Clopidogrel side effects

The most frequent side effects of clopidogrel are nausea, vomiting, and diarrhea (5% of patients). Thrombotic thrombocytopenia purpura has been reported rarely. The most serious side effect of clopidogrel is hemorrhage. 

Clopidogrel has fewer adverse effects than ticlopidine and is rarely associated with neutropenia. Thrombotic thrombocytopenic purpura associated with clopidogrel has been reported. Because of its superior side effect profile and dosing requirements, clopidogrel is preferred over ticlopidine. The antithrombotic effects of clopidogrel are dose-dependent within 5 hours after an oral loading dose of 300 mg, 80% of platelet activity will be inhibited. The maintenance dose of clopidogrel is 75 mg/d, which achieves maximum platelet inhibition. The duration of the antiplatelet effect is 7-10 days. 

In addition to the risk of bleeding, which will be detailed in the different studies, thienopyridines are able to cause skin disorders (rashes or prurit) and gastrointestinal disorders (diarrhea). In the CLASSICS study, these side effects were observed in 8.2% of patients treated with ticlopidine and in 3.5% of those taking clopidogrel treatment. The most serious problem was related to hematologic disorders neutropenia or thrombocytopenia. These disorders are much less frequent with clopidogrel than with ticlopidine 0.04% of neutropenia in the CAPRIE study and 0.05% in the CURE trial, Thrombotic thrombocytopenic purpura are exceptional one for 200,000 patients. 

The addition of ticlopidine to aspirin has been shown to have a synergistic effect on the inhibition of platelet aggregation after stent insertion (6), and this combination has also been found to be superior in terms of prevention of in-stent thrombosis to both aspirin alone and aspirin combined with warfarin (7). However, due to the rare but serious side effect of agranulocytosis associated with ticlopidine (8), and its slow onset of action, ticlopidine is no longer used in most countries. The combination of clopidogrel and aspirin has been proved to be as effective as aspirin and ticlopidine in the prevention of intrastent thrombosis (9). 

Ticlopidine is a thienopyridine antiplatelet agent, similar in structure and mechanism of action to clopidogrel. It has been shown to reduce the risk of stroke by 30% compared with placebo and by 21% compared with aspirin 325 mg/day inpatients at risk. The use of ticlopidine has been severely restricted by its side-effect profile, however. It causes bone marrow suppression, rash, diarrhea, and elevation of the serum cholesterol concentration. Neutropenia occurs in up to 2% of patients and generally is reversible. More problematic, however, is the increased risk of aplastic anemia and thrombotic thrombocytopenic purpura. Ticlopidine 250 mg twice daily is stiU available as an alternative in patients who fail or are intolerant of other therapies but is rarely needed. 

Wang F, Han J. Delayed eosinophilic gastroenteritis, a possible side effect of clopidogrel Int J Cardiol 2013 165(3) e53. ... 

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