PROSULF Solution for injection Ref.[9525] Active ingredients: Protamine

Adults

Prosulf should be administered by slow intravenous injection over a period of about 10 minutes. No more than 50mg of protamine sulfate should be given in any one dose.

The dose is dependent on the amount and type of heparin to be neutralised, its route of administration and the time elapsed since it was last given, since heparin is continuously being excreted. Ideally, the dose required to neutralise the action of heparin should be guided by blood coagulation studies or calculated from a protamine neutralisation test.

In gross excess, protamine itself acts as an anticoagulant.

Neutralisation of unfractionated (UF) heparins

1mg of protamine sulfate will usually neutralise at least 100 international units of mucous heparin or 80 units of lung heparin. The dose of protamine sulfate should be reduced if more than 15 minutes have elapsed since intravenous injection.

For example, if 30-60 minutes have elapsed since heparin was injected intravenously, 0.5-0.75mg protamine sulfate per 100 units of mucous heparin is recommended. If two hours or more have elapsed, 0.25-0.375mg per 100 units of mucous heparin should be administered.

If the patient is receiving an intravenous infusion of heparin, the infusion should be stopped and 25-50mg of protamine sulfate given by slow intravenous injection.

If heparin was administered subcutaneously, 1mg protamine sulfate should be given per 100 units of mucous heparin – 25-50mg by slow intravenous injection and the balance by intravenous infusion over 8-16 hours.

In the reversal of UF heparin following cardiopulmonary bypass, either a standard dose of protamine may be given, as above, or the dose may be titrated according to the activated clotting time.

Patients should be carefully monitored using either the activated partial thromboplastin time or the activated clotting time, carried out 5-15 minutes after protamine sulfate administration. Further doses may be needed because protamine is cleared from the blood more rapidly than heparin.

Neutralisation of low molecular weight (LMW) heparins

A dose of 1mg per 100 units is usually recommended but the manufacturer’s own guidelines should be consulted.

The anti-Xa activity of LMW heparins may not be completely reversible with protamine sulfate and may persist for up to 24 hours after administration.

The longer half-life of LMW heparins (approximately twice that of UF heparin) should also be borne in mind when estimating the dose of protamine sulfate required in relation to the time which has elapsed since the last heparin dose.

Theoretically, the dose of protamine sulfate should be halved when one half-life has elapsed since the last LMW heparin dose. Intermittent injections or continuous infusion of protamine sulfate have been recommended for the neutralisation of LMW heparin following subcutaneous administration, as there may be continuing absorption from the subcutaneous depot.

Patients should be carefully monitored. Further doses may be needed because protamine is cleared from the blood more rapidly than heparin, especially low molecular weight heparin.

Elderly

There is no current evidence for alteration of the recommended dose.

Children

Safety and efficacy in children have not been established. Not recommended.

Symptoms

Protamine has weak anticoagulating properties and if given in the absence of heparin, or at doses in excess of those required to neutralise the anticoagulant effect of heparin, exerts its own anticoagulant effect.

Hypotension, bradycardia, dyspnoea nausea, vomiting, lassitude, transitory flushing and/or a sensation of warmth may also occur.

Treatment

Includes monitoring of coagulation tests, respiratory ventilation and symptomatic treatment. If bleeding is a problem, fresh frozen plasma or fresh whole blood should be given.

48 months.

Store between 15°C and 25°C.

5ml and 10ml neutral type 1 hydrolytic glass ampoules in pack sizes of 10 ampoules in cartons.

Not applicable.