Fibrin-Specific Thrombolytic (Third-Generation tPA) Pregnancy: Contraindicated — major haemorrhage risk; use only for immediately life-threatening thrombosis; consult obstetric/haematology specialists.

Tenecteplase (TNK-tPA — STEMI/Massive PE)

Brand names: Metalyse

Adult dose

Dose: STEMI (weight-based single bolus): <60 kg: 30 mg; 60–69 kg: 35 mg; 70–79 kg: 40 mg; 80–89 kg: 45 mg; ≥90 kg: 50 mg. All given as single rapid IV bolus over 5–10 seconds. Massive PE (off-label): 50 mg IV bolus

Route: IV bolus (single injection — major advantage over alteplase infusion)

Frequency: Single dose only

Max: 50 mg (STEMI); 50 mg (PE)

Third-generation tPA — engineered for fibrin specificity (16× more than alteplase), resistance to PAI-1, and longer half-life (20–24 min vs 3–5 min for alteplase). Single-bolus administration makes it ideal for pre-hospital STEMI thrombolysis. Requires concomitant antithrombotic therapy (enoxaparin preferred in STEMI — EXTRACT-TIMI 25 NEJM 2006).

Paediatric dose

Route:

Not licensed in paediatrics.

Dose adjustments

Renal

No dose adjustment — thrombolytic cleared hepatically. Bleeding risk increased with renal failure — risk-benefit assessment required.

Hepatic

Caution in severe hepatic impairment — coagulopathy and haemorrhage risk.

Clinical pearls

ASSENT-2 trial (NEJM 1999): tenecteplase single bolus vs alteplase 90-min infusion in STEMI — equivalent 30-day mortality (6.2% vs 6.2%); tenecteplase had significantly less non-cerebral bleeding and fewer blood transfusions; simpler administration
Pre-hospital STEMI thrombolysis: tenecteplase is the preferred agent for rural/pre-hospital use where primary PCI is not achievable within 120 minutes — NICE NG185 and ESC 2023 STEMI guidelines support pharmaco-invasive strategy (thrombolyse + transfer for PCI within 3–24h)
Massive PE thrombolysis: 50 mg bolus is the evidence-based dose; PEITHO trial used alteplase, but tenecteplase is used in clinical practice — reversible with protamine if needed, though full reversal not possible; antidote (if available): andexanet alfa not applicable here; manage bleeding with FFP and cryoprecipitate

Contraindications

Recent haemorrhagic stroke or stroke of unknown origin
Ischaemic stroke within 3 months
Active major bleeding
Recent CNS surgery or trauma
Uncontrolled hypertension (SBP >185, DBP >110 mmHg)

Side effects

Bleeding (intracranial: 0.9–1.2%; major non-intracranial: 3–5%)
Reperfusion arrhythmias (accelerated idioventricular rhythm — managed conservatively)
Hypotension during and after administration
Anaphylaxis (rare)

Interactions

Anticoagulants and antiplatelets (additive haemorrhagic risk — co-administration protocols specify timing)
GIIb/IIIa inhibitors (avoid concurrent systemic use — catastrophic bleeding)

Monitoring

BP and HR every 15 minutes for 1 hour
Neurological status (ICH detection — new headache, confusion, focal neurology)
ECG (STEMI resolution — ST normalisation within 60–90 min = successful reperfusion)
aPTT (antithrombotic co-therapy monitoring)
Bleeding sites (access points, IV sites)

Reference: BNFc; BNF 90; ASSENT-2 Trial (NEJM 1999); ESC STEMI Guidelines 2023; MHRA SPC Metalyse; NICE NG185 (VTE); ESC PE Guidelines 2019. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways