Tenecteplase

Tenecteplase is a genetically modified tissue plasminogen activator that is more fibrin specific and lasts longer than alteplase, so it is given as a single bolus over about 10 seconds. It treats acute ST elevation myocardial infarction when primary intervention cannot be done within 120 minutes, and is also used for acute ischaemic stroke in many centres. Its dose is set by weight. Availability and cost limit use in East Africa.

Classification. Thrombolytic; recombinant tissue plasminogen activator.

Mechanism. Converts clot bound plasminogen to plasmin. Modified amino acids give 14 fold more fibrin specificity and 80 fold resistance to the plasminogen activator inhibitor.

Pharmacodynamics. Clot lysis begins within minutes. Minimal fibrinogen depletion.

Pharmacokinetics. Initial half life about 20 to 24 minutes; terminal half life about 90 to 130 minutes. Cleared by the liver.

Acute ST elevation myocardial infarction, adult. Single IV bolus over 5 to 10 seconds, by weight:

• Under 60 kg: 30 mg.

• 60 to under 70 kg: 35 mg.

• 70 to under 80 kg: 40 mg.

• 80 to under 90 kg: 45 mg.

• 90 kg or more: 50 mg.

• Age 75 years or over: halve the dose, as this reduces intracranial haemorrhage.

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

Acute ischaemic stroke, adult (where licensed). 0.25 mg/kg IV bolus (maximum 25 mg) within 4.5 hours of onset after imaging; some centres use 0.4 mg/kg, which has not been shown to be better.

Pulmonary embolism with shock, adult (off label). Weight banded dose of 30 to 50 mg, with heparin; specialist use only.

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; angioedema (ACE inhibitor use and African ancestry raise risk); weight must be accurate.

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

Interactions. Anticoagulants, antiplatelet drugs, non steroidal anti-inflammatory drugs: bleeding. ACE inhibitors: angioedema.

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: half dose from age 75 years in infarction.

• Kidney impairment: no adjustment.

• Liver impairment: avoid in severe disease.

Formulations. Powder for injection 40 mg and 50 mg vials with solvent; prefilled syringe of water for injection.

Administration. Reconstitute with the water supplied to 5 mg/mL; give the calculated volume as a single IV bolus over 5 to 10 seconds; flush the line with 0.9% sodium chloride and not with glucose (precipitate).

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

Monitoring. ECG for ST resolution at 60 to 90 minutes (resolution under 50% means failed lysis, so refer for rescue intervention); rhythm for reperfusion arrhythmias; blood pressure; bleeding signs; neurological state.

Stopping. Single dose; no taper.

Common prescribing errors. Using the wrong weight band; not halving the dose at age 75 years or over; giving the bolus too slowly; flushing with glucose; omitting aspirin or the anticoagulant; repeating a dose.