Protamine sulfate 1% 5ml 10 pcs. injection

Protamine sulfate

The drug is administered intravenously in a stream, slowly or drip, under medical and laboratory control of blood clotting (in particular, partial platelet generation time (ARTT) or clotting generation time (ACT), to bring coagulation ability to a normal, physiological level).

In case of heparin overdose, a solution of protamine sulfate is injected at a rate of 1 ml (10 mg) over 3 minutes. If necessary, injections are repeated at intervals of 15-30 minutes, the total dose is usually 5 ml (50 mg) of solution - administered over 10 minutes. Do not administer more than 150 mg within 1 hour.

For spontaneous bleeding, the daily dose is 5-8 mg/kg, administered intravenously in 2 doses with an interval of 6 hours.

The maximum duration of treatment is 3 days.

The dose of the drug depends on the method of administration of heparin. The calculated dose is dissolved in 300-500 ml of 0.9% sodium chloride solution.

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

If heparin was administered intravenously, it is necessary to stop the heparin infusion and administer 2.5-3 ml (25-30 mg) of protamine sulfate.

If heparin was administered subcutaneously or intramuscularly, the dose of protamine sulfate is 1.2-1.3 mg for every 100 IU of heparin.

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

If extracorporeal circulation was used during surgery, the dose of protamine sulfate is 1.2-1.3 mg for every 100 IU of heparin.

Application for neutralization of low molecular weight heparin

Protamine sulfate is used to neutralize low molecular weight heparins (LMWH), but is not able to completely eliminate antithrombic activity: 1 mg of protamine sulfate neutralizes 100 units of anti-Ha activity and no more than 60% of the anti-Xa activity of low molecular weight heparins. When choosing a dose of protamine sulfate, it is necessary to take into account the amount of low molecular weight heparin administered, the route of its administration, the pharmacokinetics of the drug used, as well as the time elapsed since the last injection of low molecular weight heparin.

Protamine sulfate is administered intravenously or as a slow infusion - 1 mg of protamine sulfate per 100 anti-Xa IU of recently administered low-molecular-weight heparin. 8 hours after the administration of low molecular weight heparin, a half dose of protamine sulfate can be used; after 12 hours, administration of the drug will most likely not be required. The duration of preservation of the effect of low-molecular-weight heparin is due to its entry from the subcutaneous tissue, therefore, infusion of a calculated dose of protamine sulfate over several hours or repeated administration of a half dose of protamine sulfate if bleeding persists is necessary.

Patients with renal and liver failure

In patients with mild to moderate renal failure (creatinine clearance ≥30 ml/min and <60 ml/min), no dose reduction is required; in patients with severe renal failure (creatinine clearance <30 ml/min) the dose should be reduced by 25%. .

Protamine sulfate should be used with caution in patients with hepatic impairment.

Protamine sulfate 1% 5ml 10 pcs. injection

pharmachologic effect

Hemostatic agent.

Composition and release form Protamine sulfate 1% 5ml 10 pcs. injection

1 ml of the drug contains: protamine sulfate - 10 mg; water for injections up to 1 ml.

2 ml or 5 ml in ampoules.

5 ampoules are placed in a blister pack made of polyvinyl chloride film.

1 or 2 blister packs together with instructions for use and an ampoule scarifier or ampoule knife are placed in a cardboard pack.

5 or 10 ampoules along with instructions for use and an ampoule scarifier or ampoule knife are placed in a cardboard box with a corrugated liner.

When using ampoules with a break point or ring, do not insert a scarifier or ampoule knife.

Description of the dosage form

Transparent colorless or yellowish liquid.

Characteristic

A specific heparin antagonist, 1 mg of which neutralizes 80-120 units of heparin in the blood.

Directions for use and doses

A solution of protamine sulfate is administered slowly intravenously by stream or drip. The rate of administration should not exceed 5 mg per minute (for example, 50 mg of the drug is administered over 10 minutes), as faster administration may cause an anaphylactoid reaction. The dose of the drug depends on the method of administration of heparin. The calculated dose is dissolved in 300-500 ml of 0.9% sodium chloride solution. Do not administer more than 150 mg of protamine sulfate within 1 hour.

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

• Time elapsed after heparin injection 15-30 minutes: Dose of protamine sulfate 1-1.5 mg per 100 IU of heparin.
• Time elapsed after heparin injection 30-60 minutes: Dose of protamine sulfate 0.5-0.75 mg per 100 IU of heparin.
• Time elapsed after heparin injection over 2 hours: Dose of protamine sulfate 0.25-0.375 mg per 100 IU of heparin.

2. If heparin was administered intravenously, 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 over 8-16 hours. Fractional administration of protamine sulfate is possible, which requires monitoring of the activated partial thromboplastin time (aPTT). For example, if 20,000 IU of heparin is administered subcutaneously, after 2 hours heparin is reabsorbed from complexes with protamine at 3,333 IU of heparin, and therefore the next dose of protamine sulfate is 33 mg.

4. In the 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, it is necessary to take into account the route of administration of heparin.

The maximum duration of treatment is 3 days.

Pharmacodynamics

Protamine sulfate is a specific heparin antagonist. 1 mg of protamine sulfate neutralizes 80-120 units 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 and lasts for 2 hours. After intravenous administration, a protamine-heparin complex is formed, which can be destroyed to release heparin. In case of overdose, it can reduce blood clotting, because Protamine sulfate itself exhibits anticoagulant activity.

Pharmacokinetics

Pharmacokinetic studies have not been conducted.

Indications for use Protamine sulfate 1% 5ml 10 pcs. injection

• Bleeding due to heparin overdose;
• before surgery in patients taking heparin for therapeutic purposes;
• after operations on the heart and blood vessels with extracorporeal circulation;
• hyperheparinemia.

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 insufficiency;
• patients taking insulin containing protamine sulfate, as well as other medications containing protamine sulfate;
• history of allergic reactions to fish.

Experience with medical use in children is limited.

Application of Protamine sulfate 1% 5ml 10 pcs. solution for injection during pregnancy and lactation

Possibly if the expected effect of therapy exceeds the potential risk to the fetus.

special instructions

The administration is carried out under the control of blood clotting. Before administration, you should ensure that the patient's blood volume is adequate (hypovolemia increases the risk of collapse).

Overdose

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

Treatment is symptomatic.

Side effects Protamine sulfate 1% 5ml 10 pcs. injection

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 flushing, feeling of lack of air (with excessively rapid administration).

Drug interactions

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.

FRAXIPARINE

special instructions

Particular attention should be paid to the specific instructions for use for each drug belonging to the class of low molecular weight heparins, because
they may use different dosage units (IU or mg). As a result, alternating Fraxiparine with other LMWHs during long-term treatment is unacceptable. It is also necessary to pay attention to which drug is used - Fraxiparine or Fraxiparine Forte, because this affects the dosage regimen. Graduated syringes are designed to select the dose depending on the patient’s body weight. Fraxiparine is not intended for intramuscular administration.

During treatment with Fraxiparine, clinical monitoring of platelet counts should be carried out.

Thrombocytopenia

Since when using heparins there is a possibility of developing thrombocytopenia (heparin-induced thrombocytopenia), platelet levels must be monitored during the entire course of treatment with Fraxiparin.

Rare cases of thrombocytopenia, sometimes severe, have been reported, which may be associated with arterial or venous thrombosis, which is important to consider in the following cases:

- with thrombocytopenia;

- with a significant decrease in platelet levels (by 30 - 50% compared to normal values);

- in case of negative dynamics of thrombosis, for which the patient is receiving treatment;

- with DIC syndrome.

In these cases, treatment with Fraxiparine should be discontinued.

These effects are immunoallergic in nature and are usually observed between the 5th and 21st days of treatment, but may occur earlier if the patient has a history of heparin-induced thrombocytopenia.

If there is a history of heparin-induced thrombocytopenia (against the background of conventional or low molecular weight heparins), treatment with Fraxiparin can be prescribed if necessary. However, in this situation, strict clinical monitoring and, at a minimum, daily platelet count measurement are indicated. If thrombocytopenia occurs, use of Fraxiparine should be stopped immediately.

If thrombocytopenia occurs against the background of heparins (regular or low molecular weight), then the possibility of prescribing anticoagulants of other groups should be considered. If other drugs are not available, another low molecular weight heparin may be used. In this case, the number of platelets in the blood should be monitored daily. If signs of initial thrombocytopenia continue to be observed after changing the drug, then treatment should be stopped as soon as possible.

It must be remembered that monitoring of platelet aggregation based on in vitro tests is of limited value in the diagnosis of heparin-induced thrombocytopenia.

Elderly patients

Before starting treatment with Fraxiparine, renal function should be assessed.

Hyperkalemia

Heparins may suppress aldosterone secretion, which may lead to hyperkalemia, especially in patients with elevated blood potassium or in patients at risk for elevated blood potassium, such as patients with diabetes mellitus, chronic renal failure, metabolic acidosis, or patients taking medications which can cause hyperkalemia. The risk of hyperkalemia increases with long-term therapy but is usually reversible with discontinuation. In patients at risk, blood potassium levels should be monitored.

Spinal/epidural anesthesia/lumbar puncture and related medications

The risk of spinal/epidural hematomas is increased in individuals with epidural catheters or concomitant use of other medications that may affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants. The risk also appears to increase with traumatic or repeated epidural or spinal taps. Thus, the issue of the combined use of neuraxial blockade and anticoagulants should be decided individually after assessing the effectiveness/risk ratio in the following situations:

- in patients already receiving anticoagulants, the need for spinal or epidural anesthesia must be justified;

- in patients planning elective surgery using spinal or epidural anesthesia, the need for anticoagulants must be justified.

If the patient is undergoing a lumbar puncture or spinal or epidural anesthesia, a sufficient time interval should be maintained between the administration of Fraxiparine and the insertion or removal of the spinal/epidural catheter or needle.

Careful monitoring of the patient is necessary to identify signs and symptoms of neurological disorders. If disturbances are detected in the patient’s neurological status, urgent appropriate therapy is required.

Salicylates, non-steroidal anti-inflammatory drugs (NSAIDs) and platelet aggregation inhibitors

When preventing or treating venous thromboembolism, as well as when preventing blood coagulation in the extracorporeal circulatory system during hemodialysis, co-administration of Fraxiparine with drugs such as acetylsalicylic acid, other salicylates, non-steroidal anti-inflammatory drugs (NSAIDs) and platelet aggregation inhibitors is not recommended, because this may increase the risk of bleeding.