Coadministration of Effient and warfarin increases the risk of bleeding [see Warnings and Precautions and Clinical Pharmacology (12.3)].
Non-Steroidal Anti-Inflammatory Drugs
Coadministration of Effient and NSAIDs (used chronically) may increase the risk of bleeding [see Warnings and Precautions ].
Other Concomitant Medications
Effient can be administered with drugs that are inducers or inhibitors of cytochrome P450 enzymes [see Clinical Pharmacology (12.3)].
Effient can be administered with aspirin (75 mg to 325 mg per day), heparin, GPIIb/IIIa inhibitors, statins, digoxin, and drugs that elevate gastric pH, including proton pump inhibitors and H2 blockers [see Clinical Pharmacology (12.3)].
Signs and Symptoms
Platelet inhibition by prasugrel is rapid and irreversible, lasting for the life of the platelet, and is unlikely to be increased in the event of an overdose. In rats, lethality was observed after administration of 2000 mg/kg. Symptoms of acute toxicity in dogs included emesis, increased serum alkaline phosphatase, and hepatocellular atrophy. Symptoms of acute toxicity in rats included mydriasis, irregular respiration, decreased locomotor activity, ptosis, staggering gait, and lacrimation.
Recommendations about Specific Treatment
Platelet transfusion may restore clotting ability. The prasugrel active metabolite is not likely to be removed by dialysis.
Effient is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage [see Warnings and Precautions and Adverse Reactions (6.1)].
Prior Transient Ischemic Attack or Stroke
Effient is contraindicated in patients with a history of prior transient ischemic attack (TIA) or stroke. In TRITON-TIMI 38 (TR ial to Assess I mprovement in T herapeutic Outcomes by O ptimizing Platelet Inhibitio N with Prasugrel), patients with a history of TIA or ischemic stroke (> 3 months prior to enrollment) had a higher rate of stroke on Effient (6.5%; of which 4.2% were thrombotic stroke and 2.3% were intracranial hemorrhage [ICH]) than on clopidogrel (1.2%; all thrombotic). In patients without such a history, the incidence of stroke was 0.9% (0.2% ICH) and 1.0% (0.3% ICH) with Effient and clopidogrel, respectively. Patients with a history of ischemic stroke within 3 months of screening and patients with a history of hemorrhagic stroke at any time were excluded from TRITON-TIMI 38. Patients who experience a stroke or TIA while on Effient generally should have therapy discontinued [see Adverse Reactions and Clinical Studies].