Heparin Antidote

Protamine Sulphate

Brand names: Protamine Sulphate Injection

Protamine sulphate is an intravenous antidote used to neutralise the anticoagulant effect of heparin, principally unfractionated heparin, for example after cardiopulmonary bypass or in heparin-related bleeding.

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: Each mg of protamine sulfate, calculated on the dried basis, neutralizes not less than 100 USP Heparin Units. Give in doses not to exceed 50 mg.

Route: Very slow intravenous injection over a 10-minute period. Intended for injection without further dilution; if further dilution is desired, 5% dextrose in water (D5-W) or normal saline may be used.

Frequency: Single dose, guided by blood coagulation studies. Because heparin disappears rapidly from the circulation, the dose of protamine sulfate required decreases rapidly with time elapsed following intravenous injection of heparin — for example, if protamine sulfate is administered 30 minutes after the heparin, one-half the usual dose may be sufficient.

Max: Doses not to exceed 50 mg per very slow intravenous injection over 10 minutes

The dosage should be guided by blood coagulation studies. Diluted solutions should not be stored, since they contain no preservative. Protamine sulfate should not be mixed with other drugs without knowledge of their compatibility — it has been shown to be incompatible with certain antibiotics, including several of the cephalosporins and penicillins. Visually inspect for particulate matter and discolouration before administration. NOT COVERED BY THIS SOURCE: this US label gives no regimen for reversal of low molecular weight heparin (the existing page entry mentions partial reversal for LMWH) and no paediatric posology; both must be sourced separately. No drug-interactions section and no pregnancy section were present in the fetched label. No UK SPC (eMC) record was present in the source bundle — this dose is from US prescribing information (Fresenius Kabi USA, label date 2024-03-18) and must be verified against UK labelling.

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 and bradycardia following intravenous administration
Transitory flushing and feeling of warmth
Dyspnoea, nausea, vomiting and lassitude
Back pain, reported in conscious patients undergoing procedures such as cardiac catheterisation
Anaphylaxis with severe respiratory distress, circulatory collapse and capillary leak (fatal anaphylaxis has been reported in a patient with no prior history of allergies)
Anaphylactoid reactions with circulatory collapse, capillary leak and non-cardiogenic pulmonary oedema; acute pulmonary hypertension; severe and potentially irreversible circulatory collapse associated with myocardial failure and reduced cardiac output

Clinical monograph

How it works

As a strongly basic protein it binds the acidic heparin molecule to form an inactive, stable salt, abolishing heparin's potentiation of antithrombin; it only partially reverses low-molecular-weight heparins.

Prescribing in practice

Rapid injection can cause severe hypotension, bradycardia and anaphylactoid reactions, so it must be given slowly with the dose titrated to the heparin to be neutralised.
An excess of protamine itself has an anticoagulant effect, so avoid overdosing.
Patients exposed to protamine-containing insulins, those with fish allergy, and vasectomised or infertile men may be at higher risk of hypersensitivity.

Monitoring

Monitor blood pressure, heart rate and the activated clotting time or APTT during and after administration to confirm heparin neutralisation.

Counselling the patient

Inform the team this is given slowly to avoid a sudden fall in blood pressure.
Reversal of low-molecular-weight heparin is only partial and bleeding may recur.
Report any flushing, breathlessness or feeling faint during administration.

Evidence & guidelines

Protamine is the established antidote for unfractionated heparin and provides partial reversal of low-molecular-weight heparins.

Reference: BCSH guidelines; 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.

Calculators

Pathways