Plogrel

Plogrel

clopidogrel

Manufacturer:

Therapharma

Distributor:

Therapharma
Full Prescribing Info
Contents
Clopidogrel bisulfate.
Action
Anti-thrombotic.
Pharmacology: Pharmacodynamics: Clopidogrel is an irreversible inhibitor of platelet aggregation. It acts by irreversibly modifying the platelet adenosine 5'-diphosphate (ADP) receptor, thus selectively inhibiting the binding of ADP to its platelet receptor and the subsequent activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Consequently, platelets exposed to clopidogrel are affected for the remainder of their lifespan. Biotransformation of clopidogrel to its active metabolite is necessary to produce inhibition of platelet aggregation.
Pharmacokinetics: Clopidogrel is rapidly but incompletely absorbed after oral doses. Absorption appears to be at least 50%. It is a prodrug and is extensively metabolized in the liver, mainly to the inactive carboxylic acid derivative; metabolism is mediated by the cytochrome P-450 isoenzymes CYP3A4 and CYP2B6 and to a lesser extent by CYP1A2, CYP1A1 and CYP2C19. The active metabolite appears to be a thiol derivative but has not been identified in plasma.
Clopidogrel and the carboxylic acid derivative are highly protein bound. Clopidogrel and its metabolites are excreted in urine and in feces. About 50% of an oral dose is recovered from the urine and about 46% from the feces.
Indications/Uses
Prevention of atherosclerotic events in patients with history of recent myocardial infarction (MI) (within a few days until <35 days from occurrence), recent ischemic stroke (from 7 days until <6 months) or established peripheral arterial disease.
Non-ST segment elevation acute coronary syndrome (unstable angina/non-Q wave MI) including patients who are managed medically with percutaneous coronary intervention (with or without stent) or coronary artery bypass graft (CABG).
It is given prophylactically as an alternative to aspirin in patient at risk of thromboembolic disorders eg, MI, peripheral arterial disease and stroke.
Dosage/Direction for Use
Recent MI or Stroke or Established Peripheral Arterial Disease: Recommended Dose: Orally, 75 mg once daily with or without food.
Prophylaxis of Thromboembolic Events: Usual Dose: Orally, 75 mg once daily.
Non-ST Segment Elevation Acute Coronary Syndrome (Unstable Angina/non-Q Wave MI): Initiate a single 300-mg loading dose and then continue at 75 mg once daily in combination with aspirin.
A higher bleeding risk associated with combined use of clopidogrel and aspirin. It is recommended that physicians monitor their patients through clinical and laboratory evaluation.
Overdosage
Symptoms of acute toxicity include vomiting, prostration, difficulty in breathing and GI hemorrhage. Platelet transfusions may be an appropriate treatment when attempting to reverse the effects of clopidogrel. After decontamination, treatment is symptomatic and supportive.
Contraindications
Known hypersensitivity to clopidogrel or any component in the formulation.
Presence of active pathological bleeding (eg, peptic ulcer, intracranial hemorrhage) or coagulation disorders.
Special Precautions
Cases of thrombocytopenic purpura (usually occurring within the first 2 weeks of therapy) have been reported. Urgent plasmapheresis is required.
Patients with platelet disorders and/or at increased risk for bleeding (eg, peptic ulcer disease, trauma or surgery), severe hepatic and renal impairment.
Consider discontinuing clopidogrel 5 days prior to elective surgery, except in patients with cardiac stents that have not completed their full course of dual antiplatelet therapy. Patient-specific situations need to be discussed with a physician or cardiologist.
Use in pregnancy & lactation: Pregnancy category B. Teratogenic effects were not observed in animal studies. There are, however, no adequate and well controlled studies in pregnant women. Use in pregnancy only if clearly needed.
Clopidogrel is distributed into milk in rats. It is not known whether the drug is distributed into milk in humans. Discontinue breastfeeding or Plogrel because of potential adverse effects in infants.
Use in children: Safety and efficacy have not been established in patients <21 years.
Use in the elderly: Dosage adjustment based solely on age does not appear to be necessary in geriatric patients.
Use In Pregnancy & Lactation
Pregnancy category B. Teratogenic effects were not observed in animal studies. There are, however, no adequate and well controlled studies in pregnant women. Use in pregnancy only if clearly needed.
Clopidogrel is distributed into milk in rats. It is not known whether the drug is distributed into milk in humans. Discontinue breastfeeding or Plogrel because of potential adverse effects in infants.
Adverse Reactions
As with all drugs which may affect hemostasis, bleeding is associated with clopidogrel. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the concurrent use of multiple agents which alter hemostasis and patient susceptibility. Other adverse effects are as follows: Gastrointestinal: Abdominal pain, vomiting, nausea, dyspepsia, gastritis, diarrhea, constipation, GI hemorrhage, pancreatitis and stomatitis.
Cardiovascular: Chest pain, edema, hypertension, atrial fibrillation, cardiac failure, palpitation, syncope, angioedema and vasculitis.
Central Nervous System: Headache, dizziness, depression, fatigue, general pain, fever, insomnia, vertigo, anxiety, hemorrhagic stroke, intracranial hemorrhage, confusion and hallucination.
Dermatologic: Rash (severe, maculopapular), pruritus, eczema, allergic reaction, anaphylactoid reaction, bullous reaction, urticaria, erythema multiforme, lichen planus, Stevens-Johnson syndrome and toxic epidermal necrolysis.
Endocrine-Metabolic: Hypercholesterolemia, gout, hyperuricemia and pancreatitis.
Immunologic: Serum sickness.
Genitourinary: Urinary tract infection, cystitis and hematuria.
Hematologic: Bleeding, thrombotic thrombocytopenic purpura (TTP), epistaxis, hematoma, anemia, agranulocytosis, bilirubinemia, granulocytopenia, hypochromic anemia, neutropenia, leukopenia, thrombocytopenia, aplastic anemia, retroperitoneal bleeding and pancytopenia.
Hepatic: Liver function test abnormalities, fatty liver, acute liver failure and hepatitis.
Neuromuscular and Skeletal: Arthralgia, back pain, arthritis, leg cramps, neuralgia, paresthesia and weakness.
Respiratory: Dyspnea, rhinitis, bronchitis, cough, upper respiratory infection, bronchospasm, hemoptysis, hemothorax, pulmonary hemorrhage and interstitial pneumonitis.
Ocular: Cataract, conjunctivitis and ocular hemorrhage.
Miscellaneous: Flu-like syndrome, ischemic necrosis, menorrhagia, hypersensitivity and taste disorder.
Drug Interactions
Aspirin: Clopidogrel may potentiate aspirin's antithrombotic effects resulting in increased risk of bleeding.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) [eg, Naproxen, Ibuprofen, Diclofenac]: Increased occult GI blood loss has also been reported in concomitant use with NSAIDs. Co-administer with caution.
Anticoagulants: Concomitant use of clopidogrel with anticoagulants (eg, warfarin, argatroban, enoxaparin, bivalirudin, heparin) may cause increased risk of bleeding.
Drugs Metabolized by CYP2C9 Isoenzyme: Clopidogrel may inhibit the cytochrome P-450 isoenzyme CYP2C9 and interactions with drugs metabolized by this isoenzyme (eg, phenytoin, tamoxifen, tolbutamide, warfarin, torsemide, fluvastatin and NSAIDs) are possible.
Bupropion: Clopidogrel has been found to reduce the conversion of bupropion to its active metabolite suggesting that clopidogrel inhibits cytochrome P-450 isoenzyme CYP2B6.
Statins and Ciclosporin: Rhadomyolysis has been reported to develop in patients administered with clopidogrel in addition to ciclosporin and a statin (eg, atorvastatin, lovastatin or simvastatin). It has been suggested that the mechanism is a 3-way interaction involving competition for binding sites on cytochrome P-450 isoenzyme CYP3A4 between statins and clopidogrel, exacerbated by ciclosporin-mediated enzyme inhibition.
Macrolide Antibiotics: CYP3A4-inhibiting macrolides (eg, clarithromycin, erythromycin and troleandomycin) may attenuate the effects of clopidogrel.
Storage
Store at temperatures not exceeding 30°C.
ATC Classification
B01AC04 - clopidogrel ; Belongs to the class of platelet aggregation inhibitors excluding heparin. Used in the treatment of thrombosis.
Presentation/Packing
FC tab 75 mg x 50's.
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