PRASUGREL

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Prasugrel is a thienopyridine prodrug that irreversibly inhibits the P2Y12 receptor on platelets, blocking ADP binding and preventing platelet aggregation.

What the body does with it

Metabolism	Prasugrel is rapidly metabolized via esterase hydrolysis to a thiolactone intermediate, which is then converted to the active metabolite primarily by CYP3A4 and CYP2B6, and to a lesser extent by CYP2C9 and CYP2C19.
Excretion	Approximately 68% of the dose is excreted in urine as inactive metabolites, and 27% in feces. No significant renal excretion of parent drug.
Half-life	The active metabolite has a terminal elimination half-life of about 7 hours (range 2–15 hours). This corresponds to once-daily dosing. Prasugrel itself is rapidly hydrolyzed and has a half-life of about 2 hours.
Protein binding	Active metabolite is approximately 98% bound to human serum albumin.
Volume of Distribution	Volume of distribution of the active metabolite is 44–68 L (approximately 0.6–0.9 L/kg). This suggests extensive distribution into tissues.
Bioavailability	Oral bioavailability is at least 80% for the active metabolite, based on urinary recovery of metabolites. Prasugrel itself is a prodrug and undergoes rapid conversion.
Onset of Action	Oral: Maximal platelet inhibition (IPA) occurs at 2–4 hours after a 60 mg loading dose. Significant inhibition is seen within 30 minutes.
Duration of Action	Platelet function returns to baseline over 5–9 days after discontinuation. Clinical effect lasts about 5 days, consistent with the lifespan of affected platelets.

Classification & Brands

Dosing & administration

60 mg orally once daily as a loading dose, then 10 mg orally once daily maintenance

Dosage form	TABLET
Renal impairment	No dose adjustment required for renal impairment, including end-stage renal disease (ESRD) on hemodialysis
Liver impairment	Contraindicated in Child-Pugh class C; no adjustment for mild-to-moderate (Child-Pugh class A or B) hepatic impairment
Pediatric use	Not indicated for pediatric patients; safety and efficacy not established
Geriatric use	No dose adjustment recommended for elderly patients; caution in those ≥75 years due to increased bleeding risk; consider lower maintenance dose (5 mg) if patients are ≥75 years or <60 kg

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Other drugs that affect hemostasis increase bleeding risk Contraindicated in patients with history of stroke or TIA.

Breastfeeding	Unknown if prasugrel is excreted in human breast milk. M/P ratio not established. Caution is advised due to potential for serious adverse reactions in nursing infants; decision to discontinue nursing or drug should consider importance of drug to mother.
Teratogenic Risk	Prasugrel is Pregnancy Category B. Animal studies have not shown fetal harm. There are no adequate and well-controlled studies in pregnant women. Use only if clearly needed. Potential risks include bleeding in the fetus, particularly during the third trimester near delivery.

Warnings & precautions

■ FDA Black Box Warning

WARNING: BLEEDING RISK – Prasugrel increases risk of bleeding, including fatal bleeding. Do not use in patients with active pathological bleeding or history of transient ischemic attack or stroke.

Side Effect Profile

Common Effects	Bleeding
Serious Effects

Absolute Contraindications

Active pathological bleeding (e.g., peptic ulcer, intracranial hemorrhage); history of transient ischemic attack or stroke; severe hepatic impairment; hypersensitivity to prasugrel or any component.

Clinical Precautions

Precautions

Bleeding risk; discontinue 7 days before surgery; use lowest dose in patients ≥75 years or <60 kg; thrombotic thrombocytopenic purpura (rare); hypersensitivity reactions.

Clinical Tips & Counseling

Drug interactions

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