SURFENT 10
-
Chemical Name:
Prasugrel ( HCl ) -
Therapeutic Category:
Cardiovascular drugs -
Pharmacologic Category:
Antiplatelet Agent - Antiplatelet Agent, Thienopyridine -
Pharmaceutical Form:
Tablets -
Composition:
Prasugrel ( HCl ) 10mg
SURFENT
Tablets
Prasugrel (hydrochloride)
1-Mechanism of Action:
Prasugrel is an inhibitor of platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets
2-Pharmacokinetics:
- Following a 60-mg loading dose of prasugrel , approximately 90% of patients had at least 50% inhibition of platelet aggregation by 1 hour. Maximum platelet inhibition was about 80%
-Platelet aggregation gradually returns to baseline values over 5-9 days after discontinuation of prasugrel
- Prasugrel is a prodrug and is rapidly metabolized to a pharmacologically active metabolite and inactive metabolites.
- The avtive metabolite half-life plasma concentration is about 7 hours.
- Prasugrel can be administered without regard to food.
The active metabolite is bound about 98% to human serum albumin. -
- Prasugrel is not detected in plasma following oral administration, It is rapidly hydrolyzed in the intestine to a thiolactone, which is then converted to the active metabolite.
-Approximately 68% of the prasugrel dose is excreted in the urine and 27% in the feces as inactive metabolites.
3-Pharmacokinetics and Drug Interactions:
Inhibitors of CYP3A (Ketoconazole, verapamil, diltiazem, indinavir, ciprofloxacin, clarithromycin, and grapefruit juice) a selective and potent inhibitor of CYP3A4 and CYP3A5 decreases the Cmax by 34% to 46%.
Drugs that elevate gastric ph like ranitidine or lansoprazole decrease the Cmax of the prasugrel active metabolite by 14% and 29%, respectively, but does not change the active metabolite’s AUC and Tmax.
A significant prolongation of the bleeding time was observed when prasugrel was coadministered with Warfarine or Heparine
4-Indications and Usage:
Acute Coronary Syndrome:
Surfent is indicated to reduce the rate of thrombotic cardiovascular (CV) events (including stent thrombosis) in patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI) as follows:
• Patients with unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI).
• Patients with ST-elevation myocardial infarction (STEMI) when managed with primary or delayed PCI.
Surfent has been shown to reduce the rate of a combined endpoint of cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke compared to clopidogrel.
5-Contraindications:
-Hypersensetivity to the active substance or any of the excipient .
-Active pathological bleeding (see warning).
-History of stroke or transient ischaemic attack(TIA).
-Severe hepatic impairment (see warning) .
6-Warnings and Precautions:
General Risk of Bleeding:
The use of prasugrel in patients at increased risk of bleeding should only be considered when the benefits in terms of prevention of ischaemic events are deemed to outweigh the risk of serious bleeding the concern applies especially to patients in the following cases:
- Age ≥ 75 years(should only be undertaken with caution after a careful individual benefit / risk evaluation by the prescribing physician , if prescribed a lower maintenance dose of 5mg should be used).
- Body weight < 60 kg.
- Propensity to bleed (e.g., recent trauma, recent surgery, recent or recurrent gastrointestinal (GI) bleeding, active peptic ulcer disease, or severe hepatic impairment)
- Medications that increase the risk of bleeding (e.g., oral anticoagulants, chronic use of non-steroidal anti-inflammatory drugs [NSAIDs], and fibrinolytic agents)
- Prasugrel should be used with caution in patients with renal impairment or moderate hepatic impairment.
Surgery:
If a patient is to undergo elective surgery and an antiplatelet effect is not desired , Prasugrel should be discontinued at least 7 days prior to surgery , the benefits and risks of prasugrel should be carefuly considered in patients in whom the coronary anatomy has not been defined and urgent CABG(coronary artery bypass graft) is a possibility.
Thrombotic thrombocytopaenic purpura ( TTP) :
TTP has been reported with the use of thienopyridiness , Prasugrel was not associated with TTP in clinical trials.
- Caution should be exercise in patients with lactose intolerance
7-Adverse Reactions:
Prasugrel is well tolerate . There is some common adverse reaction including:
Anaemia ,haematoma , epistaxis , gastrointestinal haemorrhage ,rash , ecchymosis , haematuria , puncture site haemorrhage , contution.
and some rarely adverse reaction including: eye haemorrhage , hemoptysis , retroperitoneal haemorrhage , rectal haemorrhage ,hematochezia , gingival bleeding.
8-Drug Interactions:
Warfarin:
Coadministration of prasugrel and warfarin increases the risk of bleeding .
Non-Steroidal Anti-Inflammatory Drugs:
Coadministration of Prasugrel and NSAIDs (used chronically) may increase the risk of bleeding.
Other Concomitant Medications:
Prasugrel can be administered with drugs that are inducers or inhibitors of cytochrome P450 enzymes .
Prasugrel can be administered with aspirin (75 mg to 325 mg per day).
9-Dosage and Administration:
- Initiate treatment with a single 60 mg oral loading dose (2).
- Continue at 10 mg once daily with or without food. Consider 5 mg once daily for patients < 60 kg (2).
- Patients should also take aspirin (75 mg to 325 mg) daily
Dose in patients with low body weight:
Patients treated with SURFENT had body weight <60 kg. Individuals with body weight < 60 kg had an increased risk of bleeding and an increased exposure to the active metabolite of prasugrel. Consider lowering the maintenance dose to 5 mg in patients <60 kg. The effectiveness and safety of the 5 mg dose have not been prospectively studied.
Renal Impairment:
No dosage adjustment is necessary for patients with renal impairment. There is limited experience in patients with end-stage renal disease
Hepatic Impairment:
No dosage adjustment is necessary in patients with mild to moderate hepatic impairment (Child-Pugh Class A and B). The pharmacokinetics and pharmacodynamics of prasugrel in patients with severe hepatic disease have not been studied, but such patients are generally at higher risk of bleeding
10-Use in Pregnancy:
Pregnancy Category B - There are no adequate and well-controlled studies of prasugel use in pregnant women
11-Nursing Mothers:
It is not known whether Prasugrel is excreted in human milk, prasugrel should be used during nursing only if the potential benefit to the mother justifies the potential risk to the nursing infant.
12-Packaging:
Surfent-5
Pack of 10 film coated tablets
Each film coated Tablet contains: Prasugrel (Hydrochloride) 5 mg.
Surfent-10
Pack of 10 film coated tablets
Each film coated Tablet contains: Prasugrel (Hydrochloride) 10 mg.
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