Reteplase

Reteplase is a recombinant plasminogen activator, a shortened form of tissue plasminogen activator. It is given as two IV boluses 30 minutes apart, with no weight adjustment, and is used for acute ST elevation myocardial infarction when primary intervention is not available in time. It is less fibrin specific than alteplase or tenecteplase. It is rarely available in East Africa.

Classification. Thrombolytic; recombinant plasminogen activator.

Mechanism. Converts plasminogen to plasmin, which breaks down fibrin in the clot; binds fibrin less strongly than alteplase.

Pharmacodynamics. Clot lysis begins within minutes. Fibrinogen falls moderately.

Pharmacokinetics. Half life about 13 to 16 minutes. Cleared by the kidneys and liver.

Acute ST elevation myocardial infarction, adult.

• 10 units IV bolus over 2 minutes, then a second 10 units bolus over 2 minutes 30 minutes later.

• Give within 12 hours of symptom onset, with aspirin 150 to 300 mg and an anticoagulant (heparin or enoxaparin) for up to 8 days.

Children. Not established.

Contraindications. Any history of intracranial haemorrhage; ischaemic stroke in the last 3 months; intracranial or spinal surgery or serious head injury in the last 3 months; intracranial tumour, aneurysm or arteriovenous malformation; active internal bleeding; aortic dissection; known bleeding disorder; severe uncontrolled hypertension; major surgery or trauma within 2 weeks; hypersensitivity.

Warnings. Intracranial haemorrhage; other bleeding; reperfusion arrhythmias; hypotension; cholesterol embolism; age over 75 years raises bleeding risk; severe kidney or liver disease; angioedema.

Adverse effects. Bleeding, intracranial haemorrhage, arrhythmias, hypotension, nausea, fever, allergic reaction.

Interactions. Anticoagulants, antiplatelet drugs, non steroidal anti-inflammatory drugs: bleeding. ACE inhibitors: angioedema. Heparin and reteplase are incompatible in the same line.

Reversal of bleeding. Stop other antithrombotic drugs; tranexamic acid 1 g IV over 10 minutes; cryoprecipitate 10 units; platelets if the count is low.

Special groups.

• Pregnancy: only when life threatening; limited data.

• Breastfeeding: no data.

• Patients of African ancestry: no dose change; watch for angioedema.

• Older adults: higher intracranial bleeding risk; no formal dose change.

• Kidney impairment: no adjustment; caution in severe disease.

• Liver impairment: avoid in severe disease.

Formulations. Kit with two vials of 10 units powder, two syringes of water for injection, and needles.

Administration. Reconstitute each vial with 10 mL water and give as an IV bolus over 2 minutes through a dedicated line. Flush with 0.9% sodium chloride before and after each bolus because of incompatibility with heparin.

Baseline. ECG, blood pressure, haemoglobin, platelet count, INR, creatinine, glucose.

Monitoring. ECG for ST resolution at 60 to 90 minutes; rhythm; blood pressure; bleeding signs; neurological state.

Stopping. Two doses only; no taper.

Common prescribing errors. Giving only one bolus; wrong interval between boluses; giving heparin through the same line; omitting aspirin or the anticoagulant; missing a contraindication.