Major
Clopidogrel × ritonavir
Antiplatelet agents – P2Y12 receptor inhibitors×HIV protease inhibitor / pharmacokinetic booster
Mechanism
Ritonavir blocks CYP3A4 and CYP2C19, through which clopidogrel becomes its active metabolite. The active metabolite is not formed – antiplatelet effect is lost. Ritonavir also induces glucuronidation, further reducing clopidogrel activity.
Symptoms
The patient feels no symptoms – the weakened antiplatelet effect is silent. In patients with a coronary stent or after acute coronary syndrome: risk of recurrent myocardial infarction, stent thrombosis, and ischaemic stroke.
Management
Avoid the combination. Alternative antiplatelet: ticagrelor (no CYP2C19 activation needed). If ticagrelor is impossible: prasugrel (requires activation but via a different route) with caution.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.