Table 4.

Predicted pharmacokinetic drug interactions between JAK inhibitors and other agents used for the management of COVID-19.

Pharmacokinetic Feature		DDIs with JAK-Inhibitors		Clinical Relevance and Literature Data
		Baricitinib	Ruxolitinib
P-gp substrate		-	Weak inhibitor
CYP3A4 substrate		Minor (only 10%)	Major (CYP2C9/CYP2D9 minor)
BCRP substrate		Substrate Weak inhibitor (only in vitro)	Weak inhibitor
OAT substrate		OAT3 substrate OAT1/3 inhibitor (only in vitro)	Weak inhibitor (only in vitro)
COVID-19 agents	Metabolic pathway
Remdesivir	CYP2C8–CYP2C19–CYP3A4–P-gp–OATP1B1 substrate			No relevant interactions expected
Dexamethasone	CYP3A4 substrate–moderate CYP3A4 inducer			No relevant interactions expected
Colchicine	CYP3A4 and P-gp substrate			Risk of increased colchicine exposure with concomitant use of ruxolitinib, particularly in patients with renal or hepatic impairment
IL6 inhibitors	Restoration of CYP3A4 and CYP2C19 activity			Risk of additive immunosuppression
Favipiravir	CYP2C8, OAT1, and OAT3 moderate inhibitor			Favipiravir may increase baricitinib exposure, but not in a clinically relevant extent

RED BOX: avoid co-administration (contraindicated or not recommended). ORANGE BOX: potential interaction (caution should be exercised and consider dose adjustment or alternative drugs). YELLOW BOX: potential weak interaction (monitoring for potential underexposure or toxicity). GREEN BOX: no interaction expected based on pharmacokinetic properties, although no clinical data exist. DDIs were checked through covid19-druginteractions.org/checker. BCRP: breast cancer resistance protein; CYP: cytochrome P450; OAT: organic anion transporter; and P-gp: glycoprotein P.