Table 1.

Mechanisms, Pharmacokinetics, and Dynamics of the Emerging COVID‐19 Pharmacotherapy

Pharmacotherapy	Mechanism of Action	Metabolism	Mechanism of Interaction	Clinical Manifestation
				Interaction With AADs	Interaction With Anticoagulants
Chloroquine/hydroxychloroquine	Block viral entry into cells Reduce cytokines and inhibit autophagy and lysosomal activity in host cells	CYP2C8, CYP3A4, CYP2D6, and CYP1A1	Blocks IKr CYP2D inhibitors Long half‐life	QT prolongation (TdP)	None
Azithromycin	Induction of interferon and interferon‐related genes	MRP2 and ABCB (minimally by CYP3A4)	Blocks IKr Weak CYP3A4 inhibitor Moderate P‐glycoprotein inhibitor	QT prolongation (TdP)	Increases serum DOAC
Lopinavir/ritonavir	Protease inhibitor	CYP3A4	Strong CYP3A4 inhibitor Moderate CYP2D6 inhibitor Strong P‐glycoprotein inhibitor	QT prolongation (TdP) Nephrotoxicity (may increase serum sotalol and dofetilide)	Increases serum DOAC Nephrotoxicity (may increase serum apixaban, rivaroxaban, dabigatran, and LMWH)
Remdesivir	Adenosine analog (inhibits RNA‐dependent RNA polymerase)	Mainly by phosphorylation in nonspecific organ and partially by CYP2C8, CYP2D6, and CYP3A4	CYP3A4 inhibitor (in vitro without clinical significance)	None	None
Ribavirin	Guanosine analog (inhibits RNA‐dependent RNA polymerase)	Mainly by hydrolase and partially by CYP2C8, CYP2D6, and CYP3A4	None	None	None
Favipiravir	Purine analog (inhibits RNA‐dependent RNA polymerase)	Oxidase and renally excreted	None	None	None
Umifenovir	Inhibits membrane fusion of viral envelope targeting the S‐protein/ACE2 interaction	CYP3A4	CYP3A4 substrate	Plasma concentration may be increased with amiodarone, diltiazem, and verapamil (no documented evidence)	None
Interferon	Interfering with viral replication and promoting activation of the adaptive immune system	Proteolytic degradation by lysosomal enzymes, which are excreted in urine	None	None	None
Tocilizumab	Interleukin‐6 inhibitors	Unknown (expected to undergo catabolism)	Increases mRNA expression of CYP enzymes	None	May increase warfarin metabolism
Sarilumab	Interleukin‐6 inhibitors	Unknown (expected to undergo catabolism)	Increases mRNA expression of CYP enzymes	None	May increase warfarin metabolism
Pirfenidone	Interleukin‐β1 and interleukin‐4 inhibitors	CYP1A2 and renally excreted	None	Amiodarone, a CYP1A2 inhibitor, may increase pirfenidone plasma concentration	None
Bevacizumab	VEGF inhibitor monoclonal antibody	The reticuloendothelial system	None	None	None
Eculizumab	Compliment inhibitor monoclonal antibody	The reticuloendothelial system	None	None	None
Lenzilumab	GM‐CSF inhibitor monoclonal antibody	The reticuloendothelial system	None	None	None
Methylprednisolone	Anti‐inflammatory agent Alters gene expression	CYP3A4	CYP3A4 substrate	Plasma concentration may increase with amiodarone, diltiazem, and verapamil (no documented evidence) Hypokalemia‐induced digoxin toxicity	May interfere with warfarin metabolism and bioavailability
Fingolimod	Sphingosine 1‐phosphate receptor modulator	CYP4F2	Blocks IKach and ICaL	QT prolongation (TdP) Atrioventricular block	None

AAD indicates antiarrhythmic drug; ABCB, ATP binding cassette subfamily B; ACE2, angiotensin‐converting enzyme 2; COVID‐19, coronavirus disease 2019; CYP, cytochrome P; DOAC, direct oral anticoagulant; GM‐CSF, granulocyte‐macrophage colony‐stimulating factor; I_CaL, L‐type calcium channel; I_Kach, acetylcholine‐dependent potassium channels; I_Kr, potassium channel; LMWH, low‐molecular‐weight heparin; MRP2, multidrug resistance‐associated protein 2; TdP, torsade de pointes; and VEGF, vascular endothelial growth factor.