PLASTIC This package is contained within the CARTON (21091-183-04)
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date unapproved drug other 10/09/2009
Labeler - Sergeant's Pet Care Products, Inc. (876995171) Revised: 01/2010Sergeant's Pet Care Products, Inc.

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Vet One Chlorhexidine



Dosage Form: FOR ANIMAL USE ONLY
MWI/Vet One 2% Chlorhexidine solution MWI/Vet One 2% Chlorhexidine solution

ACTIVE INGREDIENTS:
2% Chlorhexidine Gluconate.

CAUTION:
Avoid contact with eyes and mucous membranes. This product is not to be used in ears. If contact is made, flush immediately and thoroughly with clean water. For use on horses and dogs.

Product No. 1CHL008
8CHL008-108
Distributed by:
MWI
Meridian, ID 83680
(888) 694-8381
MWI/Vet One 2% Chlorhexidine solution

PRODUCT DESCRIPION:
A topical aqueous cleaning solution for use on horses and dogs for application to superficial cuts, abrasions or insect stings.

DILUTE:
1 ounce (2 tablespoons) of Chlorhexidine Solution per gallon of clean water.
DIRECTIONS FOR USE:
Rinse skin area to be treated with Chlorhexidine Solution. Wipe away excess and pat dry with sterilized gauze or sponge.
MWI/Vet One 2% Chlorhexidine solution


Vet One Chlorhexidine 
chlorhexidine gluconate  solution Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 13985-017 Route of Administration TOPICAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Chlorhexidine Gluconate (CHLORHEXIDINE) Chlorhexidine Gluconate 2 g  in 0.1 L Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 13985-017-80 3.785 L In 1 JUG None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date unapproved drug other 01/01/2010
Labeler - MWI VETERINARY SUPPLY CO (019926120) Revised: 01/2010MWI VETERINARY SUPPLY CO

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Hex-Plus


Generic Name: chlorhexidine gluconate liquid
Dosage Form: FOR ANIMAL USE ONLY
Hex-Plus

USE DIRECTIONS:
Use at full strength, do not dilute.


POST-MILKING:
Dip entire teat in Hex-Plus.  Allow to air dry.
If solution in cup becomes visibly dirty.  Then
replenish with Hex-Plus at full strength.  Do
not return unused product to original container.
PROTECT FROM FREEZING
IF FROZEN: SHAKE VIGOROUSLY
AFTER THAWING

WARNING:  CONTAINS CHLORHEXIDINE
GLUCONATE.

Not for human use.
Avoid contamination of food.  Avoid contact
with eyes.  Not for internal use.


OBSERVE LABEL DIRECTIONS

KEEP OUT OF REACH OF CHILDREN!

FIRST AID:
INTERNAL:  If swallowed, do not induce vomiting.
Drink large quantities of water.  See physician immediately.

EYES:  Flush eyes with clear water for 15 minutes.If irritated, obtain medical guidance.
GET MEDICAL ATTENTION IMMEDIATELY.

Hex-Plus

SANITIZING CHLORHEXIDINE TEAT DIP
FORMULATED WITH EMOLLIENTS AND
DERMAL CONDITIONERS


This product, when properly used, is effective as an aid
in reducing the spread of organisms which may cause
mastitis.
Active Ingredient..........1.0% Chlorhexidine Gluconate
Contains 10% Emollient
Lot#:______________________

Exp. Date:___________________

Next Content:________________


Manufactured For:
Tetradyne LLC
PO Box 17003
Reno, NV 89511


Hex-Plus 
teat dip  liquid Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 66399-742 Route of Administration TOPICAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CHLORHEXIDINE GLUCONATE (CHLORHEXIDINE) CHLORHEXIDINE GLUCONATE 1.0 L  in 100 L Inactive Ingredients Ingredient Name Strength GLYCERIN 10 L  in 100 L Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 66399-742-01 3.78 L In 1 JUG None 2 66399-742-02 18.9 L In 1 PAIL None 3 66399-742-03 56.7 L In 1 DRUM None 4 66399-742-04 113.4 L In 1 DRUM None 5 66399-742-05 207.9 L In 1 DRUM None 6 66399-742-06 945 L In 1 CONTAINER, FLEXIBLE INTERMEDIATE BULK None 7 66399-742-07 1039.5 L In 1 CONTAINER, FLEXIBLE INTERMEDIATE BULK None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date unapproved drug other 09/10/2001
Labeler - Tetradyne LLC (130969293) Revised: 11/2010Tetradyne LLC

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Hex-Tra


Generic Name: chlorhexidine gluconate liquid
Dosage Form: FOR ANIMAL USE ONLY
Hex-Tra

USE DIRECTIONS:
Use at full strength, do not dilute.


POST-MILKING:
Dip entire teat in Hex-Tra.  Allow to air dry.
If solution in cup becomes visibly dirty.  Then
replenish with Hex-Tra at full strength.  Do
not return unused product to original container.
PROTECT FROM FREEZING
IF FROZEN: SHAKE VIGOROUSLY
AFTER THAWING

WARNING:  CONTAINS CHLORHEXIDINE
GLUCONATE.

Not for human use.
Avoid contamination of food.  Avoid contact
with eyes.  Not for internal use.


OBSERVE LABEL DIRECTIONS

KEEP OUT OF REACH OF CHILDREN!

FIRST AID:
INTERNAL:  If swallowed, do not induce vomiting.
Drink large quantities of water.  See physician immediately.

EYES:  Flush eyes with clear water for 15 minutes.If irritated, obtain medical guidance.
GET MEDICAL ATTENTION IMMEDIATELY.

Hex-Tra

SANITIZING CHLORHEXIDINE TEAT DIP
FORMULATED WITH EMOLLIENTS AND
DERMAL CONDITIONERS


This product, when properly used, is effective as an aid
in reducing the spread of organisms which may cause
mastitis.
Active Ingredient..........0.50% Chlorhexidine Gluconate
Contains an Emollient System
Lot#:______________________

Exp. Date:___________________

Next Content:________________


Manufactured For:
Tetradyne LLC
PO Box 17003
Reno, NV 89511


Hex-Tra 
teat dip  liquid Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 66399-083 Route of Administration TOPICAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CHLORHEXIDINE GLUCONATE (CHLORHEXIDINE) CHLORHEXIDINE GLUCONATE 0.50 L  in 100 L Inactive Ingredients Ingredient Name Strength GLYCERIN 5.0 L  in 100 L Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 66399-083-01 3.78 L In 1 JUG None 2 66399-083-02 18.9 L In 1 PAIL None 3 66399-083-03 56.7 L In 1 DRUM None 4 66399-083-04 113.4 L In 1 DRUM None 5 66399-083-05 207.9 L In 1 DRUM None 6 66399-083-06 945 L In 1 CONTAINER, FLEXIBLE INTERMEDIATE BULK None 7 66399-083-07 1039.5 L In 1 CONTAINER, FLEXIBLE INTERMEDIATE BULK None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date unapproved drug other 09/10/2001
Labeler - Tetradyne LLC (130969293) Revised: 11/2010Tetradyne LLC

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High Cholesterol Medications


Definition of High Cholesterol: Acquired lipid disorders is a group of disorders characterized by an excess of fatty substances, such as cholesterol, triglycerides, and lipoproteins present in the blood.

Drugs associated with High Cholesterol

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

See sub-topics

Topics under High Cholesterol High Cholesterol, Familial Heterozygous (14 drugs) High Cholesterol, Familial Homozygous (6 drugs) Hyperlipoproteinemia (128 drugs in 6 topics) Hypertriglyceridemia (30 drugs) Niacin Flush (34 drugs) Sitosterolemia (1 drug) Learn more about High Cholesterol

Medical Encyclopedia:

Familial hypercholesterolemia High blood cholesterol levels

Harvard Health Guide:

Symptoms and treatment for High Cholesterol (Hypercholesterolemia)

Drugs.com Health Center:

Cholesterol Center
Drug List: Advicor Altocor Altoprev-Extended-Release-Tablets Atromid-S B-3-50-Nicotinic-Acid B3-500-Gr-Nicotinic-Acid Baycol Choloxin Crestor Evening-Primrose-Oil Fibricor Juvisync Lescol Lescol-Xl-Extended-Release-Tablets Lipitor Livalo Lopid Mevacor Niacin-Sr-Nicotinic-Acid Niacor Niaspan Nicotinex Pravachol Pravigard_Pac Primrose-Oil Simcor Slo-Niacin-Controlled-Release-Capsules Trilipix Vytorin Welchol Zetia Zocor
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Natrecor


nesiritide
Dosage Form: injection, powder, lyophilized, for solution
Natrecor® (nesiritide)

FOR INTRAVENOUS INFUSION ONLY

Natrecor Description

Natrecor® (nesiritide) is a sterile, purified preparation of a new drug class, human B-type natriuretic peptide (hBNP), and is manufactured from E. coli using recombinant DNA technology. Nesiritide has a molecular weight of 3464 g/mol and an empirical formula of C143H244N50O42S4. Nesiritide has the same 32 amino acid sequence as the endogenous peptide, which is produced by the ventricular myocardium.

Natrecor is formulated as the citrate salt of rhBNP, and is provided in a sterile, single-use vial. Each 1.5 mg vial contains a white- to off-white lyophilized powder for intravenous (IV) administration after reconstitution. The quantitative composition of the lyophilized drug per vial is: nesiritide 1.58 mg, mannitol 20.0 mg, citric acid monohydrate 2.1 mg, and sodium citrate dihydrate 2.94 mg.

Mechanism of Action

Human BNP binds to the particulate guanylate cyclase receptor of vascular smooth muscle and endothelial cells, leading to increased intracellular concentrations of guanosine 3'5'-cyclic monophosphate (cGMP) and smooth muscle cell relaxation. Cyclic GMP serves as a second messenger to dilate veins and arteries. Nesiritide has been shown to relax isolated human arterial and venous tissue preparations that were precontracted with either endothelin-1 or the alpha-adrenergic agonist, phenylephrine.

In human studies, nesiritide produced dose-dependent reductions in pulmonary capillary wedge pressure (PCWP) and systemic arterial pressure in patients with heart failure.

In animals, nesiritide had no effects on cardiac contractility or on measures of cardiac electrophysiology such as atrial and ventricular effective refractory times or atrioventricular node conduction.

Naturally occurring atrial natriuretic peptide (ANP), a related peptide, increases vascular permeability in animals and humans and may reduce intravascular volume. The effect of nesiritide on vascular permeability has not been studied.

Pharmacokinetics

In patients with congestive heart failure (CHF), Natrecor administered intravenously by infusion or bolus exhibits biphasic disposition from the plasma. The mean terminal elimination half-life (t1/2) of Natrecor is approximately 18 minutes and was associated with approximately 2/3 of the area-under-the-curve (AUC). The mean initial elimination phase was estimated to be approximately 2 minutes. In these patients, the mean volume of distribution of the central compartment (Vc) of Natrecor was estimated to be 0.073 L/kg, the mean steady-state volume of distribution (Vss) was 0.19 L/kg, and the mean clearance (CL) was approximately 9.2 mL/min/kg. At steady state, plasma BNP levels increase from baseline endogenous levels by approximately 3-fold to 6-fold with Natrecor infusion doses ranging from 0.01 to 0.03 mcg/kg/min.

Elimination

Human BNP is cleared from the circulation via the following three independent mechanisms, in order of decreasing importance: 1) binding to cell surface clearance receptors with subsequent cellular internalization and lysosomal proteolysis; 2) proteolytic cleavage of the peptide by endopeptidases, such as neutral endopeptidase, which are present on the vascular lumenal surface; and 3) renal filtration.

Special Populations

Although Natrecor is eliminated, in part, through renal clearance, clinical data suggest that dose adjustment is not required in patients with renal insufficiency. The effects of Natrecor on PCWP, cardiac index (CI), and systolic blood pressure (SBP) were not significantly different in patients with chronic renal insufficiency (baseline serum creatinine ranging from 2 mg/dL to 4.3 mg/dL), and patients with normal renal function. The population pharmacokinetic (PK) analyses carried out to determine the effects of demographics and clinical variables on PK parameters showed that clearance of Natrecor is proportional to body weight, supporting the administration of weight-adjusted dosing of Natrecor (i.e., administration on a mcg/kg/min basis). Clearance was not influenced significantly by age, gender, race/ethnicity, baseline endogenous hBNP concentration, severity of CHF (as indicated by baseline PCWP, baseline CI, or New York Heart Association [NYHA] classification), or concomitant administration of an ACE inhibitor.

Effects of Concomitant Medications

The co-administration of Natrecor with enalapril did not have significant effects on the PK of Natrecor. The PK effect of co-administration of Natrecor with other IV vasodilators such as nitroglycerin, nitroprusside, milrinone, or IV ACE inhibitors has not been evaluated. During clinical studies, Natrecor was administered concomitantly with other medications, including: diuretics, digoxin, oral ACE inhibitors, anticoagulants, oral nitrates, statins, class III antiarrhythmic agents, beta-blockers, dobutamine, calcium channel blockers, angiotensin II receptor antagonists, and dopamine. Although no PK interactions were specifically assessed, there did not appear to be evidence suggesting any clinically significant PK interaction.

Pharmacodynamics

The recommended dosing regimen of Natrecor is a 2 mcg/kg IV bolus followed by an intravenous infusion dose of 0.01 mcg/kg/min. With this dosing regimen, 60% of the 3-hour effect on PCWP reduction is achieved within 15 minutes after the bolus, reaching 95% of the 3-hour effect within 1 hour. Approximately seventy percent of the 3-hour effect on SBP reduction is reached within 15 minutes. The pharmacodynamic (PD) half-life of the onset and offset of the hemodynamic effect of Natrecor is longer than what the PK half-life of 18 minutes would predict. For example, in patients who developed symptomatic hypotension in the VMAC (Vasodilation in the Management of Acute Congestive Heart Failure) trial, half of the recovery of SBP toward the baseline value after discontinuation or reduction of the dose of Natrecor was observed in about 60 minutes. When higher doses of Natrecor were infused, the duration of hypotension was sometimes several hours.

Clinical Trials

Natrecor has been studied in 10 clinical trials including 941 patients with CHF (NYHA class II–III 61%, NYHA class IV 36%; mean age 60 years, women 28%). There were five randomized, multi-center, placebo- or active-controlled studies (comparative agents included nitroglycerin, dobutamine, milrinone, nitroprusside, or dopamine) in which 772 patients with decompensated CHF received continuous infusions of Natrecor at doses ranging from 0.01 to 0.03 mcg/kg/min. (See the ADVERSE REACTIONS section for relative frequency of adverse events at doses ranging from the recommended dose up to 0.03 mcg/kg/min). Of these patients, the majority (n = 541, 70%) received the Natrecor infusion for at least 24 hours; 371 (48%) received Natrecor for 24–48 hours, and 170 (22%) received Natrecor for greater than 48 hours.

In controlled trials, Natrecor has been used alone or in conjunction with other standard therapies, including diuretics (79%), digoxin (62%), oral ACE inhibitors (55%), anticoagulants (38%), oral nitrates (32%), statins (18%), class III antiarrhythmic agents (16%), beta-blockers (15%), dobutamine (15%), calcium channel blockers (11%), angiotensin II receptor antagonists (6%), and dopamine (4%). Natrecor has been studied in a broad range of patients, including the elderly (42% > 65 years of age), women (30%), minorities (26% black), and patients with a history of significant morbidities such as hypertension (67%), previous myocardial infarction (50%), diabetes (44%), atrial fibrillation/flutter (34%), nonsustained ventricular tachycardia (25%), ventricular tachycardia/fibrillation (12%), preserved systolic function (9%), and acute coronary syndromes less than 7 days before the start of Natrecor (4%).

The VMAC (Vasodilation in the Management of Acute Congestive Heart Failure) trial was a randomized, double-blind study of 489 patients (246 patients requiring a right heart catheter, 243 patients without a right heart catheter) who required hospitalization for management of shortness of breath at rest due to acutely decompensated CHF. The study compared the effects of Natrecor, placebo, and IV nitroglycerin when added to background therapy (IV and oral diuretics, non-IV cardiac medications, dobutamine, and dopamine). Patients with acute coronary syndrome, preserved systolic function, arrhythmia, and renal insufficiency were not excluded. The primary endpoints of the study were the change from baseline in PCWP and the change from baseline in patients' dyspnea, evaluated after three hours. Close attention was also paid to the occurrence and persistence of hypotension, given nesiritide's relatively long (compared to nitroglycerin) PK and PD half-life.

Natrecor was administered as a 2 mcg/kg bolus over approximately 60 seconds, followed by a continuous fixed dose infusion of 0.01 mcg/kg/min. After the 3-hour placebo-controlled period, patients receiving placebo crossed over to double-blinded active therapy with either Natrecor or nitroglycerin. The nitroglycerin dose was titrated at the physician's discretion. A subset of patients in the VMAC trial with central hemodynamic monitoring who were treated with Natrecor (62 of 124 patients) were allowed dose increases of Natrecor after the first 3 hours of treatment if the PCWP was ? 20 mm Hg and the SBP was ? 100 mm Hg. Dose increases of a 1 mcg/kg bolus followed by an increase of the infusion dose by 0.005 mcg/kg/min were allowed every 3 hours, up to a maximum dose of 0.03 mcg/kg/min. Overall, 23 patients in this subset had the dose of Natrecor increased in the VMAC trial.

In a second double-blind study, 127 patients requiring hospitalization for symptomatic CHF were randomized to placebo or to one of two doses of Natrecor (0.015 mcg/kg/min preceded by an IV bolus of 0.3 mcg/kg, and 0.03 mcg/kg/min preceded by an IV bolus of 0.6 mcg/kg). The primary endpoint of the trial was the change in PCWP from baseline to 6 hours, but the effect on symptoms also was examined.

Effects on Symptoms

In the VMAC study, patients receiving Natrecor reported greater improvement in their dyspnea at 3 hours than patients receiving placebo (p = 0.034).

In the dose-response study, patients receiving both doses of Natrecor reported greater improvement in dyspnea at 6 hours than patients receiving placebo.

Effects on Hemodynamics

The PCWP, right atrial pressure (RAP), CI, and other hemodynamic variables were monitored in 246 of the patients in the VMAC trial. There was a reduction in mean PCWP within 15 minutes of starting the Natrecor infusion, with most of the effect seen at 3 hours being achieved within the first 60 minutes of the infusion (see Pharmacodynamics).

In several studies, hemodynamic parameters were measured after Natrecor withdrawal. Following discontinuation of Natrecor, PCWP returns to within 10% of baseline within 2 hours, but no rebound increase to levels above baseline state was observed. There was also no evidence of tachyphylaxis to the hemodynamic effects of Natrecor in the clinical trials.

The following table and graph summarize the changes in the VMAC trial in PCWP and other measures during the first 3 hours.

Mean Hemodynamic Change from Baseline Effects at 3 Hours Placebo
(n = 62) Nitroglycerin
(n = 60) Natrecor
(n = 124) * p < 0.05 compared to placebo † Based on all treated subjects: placebo n = 142, nitroglycerin n = 143, Natrecor n = 204 Pulmonary capillary wedge pressure (mm Hg) -2.0 -3.8 -5.8* Right atrial pressure (mm Hg) 0.0 -2.6 -3.1* Cardiac index (L/min/M2) 0.0 0.2 0.1 Mean pulmonary artery pressure (mm Hg) -1.1 -2.5 -5.4* Systemic vascular resistance (dynes*sec*cm-5) -44 -105 -144 Systolic blood pressure† (mm Hg) -2.5 -5.7* -5.6*

The VMAC study does not constitute an adequate effectiveness comparison with nitroglycerin. In this trial, the nitroglycerin group provides a rough landmark using a familiar therapy and regimen.

Effect on Urine Output

In the VMAC trial, in which the use of diuretics was not restricted, the mean change in volume status (output minus input) during the first 24 hours in the nitroglycerin and Natrecor groups was similar: 1279 ± 1455 mL and 1257 ± 1657 mL, respectively.

Indications and Usage for Natrecor

Natrecor (nesiritide) is indicated for the intravenous treatment of patients with acutely decompensated congestive heart failure who have dyspnea at rest or with minimal activity. In this population, the use of Natrecor reduced pulmonary capillary wedge pressure and improved dyspnea.

Contraindications

Natrecor is contraindicated in patients who are hypersensitive to any of its components. Natrecor should not be used as primary therapy for patients with cardiogenic shock or in patients with a systolic blood pressure < 90 mm Hg.

Warnings

Administration of Natrecor should be avoided in patients suspected of having, or known to have, low cardiac filling pressures.

Precautions General

Parenteral administration of protein pharmaceuticals or E. coli-derived products should be attended by appropriate precautions in case of an allergic or untoward reaction.

Natrecor is not recommended for patients for whom vasodilating agents are not appropriate, such as patients with significant valvular stenosis, restrictive or obstructive cardiomyopathy, constrictive pericarditis, pericardial tamponade, or other conditions in which cardiac output is dependent upon venous return, or for patients suspected to have low cardiac filling pressures (see CONTRAINDICATIONS).

Renal

Natrecor may affect renal function in susceptible individuals. In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with Natrecor may be associated with azotemia. When Natrecor was initiated at doses higher than 0.01 mcg/kg/min (0.015 and 0.03 mcg/kg/min), there was an increased rate of elevated serum creatinine over baseline compared with standard therapies, although the rate of acute renal failure and need for dialysis was not increased. In the 30-day follow-up period in the VMAC trial, 5 patients in the nitroglycerin group (2%) and 9 patients in the Natrecor group (3%) required first-time dialysis.

Cardiovascular

Natrecor may cause hypotension. In the VMAC trial, in patients given the recommended dose (2 mcg/kg bolus followed by a 0.01 mcg/kg/min infusion) or the adjustable dose, the incidence of symptomatic hypotension in the first 24 hours was similar for Natrecor (4%) and IV nitroglycerin (5%). When hypotension occurred, however, the duration of symptomatic hypotension was longer with Natrecor (mean duration was 2.2 hours) than with nitroglycerin (mean duration was 0.7 hours). In earlier trials, when Natrecor was initiated at doses higher than the 2 mcg/kg bolus followed by a 0.01 mcg/kg/min infusion (i.e., 0.015 and 0.03 mcg/kg/min preceded by a small bolus), there were more hypotensive episodes and these episodes were of greater intensity and duration. They were also more often symptomatic and/or more likely to require medical intervention (see ADVERSE REACTIONS). Natrecor should be administered only in settings where blood pressure can be monitored closely, and the dose of Natrecor should be reduced or the drug discontinued in patients who develop hypotension (see Dosing Instructions). The rate of symptomatic hypotension may be increased in patients with a blood pressure < 100 mm Hg at baseline, and Natrecor should be used cautiously in these patients. The potential for hypotension may be increased by combining Natrecor with other drugs that may cause hypotension. For example, in the VMAC trial in patients treated with either Natrecor or nitroglycerin therapy, the frequency of symptomatic hypotension in patients who received an oral ACE inhibitor was 6%, compared to a frequency of symptomatic hypotension of 1% in patients who did not receive an oral ACE inhibitor.

Drug Interactions

No trials specifically examining potential drug interactions with Natrecor were conducted, although many concomitant drugs were used in clinical trials. No drug interactions were detected except for an increase in symptomatic hypotension in patients receiving oral ACE inhibitors (see PRECAUTIONS, Cardiovascular).

The co-administration of Natrecor with IV vasodilators such as nitroglycerin, nitroprusside, milrinone, or IV ACE inhibitors has not been evaluated (these drugs were not co-administered with Natrecor in clinical trials).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate the carcinogenic potential or the effect on fertility of nesiritide. Nesiritide did not increase the frequency of mutations when used in an in vitro bacterial cell assay (Ames test). No other genotoxicity studies were performed.

Pregnancy Category C

It is not known whether Natrecor can cause fetal harm when administered to pregnant women or if it can affect reproductive capacity. A developmental reproductive toxicology study was conducted in pregnant rabbits using doses up to 1440 mcg/kg/day given by constant infusion for 13 days. At this level of exposure (based on AUC, approximately 70 ? human exposure at the recommended dose) no adverse effects on live births or fetal development were observed. Natrecor should be used during pregnancy only if the potential benefit justifies any possible risk to the fetus.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Therefore, caution should be exercised when Natrecor is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of Natrecor in pediatric patients has not been established.

Geriatric Use

Of the total number of subjects in clinical trials treated with Natrecor (n = 941), 38% were 65 years or older and 16% were 75 years or older. No overall differences in effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. Some older individuals may be more sensitive to the effect of Natrecor than younger individuals.

Adverse Reactions

Adverse events that occurred with at least a 3% frequency during the first 24 hours of Natrecor infusion are shown in the following table.

Adverse Event VMAC Trial Other Long Infusion Trials Nitroglycerin
(n = 216) Natrecor Recommended Dose
(n = 273) Control*
(n = 256) Natrecor
mcg/kg/min 0.015
(n = 253) 0.03
(n = 246) * Includes dobutamine, milrinone, nitroglycerin, placebo, dopamine, nitroprusside, or amrinone Cardiovascular Hypotension 25 (12%) 31 (11%) 20 (8%) 56 (22%) 87 (35%)   Symptomatic Hypotension 10 (5%) 12 (4%) 8 (3%) 28 (11%) 42 (17%)   Asymptomatic Hypotension 17 (8%) 23 (8%) 13 (5%) 31 (12%) 49 (20%) Ventricular Tachycardia (VT) 11 (5%) 9 (3%) 25 (10%) 25 (10%) 10 (4%)   Non-sustained VT 11 (5%) 9 (3%) 23 (9%) 24 (9%) 9 (4%) Ventricular Extrasystoles 2 (1%) 7 (3%) 15 (6%) 10 (4%) 9 (4%) Angina Pectoris 5 (2%) 5 (2%) 6 (2%) 14 (6%) 6 (2%) Bradycardia 1 (< 1%) 3 (1%) 1 (< 1%) 8 (3%) 13 (5%) Body as a Whole Headache 44 (20%) 21 (8%) 23 (9%) 23 (9%) 17 (7%) Abdominal Pain 11 (5%) 4 (1%) 10 (4%) 6 (2%) 8 (3%) Back Pain 7 (3%) 10 (4%) 4 (2%) 5 (2%) 3 (1%) Nervous Insomnia 9 (4%) 6 (2%) 7 (3%) 15 (6%) 15 (6%) Dizziness 4 (2%) 7 (3%) 7 (3%) 16 (6%) 12 (5%) Anxiety 6 (3%) 8 (3%) 2 (1%) 8 (3%) 4 (2%) Digestive Nausea 13 (6%) 10 (4%) 12 (5%) 24 (9%) 33 (13%) Vomiting 4 (2%) 4 (1%) 2 (1%) 6 (2%) 10 (4%)

Adverse events that are not listed in the above table that occurred in at least 1% of patients who received any of the above Natrecor doses included: Tachycardia, atrial fibrillation, AV node conduction abnormalities, catheter pain, fever, injection site reaction, confusion, paresthesia, somnolence, tremor, increased cough, hemoptysis, apnea, increased creatinine, sweating, pruritus, rash, leg cramps, amblyopia, anemia. All reported events (at least 1%) are included except those already listed, those too general to be informative, and those not reasonably associated with the use of the drug because they were associated with the condition being treated or are very common in the treated population.

In placebo and active-controlled clinical trials, Natrecor has not been associated with an increase in atrial or ventricular tachyarrhythmias. In placebo-controlled trials, the incidence of VT in both Natrecor and placebo patients was 2%. In the PRECEDENT (Prospective Randomized Evaluation of Cardiac Ectopy with Dobutamine or Natrecor Therapy) trial, the effects of Natrecor (n = 163) and dobutamine (n = 83) on the provocation or aggravation of existing ventricular arrhythmias in patients with decompensated CHF was compared using Holter monitoring. Treatment with Natrecor (0.015 and 0.03 mcg/kg/min without an initial bolus) for 24 hours did not aggravate pre-existing VT or the frequency of premature ventricular beats, compared to a baseline 24-hour Holter tape.

Clinical Laboratory

In the PRECEDENT trial, the incidence of elevations in serum creatinine to > 0.5 mg/dL above baseline through day 14 was higher in the Natrecor 0.015 mcg/kg/min group (17%) and the Natrecor 0.03 mcg/kg/min group (19%) than with standard therapy (11%). In the VMAC trial, through day 30, the incidence of elevations in creatinine to > 0.5 mg/dL above baseline was 28% and 21% in the Natrecor (2 mcg/kg bolus followed by 0.01 mcg/kg/min) and nitroglycerin groups, respectively.

Effect on Mortality

Data from all seven studies in which 30-day data were collected are presented in the chart below. The data depict hazard ratios and confidence intervals of mortality data for randomized and treated patients with Natrecor® relative to active controls through day 30 for each of the 7 individual studies (Studies 311, 325, 326, 329 [PRECEDENT], 339 [VMAC], 341 [PROACTION], and 348 [FUSION I]).

The figure (on logarithmic scale) also contains a plot for the six studies involving hospitalized or Emergency Department patients combined (n = 1507), and for all 7 studies combined (n = 1717). The percentage is the Kaplan-Meier estimate.

The figure below represents 180-day mortality hazard ratios for randomized and treated patients from all five individual studies where 180-day data were collected, 16 week hazard ratios for Study 348 (180-day data were not collected), and the five studies with 180-day data pooled (n = 1404).

There were few deaths in these studies, so the confidence limits around the hazard ratios for mortality are wide. The studies are also small, so some potentially important baseline imbalances exist among the treatment groups, the effects of which cannot be ascertained.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Natrecor. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency: hypersensitivity reactions.

Overdosage

Overdose with Natrecor therapy has been reported and is primarily the result of either a miscalculated Natrecor dose or a mechanical error such as an infusion-pump malfunction or an infusion-pump programming error. The most frequently reported adverse event reported with Natrecor overdose is hypotension, which may be asymptomatic and most often resolves with drug stoppage, although in some cases hypotension may persist for several hours beyond discontinuation. Treatment of Natrecor overdose should include drug discontinuation and the administration of supportive measures (see PRECAUTIONS — Cardiovascular).

Natrecor Dosage and Administration

The Natrecor bolus must be drawn from the prepared infusion bag.

Natrecor (nesiritide) is for intravenous use only. There is limited experience with administering Natrecor for longer than 48 hours. Blood pressure should be monitored closely during Natrecor administration.

If hypotension occurs during the administration of Natrecor, the dose should be reduced or discontinued and other measures to support blood pressure should be started (IV fluids, changes in body position). In the VMAC trial, when symptomatic hypotension occurred, Natrecor was discontinued and subsequently could be restarted at a dose that was reduced by 30% (with no bolus administration) once the patient was stabilized. Because hypotension caused by Natrecor may be prolonged (up to hours), a period of observation may be necessary before restarting the drug.

Preparation

The Natrecor bolus must be drawn from the prepared infusion bag.

Reconstitute one 1.5 mg vial of Natrecor by adding 5 mL of diluent removed from a pre-filled 250 mL plastic IV bag containing the diluent of choice. After reconstitution of the vial, each mL contains 0.32 mg of nesiritide. The following preservative-free diluents are recommended for reconstitution: 5% Dextrose Injection (D5W), USP; 0.9% Sodium Chloride Injection, USP; 5% Dextrose and 0.45% Sodium Chloride Injection, USP, or 5% Dextrose and 0.2% Sodium Chloride Injection, USP. Do not shake the vial. Rock the vial gently so that all surfaces, including the stopper, are in contact with the diluent to ensure complete reconstitution. Use only a clear, essentially colorless solution. Withdraw the entire contents of the reconstituted Natrecor vial and add to the 250 mL plastic IV bag. This will yield a solution with a concentration of Natrecor of approximately 6 mcg/mL. The IV bag should be inverted several times to ensure complete mixing of the solution. Use the reconstituted solution within 24 hours, as Natrecor contains no antimicrobial preservative. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Reconstituted vials of Natrecor may be stored at 2–25°C (36–77°F) for up to 24 hours. Dosing Instructions

The Natrecor bolus must be drawn from the prepared infusion bag.

The recommended dose of Natrecor is an IV bolus of 2 mcg/kg followed by a continuous infusion of 0.01 mcg/kg/min. Natrecor should not be initiated at a dose that is above the recommended dose.

Prime the IV tubing with 5 mL of the solution for infusion prior to connecting to the patient's vascular access port and prior to administering the bolus or starting the infusion.

The administration of the recommended dose of Natrecor is a two step process:

Step 1. Administration of the IV Bolus

After preparation of the infusion bag, as described previously, withdraw the bolus volume (see Weight-Adjusted Bolus Volume table) from the Natrecor infusion bag, and administer it over approximately 60 seconds through an IV port in the tubing.

Bolus Volume (mL) = Patient Weight (kg) / 3

Natrecor Weight-Adjusted Bolus Volume Administered Over 60 Seconds (Final Concentration = 6 mcg/mL) Patient Weight (kg) Volume of Bolus (mL = kg/3) 60 20.0 70 23.3 80 26.7 90 30.0 100 33.3 110 36.7

Step 2. Administration of the Continuous Infusion

Immediately following the administration of the bolus, infuse Natrecor at a flow rate of 0.1 mL/kg/hr. This will deliver a Natrecor infusion dose of 0.01 mcg/kg/min.

To calculate the infusion flow rate to deliver a 0.01 mcg/kg/min dose, use the following formula (see the following Weight-Adjusted Infusion Flow Rate for Dosing table):

Infusion Flow Rate (mL/hr) = Patient Weight (kg) ? 0.1

Natrecor Weight-Adjusted Infusion Flow Rate for a 0.01 mcg/kg/min Dose following Bolus (Final Concentration = 6 mcg/mL) Patient Weight (kg) Infusion Flow Rate (mL/hr) 60 6 70 7 80 8 90 9 100 10 110 11 Dose Adjustments

The dose-limiting side effect of Natrecor is hypotension. Do not initiate Natrecor at a dose that is higher than the recommended dose of a 2 mcg/kg bolus followed by an infusion of 0.01 mcg/kg/min. In the VMAC trial there was limited experience with increasing the dose of Natrecor above the recommended dose (23 patients, all of whom had central hemodynamic monitoring). In those patients, the infusion dose of Natrecor was increased by 0.005 mcg/kg/min (preceded by a bolus of 1 mcg/kg), no more frequently than every 3 hours up to a maximum dose of 0.03 mcg/kg/min. Natrecor should not be titrated at frequent intervals as is done with other IV agents that have a shorter half-life (see Clinical Trials).

Chemical/Physical Interactions

Natrecor is physically and/or chemically incompatible with injectable formulations of heparin, insulin, ethacrynate sodium, bumetanide, enalaprilat, hydralazine, and furosemide. These drugs should not be co-administered as infusions with Natrecor through the same IV catheter. The preservative sodium metabisulfite is incompatible with Natrecor. Injectable drugs that contain sodium metabisulfite should not be administered in the same infusion line as Natrecor. The catheter must be flushed between administration of Natrecor and incompatible drugs.

Natrecor binds to heparin and therefore could bind to the heparin lining of a heparin-coated catheter, decreasing the amount of Natrecor delivered to the patient for some period of time. Therefore, Natrecor must not be administered through a central heparin-coated catheter. Concomitant administration of a heparin infusion through a separate catheter is acceptable.

STORAGE

Store below 25°C. Do not freeze. Keep the vial in the outer carton in order to protect from light.

How is Natrecor Supplied

Natrecor (nesiritide) is provided as a sterile lyophilized powder in 1.5 mg, single-use vials. Each carton contains one vial and is available in the following package:

1 vial/carton (NDC 65847-205-25)

US patent No. 5,114,923 and 5,674,710.

Manufactured for Scios Inc.
Titusville, NJ 08560

Copyright 2007 Scios Inc.

Revised: June 2009

PRINCIPAL DISPLAY PANEL - 1.5 mg Vial Carton

Scios Inc.
NDC 65847-205-25

Natrecor®
(nesiritide)
for Injection

1.5 mg
Single-use vial

For IV Infusion Only

Store below 25°C. Do not freeze. Keep the vial
in the outer carton in order to protect from light.

Rx only


Natrecor 
nesiritide  injection, powder, lyophilized, for solution Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 65847-205 Route of Administration INTRAVENOUS DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength NESIRITIDE (NESIRITIDE) NESIRITIDE 1.5 mg  in 5 mL Inactive Ingredients Ingredient Name Strength MANNITOL 20 mg  in 5 mL CITRIC ACID MONOHYDRATE 2.1 mg  in 5 mL TRISODIUM CITRATE DIHYDRATE 2.94 mg  in 5 mL Product Characteristics Color WHITE (white to off white) Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 65847-205-25 1 VIAL In 1 CARTON contains a VIAL, SINGLE-USE 1 5 mL In 1 VIAL, SINGLE-USE This package is contained within the CARTON (65847-205-25)
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020920 08/01/2001
Labeler - Scios Inc. (015904436) Establishment Name Address ID/FEI Operations Hospira, Inc. 030606222 MANUFACTURE Establishment Name Address ID/FEI Operations Sandoz GmbH, BiochemiestraB 10 300220969 MANUFACTURE, ANALYSIS Establishment Name Address ID/FEI Operations Sandoz GmbH, A-6330 Schaftenau 301698247 MANUFACTURE Revised: 08/2010Scios Inc. More Natrecor resources Natrecor Side Effects (in more detail)Natrecor Use in Pregnancy & BreastfeedingNatrecor Drug InteractionsNatrecor Support Group0 Reviews for Natrecor - Add your own review/rating Natrecor Monograph (AHFS DI) Natrecor Consumer Overview Natrecor Advanced Consumer (Micromedex) - Includes Dosage Information Natrecor MedFacts Consumer Leaflet (Wolters Kluwer) Nesiritide Professional Patient Advice (Wolters Kluwer) Compare Natrecor with other medications Heart Failure
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Heparin Lock Flush Solution


Generic Name: heparin sodium
Dosage Form: injection, solution
Heparin Lock Flush Solution, USP

FOR MAINTENANCE OF PATENCY OF INTRAVENOUS INJECTION DEVICES ONLY.

NOT FOR ANTICOAGULANT THERAPY.

DERIVED FROM PORCINE INTESTINAL MUCOSA.

PRESERVATIVE FREE.

Heparin Lock Flush Solution Description

Heparin is a heterogeneous group of straight-chain anionic mucopolysaccharides, called glycosaminoglycans having anticoagulant properties. Although others may be present, the main sugars occurring in heparin are: (1) ?-L-iduronic acid 2-sulfate, (2) 2-deoxy-2-sulfamino-?-D-glucose 6-sulfate, (3) ?-D-glucuronic acid, (4) 2-acetamido-2-deoxy-?-D-glucose and (5) ?-L-iduronic acid.  These sugars are present in decreasing amounts, usually in the order (2)> (1)> (4)> (3)> (5), and are joined by glycosidic linkages, forming polymers of varying sizes.  Heparin is strongly acidic because of its content of covalently linked sulfate and carboxylic acid groups.  In heparin sodium, the acidic protons of the sulfate units are partially replaced by sodium ions.

Heparin Lock Flush Solution, USP is a sterile preparation of heparin sodium derived from porcine intestinal mucosa, standardized for anticoagulant activity, with sufficient sodium chloride to make it isotonic with blood.  The potency is determined by a biological assay using a USP reference standard based on units of heparin activity per milligram. 

Structure of Heparin Sodium (representative subunits):

 

Each mL contains: 10 USP Units Heparin sodium (porcine); 9 mg sodium chloride; Water for Injection q.s.  Sodium hydroxide and/or hydrochloric acid for pH adjustment (5.0-7.5).

Each mL contains: 100 USP Units Heparin sodium (porcine); 9 mg sodium chloride; Water for Injection q.s.  Sodium hydroxide and/or hydrochloric acid for pH adjustment (5.0-7.5).

Heparin Lock Flush Solution - Clinical Pharmacology

Heparin inhibits reactions that lead to the clotting of blood and the formation of fibrin clots both in vitro and in vivo.  Heparin acts at multiple sites in the normal coagulation system.  Small amounts of heparin in combination with antithrombin III (heparin cofactor) can inhibit thrombosis by inactivating activated Factor X and inhibiting the conversion of prothrombin to thrombin.  Once active thrombosis has developed, larger amounts of heparin can inhibit further coagulation by inactivating thrombin and preventing the conversion of fibrinogen to fibrin.  Heparin also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor.

Bleeding time is usually unaffected by heparin.  Clotting time is prolonged by full therapeutic doses of heparin; in most cases it is not measurably affected by low doses of heparin.  Loglinear plots of heparin plasma concentrations with time, for a wide range of dose levels, are linear, which suggests the absence of zero order processes.  Liver and the reticulo-endothelial system are the sites of biotransformation.  The biphasic elimination curve, a rapidly declining alpha phase (t?= 10 minutes) and after the age of 40 a slower beta phase, indicates uptake in organs.  The absence of a relationship between anticoagulant half-life and concentration half-life may reflect factors such as protein binding of heparin.

Patients over 60 years of age, following similar doses of heparin, may have higher plasma levels of heparin and longer activated partial thromboplastine times (APTTs) compared with patients under 60 years of age.

Heparin does not have fibrinolytic activity; therefore, it will not lyse existing clots.

Indications and Usage for Heparin Lock Flush Solution

Heparin Lock Flush Solution, USP is intended to maintain patency of an indwelling venipuncture device designed for intermittent injection or infusion therapy or blood sampling.  Heparin Lock Flush Solution may be used following initial placement of the device in the vein, after each injection of a medication or after withdrawal of blood for laboratory tests (see DOSAGE AND ADMINISTRATION, Maintenance of Patency of IV Devices for directions for use).

Heparin Lock Flush Solution is not to be used for anticoagulant therapy.

Contraindications

Heparin sodium should NOT be used in patients with the following conditions: severe thrombocytopenia; an uncontrollable active bleeding state (see WARNINGS), except when this is due to disseminated intravascular coagulation.

Warnings

Heparin is not intended for intramuscular use.

Hypersensitivity

Patients with documented hypersensitivity to heparin should be given the drug only in clearly life-threatening situations (see Adverse Reactions, Hypersensitivity).

Hemorrhage

Hemorrhage can occur at virtually any site in patients receiving heparin.  An unexplained fall in hematocrit, fall in blood pressure or any other unexplained symptom should lead to serious consideration of a hemorrhagic event.

Heparin sodium should be used with extreme caution in infants and in patients with disease states in which there is increased danger of hemorrhage.  Some of the conditions in which increased danger of hemorrhage exists are:

Cardiovascular–Subacute bacterial endocarditis, severe hypertension.

Surgical–During and immediately following (a) spinal tap or spinal anesthesia or (b) major surgery, especially involving the brain, spinal cord or eye.

Hematologic–Conditions associated with increased bleeding tendencies, such as hemophilia, thrombocytopenia and some vascular purpuras.

Gastrointestinal–Ulcerative lesions and continuous tube drainage of the stomach or small intestine.

Other–Menstruation, liver disease with impaired hemostasis.

Thrombocytopenia

Thrombocytopenia has been reported to occur in patients receiving heparin with a reported incidence of 0 to 30%.  Platelet counts should be obtained at baseline.  Mild thrombocytopenia (count greater than 100,000/mm3) may remain stable or reverse even if heparin is continued.  However, thrombocytopenia of any degree should be monitored closely.  If the count falls below 100,000/mm3 or if recurrent thrombosis develops (see Heparin-induced Thrombocytopenia and Heparin-induced Thrombocytopenia and Thrombosis), the heparin product should be discontinued and, if necessary, an alternative anticoagulant administered.

Heparin-induced Thrombocytopenia (HIT) and Heparin-induced Thrombocytopenia and Thrombosis (HITT)

Heparin-induced Thrombocytopenia (HIT) is a serious antibody-mediated reaction resulting from irreversible aggregation of platelets.  HIT may progress to the development of venous and arterial thromboses, a condition referred to as Heparin-induced Thrombocytopenia and Thrombosis (HITT).  Thrombotic events may also be the initial presentation for HITT.  These serious thromboembolic events include deep vein thrombosis, pulmonary embolism, cerebral vein thrombosis, limb ischemia, stroke, myocardial infarction, mesenteric thrombosis, renal arterial thrombosis, skin necrosis, gangrene of the extremities that may lead to amputation, and possibly death.  Thrombocytopenia of any degree should be monitored closely.  If the platelet count falls below 100,000/mm3 or if recurrent thrombosis develops, the heparin product should be promptly discontinued and alternative anticoagulants considered if patients require continued anticoagulation.

Delayed Onset of HIT and HITT

Heparin-induced Thrombocytopenia and Heparin-induced Thrombocytopenia and Thrombosis can occur up to several weeks after the discontinuation of heparin therapy.  Patients presenting with thrombocytopenia or thrombosis after discontinuation of heparin should be evaluated for HIT and HITT.

Use in Neonates

Preservative-Free Heparin Lock Flush Solution, USP should be used for maintaining the patency of intravenous injection devices in neonates.

Precautions General

In infants, the cumulative amounts of heparin received from the frequent administration of Heparin Lock Flush Solution, USP during a 24- hour period should be considered.

Precautions must be exercised when drugs which are incompatible with heparin are administered through an indwelling intravenous catheter containing Heparin Lock Flush Solution, USP (see DOSAGE AND ADMINISTRATION, Maintenance of Patency of IV Devices).

Thrombocytopenia, Heparin-induced Thrombocytopenia (HIT) and Heparin-induced Thrombocytopenia and Thrombosis (HITT)

See WARNINGS.

Increased Risk to Older Patients, Especially Women–A higher incidence of bleeding has been reported in patients, particularly women over 60 years of age.

Laboratory Tests

Periodic platelet counts, hematocrits and tests for occult blood in stool are recommended during the entire course of heparin use (see DOSAGE AND ADMINISTRATION).

Drug Interactions

Platelet Inhibitors–Drugs such as acetylsalicylic acid, dextran, phenylbutazone, ibuprofen, indomethacin, dipyridamole, hydroxychloroquine and others that interfere with platelet-aggregation reactions (the main hemostatic defense of heparinized patients) may induce bleeding and should be used with caution in patients receiving heparin sodium.

Other Interactions–Digitalis, tetracyclines, nicotine or antihistamines may partially counteract the anticoagulant action of heparin sodium.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term studies in animals have been performed to evaluate the carcinogenic potential of heparin.  Also, no reproduction studies in animals have been performed concerning mutagenesis or impairment of fertility.

Pregnancy

Teratogenic Effects: Pregnancy Category C–

Animal reproduction studies have not been conducted with heparin sodium.  It is also not known whether heparin sodium can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.  Heparin sodium should be given to a pregnant woman only if clearly needed.

Nonteratogenic Effects–Heparin does not cross the placental barrier.

Nursing Mothers

Heparin is not excreted in human milk.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.  Not for use in neonates (see WARNINGS).

Geriatric Use

A higher incidence of bleeding has been reported in patients over 60 years of age, especially women (see PRECAUTIONS, General and CLINICAL PHARMACOLOGY).

Adverse Reactions Hemorrhage

Hemorrhage is the chief complication that may result from heparin use (see WARNINGS).  An overly prolonged clotting time or minor bleeding during therapy can usually be controlled by withdrawing the drug (see OVERDOSAGE).

Thrombocytopenia, Heparin-induced Thrombocytopenia (HIT) and Heparin-induced Thrombocytopenia and Thrombosis (HITT) and Delayed Onset of HIT and HITT

See WARNINGS.

Local irritation and erythema have been reported with the use of Heparin Lock Flush Solution.

Hypersensitivity

Generalized hypersensitivity reactions have been reported, with chills, fever and urticaria as the most usual manifestations, and asthma, rhinitis, lacrimation, headache, nausea and vomiting, and anaphylactoid reactions, including shock, occurring more rarely.  Itching and burning, especially on the plantar side of the feet, may occur.

Thrombocytopenia has been reported to occur in patients receiving heparin, with a reported incidence of 0 to 30%.  While often mild and of no obvious clinical significance, such thrombocytopenia can be accompanied by severe thromboembolic complications such as skin necrosis, gangrene of the extremities that may lead to amputation, myocardial infarction, pulmonary embolism, stroke, and possibly death (see WARNINGS and PRECAUTIONS).

Certain episodes of painful, ischemic and cyanosed limbs have in the past been attributed to allergic vasospastic reactions.  Whether these are in fact identical to the thrombocytopenia-associated complications remains to be determined.

Overdosage Symptoms

Bleeding is the chief sign of heparin overdosage.  Nosebleeds, blood in urine or tarry stools may be noted as the first sign of bleeding.  Easy bruising or petechial formations may precede frank bleeding.

Treatment - Neutralization of Heparin Effect

When clinical circumstances (bleeding) require reversal of heparinization, protamine sulfate (1% solution) by slow infusion will neutralize heparin sodium.  No more than 50 mg should be administered, very slowly, in any 10 minute period.  Each mg of protamine sulfate neutralizes approximately 100 USP heparin units.  The amount of protamine required decreases over time as heparin is metabolized.  Although metabolism of heparin is complex, it may, for the purpose of choosing a protamine dose, be assumed to have a half-life of about 1/2 hour after intravenous injection.

Administration of protamine sulfate can cause severe hypotensive and anaphylactoid reactions.  Because fatal reactions often resembling anaphylaxis have been reported, the drug should be given only when resuscitation techniques and treatment of anaphylactoid shock are readily available.

For additional information consult the labeling of Protamine Sulfate Injection, USP products.

DOSAGE AND ADMINISTRATION

Parental drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.  Slight discoloration does not alter potency.

Heparin Lock Flush Solution, USP is not recommended for use in the neonate (see WARNINGS).

Maintenance of Patency of IV Devices

To prevent clot formation in a heparin lock set or central venous catheter following its proper insertion, Heparin Lock Flush Solution, USP is injected via the injection hub in a quantity sufficient to fill the entire device.  This solution should be replaced each time the device is used.  Aspirate before administering any solution via the device in order to confirm patency and location of needle or catheter tip.  If the drug to be administered is incompatible with heparin, the entire device should be flushed with normal saline before and after the medication is administered; following the second saline flush, the Heparin Lock Flush Solution may be reinstilled into the device.  The device manufacturer’s instructions should be consulted for specifics concerning its use.  Usually this dilute heparin solution will maintain anticoagulation within the device for up to 4 hours.

NOTE:  Since repeated injections of small doses of heparin can alter tests for activated partial thromboplastin time (APTT), a baseline value for APTT should be obtained prior to insertion of a heparin lock set.

Withdrawal of Blood Samples

Heparin Lock Flush Solution may also be used after each withdrawal of blood for laboratory tests.  When heparin would interfere with or alter the results of blood tests, the heparin solution should be cleared from the device by aspirating and discarding it before withdrawing the blood sample.

HOW SUPPLIED

Product

No.

NDC

No.

 


504901

63323-549-01

Heparin Lock Flush Solution, USP, Preservative Free, 100 USP Units/mL, 1 mL fill, in a 3 mL flip-top, single dose plastic vial, in packages of 25.

505701

63323-557-01

Heparin Lock Flush Solution, USP, Preservative Free, 10 USP Units/mL, 1 mL fill, in a 3 mL flip-top, single dose plastic vial, in packages of 25.

Unused portion of the vial should be discarded.

Use only if solution is clear and seal intact.


STORAGE

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

REFERENCES
Tahata T, Shigehito M, Kusuhara K, Ueda Y, et al. Delayed-Onset of Heparin-Induced Thrombocytopenia – A Case Report – J Jpn Assn Torca Surg. 1992;40(3):110-111. Warkentin T, Kelton J. Delayed-Onset Heparin-Induced Thrombocytopenia and Thrombosis. Annals of Internal Medicine. 2001;135:502-506. Rice L, Attisha W, Drexler A, Francis J. Delayed-Onset Heparin-Induced Thrombocytopenia.  Annals of Internal Medicine, 2002;136:210-215. Dieck J., C. Rizo-Patron, et al. (1990). “A New Manifestation and Treatment Alternative for Heparin-Induced Thrombosis.” Chest 98(1524-26). Smythe M, Stephens J, Mattson. Delayed-Onset Heparin-Induced Thrombocytopenia.  Annals of Emergency Medicine, 2005;45(4): 417-419. Divgi A. (Reprint), Thumma S., Hari P., Friedman K. Delayed Onset Heparin-Induced Thrombocytopenia (HIT) Presenting After Undocumented Drug Exposure as Post-Angiography Pulmonary Embolism. Blood.  2003;102(11):127b.

For Product Inquiry: 1-800-551-7176

451198A

Issued: July 2010

PACKAGE LABEL - PRINCIPAL DISPLAY - Heparin Lock Flush Solution 1 mL Single Dose Vial Label

NDC 63323-549-01

504901

Heparin Lock Flush Solution, USP

100 USP Units/mL

(Derived from Porcine Intestinal Mucosa)

Preservative Free                 Rx only

1 mL Single Dose Vial



PACKAGE LABEL - PRINCIPAL DISPLAY - Heparin Lock Flush Solution 1 mL Single Dose Vial Tray Label

NDC 63323-549-01

504901

Heparin Lock Flush Solution, USP

100 USP Units/mL

(Derived from Porcine Intestinal Mucosa)

1 mL Single Dose Vial

Rx only



PACKAGE LABEL - PRINCIPAL DISPLAY - Heparin Lock Flush Solution 1 mL Single Dose Vial

NDC 63323-557-01

505701

Heparin Lock Flush Solution, USP

10 USP Units/mL

(Derived from Porcine Intestinal Mucosa)

Preservative Free                 Rx only

1 mL Single Dose Vial



PACKAGE LABEL - PRINCIPAL DISPLAY - Heparin Lock Flush Solution 1 mL Single Dose Vial Tray Label

NDC 63323-557-01

505701

Heparin Lock Flush Solution, USP

10 USP Units/mL

(Derived from Porcine Intestinal Mucosa)

1 mL Single Dose Vial

Rx only



HEPARIN LOCK FLUSH 
heparin sodium  injection, solution Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 63323-557 Route of Administration INTRAVENOUS DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength HEPARIN SODIUM (HEPARIN) HEPARIN SODIUM 10 [USP'U]  in 1 mL Inactive Ingredients Ingredient Name Strength SODIUM CHLORIDE 9 mg  in 1 mL SODIUM HYDROXIDE   HYDROCHLORIC ACID   Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 63323-557-01 25 VIAL In 1 BOX contains a VIAL 1 1 mL In 1 VIAL This package is contained within the BOX (63323-557-01)
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date Premarket Notification K092938 08/29/2009
HEPARIN LOCK FLUSH 
heparin sodium  injection, solution Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 63323-549 Route of Administration INTRAVENOUS DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength HEPARIN SODIUM (HEPARIN) HEPARIN SODIUM 100 [USP'U]  in 1 mL Inactive Ingredients Ingredient Name Strength SODIUM CHLORIDE 9 mg  in 1 mL HYDROCHLORIC ACID   SODIUM HYDROXIDE   Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 63323-549-01 25 VIAL In 1 TRAY contains a VIAL 1 1 mL In 1 VIAL This package is contained within the TRAY (63323-549-01)
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date Premarket Notification K092938 08/12/2009
Labeler - APP Pharmaceuticals, LLC (608775388) Establishment Name Address ID/FEI Operations APP Pharmaceuticals, LLC 840771732 MANUFACTURE Revised: 12/2010APP Pharmaceuticals, LLC More Heparin Lock Flush Solution resources Heparin Lock Flush Solution Dosage Heparin Lock Flush Solution Use in Pregnancy & Breastfeeding Heparin Lock Flush Solution Drug Interactions Heparin Lock Flush Solution Support Group 0 Reviews for Heparin Lock Flush - Add your own review/rating Compare Heparin Lock Flush Solution with other medications Angina Anticoagulation During Pregnancy Antiphospholipid Syndrome Deep Vein Thrombosis Deep Vein Thrombosis, Prophylaxis Heart Attack Pulmonary Embolism Thrombotic/Thromboembolic Disorder
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Quinocort Cream


1. Name Of The Medicinal Product QUINOCORT™ CREAM 2. Qualitative And Quantitative Composition

Potassium Hydroxyquinoline Sulphate BP

0.5%

Hydrocortisone BP

1.0%

3. Pharmaceutical Form

Quinocort Cream is a faintly yellow vanishing cream. It is intended for topical use only.

4. Clinical Particulars 4.1 Therapeutic Indications

The treatment of infected eczema, intertrigo and other steroid-responsive dermatoses where anti-infective cover is appropriate.

4.2 Posology And Method Of Administration

Route of administration: For topical use only.

Adults, children and the elderly

By gentle massage over all the affected area two to three times daily.

4.3 Contraindications

Patients with known sensitivity or intolerance to any of the ingredients.

4.4 Special Warnings And Precautions For Use

Contact with eyes and other mucosal surfaces should be avoided. Caution should be exercised when using this preparation in infants. Long term continuous topical therapy should be avoided in infants - adrenal suppression can occur even without occlusion.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Not applicable.

4.6 Pregnancy And Lactation

In pregnant animals administration of corticosteroids can cause abnormalities of foetal development. The relevance of this finding in human beings has not been established. However, topical steroids should not be used extensively in pregnancy i.e. in large amounts for long periods.

4.7 Effects On Ability To Drive And Use Machines

Not applicable.

4.8 Undesirable Effects

Not applicable.

4.9 Overdose

Not applicable.

5. Pharmacological Properties

Hydrocortisone provides anti-inflammatory action yet is the least potent topical corticosteroid available. Potassium hydroxyquinoline sulphate provides broad spectrum antibacterial and anticandidal activity. The combination facilitates treatment of steroid-responsive dermatoses where complication by infection with bacteria or yeasts is evident suspected, or a possibility.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Lactic Acid BP, White Soft Paraffin BP, Edetic Acid BP, Sodium Acid Phosphate BP, Maize Starch BP, cetyl stearyl alcohol, sodium cetyl stearyl sulphate, PEG 40 castor oil, Chlorocresol BP, Purified Water BP.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

Two years.

6.4 Special Precautions For Storage

Quinocort Cream should be stored in a cool, dry place avoiding extremes of temperature i.e. not less than 5°C and not more than 30°C.

6.5 Nature And Contents Of Container

Quinocort Cream is available in heat sealed low density polyethylene tubes with flush fitting cap containing 30 g of product. Each tube is cartoned and contains a patient information leaflet.

6.6 Special Precautions For Disposal And Other Handling

For topical use only.

8. Marketing Authorisation Number(S)

0291/0014.

10. Date Of Revision Of The Text

May 1995.

Legal category

POM.


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Amprolium P



Dosage Form: FOR ANIMAL USE ONLY
Amprolium-P
(amprolium) 9.6%
Oral Solution
Coccidiostat Active ingredient

amprolium …………… 9.6%

INDICATIONS

Amprolium-P (amprolium) 9.6% Oral Solution is intended for the treatment of coccidiosis in growing chickens, turkeys and laying hens. If no improvement is noted within 3 days, have the diagnosis confirmed and follow the instructions of your veterinarian or poultry pathologist. Losses may result from intercurrent disease or other conditions affecting drug intake which can contribute to the virulence of coccidiosis under field conditions.

USE DIRECTIONS:

Give amprolium at the 0.012% level (8 fl oz per 50 gallons) as soon as coccidiosis is diagnosed and continue for 3 to 5 days. (In severe outbreaks, give amprolium at the 0.024% level.) Cointinue with 0.006% amprolium medicated water for an addition 1 to 2 weeksl;. No other source of drinking water should be available to the birds during this time.l Use as sole source of amprolium see WARNING

WARNING

Keep this and all drugs out of the reach of children. NOT FOR HUMAN USE

Precautions

FOR ORAL USE IN ANIMALS ONLY. MAY CAUSE EYE IRRITATION. For irritation, flush with plenty of water; get medical attention.

Restricted Drug (California)-Use only as Directed

Store at controlled room temperatures 20°-25°C (68°-77°F).

Benzoic acid 0.1% added as preservative

For questions, please call 1-800-759-3664

Manufactured by Teva Animal Health, Inc.

St. Joseph, MO. 64503

500034P

Rev0309

Lot No.

Exp. Date

Principle Display Panel
Amprolium P 
amproliium p  solution Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 59130-812 Route of Administration ORAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength AMPROLIUM (AMPROLIUM) AMPROLIUM 96 mg  in 1 mL Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 59130-812-18 946 mL In 1 BOTTLE, PLASTIC None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANADA ANADA200463 11/11/2009 11/11/2009
Labeler - Teva Animal Health, Inc. (625254461) Revised: 12/2009Teva Animal Health, Inc.

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Sani-Clens


Generic Name: glycerin and witch hazel topical (GLISS er in and WITCH hay zel TOP ik al)
Brand Names: A.E.R. Witch Hazel, Hemorrhoidal Hygiene Pads, Hygenic Cleansing Pad, Medi-Pad, Sani-Clens, Sani-pads with Aloe, Tucks

What is Sani-Clens (glycerin and witch hazel topical)?

Glycerin protects the skin and creates a protective barrier over hemorrhoids, allowing them to heal. Glycerin also prevents drying of these tissues and reduces itching.

Witch hazel is an astringent. It shrinks swollen tissue and provide relief from itching and irritation.

The combination of glycerin and witch hazel topical (for the skin) is used to relieve rectal pain, pressure, irritation, and mild bleeding caused by hemorrhoids. This medicine will not treat or cure a hemorrhoid, it will only relieve the symptoms.

Glycerin and witch hazel topical is also used to relieve vaginal discomfort after childbirth. This medication may also be applied to the diaper area of a baby.

Glycerin and witch hazel topical may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Sani-Clens (glycerin and witch hazel topical)? Do not take glycerin and witch hazel topical by mouth. It is for use only on your rectum. Stop using this medicine and call your doctor at once if you have bloody diarrhea or severe pain, bleeding, or irritation around your rectum.

Avoid using laxatives in combination with glycerin and witch hazel topical unless your doctor has told you to.

What should I discuss with my healthcare provider before using Sani-Clens (glycerin and witch hazel topical)? You should not use this medication if you are allergic to glycerin or witch hazel. It is not known whether this medication will harm an unborn baby. Do not use glycerin and witch hazel topical without medical advice if you are pregnant. It is not known whether this medication passes into breast milk or if it could harm a nursing baby. Do not use glycerin and witch hazel topical without medical advice if you are breast-feeding a baby. How should I use Sani-Clens (glycerin and witch hazel topical)?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended.

It is best to use this medication after using the bathroom or having a bowel movement.

You may use a glycerin and witch hazel topical medicated pad up to 6 times per day.

After using the medicated pad, you may flush it down a toilet or septic system.

Store at room temperature away from moisture and heat. What happens if I miss a dose?

Since glycerin and witch hazel topical is used as needed, it does not have a daily dosing schedule. Call your doctor if your symptoms do not improve after using glycerin and witch hazel topical .

What happens if I overdose?

An overdose of glycerin and witch hazel topical is not expected to be dangerous.

What should I avoid while using Sani-Clens (glycerin and witch hazel topical)? Do not take glycerin and witch hazel topical by mouth. It is for use only on your rectum.

Avoid using laxatives in combination with glycerin and witch hazel topical unless your doctor has told you to.

Sani-Clens (glycerin and witch hazel topical) side effects Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Stop using glycerin and witch hazel topical and call your doctor at once if you have a serious side effect such as:

bloody diarrhea; or

severe pain, bleeding, or irritation of the skin around your rectum.

Less serious side effects are more likely, and you may have none at all.

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

What other drugs will affect Sani-Clens (glycerin and witch hazel topical)?

There may be other drugs that can interact with glycerin and witch hazel topical. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Sani-Clens resources Sani-Clens Side Effects (in more detail) Sani-Clens Use in Pregnancy & Breastfeeding Sani-Clens Drug Interactions Sani-Clens Support Group 0 Reviews for Sani-Clens - Add your own review/rating Compare Sani-Clens with other medications Hemorrhoids Where can I get more information? Your pharmacist can provide more information about glycerin and witch hazel topical.

See also: Sani-Clens side effects (in more detail)


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Sentry HC Dermasphere Medicated Shampoo



Dosage Form: FOR ANIMAL USE ONLY
Medicated Shampoo For Dogs Indications and Usage for Sentry HC Dermasphere Medicated Shampoo Sentry HC Dermasphere Medicated Shampoo For Dogs is an antiseborrheic shampoo that aids in the removal of scales, crust, and excessive skin oil associated with seborrhea and other non-specific skin conditions.  Combines the proven benefits of oatmeal, sulfur and salicylic acid.  Contains Dermaspheres, a micro encapsulation technology that holds key ingredients in miscroscopic spheres and improves th effectiveness of the shampoo.
SIGNS:  Recommended for dogs with oily skin and coat.
Specially formulated for seborrhea and other skin conditions
Medicated Dermaspheres attach to skin and coat and release over time
Aids in the removal of scales, crust and excessive skin oil
DIRECTIONS FOR USE Shake well before use.  Wet the hair coat with warm water.  Apply a thin line of shampoo from the base of the neck to the base of the tail.  Massage the shampoo into wet hair coat.  Rinse and repeat.  May be used two to three times a week.  Discontinue use and consult a veterinarian if undue skin irritation develops or increases, or if the condition persists or recurs, as symptoms may be indicative of an underlying serious condition.
CAUTION For Animal Use Only.  FOR EXTERNAL USE ONLY.  Avoid contact with eyes or mucous membranes.  In case of contact, flush eyes with water and seek medical attention if irritation persists. KEEP OUT OF REACH OF CHILDREN
Warnings Wash hands after use.  In case if accidental ingestion, seek professional assistance or contact a Poison Control Center immediately. ACTIVE INGREDIENTS Salicylic Acid 2%, Solubilized Sulfur 2%. OTHER INGREDIENTS Water, Sodium Lauryl Sulfate, Lauramide DEA, Glycerin, Colloidal Oatmeal, Dermaspheres, Magnesium Aluminum Silicate, Sodium Hydroxide, Fragrance, Hydroxypropyl Cellulosa, FD and C Blue #1.  May also contain sodium chloride and/or sodium hydroxide. How is Sentry HC Dermasphere Medicated Shampoo Supplied Net 12 fl oz (354 mL)
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL Distributed by:  Sergeant's Pet Care Products, Inc., Omaha NE 68130
Made in USA
PATENTED DERMASPHERE TECHNOLOGY
Patent #6,277,404
Sentry HC Dermasphere Medicated Shampoo FOR DOGS 
salicylic acid, solubilized sulfur  lotion/shampoo Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 21091-074 Route of Administration TOPICAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength SALICYLIC ACID (SALICYLIC ACID) SALICYLIC ACID 7.08 mL  in 354 mL SULFUR (SULFUR) SULFUR 7.08 mL  in 354 mL Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found Product Characteristics Color blue (Aqua Blue) Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 21091-074-12 354 mL In 1 BOTTLE, PUMP None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date unapproved drug other 11/19/2008
Labeler - Sergeant's Pet Care Products, Inc. (876995171) Revised: 04/2010Sergeant's Pet Care Products, Inc.

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gadobenate dimeglumine


Generic Name: gadobenate dimeglumine (GAD oh BEN ate dye MEG loo meen)
Brand Names: Multihance

What is gadobenate dimeglumine?

Gadobenate dimeglumine is a contrast agent that produces magnetic effects. It is used in combination with magnetic resonance imaging (MRI) to allow blood vessels, organs, and other non-bony tissues to be seen more clearly on the MRI.

Gadobenate dimeglumine is used to help diagnose certain disorders of the brain and spine (central nervous system).

Gadobenate dimeglumine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about gadobenate dimeglumine? Gadobenate dimeglumine can cause a life-threatening condition in people with advanced kidney disease. The symptoms of this condition include:

burning, itching, swelling, scaling, and tightening or hardening of your skin;

muscle weakness;

joint stiffness in your arms, hands, legs, or feet;

deep bone pain in your ribs or your hips;

trouble moving; or

skin redness or discoloration.

Before receiving this medication, tell your doctor if you have kidney disease or if you are on dialysis. You may not be able to receive gadobenate dimeglumine.

Also tell your doctor if you have diabetes, high blood pressure, liver disease (or liver transplant), a heart rhythm disorder, a personal or family history of "Long QT Syndrome," asthma or allergies, a history of seizures, a genetic bilirubin disorder (Dubin Johnson syndrome), if you are over 60 years old, if you have ever had a reaction to a contrast agent, or if you have recently had an injury, surgery, or severe infection.

Your doctor or other healthcare provider may want to watch you for a short time after your test is over. This is to make sure you do not have any unwanted side effects or delayed reactions. What should I discuss with my healthcare provider before receiving gadobenate dimeglumine? Gadobenate dimeglumine can cause a life-threatening condition in people with advanced kidney disease. The symptoms of this condition include:

burning, itching, swelling, scaling, and tightening or hardening of your skin;

muscle weakness;

joint stiffness in your arms, hands, legs, or feet;

deep bone pain in your ribs or your hips;

trouble moving; or

skin redness or discoloration.

Before receiving this medication, tell your doctor if you have kidney disease or if you are on dialysis. You may not be able to receive gadobenate dimeglumine.

To make sure you can safely receive this medication, tell your doctor if you have any of these other conditions:

diabetes;

high blood pressure;

liver disease (or liver transplant);

a heart rhythm disorder;

a personal or family history of "Long QT Syndrome";

asthma, hay fever, or a history of food or drug allergies;

a history of seizures;

a genetic bilirubin disorder called Dubin Johnson syndrome (chronic jaundice);

if you are over 60 years old;

if you have ever had any type of reaction to a contrast agent; or

if you have recently had an injury, surgery, or severe infection.

FDA pregnancy category C. It is not known whether gadobenate dimeglumine will harm an unborn baby. Before you receive this medication, tell your doctor if you are pregnant. It is not known whether gadobenate dimeglumine passes into breast milk or if it could harm a nursing baby. Do not breast-feed for at least 24 hours after receiving gadobenate dimeglumine. If you use a breast pump during this time, throw out any milk you collect. Do not feed it to your baby. How should I take gadobenate dimeglumine?

Gadobenate dimeglumine is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting during your MRI.

Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when the medicine is injected.

Your doctor or other healthcare provider may want to watch you for a short time after your test is over. This is to make sure you do not have any unwanted side effects or delayed reactions.

See also: Gadobenate dimeglumine dosage (in more detail)

What happens if I miss a dose?

Since gadobenate dimeglumine is used only during your MRI, you will not be on a dosing schedule.

What happens if I overdose?

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

What should I avoid after receiving gadobenate dimeglumine?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Gadobenate dimeglumine side effects Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

urinating less than usual or not at all;

drowsiness, confusion, mood changes, increased thirst, loss of appetite;

swelling, weight gain, feeling short of breath;

seizure (convulsions);

fast, uneven heart rate; or

pain, burning, swelling, blistering, or skin changes where the injection was given (may occur up to several days after injection).

Less serious side effects may include:

headache, dizziness;

nausea, vomiting;

fever, sweating, feeling unusually hot;

unusual or unpleasant taste in your mouth;

mild skin rash; or

numbness, burning pain, or tingling in your hands or feet;

cold feeling, warmth, pain, or bruising where the medicine was injected.

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

Gadobenate dimeglumine Dosing Information

Usual Adult Dose for CNS Magnetic Resonance Imaging:

0.1 mmol/kg (0.2 mL/kg) as a rapid bolus intravenous injection. To ensure complete injection of the medium, the injection should be followed by a saline flush of at least 5 mL.

Usual Pediatric Dose for CNS Magnetic Resonance Imaging:

2 years and older:
0.1 mmol/kg (0.2 mL/kg) as a rapid bolus intravenous injection. To ensure complete injection of the medium, the injection should be followed by a saline flush of at least 5 mL.

What other drugs will affect gadobenate dimeglumine?

This medication can harm the kidneys in certain people, and this effect may be increased if you also use other medicines harmful to the kidneys. Many other drugs (including some over-the-counter medicines) can harm your kidneys. Tell your doctor if you are receiving chemotherapy, or using antiviral medication, pain or arthritis medicine, any injected antibiotics, or medicines to treat a bowel disorder or prevent organ transplant rejection. You may need dose adjustments or special tests if you have recently used any of these medications.

Tell your doctor about all other medicines you use, especially:

cisplatin (Platinol);

daunorubicin (Daunoxome, Cerubidine);

docetaxel (Docefrez, Taxotere);

doxorubicin (Adriamycin, Doxil);

epirubicin (Ellence);

etoposide (Etopophos, Toposar, VePesid);

methotrexate (Rheumatrex, Trexall);

paclitaxel (Taxol, Abraxane);

rifampin (Rifater, Rifadin, Rifamate);

tamoxifen (Soltamox);

vinblastine (Velban), vincristine (Oncovin, Vincasar), vinorelbine (Navelbine);

heart or blood pressure medicine such as atenolol (Tenormin, Tenoretic), carvedilol (Coreg), labetalol (Normodyne, Trandate), metoprolol (Dutoprol, Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), sotalol (Betapace), and others; or

HIV or AIDS medication such as atazanavir (Reyataz), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (VIracept), ritonavir (Norvir, Kaletra) or saquinavir (Invirase).

There may be other drugs that can affect gadobenate dimeglumine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More gadobenate dimeglumine resources Gadobenate dimeglumine Side Effects (in more detail)Gadobenate dimeglumine DosageGadobenate dimeglumine Use in Pregnancy & BreastfeedingGadobenate dimeglumine Drug InteractionsGadobenate dimeglumine Support Group0 Reviews for Gadobenate dimeglumine - Add your own review/rating Gadobenate Dimeglumine Professional Patient Advice (Wolters Kluwer) MultiHance Prescribing Information (FDA) Multihance Advanced Consumer (Micromedex) - Includes Dosage Information Compare gadobenate dimeglumine with other medications CNS Magnetic Resonance Imaging Where can I get more information? Your doctor or pharmacist can provide more information about gadobenate dimeglumine.

See also: gadobenate dimeglumine side effects (in more detail)


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samarium sm 153 lexidronam Intravenous


sa-MAR-ee-um Sm 153 lex-ID-roe-nam

Commonly used brand name(s)

In the U.S.

Quadramet

Available Dosage Forms:

Injectable Solution

Therapeutic Class: Radiopharmaceutical, Antineoplastic

Uses For samarium sm 153 lexidronam

Samarium Sm 153 lexidronam is a radiopharmaceutical. Radiopharmaceuticals are radioactive agents that may be used to diagnose some diseases by studying the function of the body's organs or to treat certain diseases.

Samarium Sm 153 lexidronam is used to help relieve the bone pain that may occur with certain kinds of cancer. The radioactive samarium is taken up in the bone cancer area and gives off radiation that helps provide relief of pain.

Samarium Sm 153 lexidronam is to be given only by or under the direct supervision of a doctor with specialized training in nuclear medicine or radiation oncology.

Before Using samarium sm 153 lexidronam

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For samarium sm 153 lexidronam, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to samarium sm 153 lexidronam or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Studies on samarium sm 153 lexidronam have been done only in adult patients, and there is no specific information comparing use of samarium Sm 153 lexidronam in children with use in other age groups.

Geriatric

Samarium Sm 153 lexidronam has been used in older people and has not been shown to cause different side effects or problems in older people than it does in younger adults.

Pregnancy Pregnancy Category Explanation All Trimesters D Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk. Breast Feeding

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

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

The presence of other medical problems may affect the use of samarium Sm 153 lexidronam. Make sure you tell your doctor if you have any other medical problems.

Proper Use of samarium sm 153 lexidronam

Your doctor may have special instructions for you to follow to get ready for your treatment. If you do not understand them or if you have not received such instructions, check with your doctor in advance.

This radiopharmaceutical may accumulate in your bladder. Therefore, to increase the flow of urine and lessen the amount of radiation to your bladder your doctor may instruct you to drink plenty of liquids before receiving samarium Sm 153 lexidronam and urinate often afterwards.

If you have a problem controlling your bladder, tell your doctor before receiving samarium Sm 153 lexidronam. Special precautions will need to be taken to prevent radiation contamination of clothing, bed linens, and the environment.

Dosing

The dose of samarium sm 153 lexidronam will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of samarium sm 153 lexidronam. If your dose is different, do not change it unless your doctor tells you to do so.

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

Precautions While Using samarium sm 153 lexidronam

It is very important that your doctor check your progress at regular visits to make sure that samarium sm 153 lexidronam is working properly and to check for unwanted effects. You may need to have blood tests done regularly.

Follow these guidelines for 12 hours after receiving samarium Sm 153 lexidronam, to help reduce the chance of contaminating other persons or the environment with radiation:

Use a normal toilet, if available, instead of a urinal. Samarium Sm 153 lexidronam is passed mainly in the urine. To prevent contamination of your home environment, flush the toilet twice after using. Wipe any spilled urine with a tissue and flush it away. Wash your hands after using or cleaning the toilet. Wash your clothes and bed linens immediately, if they become soiled with your urine or blood. Wash them separately from other clothes. If you cut yourself, wash away any spilled blood.

Samarium Sm 153 lexidronam can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If your blood count becomes abnormally low, there are certain precautions you can take to reduce the risk of infection or bleeding, such as:

With abnormally low white blood cell counts: If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination. Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done. Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime. With abnormally low platelet blood counts: Check with your doctor immediately if you notice any unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on your skin. Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters. Avoid contact sports or other situations where bruising or injury could occur. samarium sm 153 lexidronam Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Blood problems, such as a decrease in the number of white blood cells or platelets, may occur in some patients using samarium Sm 153 lexidronam.

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

More common Black, tarry stools blood in urine or stools cough or hoarseness fever or chills lower back or side pain painful or difficult urination pinpoint red spots on skin unusual bleeding or bruising

Check with your doctor as soon as possible if any of the following side effects occur:

Less common Irregular heartbeat

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

Less common Increase in bone pain (transient) nausea and vomiting

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

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

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

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

More samarium sm 153 lexidronam Intravenous resources Samarium sm 153 lexidronam Intravenous Drug Interactions Samarium sm 153 lexidronam Intravenous Support Group 0 Reviews · Be the first to review/rate this drug
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Quinoderm 10% / 0.5% w / w Cream


1. Name Of The Medicinal Product

Quinoderm 10% / 0.5% w/w Cream

2. Qualitative And Quantitative Composition

Benzoyl Peroxide, hydrous

10.0% w/w

Potassium Hydroxyquinoline Sulphate

0.5% w/w

Excipients: Also includes cetostearyl alcohol, approx 0.825% w/w

For full list of excipients, see section 6.1

3. Pharmaceutical Form

Quinoderm Cream is a creamy white astringent vanishing cream. It is intended for topical use only.

4. Clinical Particulars 4.1 Therapeutic Indications

Acne vulgaris, acneform eruptions, folliculitis.

4.2 Posology And Method Of Administration

Route of administration

For topical use only.

Adults, children and the elderly

By gentle massage over all the affected area two or three times daily.

4.3 Contraindications

Acne rosacea. Patients with known sensitivity to either of the active ingredients should not use Quinoderm Cream.

4.4 Special Warnings And Precautions For Use

Contact with mouth and eyes should be avoided. Care should be taken to avoid contact with dyed fabrics as this product may adversely affect dye fastness.

In a few isolated cases, overreaction to Quinoderm Cream may occur. To minimise this possibility, select a small area of skin behind the ear, apply the cream and leave for 12 hours. If severe irritation or pronounced redness occurs, do not proceed with treatment.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Benzoyl Peroxide is an oxidising agent. Hence, Quinoderm Cream should not be used at the same time as other topical agents which would react with an oxidising agent.

4.6 Pregnancy And Lactation

Quinoderm Cream is not contra-indicated in pregnancy or lactation.

4.7 Effects On Ability To Drive And Use Machines

Not applicable.

4.8 Undesirable Effects

Skin & Subcutaneous Tissue Disorders

Local irritation or inflammation may result; in such cases use should be interrupted or frequency reduced. Itch or rash may occur in which instance treatment should cease and a Physician or Pharmacist consulted.

4.9 Overdose

Not applicable.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Pharmacotherapeutic Group: Peroxides, Benzoyl Peroxide

ATC Code: D10AE01

Potassium Hydroxyquinoline Sulphate – not known.

The combination of the mild keratolytic properties of benzoyl peroxide and the antibacterial and antifungal properties of potassium hydroxyquinoline sulphate in a specially formulated bland water-miscible base make this preparation valuable in the treatment of acne vulgaris, acneform eruptions and folliculitis.

5.2 Pharmacokinetic Properties

Not applicable.

5.3 Preclinical Safety Data

None stated.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Lactic Acid,

White Soft Paraffin,

Edetic Acid,

Sodium Dihydrogen Phosphate Dihydrate ,

Maize Starch,

Cetostearyl Alcohol

Sodium Cetostearyl Sulphate

Macrogol 40 Castor Oil

Purified Water.

6.2 Incompatibilities

Any topical agent that would react with an oxidising agent

6.3 Shelf Life

Three years.

6.4 Special Precautions For Storage

Do not store above 25?C. Do not refrigerate.

6.5 Nature And Contents Of Container

Quinoderm Cream is available in heat sealed low density polyethylene tubes with flush fitting cap containing 25 g, 40g and 50 g of product. Each tube is cartoned and contains a patient information leaflet.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Ferndale Pharmaceuticals Ltd,

12 York Place,

Leeds,

LS1 2DS,

United Kingdom.

8. Marketing Authorisation Number(S)

PL 20685/0022

9. Date Of First Authorisation/Renewal Of The Authorisation

23 April 2004

10. Date Of Revision Of The Text

05 November 2010

11 DOSIMETRY

n/a

12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS (IF APPLICABLE)

n/a


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Sodium Sulfacetamide Sulfur Cleansing Pads


Generic Name: sulfacetamide sodium and sulfur swab
Dosage Form: swab
Sodium Sulfacetamide 10% - Sulfur 4% Cleansing Pads In a vehicle containing Green Tea and Aloe Rx Only

DESCRIPTION: Sodium sulfacetamide is a sulfonamide with antibacterial activity while sulfur acts as a keratolytic agent.
Chemically sodium sulfacetamide is N-[(4-aminophenyl) sulfonyl]-acetamide, monosodium salt, monohydrate.
The structural formula is:


Each pad of Sodium Sulfacetamide 10% - Sulfur 4% Cleansing Pads are coated with a cleanser-based formulation. Each gram of this cleanser-based
formulation contains 100 mg of Sodium Sulfacetamide and 40 mg of Sulfur. The cleanser base consists of: purified water, sodium cocoyl isethionate
disodium oleamido MEA sulfosuccinate, green tea extract, cetyl alcohol, stearyl alcohol, glycerol stearate and PEG 100 stearate methyl paraben, propyl
paraben, butylated hydroxytoluene, aloe vera gel, sodium thiosulfate, disodium EDTA, magnesium aluminum silicate, xanthan gum, sodium methyl cocoyl
taurate, white petrolatum.

CLINICAL PHARMACOLOGY: The most widely accepted mechanism of action of sulfonamides is the Woods-Fildes theory, which is based on the fact
that sulfonamides act as competitive antagonists to para-aminobenzoic acid (PABA), an essential component for bacterial growth. While absorption
through intact skin has not been determined, sodium sulfacetamide is readily absorbed from the gastrointestinal tract when taken orally and excreted in
the urine, largely unchanged. The biological half-life has variously been reported as 7 to 12.8 hours. The exact mode of action of sulfur in the treatment of
acne is not known, but it has been reported that it inhibits the growth of Propionibacterium acnes and the formation of free fatty acids.

INDICATIONS: Sodium Sulfacetamide 10% - Sulfur 4% Cleansing Pads are indicated in the topical control of acne vulgaris, acne rosacea and seborrheic dermatitis.

CONTRAINDICATIONS: Sodium Sulfacetamide 10% - Sulfur 4% Cleansing Pads are contraindicated for use by patients having known hypersensitivity
to sulfonamides, sulfur or ony other component of this preparation. Sodium Sulfacetamide 10% - Sulfur 4% Cleansing Pads are not to be used by
patients with kidney disease.

WARNINGS: Although rare, sensitivity to sodium sulfacetaminde may occur. Therefore, caution and careful supervision should be observed when
prescribing this drug for patients who may be prone to hypersensitivity to topical sulfonamides. Systemic toxic reactions such as agranulocytosis, acute
hemolytic anemia, purpura hemorrhagica, drug fever, jaundice and contact dermatitis indicate hypersensitivity to sulfonamides. Particular caution should
be employed if areas of denuded or abraded skin are involved.
FOR EXTERNAL USE ONLY. Keep away from eyes. Keep out of reach of children. Keep container tightly closed.

PRECAUTIONS: General - If irritaition develops, use of the product should be discontinued and appropriate therapy instituted. Patients should be
carefully observed for possible local irritation or sensitization during long-term therapy. The object of this therapy is to achieve desqamation withour
irritation, but sodium sulfacetamide and sulfur can cause reddening and scaling of the epidermis. These side effects are not unusual in the treatment of
acne vulfaris, but patients should be cautioned about the possibility.
Information for patients - Avoid contact with eyes, eyelids, lips and mucous membranes. If accidental contact occurs, rinse with water. If excessive
irritation develops, discontinue use and consult your physician.

PREGNANCY: Pregnancy Category C. Animal reproduction studies have not been conducted with Sodium Sulfacetamide 10% - Sulfur 4% Cleansing
Pads. It is not known whether Sodium Sulfacetamide 10% - Sulfur 4% Cleansing Pads can cause fetal harm when administered to a pregnant woman or
can affect reproduction capacity. Sodium Sulfacetamide 10% - Sulfur 4% Cleansing Pads should be given to a pregnant woman only if clearly needed.

NURSING MOTHERS: It is not known whether sodium sulfacetamide is excreted in the human milk following topical use of Sodium Sulfacetamide 10% -
Sulfur 4% Cleansing Pads. However, small amounts of orally administered sulfonamides have been reported to be eliminated in human milk. In view of
this and because many drugs are excreted in human milk, caution should be exercised when Sodium Sulfacetamide 10% - Sulfur 4% Cleansing Pads are
administered to a nursing woman.

PEDIATRIC USE: Safety and effectiveness in children under the age of 12 have not been established.

ADVERSE REACTIONS: Although rare, sodium sulfacetamide may cause local irritation.

DOSAGE AND ADMINISTRATION: Wash affected area(s) with cleansing pad once or twice dialy, or as directed by your physician. Wet area(s) with
water. Wet pad with a little water and work into a full lather. Cleanse area(s) with pad for 10-20 seconds, avoiding eyes. Rinse thoroughly and pat dry.
Discard pad. Do not flush.

HOW SUPPLIED: Sodium Sulfacetamide 10% - Sulfur 4% Cleansing Pads are available in boxes of 60 cloths (3.7 g), (NDC 42192-113-60).
Store at controlled room temperature, 15° - 25° (59° - 77°F).
All prescription substitutions using this product shall be made subject to state and federal statutes as applicable. Please note: this is not an Orange Book
product and has not been subjected to FDA therapeutic equivalency or other equivalency testing. Each person recommending a prescription substitution
using this product shall make such recommendations based on each such person’s professional opinion and knowledge, upon evaluating the active
ingredients, incipients, inactive ingredients and chemical formulation information provided herein.

MANUFACTURED FOR: Acella Pharmaceuticals, LLC
9005 Westside Parkway
Alpharetta, GA 30009
1-800-541-4802

Sodum Sulfacetamide 10%-

Sulfur 4% Cleansing Pads


In a vehicle containing Green Tea and Aloe
Rx Only
60 cleansing pads
Net wegith 3.7g each
Acella pharmaceuticals
Directions: Wash affected areas with Sodium Sulfacetamide 10% - Sulfur 4% once or twice daily or as direted by your physician.
1. Wet affected areas with water
2. Wet Sodium Sulfacetamide 10% - Sulfur 4% cleansing pad with water and work into a full lather.
3. Cleanse face with Sodium Sulfacetamide 10% - Sulfur 4% for 10 -20 seconds, avoiding eyes
4. Rinse thoroughly and pat dry
5. Discard pad. Do not flush.
Warnings for external use only. Keep out of reach of children. Avoid contact with eyes.
Indications: for the typical control of acne vulgaris and seborrheic dermatitis. See package insert for full prescribing information.
Contraindications: Sodium Sulfacetamide 10% - Sulfur 4% cleansing pads are contraindicated for use in patients having known hypersensitivity to sulfonamides, sulfur or anyother component of the preparation. Sodium Sulfacetamide 10% - Sulfur 4% cleansing pads are not to be used by patients with kidney disease.
 
Contents: Sodium Sulfacetamide 10% - Sulfur 4%. Other Ingredients: purified water, sodium cocoyl isethionate, disodium oleamido MEA sulfosuccinate, green tea extract, cetyl alcohol, stearyl alcohol, glycerol stearate and PEG 100 stearate methyl paraben, propyl paraben, butylated hydroxytoluene, aloe vera gel, sodium thiosufate, disodium EDTA, magnesium aluminum siliate, xanthan gum, sodium methyl cocoyl l-taurate, white petrolatum
Acella Pharmaceuticals
Store at 15 degrees to 25 degrees C or 59-77 degrees F)
All prescription substitutions and/or recommendations using this product shall be made subject to state and federal statutes as applicable. NOTE. This is not an Orange Book product. No representation is made as to generic status or bioequivalency. Please see package insert for more information.
Manufactured For:
Acella Pharmaceuticals, LLC
9005 Westside Parkway
Alpharetta, GA 30009
1-800-541-4802


SODIUM SULFACETAMIDE - SULFUR CLEANSING PADS 
sodium sulfacetamide, sulfur  swab Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 42192-113 Route of Administration TOPICAL DEA Schedule      Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength SULFACETAMIDE SODIUM (SULFACETAMIDE) SULFACETAMIDE SODIUM 10 g  in 100 g SULFUR (SULFUR) SULFUR 4 g  in 100 g Inactive Ingredients Ingredient Name Strength WATER   ALOE VERA LEAF   SODIUM THIOSULFATE   EDETATE DISODIUM   MAGNESIUM ALUMINUM SILICATE   XANTHAN GUM   Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains          Packaging # NDC Package Description Multilevel Packaging 1 42192-113-60 60 POUCH In 1 BOX contains a POUCH 1 3.7 g In 1 POUCH This package is contained within the BOX (42192-113-60)
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date unapproved drug other 09/16/2010
Labeler - Acella Pharmaceuticals, LLC (825380939) Revised: 12/2010Acella Pharmaceuticals, LLC
More Sodium Sulfacetamide Sulfur Cleansing Pads resources Sodium Sulfacetamide Sulfur Cleansing Pads Side Effects (in more detail)Sodium Sulfacetamide Sulfur Cleansing Pads Use in Pregnancy & BreastfeedingSodium Sulfacetamide Sulfur Cleansing Pads Drug InteractionsSodium Sulfacetamide Sulfur Cleansing Pads Support Group18 Reviews for Sodium Sulfacetamide Sulfur Cleansings - Add your own review/rating Compare Sodium Sulfacetamide Sulfur Cleansing Pads with other medications AcneRosaceaSeborrheic Dermatitis
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Quinoderm 5% / 0.5% w / w Cream


1. Name Of The Medicinal Product

Quinoderm 5% / 0.5% w/w Cream

2. Qualitative And Quantitative Composition

Benzoyl Peroxide, hydrous

5.0% w/w

Potassium Hydroxyquinoline Sulphate

0.5% w/w

Excipients: Also includes cetostearyl alcohol, approx 0.825% w/w

For full list of excipients, see section 6.1

3. Pharmaceutical Form

Quinoderm Cream is a creamy white astringent vanishing cream. It is intended for topical use only.

4. Clinical Particulars 4.1 Therapeutic Indications

Acne vulgaris, acneform eruptions, folliculitis.

4.2 Posology And Method Of Administration

Route of administration

For topical use only.

Adults, children and the elderly

By gentle massage over all the affected area two or three times daily.

4.3 Contraindications

Acne rosacea. Patients with known sensitivity to either of the active ingredients should not use Quinoderm Cream.

4.4 Special Warnings And Precautions For Use

Contact with mouth and eyes should be avoided. Care should be taken to avoid contact with dyed fabrics as this product may adversely affect dye fastness.

In a few isolated cases, overreaction to Quinoderm Cream may occur. To minimise this possibility, select a small area of skin behind the ear, apply the cream and leave for 12 hours. If severe irritation or pronounced redness occurs, do not proceed with treatment.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Benzoyl Peroxide is an oxidising agent. Hence, Quinoderm Cream should not be used at the same time as other topical agents which would react with an oxidising agent.

4.6 Pregnancy And Lactation

Quinoderm Cream is not contra-indicated in pregnancy or lactation.

4.7 Effects On Ability To Drive And Use Machines

Not applicable.

4.8 Undesirable Effects

Skin & Subcutaneous Tissue Disorders

Local irritation or inflammation may result; in such cases use should be interrupted or frequency reduced. Itch or rash may occur in which instance treatment should cease and a Physician or Pharmacist consulted.

4.9 Overdose

Not applicable.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Pharmacotherapeutic Group: Peroxides, Benzoyl Peroxide

ATC Code: D10AE01

Potassium Hydroxyquinoline Sulphate – not known.

The combination of the mild keratolytic properties of benzoyl peroxide and the antibacterial and antifungal properties of potassium hydroxyquinoline sulphate in a specially formulated bland water-miscible base make this preparation valuable in the treatment of acne vulgaris, acneform eruptions and folliculitis.

5.2 Pharmacokinetic Properties

Not applicable.

5.3 Preclinical Safety Data

None stated.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Lactic Acid,

White Soft Paraffin,

Edetic Acid,

Sodium Dihydrogen Phosphate Dihydrate ,

Maize Starch,

Cetostearyl Alcohol

Sodium Cetostearyl Sulphate

Macrogol 40 Castor Oil

Purified Water.

6.2 Incompatibilities

Any topical agent that would react with an oxidising agent

6.3 Shelf Life

Three years.

6.4 Special Precautions For Storage

Do not store above 25?C. Do not refrigerate.

6.5 Nature And Contents Of Container

Quinoderm Cream is available in heat sealed low density polyethylene tubes with flush fitting cap containing 25 g, and 50 g of product. Each tube is cartoned and contains a patient information leaflet.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Ferndale Pharmaceuticals Ltd,

12 York Place,

Leeds,

LS1 2DS,

United Kingdom.

8. Marketing Authorisation Number(S)

PL 20685/0023

9. Date Of First Authorisation/Renewal Of The Authorisation

09 September 2005

10. Date Of Revision Of The Text

05 November 2010

11 DOSIMETRY

n/a

12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS (IF APPLICABLE)

n/a

Recent History:

05/11/2010 Var 0015

Type IB Az – administrative changes to SmPC 2, 4.8, 5.1, 6.1, 6.2, 6.4, 6.5.


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