No pharmaceutical opinion available for this interaction.
Darunavir / cobicistat can inhibit the metabolism (CYP 3A4) and decrease the active metabolite formation of Clopidogrel.
3A4 (major) and 2D6 (minor)
3A4 (potent) and 2D6 (weak), P-gp, MATE 1, BCRP, OATP1B1 and OATP1B3.
2C19 (major), 3A4, 2B6, 2C9 and 1A2
2B6 (moderate), 2C9 (weak)
Possible decrease of clinical efficacy.
Use with caution or choose an alternative.
Closely monitor clinical effectiveness.
Ref #3447 : A randomized crossover study evaluated the impact of boosted antiretrovirals on the pharmacokinetics of the active metabolites of clopidogrel and prasugrel and on their efficacy in HIV-positive patients. In patients receiving clopidogrel 300 mg concomitantly with a ritonavir or cobicistat containing regimen, there was a significant 69% decrease in AUC and Cmax of clopidogrel active metabolite compared to healthy patients receiving clopidogrel alone. Platelet inhibition was insufficient in 44% of patients taking ritonavir or cobicistat while it was adequate in all patients without ritonavir or cobicistat. For patients receiving prasugrel 60 mg with ritonavir or cobicistat, there was a 52% decrease in AUC and 41% in the Cmax of prasugrel active metabolite. On the other hand, all patients undergoing prasugrel show potent platelet inhibition. The authors conclude that prasugrel remains an adequate antiplatelet agent in HIV-infected patients and could be preferred to clopidogrel in this setting, regardless of the metabolic interaction and inhibition of its bioactivation pathways.
Ref #3449 : Another study in healthy patients receiving clopidogrel (300 mg on the first day followed by 75 mg QD) and ritonavir (100 mg BID) showed a decrease in clopidogrel active metabolite AUC and Cmax of 52% and 49%, respectiveley. Mean and maximum platelet inhibition were reduced to 31% and 40%, respectively. The authors conclude that it is recommended to avoid the concomitant administration of clopidogrel with ritonavir-containing regimens.
Ref #3448 : Case report of a 45-year-old HIV-positive patient treated with darunavir/ritonavir and emtricitabine/ tenofovir. Following coronary intervention, the patient began double antiplatelet therapy with aspirin and clopidogrel while his antiretroviral therapy was maintained. Six months later, the patient presented with an episode of chest pain with electrocardiographic signs of acute anterior myocardial infarction and signs of thrombosis of the implanted stent. Following a new intervention, clopidogrel is replaced by prasugrel, while darunavir/ritonavir is maintained. No new episodes of thrombosis were observed.
Ref #3134 : Ketoconazole 400 mg decreased clopidogrel active metabolite AUC by 22-29% and platelet aggregation by 22–33% in healthy volunteers.
Ref #3162 : Case report of decreased responsiveness to clopidogrel in a HIV-positive patient receiving isoniazid (CYP2C19, 3A4 inhibitor) and darunavir/ritonavir QD suggesting decreased effect due to potential 3A4 inhibition.
In a study with erythromycin (CYP3A4 inhibitor), the following results were observed: baseline platelet aggregation of 93%, platelet aggregation of 42% with the addition of clopidogrel, and platelet aggregation of 55% when clopidogrel and erythromycin were administered together. The author concluded that the addition of a CYP3A4 inhibitor can potentially decrease the antiplatelet effect of clopidogrel. Moreover, although the findings vary from one study to another, several studies have also reported a loss of efficacy when atorvastatin (CYP3A4 inhibitor) is combined with clopidogrel.