Drug information of Prasugrel
Mechanism of effect
Prasugrel , an inhibitor of platelet activation and aggregation, is a prodrug that is metabolized to both active (R-138727) and inactive metabolites. The active metabolite irreversibly blocks the P2Y12 component of ADP receptors on the platelet, which prevents activation of the GPIIb/IIIa receptor complex, thereby reducing platelet activation and aggregation.
dependent on hepatic transformation to an active metabolite.
Active metabolite binds irreversibly to P2Y12 class of ADP receptors on platelet surfaces, thereby inhibiting ADP-dependent platelet activation and aggregation.
ADP receptor is irreversibly modified; platelets exposed to prasugrel remain affected for the remainder of their lifespan (about 7–10 days).
Absorption isRapid; ≥79%. Rapid intestinal and serum metabolism via esterase-mediated hydrolysis to a thiolactone intermediate (inactive), which is then converted, via CYP450-mediated . Excretion is in Urine (~68% inactive metabolites) and feces (27% inactive metabolites). Inhibition of platelet aggregation (IPA) is Dose dependent.
Duration of effect : Platelet aggregation gradually returns to baseline values over 5-9 days after discontinuation; reflective of new platelet production. Half-life elimination in Active metaboliin is ~7 hours (range: 2-15 hours). Protein Bindingin Active metaboliteinis 98%.
Usual Adult Dose for Acute Coronary Syndrome :
Initial dose: 60 mg orally once
Maintenance dose: 10 mg orally once a day
Usual Geriatric Dose for Acute Coronary Syndrome :
65 to less than 75 years :
-Initial dose: 60 mg orally once
-Maintenance dose: 10 mg orally once a day
75 years or older : Use is generally not recommended in such patients, except in high-risk situations (e.g., diabetes or prior myocardial infarction) when benefit outweighs risk.
-No clear benefit was observed when the loading dose of this drug was administered prior to diagnostic coronary angiography compared to at the time of percutaneous coronary intervention (PCI); however, risk of bleeding was increased with early administration in patients undergoing PCI or early coronary artery bypass graft surgery (CABG).
-Aspirin 75 to 325 mg daily should be taken with this drug.
Drug contraindicationshypersensitivity to drug or its components.
Side effectsnausea , Headache , Bradycardia , vertigo , Diarrhea , Peripheral edema , Cough , fever , hyperlipidemia , Hyper-cholesteremia , skin rush , tiredness , gastrointestinal hemorrhage , Back pain
InteractionsOmega 3 , Protamine sulfat , Policosanol , Apixaban , Desirudin , Tinzaparin , Tositumomab , Ibritumomab tiuxetan , Antithrombin III , icosapent , Betrixaban , Urokinase , pentoxifylline , Ranitidine , Rifampin , Multivitamin mineral , Vitamin E , Rivaroxaban , Dabigatran , morphine , deoxycholic acid
• Bleeding : May cause significant, sometimes fatal, bleeding. Do not use prasugrel in patients with active pathological bleeding or a history of TIA or stroke.
Additional risk factors for bleeding include body 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), and concomitant use of medications that increase the risk of bleeding (eg, warfarin, heparin, fibrinolytic therapy, long-term use of NSAIDs).
Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, PCI, CABG, or other surgical procedures in the setting of prasugrel.
If possible, manage bleeding without discontinuing prasugrel. Discontinuing prasugrel, particularly in the first few weeks after ACS, increases the risk of subsequent cardiovascular events. Management of bleeding episodes includes the use of PRBCs and platelet transfusion.
• Hypersensitivity : Hypersensitivity, including angioedema, has been reported, including in patients with a previous history of thienopyridine hypersensitivity.
Because of structural similarities, cross-reactivity is possible among the thienopyridines (clopidogrel, prasugrel, and ticlopidine); use with caution or avoid in patients with previous history of thienopyridine hypersensitivity. Use of prasugrel is contraindicated in patients with hypersensitivity (eg, anaphylaxis) to prasugrel .
• Thrombotic thrombocytopenic purpura (TTP) : Cases of TTP (usually occurring within the first 2 weeks of therapy), resulting in some fatalities, have been reported with prasugrel; urgent plasmapheresis is required.
• GI disease : Use with caution in patients with recent or recurrent GI bleeding or active peptic ulcer disease (patients are generally at higher risk of bleeding).
• Hepatic impairment : Use with caution in patients with severe hepatic impairment (patients are generally at higher risk of bleeding).
• Renal impairment : Use with caution in patients with moderate to severe renal impairment (patients are generally at higher risk of bleeding).
• Elderly : In patients ≥75 years, use is generally not recommended due to increased risk of fatal and intracranial bleeding and uncertain benefit, except in high-risk situations (patients with diabetes or a history of MI) in which its effect appears to be greater and its use may be considered.
• Drug discontinuation : Discontinue therapy for active bleeding, elective surgery, stroke, or TIA; reinitiate therapy as soon as possible unless patient suffers stroke or TIA where subsequent use is contraindicated; if possible, manage bleeding without discontinuing therapy since premature discontinuation of treatment may cause increased risk for cardiac adverse events; lapses in treatment should be avoided.
Points of recommendation
Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you :
• if you are pregnant, planning to become pregnant, or are breast-feeding
• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
• if you have allergies to medicines, foods, or other substances
• if you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to any other thienopyridine (eg, clopidogrel)
• if you have diabetes, liver problems, or kidney problems
• if you have a history of heart attack, stomach or bowel problems (eg, bleeding, ulcers, polyps, diverticulosis), easy or persistent bleeding, or recent injury or surgery
• if you will be having surgery (including dental surgery)
• if you weigh less than 132 lbs (60 kg)
Take prasugrel by mouth with or without food.
Do not break prasugrel before you swallow it.
If you miss a dose of prasugrel , take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once unless your doctor tells you to.