Table 2.

Potential interactions between COVID-19 treatments under investigation and CCM drugs.

COVID-19 treatments under investigation	Potential interactions with CCM drugs
Chloroquine-hydroxychloroquine	Inhibits CYP2D6 (increasing half-life of most of the beta blockers [74] and amiodarone), and inhibits and downregulates PgP [75]. They do not interact with novel oral anticoagulants (NOACS) or vitamin K antagonists (VKAs) [76].
Protease inhibitors (lopinavir-ritonavir)	By inhibiting CYP3A4, they increase plasma levels of most of CV drugs. May lower the effect of VKAs by induction of CYP2C19 and increase plasma levels of NOACs. Also may increase amiodarone levels [77].
Azithromycin	Increases levels of warfarin/acenocoumarol, these anticoagulants should be withdrawn during azithromycin treatment. Due to PgP inhibition, dose reduction of NOACs may be required.
Atazanavir	Increases levels of VKAs and NOACs (should be discontinued). May increase amiodarone levels and effect. May increase digoxin levels. Mild increase in atenolol levels (beta blocker) [77].
Remdesivir	No relevant interactions.
Favipiravir, Bevacizumab, Ecolizumab, Fingolimod, Pirfenidone, Interferon Methylprednisone	No relevant interactions.
Tocilizumab	May lower effect of anticoagulants.
Nitazoxanide	May increase VKA levels; do not use concomitantly.
Sarilumab	It is a CYP3A4 inducer, but dose modifications are not recommended.
Interferon and Methylprednisolone	Reduction of VKAs is advised.
Ribavirin	Interferes with the absorption of VKAs, possible dose increase indicated. Enalapril and other ACE2 inhibitors may provoke dry cough as well as ribavirin [78].
Ivermectin	May decrease the effect of warfarin and dicoumarol. Risk of myopathy with captopril [79].
Oseltamivir	No CYP interactions with CV drugs. However, case reports and series show some increase in the effect of VKAs [75].
Arbidol (Umifenovir)	May decrease metabolism of labetalol (beta-blocker) [80].
Canakinumab	No known drug interactions, but upregulation of CYP enzymes may further modify metabolization of CV drugs [81,82].
Anakinra	No drug interactions.
Emapalumab	No known drug interactions, but upregulation of CYP enzymes may further modify metabolization of CV drugs [83].
Siltuximab	VKA interaction through CYP3450. Close monitoring [84].
Cyclosporin A	Cyclosporin may increase digoxin levels. Amiodarone, losartan, and valsartan increase cyclosporin levels; ACE inhibitors increase nephrotoxicity [85,86].
Sirolimus	Serious warning; may increase risk of ACE inhibitor related angioedema. CYP450 and PgP interactions [87].
Darunavir/cobicistat	Drugs metabolized by CYP3A4, CYP2D6, or that use the transporters PgP, BCRP, MATE1, OATP1B1 or OATP1B3 may have interactions [88]. Anticoagulants, beta blockers, and digoxin should be used with caution.