PROTAMINE SULPHATE INJECTION (Each ml contains Protamine Sulphate 10mg)

Indications

• Reversal of heparin anticoagulation during or after surgical procedures
• Management of heparin overdose

Dosage

Children: Refer to clinical guidelines for specific dosing based on the amount of heparin to be reversed in children.

Adults: Refer to clinical guidelines for specific dosing based on the amount of heparin to be reversed.

Mechanism of action

Protamine functions by forming stable complexes with heparin due to its positive charge, effectively neutralizing heparin's anticoagulant properties. This interaction occurs because heparin is negatively charged, leading to the formation of a protamine-heparin complex that is inactive.

Pharmacodynamics

The primary pharmacodynamic effect of protamine is the reversal of the anticoagulant effects of heparin. The onset of action is rapid, typically occurring within minutes of administration. The duration of action varies depending on the dose and the concentration of heparin present in the bloodstream.

Pharmacokinetics

Protamine is administered intravenously and has a rapid onset of action. It is metabolized in the liver and has a short half-life, typically ranging from 7 to 10 minutes. The elimination of protamine occurs through renal pathways, and its effects can be influenced by the presence of heparin in the bloodstream as well as by the dose of protamine administered.

Contra-indications

• Hypersensitivity to protamine
• Severe allergic reactions to fish
• Hypersensitivity to heparin

Adverse effects

• Hypotension
• Bradycardia
• Anaphylaxis
• Nausea
• Vomiting
• Flushing
• Rash
• Itching

Interactions

• Heparin
• Warfarin
• Anticoagulants
• Other blood thinners

Precautions

• Use with caution in patients with a history of allergies
• Monitor blood pressure and heart rate during administration
• Careful in patients with fish allergies
• Consider potential for heparin rebound effect

Pregnancy

Use only if clearly needed. Consult relevant guidelines and risk assessments.

Breast-feeding

Unknown whether excreted in human milk. Use caution and consider benefits vs risks.

Storage

Store at room temperature, protect from light, and do not freeze.

Formulations

• Injection

Indications

• Overdose of unfractionated heparin
• Management of digoxin toxicity

Dosage

Children: For children, the recommended dosage for reversing heparin overdose is 375–500 micrograms, administered at a rate not exceeding 5 mg/minute, with a maximum per dose of 50 mg.

Adults: For overdose of unfractionated heparin, the typical dose is 1 mg of protamine sulfate for every 100 units of heparin administered, administered intravenously at a rate not exceeding 5 mg/minute.

Mechanism of action

Protamine sulfate binds to heparin, neutralizing its anticoagulant effects by forming a stable protamine-heparin complex. This mechanism effectively reverses the actions of heparin in the body, restoring normal coagulation.

Pharmacodynamics

The pharmacodynamics of protamine sulfate are characterized by its rapid onset of action upon intravenous administration. The binding of protamine to heparin leads to an immediate reversal of heparin-induced anticoagulation, which can be crucial in emergency situations such as surgical bleeding or overdose.

Pharmacokinetics

Protamine sulfate is typically administered intravenously, allowing for quick distribution and action. The elimination half-life varies, but factors such as the extent of heparin overdose and the individual’s metabolic capacity can influence it. The drug is generally well-tolerated, but caution is advised in patients with hepatic impairment due to potential alterations in metabolism.

Contra-indications

• Life-threatening condition (e.g. raised intracranial pressure, status epilepticus) controlled by benzodiazepines

Adverse effects

• Hypotension
• Nausea
• Vomiting
• Palpitations
• Tremor
• Insomnia
• Dizziness
• Hyperventilation
• Abnormal hearing
• Arrhythmias
• Seizures (more common in patients with epilepsy)
• Withdrawal syndrome

Interactions

• Caution with other anticoagulants or antiplatelet agents due to increased bleeding risk

Precautions

• Avoid rapid injection following major surgery
• Caution in patients with hepatic impairment (risk of increased half-life)
• Caution in high-risk or anxious patients
• Benzodiazepine therapy for epilepsy due to risk of convulsions

Pregnancy

Not known to be harmful.

Breast-feeding

Avoid breast-feeding for 24 hours.

Storage

Store below 25°C. Protect from light.

Formulations

• Powder for solution for infusion
• Solution for injection