P2Y12 ADP Receptor Antagonist (Thienopyridine Prodrug) Pregnancy: Avoid — insufficient data; use only if clearly indicated for life-threatening thrombosis.

Prasugrel (P2Y12 Antiplatelet — ACS/PCI)

Brand names: Efient

Adult dose

Dose: Loading: 60 mg oral single dose at time of PCI; Maintenance: 10 mg once daily (reduce to 5 mg/day if weight <60 kg). Duration: 12 months post-ACS with PCI

Route: Oral

Frequency: Once daily (maintenance)

Max: 10 mg/day (standard); 5 mg/day (weight <60 kg or age ≥75 years)

More potent and faster onset than clopidogrel — requires only one metabolic step for activation (vs two for clopidogrel). No CYP2C19 polymorphism issue. Contraindicated with prior stroke/TIA. NICE TA317: recommended with aspirin for up to 12 months in ACS managed with PCI.

Paediatric dose

Route:

Not licensed in paediatrics.

Dose adjustments

Renal

No dose adjustment required. Caution in severe renal impairment — bleeding risk increased.

Hepatic

Avoid in severe hepatic impairment (Child-Pugh C) — coagulopathy risk.

Clinical pearls

TRITON-TIMI 38 (Wiviott et al. NEJM 2007): prasugrel vs clopidogrel in ACS with planned PCI — 19% relative reduction in CV death/MI/stroke with prasugrel; significantly more major bleeding (2.4% vs 1.8%). Net clinical benefit only in patients without prior stroke/TIA, not aged ≥75, and weight ≥60 kg
CYP2C19 advantage: prasugrel bypasses the CYP2C19 polymorphism issue affecting clopidogrel (20–30% of patients are poor/intermediate metabolisers with minimal clopidogrel activity) — prasugrel efficacy is consistent across genetic variants; important in high-risk PCI
Prasugrel vs ticagrelor: both superior to clopidogrel; prasugrel is a prodrug (one activation step), ticagrelor is direct-acting reversible. Ticagrelor preferred by ESC 2023 ACS guidelines for NSTEMI/STEMI in most patients; prasugrel remains an option, particularly post-STEMI PCI

Contraindications

Prior stroke or TIA (absolute — significantly increased risk of intracranial haemorrhage; TRITON-TIMI 38 net harm in this subgroup)
Active pathological bleeding
Age ≥75 years (generally avoid — net harm in TRITON subgroup; use 5 mg if unavoidable)
Severe hepatic impairment

Side effects

Major bleeding (significantly more than clopidogrel — especially ICH in elderly and those with prior stroke)
Minor bleeding (bruising, epistaxis)
Thrombotic thrombocytopenic purpura (TTP — rare)
Hypersensitivity reactions

Interactions

Anticoagulants (warfarin, DOACs — triple therapy increases bleeding risk dramatically; avoid unless essential — MASTER DAPT NEJM 2021)
NSAIDs (additive bleeding)
SSRIs (additive bleeding risk via platelet serotonin depletion)

Monitoring

Platelet aggregation (if therapeutic drug monitoring available — ADP-induced aggregation)
CBC (TTP surveillance)
Bleeding signs
Weight (dose reduction criterion <60 kg)

Reference: BNFc; BNF 90; TRITON-TIMI 38 (Wiviott et al. NEJM 2007); NICE TA317 (Prasugrel in ACS); ESC ACS NSTEMI Guidelines 2023; MHRA SPC Efient. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways