ADMINISTRATION ROUTES:
IV
ALTERNATIVE NAMES:
Protamine
ICU INDICATIONS:
- Reversal of heparin
PRESENTATION AND ADMINISTRATION:
IV:
50 mg in 5 mL (10 mg/mL) solution
Administer by slow IV injection over no greater than 1 mL/minute (i.e. 50 mg over 5 minutes). If invasive blood pressure monitoring is present, watch the trace closely during administration and slow rate of infusion if the blood pressure drops.
Administration by IV infusion is described but is not generally preferred. To administer by IV infusion, add to a suitable volume of compatible IV fluid and administer over required time period.
Compatible with the following IV fluids: 0.9% sodium chloride, 5% dextrose, Glucose and sodium chloride
Store at room temperature. Protect from light.
DOSAGE:
IV:
For reversal of unfractionated heparin:
Dose depending on amount of heparin (measured in International Unit) to reverse and time since administration.
1 mg per 100 IU mucous heparin or 80 IU lung heparin given
Dose of protamine sulphate should be reduced if > 15 mins since intravenous heparin administration.
- If 30 - 60 mins since IV heparin, give 0.5 - 0.75 mg protamine sulphate per 100 IU heparin given
- If > 2 hrs, give, 0.25 - 0.375 mg per 100 IU heparin given
Heparin infusion:
Stop infusion
25 - 50 mg protamine by slow injection IV
For reversal of unfractionated heparin (UFH) after cardiopulmonary bypass, use either standard dose of protamine (as above) or titrate dose according to the Activated Clotting Time (ACT) or thromboelastogram (TEG).
Reversal of low molecular weight heparin (LMWH):
1 mg per 100 IU LMWH
The anti-Xa activity of LMWH may not be completely reversed with protamine sulphate and may persist for up to 24 hours after administration. LMWH has twice the half-life of UFH which should be considered when estimating protamine dosage & time elapsed. Protamine dose should be halved when one half-life has elapsed since the last LMWH dose.
Intermittent injections or continuous infusion of protamine sulphate have been recommended for reversal of LMWH following subcutaneous administration as there may be continuing absorption from the subcutaneous depot.
DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:
Dose as in normal renal function
DOSAGE IN PAEDIATRICS:
IV:
1 mg per 100 IU of heparin
0.5 mg/100 IU of heparin if > 1 hr since heparin given
Subsequent doses of protamine 1 mg/kg (max 50 mg)
CLINICAL PHARMACOLOGY:
Protamine is used to counteract the anticoagulant effect of heparin through the formation of heparin-protamine complexes. The onset of action of protamine occurs within five minutes following intravenous administration. The protamine-heparin complex is then removed by the reticuloendothelial system. Protamine is made from low-molecular weight cationic proteins prepared from salmon sperm.
Protamine will not reverse the effects of oral anticoagulants.
CONTRAINDICATIONS:
- Hypersensitivity to protamine
WARNINGS:
Allergic reactions
Some patient groups may be at increased risk of allergic reaction to protamine. These include:
- Patients who have previously undergone cardiopulmonary bypass or angiography with protamine administration
- Diabetics treated with protamine insulin
- Patients allergic to fish
- Infertile or vasectomised men who may have antibodies to protamine
Hypotension
Rapid administration of protamine may lead to severe hypotension and anaphylactoid reactions.
PRECAUTIONS:
General:
In patients who have had cardiac surgery with cardiopulmonary bypass, a rebound bleeding effect may occur several hours post-operatively. This responds to further doses of protamine.
Laboratory Tests:
No tests in addition to routine ICU tests are required
Drug/Laboratory Test Interactions:
None known
IMPORTANT DRUG INTERACTIONS IN ICU:
None known
ADVERSE REACTIONS:
Body as a Whole:
Anaphylaxis, angioedema
Cardiovascular System:
Hypotension, flushing, bradycardia
Respiratory System:
Dysponea, non cardiogenic pulmonary oedema
Haematological System:
Anticoagulant effects when used at doses higher than that required to reverse heparin
Digestive System:
Nausea, vomiting