Table 3.
Potential Drug Interactions Between Antiplatelet Agents and Investigational Therapies for COVID-19
| Investigational COVID-19 Therapy | Mechanism of Action of COVID-19 Therapy | P2Y12 Platelet Receptor Inhibitors |
Phosphodiesterase III Inhibitor |
||
|---|---|---|---|---|---|
| Clopidogrel | Prasugrel | Ticagrelor | Cilostazol | ||
| Lopinavir/ritonavir | Lopinavir is a protease inhibitor; Ritonavir inhibits CYP3A4 metabolism increasing lopinavir levels. | CYP 3A4 Inhibition (minor pathway): Reduction in clopidogrel active metabolite. Do not coadminister or if available utilize P2Y12 platelet function assays for monitoring.† With limited clinical data, prasugrel may be considered as alternative, if no contraindications. | CYP3A4 Inhibition: Decreased active metabolite but maintained platelet inhibition. Can administer with caution. | CYP3A4 Inhibition: Increased effects of ticagrelor. Do not coadminister or if available utilize P2Y12 monitoring or consider dose-reduced ticagrelor.∗ | CYP3A4 Inhibition: Recommend decreasing dose to maximum of 50 mg twice a day. |
| Remdesivir | Nucleotide-analog inhibitor of RNA-dependent RNA polymerases. | Reported inducer of CYP3A4 (minor pathway): no dose adjustment recommended. | Reported inducer of CYP3A4 (major pathway): no dose adjustment recommended. | Reported inducer of CYP3A4 (major pathway): no dose adjustment recommended. | Reported inducer of CYP3A4 (major pathway): no dose adjustment recommended. |
| Tocilizumab | Inhibits IL-6 receptor: may potentially mitigate cytokine release syndrome symptoms in severely ill patients. | Reported increase in expression of 2C19 (major pathway) and 1A2, 2B6, and 3A4 (minor pathways: no dose adjustment recommended. | Reported increase in expression of 3A4 (major pathway) and 2C9 and 2C19 (minor pathway): no dose adjustment recommended. | Reported increase in expression of 3A4 (major pathway): No dose adjustment recommended. | Reported increase in expression of 3A4 (major pathway): no dose adjustment recommended. |
| Sarilumab | Binds specifically to both soluble and membrane-bound IL-6Rs (sIL-6Rα and mIL-6Rα) and has been shown to inhibit IL-6-mediated signaling: may potentially mitigate cytokine release syndrome symptoms in severely ill patients. | Reported increase in expression of 3A4 (minor pathways): no dose adjustment recommended. | Reported increase in expression of 3A4 (major pathway): no dose adjustment recommended. | Reported increase in expression of CYP3A4 (major pathway): no dose adjustment recommended. | Reported increase in expression of 3A4 (major pathway): no dose adjustment recommended. |
Other drugs being studied to treat COVID-19 include azithromycin, bevacizumab, chloroquine/hydroxychloroquine, eculizumab, fingolimod, interferon, losartan, methylprednisolone, pirfenidone, and ribavirin. Drug-drug interactions between these medications and antiplatelet agents have yet to be identified.
IL = interleukin; other abbreviations as in Table 1.
Cangrelor, aspirin, dipyridamole, and glycoprotein IIb/IIIa inhibitors (eptifibatide, tirofiban, abciximab) are not known to interact with investigational therapies for COVID-19.
Monitoring of P2Y12 levels can be assessed through the VerifyNow assay, or others. Evaluation of effect of protease inhibitors on P2Y12 inhibitors has not been extensively studied. Dose reduction recommendations for P2Y12 inhibitors or P2Y12 platelet function assay monitoring is not commonly practiced.