Dosing and uses of Effient (prasugrel)
Adult dosage forms and strengths
tablet
- 5mg
- 10mg
Acute Coronary Syndrome
Reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome (ACS) managed by means of percutaneous coronary intervention (PCI) who have either (a) unstable angina or non-ST-elevation MI (NSTEMI) or (b) ST-elevation MI (STEMI) when managed with primary or delayed PCI
60 mg PO once as loading dose, then 10 mg/day PO in combination with aspirin 81-325 mg/day; if patient <60 kg, consider 5 mg/day PO because of potentially increased bleeding risk (efficacy and safety not established)
Dosing Modifications
Renal impairment
- Dose adjustment not necessary
Hepatic impairment
- Mild-to-moderate: Dose adjustment not necessary
- Severe: Not studied
Sickle Cell Disease (Orphan)
Orphan designation for treatment of sickle cell disease
Sponsor
- Eli Lilly; Lilly Corporate Center; Indianapolis, IN 46285
Pediatric dosage forms and strengths
Not recommended
Geriatric dosage forms and strengths
Acute Coronary Syndrome
<75 years
60 mg PO once as loading dose, then 10 mg/day PO in combination with aspirin 81-325 mg/day
Weight <60 kg: consider 5 mg/day because of potentially increased bleeding risk (efficacy and safety not established)
≥75 years
Generally not recommended, because of increased risk of fatal and intracranial bleeding and uncertain benefit, except in high-risk patients (diabetes or prior MI), for whom effect appears to be greater and use may be considered
Effient (prasugrel) adverse (side) effects
1-10%
Bleeding
Anemia
Atrial fibrillation
Back pain
Bradycardia
Dizziness
Dyspnea
Headache
Hypertension
Nausea
<1%
Thrombotic thrombocytopenic purpura
Abnormal hepatic function
Angioedema
Hematoma
Hemolysis
Hemorrhage
Abnormal liver function
Warnings
Black box warnings
Potential for significant, sometimes fatal, bleeding
- Do not use in patients with active bleeding or a history of transient ischemic attack (TIA) or stroke
- Generally not recommended for age >75 years (increased risk of fatal and intracranial bleeding and uncertain benefit, except in high-risk patients [diabetes or prior MI])
- Do not initiate in patients undergoing urgent coronary artery bypass grafting (CABG); if possible, discontinue at least 7 days before any surgical procedure
- If possible, manage bleeding without discontinuing (risk of subsequent cardiovascular events is increased if prasugrel stopped, particularly in first few weeks after ACS)
Additional risk factors for bleeding
- Weight <60 kg
- Propensity to bleed (eg, recent trauma, recent surgery, recent or recurrent GI bleeding, active peptic ulcer disease, severe hepatic impairment, or moderate-to-severe renal impairment)
- Concomitant use of other drugs that increase bleeding risk
Contraindications
Hypersensitivity
Active pathologic bleeding (eg, peptic ulcer, intracranial hemorrhage)
Prior TIA or stroke
Cautions
Hypersensitivity with angioedema reported
Bleeding diathesis
Thrombocytopenic purpura occurring within 2 weeks of initiation of therapy reported
Use caution in severe hepatic impairment and end-stage renal disease
Use caution in patients taking anticoagulants, nonsteroidal anti-inflammatory drugs (NSAIDs), or fibrinolytics
Bleeding may increase in patients <60 kg
See Black box warnings
Pregnancy and lactation
Pregnancy: Due to mechanism of action and associated identified risk of bleeding, consider benefits and risks of therapy and possible risks to fetus when prescribing drug to a pregnant woman
Lactation: There is no information regarding presence of prasugrel in human milk, the effects on breastfed infant, or effects on milk production; consider developmental and health benefits of breastfeeding along with mother’s clinical need for therapy and any potential adverse effects on the breastfed child from drug or from underlying maternal condition
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Effient (prasugrel)
Mechanism of action
Prasugrel is a prodrug, a thienopyridine that inhibits platelet activation and aggregation through irreversible binding of active metabolite to adenosine phosphate (ADP) platelet receptors (specifically, P2Y12 receptor)
Absorption
Bioavailability: >78%
Peak plasma time: 30 min
Absorption: >79%
Distribution
Protein bound: Active metabolite, 98%
Vd: 44-48 L
Metabolism
Rapidly hydrolyzed in intestine to active metabolite via CYP3A4 and CYP2B6
Elimination
Half-life: 7 hr (range, 2-15 hr)
Clearance: 112-166 L/hr
Excretion: Urine (68%), feces (27%)
