Protamine sulfate BP (Protamine)

Uses

Protamine sulfate BP (Protamine) Injection is used for the treatment of heparin overdosage

Protamine sulfate BP (Protamine) is also used to associated treatment for these conditions: Heparin overdose

How Protamine sulfate BP (Protamine) works

It is generally understood that, when administered as an antidote to heparin, protamine sulfate is a fairly strong basic protein that subsequently binds with strongly acidic heparin to produce a stable and inactive complex (salt) . This inactive complex between protamine sulfate and heparin neutralizes the anticoagulant effect of both solitary protamine and heparin . In this way, protamine sulfate is used as an effective antidote to reverse the activity of heparin, and is useful for treating hemorrhage as a result of severe heparin or low-molecular weight heparin overdosage . Moreover, protamine sulfate is also frequently used in the same manner to neutralize the effect of heparin given before surgery and during extracorporeal circulation procedures like those performed in hemodialysis or cardiac surgery .

Dosage

Protamine sulfate BP (Protamine) dosage

Each mg of Protamine sulfate BP (Protamine) will neutralize approximately 90 units of heparin activity derived from beef lung tissue or about 115 units of heparin activity derived from porcine intestinal mucosa.

Protamine sulfate BP (Protamine) Injection, should be given by very slow intravenous injection in doses not to exceed 50 mg of Protamine sulfate BP (Protamine) in any 10 minute period.

Protamine sulfate BP (Protamine) is intended for injection without further dilution; however,if further dilution is desired, 5% Dextrose Injection,or 0.9% Sodium Chloride Injection may be used. Diluted solutions should not be stored since they contain no preservative.

Protamine sulfate BP (Protamine) should not be mixed with other drugs without knowledge of their compatibility, because Protamine sulfate BP (Protamine) has been shown to be incompatible with certain antibiotics,including several of the cephalosporins and penicillins.

Because heparin disappears rapidly from the circulation, the dose of Protamine sulfate BP (Protamine) required also decreases rapidly with the time elapsed following intravenous injection of heparin.For example, if the Protamine sulfate BP (Protamine) is administered 30 minutes after the heparin, one-half the usual dose may be sufficient.

The dosage of Protamine sulfate BP (Protamine) should be guided by blood coagulation studies.Parenteral drug products should be visually inspected for particulate matter and discolouration prior to administration, whenever solution and container permit.

Side Effects

Intravenous injections of Protamine sulfate may cause a sudden fall in blood pressure, bradycardia, pulmonary hypertension, dyspnea, or transitory flushing and a feeling of warmth. There have been reports of anaphylaxis that resulted in respiratory embarrassment. Other reported adverse reactions include systemic hypertension, nausea, vomiting and lassitude. Back pain has been reported rarely in conscious patients undergoing such procedures as cardiaccatheterization. Because fatal reactions often resembling anaphylaxis have been reported after administration of Protamine sulfate, the drug should be given only when resuscitation techniques and treatment of anaphylactoid shock are readily available.

Toxicity

Administration of protamine sulfate intravenously could result in severe drop in blood pressure, dyspnea, bradycardia, pulmonary hypertension and anaphylaxis . Systemic hypertension, nausea, vomiting and lassitude were also reported . Overdosage of this drug may theoretically result in hemorrhage .

Nevertheless, any possible carcinogenicity, mutagenicity, effects upon pregnancy, effects on the newborn, on children, elderly individuals and a few other groups at risk have revealed there to be no animal toxicology cited in the literature to indicate that any of these risk factors might be present for protamine sulfate .

Precaution

Patient at risk of developing hypersensitivity to protamine (e.g. previous history of procedures such as coronary angioplasty or cardiopulmonary bypass surgery where protamine is frequently used, diabetics using protamine insulin, allergy to fish, vasectomised or infertile males who may have antibodies to protamine). Pregnancy and lactation.

Interaction

Protamine sulfate has been shown to be incompatible with certain antibiotics, including several of the cephalosporins and penicillins

Food Interaction

Volume of Distribution

In a study group of twenty-six patients aged between 26 to 80 years and undergoing a cardiac operation with cardiopulmonary bypass, the volume of distribution of protamine sulfate administered was recorded as being 5.4L (with a range of 0.82 to 34L) .

Elimination Route

In general, based on data obtained from protamine sulfate administered in healthy humans the AUC demonstrated during the initial infusion is concave . Protamine concentrations were less than the limit of detection after twenty minutes or less, although the onset of action had been reported to appear within thirty to sixty seconds after intravenous administration It is, however, generally documented that the neutralization of heparin occurs within five minutes after the intravenous administration of protamine sulfate .

Moreover, protamine concentration-versus-time data appears to be substantially different between men and women, where weight-adjusted protamine sulfate dosing ended up in significantly decreased AUC and substantially greater plasma clearance and volume of distribution at steady state in women as compared to men .

Half Life

The half-life of protamine sulfate in healthy individual volunteers without heparin in the body was determined to be about a median 7.4 minutes (from a range of 5.9-9.3 minutes) . For surgical patients undergoing a cardiac operation with cardiopulmonary bypass with the use/presence of heparin in the body, the half-life recorded was a median 4.5 minutes (from a range of 1.9-18 minutes) .

Clearance

In a study group of twenty-six patients aged between 26 to 80 years and undergoing a cardiac operation with cardiopulmonary bypass, the clearance of protamine sulfate administered was recorded as being 1.4 L/min (with a range of 0.61 to 3.8 L/min) .

Elimination Route

Data from limited studies regarding the elimination of protamine sulfate from the human body have determined that protamine excretion is predominantly renal .

Pregnancy & Breastfeeding use

Usage in Pregnancy: Animal reproduction studies have not been conducted with Protamine sulfate . It is also not known whether Protamine sulfate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Protamine sulfate should be given to a pregnant woman only if clearly needed.

Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Protamine sulfate is administered to a nursing woman.

Contraindication

Protamine sulfate is contraindicated in patients who have shown previous intolerance to the drug.

Special Warning

Usage in Children: Safety and effectiveness in children have not been established.

Acute Overdose

Because of the anticoagulant effect of Protamine sulfate , overdosage of this drug may theoretically result in hemorrhage. However, in one study, overdosage of 600 to 800 mg of intravenous Protamine sulfate had only minimal, transient effects on blood coagulation tests.The patient should be followed with coagulation studies and treated symptomatically. The LD50 of Protamine sulfate is 100 mg/kg in mice.

Storage Condition

Store between 20-25° C. Do not freeze.

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