Table 4.

Potential DDI between drugs used in the course of COVID-19 and medications for comorbidities.

Co-administered Drugs (CAD)	*CAD bioavailability (%)	*CAD Protein Binding (%)	Drug used the course of COVID-19	Mechanism of interaction	Example of interaction effect on AUC of CAD	Consequences of interaction	b Recommendations
Apixaban	50	92 - 94	Lopinavir/ritonavir	CYP3A4	Ketoconazole increases AUC of apixaban by 2-fold	Increased plasma concentration and bleeding	Avoid coadministration. Consider alternative anticoagulants
Amiodarone	35 - 65	96	Lopinavir/ritonavir	CYP3A4 inhibition	Indinavir increased amiodarone plasma concentration by 44 % via CYP3A4 inhibition	Increased amiodarone effects e.g. QTc-time prolongation, bradycardia, hypotension	Use with caution, monitor ECG, and adjust amiodarone
Bepridil	60	99	Atazanavir, lopinavir/ritonavir	–	–	Increased bepridil level effects. E.g. (QTc-time prolongation, hypotension	Do not co-administer
Bosentan	50	98	Atazanavir	–	Expected decreased atazanavir levels	Potential loss of antiviral activity	Do not co-administer bosentan with un-boosted atazanavir
Dabigatran	3 - 7	35	Atazanavir	P-gp inhibition	Dabigatran AUC increased by 110−127% via inhibition of intestinal P-gp by cobicistat	Increased risk of bleeding because of elevated dabigatran level	No dose adjustment if CrCL > 50 mL/min. avoid co-usage if CrCL < 50 mL/min
Eplerenone	69	50	Atazanavir, lopinavir/ritonavir	CYP3A4 inhibition	Ketoconazole as CYP3A4 inhibitor increases eplerenone AUC by 44 %	Increased plasma concentration, risk of hyperkalemia	Avoid co-administration
Lercanidipine	10	>98	Atazanavir, lopinavir/ritonavir	CYP3A4 inhibition	–	Increased plasma concentration	Monitor and adjust lercanidipine levels
Mexiletine	90	50 - 60	Chloroquine, hydroxychloroquine	CYP2D6 inhibition	–	Possible increased mexiletine effect e.g. Cardiac arrythmias	Do not co-administer
Quinidine	76 - 88	80 - 88	Atazanavir	CYP3A4 inhibition		Enhanced quinidine effects e.g. cardiac arrhythmia	Use with caution. Monitor for toxicity
Ranolazine	73	62	Atazanavir, lopinavir/ritonavir	CYP3A4 inhibition	Ketoconazole increased ranolazine AUC by 3.2-fold	QTc-time prolongation, cardiac arrythmias	Do not co-administer
Repaglinide	56	>98	Atazanavir	CYP3A4 inhibition	Clarithromycin increases repaglinide AUC by 40 %	Increase risk of hypoglycemia	Monitor repaglinide clinical effect and lower the dose if necessary
Salmeterol	–	96	Lopinavir/ritonavir	CYP3A4 inhibition	–	Potential increased salmeterol effects. E.g. QT prolongation, palpitations, sinus tachycardia	Do not co-administer
sildenafil	40	96	Lopinavir/ritonavir	CY3A4 inhibition	Clarithromycin and ciprofloxacin increased sildenafil AUC by 128 % and 110 %	Increased sildenafil effects. E.g. hypotension, priapism, visual changes	Start sildenafil at 25 mg QOD-QD; adjust dose, not recommended to exceed 25 mg in a 48 h period
Simvastatin	60	95	Lopinavir/ritonavir	CYP3A4 inhibition	Simvastatin acid exposure increased by 30-fold when co-administered with ritonavir/saquinavir	Increased plasma concentration effects (e.g. myopathy, rhabdomyolysis)	Do not co-administer. Alternative agents e.g. atorvastatin (low dose), pravastatin
Lovastatin	5	>95

^*Bioavailability and protein binding information collected from Drugbank and product information.

^bRecommendations obtained from http://hivinsite.ucsf.edu/interactions.