Heparin Reversal Agent

Protamine Sulphate

Brand names: Prosulf

Protamine sulphate is a heparin antagonist used to reverse the anticoagulant effect of unfractionated heparin, most commonly after cardiopulmonary bypass.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Guided by the amount of heparin to be neutralised — each mg of protamine sulfate neutralises not less than 100 USP Heparin Units

Route: Very slow intravenous injection

Frequency: over a 10-minute period

Max: 50 mg (dose must not exceed 50 mg)

Because heparin disappears rapidly from the circulation, the required protamine dose decreases rapidly with time elapsed after the heparin injection — e.g. if given 30 minutes after heparin, one-half the usual dose may be sufficient. Dosage should be guided by blood coagulation studies. Intended for injection without further dilution (D5-W or normal saline may be used if dilution is desired; do not store diluted solutions — no preservative). Do not mix with other drugs without knowledge of compatibility (incompatible with certain antibiotics including several cephalosporins and penicillins). Source is US labelling (Fresenius Kabi) — no UK SPC was fetched; verify against UK SPC.

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Patients who have shown previous intolerance to the drug

Side effects

Sudden fall in blood pressure (hypotension)
Bradycardia
Transitory flushing and feeling of warmth; dyspnoea
Nausea, vomiting and lassitude; back pain (in conscious patients)
Severe anaphylaxis / anaphylactoid reactions with circulatory collapse, capillary leak and noncardiogenic pulmonary oedema (may be fatal)

Interactions

Incompatible with certain antibiotics including several cephalosporins and penicillins — do not mix without knowledge of compatibility

Clinical monograph

How it works

Being strongly basic, it binds the acidic heparin molecule to form a stable inactive complex, neutralising heparin's anticoagulant activity.

Prescribing in practice

It can cause severe hypotension, bradycardia and anaphylactoid reactions, especially with rapid administration, so it must be given slowly with resuscitation facilities available.
Given in excess or without circulating heparin it has an intrinsic anticoagulant effect, and it only partially reverses low-molecular-weight heparins.
Risk of serious reactions is increased in patients previously exposed to protamine-containing insulins, those with fish allergy and men who have had a vasectomy.

Monitoring

Monitor blood pressure, heart rate and clotting status, using anticoagulation assays such as activated clotting time to guide and confirm reversal.

Counselling the patient

Given slowly by trained staff with close cardiovascular monitoring.
Flag any history of fish allergy, previous protamine reactions or protamine-containing insulin use before administration.

Evidence & guidelines

Its use for heparin reversal after cardiac surgery is standard practice supported by the SPC and cardiothoracic anaesthesia guidance.

Reference: AAGBI Guidelines; Society of Thoracic Surgeons Guidelines on Anticoagulation; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

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