Protamine-Binergia (Solution) Instructions for Use

Marketing Authorization Holder

Binergia JSC (Russia)

Manufactured By

Armavir Biopharmaceutical Plant, FSE (Russia)

ATC Code

V03AB14 (Protamine sulfate)

Active Substance

Protamine sulfate (Rec.INN registered by WHO)

Dosage Form

Protamine-Binergia

Solution for intravenous administration 10 mg/1 ml: amp. 5 ml 5, 10, 100, 125, 250, 500, or 1000 pcs.

Dosage Form, Packaging, and Composition

Excipients: 0.05 M sulfuric acid solution to pH 4.0-6.0, water for injections up to 1 ml.

5 ml – ampoules (5) – plastic contour packs (1) – cardboard packs.
5 ml – ampoules (5) – plastic contour packs (2) – cardboard packs.
5 ml – ampoules (5) – cell contour packs (1) – cardboard packs.
5 ml – ampoules (5) – cell contour packs (2) – cardboard packs.
5 ml – ampoules (5) – plastic contour packs (20) – cardboard boxes (for hospitals).
5 ml – ampoules (5) – plastic contour packs (25) – cardboard boxes (for hospitals).
5 ml – ampoules (5) – plastic contour packs (50) – cardboard boxes (for hospitals).
5 ml – ampoules (5) – plastic contour packs (100) – cardboard boxes (for hospitals).
5 ml – ampoules (5) – plastic contour packs (200) – cardboard boxes (for hospitals).
5 ml – ampoules (5) – cell contour packs (20) – cardboard boxes (for hospitals).
5 ml – ampoules (5) – cell contour packs (25) – cardboard boxes (for hospitals).
5 ml – ampoules (5) – cell contour packs (50) – cardboard boxes (for hospitals).
5 ml – ampoules (5) – cell contour packs (100) – cardboard boxes (for hospitals).
5 ml – ampoules (5) – cell contour packs (200) – cardboard boxes (for hospitals).

Clinical-Pharmacological Group

Heparin antidote

Pharmacotherapeutic Group

Other therapeutic products; antidotes

Pharmacological Action

Protamine sulfate is a specific antagonist of heparin.

1 mg of protamine sulfate neutralizes 80 – 120 IU of heparin in the blood. Complex formation is due to the abundance of cationic groups (due to arginine), which bind to the anionic centers of heparin.

The effect of the drug after intravenous administration occurs instantly (“on the needle”) and lasts for 2 hours.

After intravenous administration, a protamine-heparin complex is formed, which can be destroyed with the release of heparin.

In case of overdose, it can reduce blood clotting, since Protamine sulfate itself exhibits anticoagulant activity.

Pharmacokinetics

Pharmacokinetic studies have not been conducted.

Indications

• Bleeding due to heparin overdose;
• Before surgery in patients who are taking heparin for therapeutic purposes;
• After heart and blood vessel surgery with extracorporeal circulation;
• Hyperheparinemia.

ICD codes

Dosage Regimen

The protamine sulfate solution is administered slowly intravenously by bolus or drip.

The rate of administration should not exceed 5 mg per minute (for example, 50 mg of the drug should be administered over 10 minutes), since faster administration can cause an anaphylactoid reaction.

The dose of the drug depends on the method of heparin administration.

The calculated dose is dissolved in 300-500 ml of 0.9% sodium chloride solution.

No more than 150 mg of protamine sulfate should be administered within 1 hour.

1. For heparin bolus injections, the dose of protamine sulfate is reduced depending on the time elapsed since heparin administration, since the latter is continuously removed from the body.

2. If heparin was administered intravenously by drip, it is necessary to stop its infusion and administer 25-30 mg of protamine sulfate.

3. For subcutaneous injections of heparin, the dose of protamine sulfate is 1 – 1.5 mg for every 100 IU of heparin.

The first 25-50 mg of protamine sulfate should be administered intravenously slowly, and the remaining dose should be administered intravenously by drip over 8-16 hours.

Fractional administration of protamine sulfate is possible, which requires monitoring of activated partial thromboplastin time (aPTT).

For example, if 20,000 IU of heparin was administered subcutaneously, after 2 hours, resorption of heparin from complexes with protamine occurs at a rate of 3333 IU of heparin, therefore the next dose of protamine sulfate is 33 mg.

4. In case of using extracorporeal circulation during surgery, the dose of protamine sulfate is 1.5 mg for every 100 IU of heparin.

When determining the dose of protamine, the route of heparin administration must be taken into account.

Adverse Reactions

From the cardiovascular system decreased blood pressure, bradycardia.

From the digestive system nausea, vomiting.

From the immune system skin rash, itching, development of anaphylactoid reactions.

Other feeling of heat, skin hyperemia, feeling of shortness of breath (with excessively rapid administration).

Contraindications

• Hypersensitivity to the components of the drug;
• Idiopathic or congenital hyperheparinemia (in such cases the drug is not effective and may increase bleeding);
• Severe arterial hypotension;
• Thrombocytopenia;
• Adrenal cortex insufficiency;
• Use by patients of insulins containing Protamine sulfate, as well as other medicinal products containing Protamine sulfate;
• History of allergic reactions to fish.

There are no data on the use of the drug in children.

Use in Pregnancy and Lactation

The drug should be used in pregnant women only if the intended benefit to the mother outweighs the potential risk to the fetus (adverse effects on the fetus have been identified in experiments) and/or child.

Pediatric Use

There are no data on the use of the drug in children.

Special Precautions

Administration is carried out under the control of blood clotting.

Before administration, it is necessary to ensure the adequacy of the patient’s blood volume (hypovolemia increases the risk of collapse).

Overdose

May be accompanied by bleeding, since protamine has its own anticoagulant activity.

Treatment is symptomatic.

Drug Interactions

Pharmaceutically incompatible with cephalosporins and penicillins.

It is an antagonist of low molecular weight heparins.

May increase the intensity and duration of action of non-depolarizing muscle relaxants.

Storage Conditions

In a light-protected place at a temperature of 4 to 10°C (50°F), avoid freezing.

Keep out of reach of children.

Shelf Life

Shelf life – 3 years.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.