Apolets Special Precautions

General: Bleeding: Clopidogrel prolongs the bleeding time and therefore should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery, or other pathological conditions (particularly gastrointestinal and intraocular). If a patient is to undergo elective surgery and an antiplatelet effect is not desired, clopidogrel should be discontinued 5-10 days prior to surgery. Due to the risk of bleeding and undesirable hematological effects, blood cell count determination and/or other appropriate testing should be promptly considered, whenever such suspected clinical symptoms arise during the course of treatment. The concomitant administration of clopidogrel with oral anticoagulants (e.g. warfarin) is not recommended since it may increase the intensity of bleeding (See Adverse Reactions).
In patients with recent TIA or stroke who are at high risk for recurrent ischemic events, the combination of aspirin and clopidogrel has not been shown to be more effective than clopidogrel alone, but the combination has been shown to increase major bleeding.
Patients should be told that they may bleed more easily and it may take them longer than usual to stop bleeding when they take clopidogrel or clopidogrel combined with aspirin, and that they should report any unusual bleeding to their physician. Patients should inform physicians and dentists that they are taking clopidogrel and/or any other product known to affect bleeding before any surgery is scheduled and before any new drug is taken.
GI Bleeding: In CAPRIE, clopidogrel was associated with a rate of gastrointestinal bleeding of 2% vs. 2.7% on aspirin. In CURE, the incidence of major gastrointestinal bleeding was 1.3% vs. 0.7% (clopidogrel + aspirin vs. placebo + aspirin, respectively). Clopidogrel should be used with caution in patients who have lesions with a propensity to bleed (such as ulcers). Drugs that might induce such lesions should be used with caution in patients taking clopidogrel.
Carcinogenesis, Mutagenesis, Impairment of Fertility: There was no evidence of tumorigenicity when clopidogrel was administered for 78 weeks to mice and 104 weeks to rats at dosages up to 77 mg/kg per day, which afforded plasma exposures >25 times that in humans at the recommended daily dose of 75 mg.
Clopidogrel was not genotoxic in four in vitro tests (Ames test, DNA-repair test in rat hepatocytes, gene mutation assay in Chinese hamster fibroblasts, and metaphase chromosome analysis of human lymphocytes) and in one in vivo test (micronucleus test by oral route in mice).
Clopidogrel was found to have no effect on fertility of male and female rats at oral doses up to 400 mg/kg per day) 52 times the recommended human dose on a mg/m² basis).