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Concomitant use of baricitinib with biologic disease-modifying antirheumatic drugs (DMARDs), biologic immunomodulators, or other Janus kinase (JAK) inhibitors has not been studied. In rheumatoid arthritis and juvenile idiopathic arthritis, clinical studies have provided limited data on the concomitant use of baricitinib with potent immunosuppressive drugs (e.g., azathioprine, tacrolimus, or cyclosporine), and the risk of additive immunosuppression cannot be ruled out. In atopic dermatitis and alopecia areata, concomitant use with cyclosporine or other potent immunosuppressants has not been studied and is not recommended (see Section 4.4).
In vitro, baricitinib is a substrate of organic anion transporter 3 (OAT3), P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug and toxin extrusion protein 2-K (MATE2-K). In a clinical pharmacology study, administration of probenecid (an OAT3 inhibitor with strong inhibitory potential) increased the area under the concentration-time curve of baricitinib from time zero to infinity (AUC₀₋∞) by approximately 2-fold, with no changes in time to maximum concentration (Tₘₐₓ) or maximum concentration (Cₘₐₓ). Therefore, for patients taking OAT3 inhibitors with strong inhibitory potential (e.g., probenecid), the recommended dose of baricitinib should be halved (see Section 4.2). No clinical pharmacology studies have been conducted on OAT3 inhibitors with lower inhibitory potential. The prodrug leflunomide is rapidly converted to teriflunomide, a weak OAT3 inhibitor, which may therefore increase baricitinib exposure. Since no dedicated interaction study has been conducted, caution should be exercised when leflunomide or teriflunomide is administered concomitantly with baricitinib. Concomitant use of the OAT3 inhibitors ibuprofen and diclofenac may increase baricitinib exposure; however, their OAT3 inhibitory potential is lower than that of probenecid, so clinically relevant interactions are not expected. Concomitant administration of baricitinib with cyclosporine (a P-gp/BCRP inhibitor) or methotrexate (a substrate of multiple transporters, including organic anion-transporting polypeptide 1B1 [OATP1B1], organic anion transporter 1 [OAT1], OAT3, BCRP, multidrug resistance-associated protein 2 [MRP2], MRP3, and MRP4) has no clinically meaningful effect on baricitinib exposure.
In vitro, baricitinib is a substrate of cytochrome P450 enzyme 3A4 (CYP3A4), although less than 10% of the dose is metabolized via oxidation. In clinical pharmacology studies, concomitant administration of baricitinib with ketoconazole (a potent CYP3A inhibitor) had no clinically meaningful effect on the pharmacokinetics of baricitinib. Concomitant administration of baricitinib with fluconazole (a moderate inhibitor of CYP3A/CYP2C19/CYP2C9) or rifampicin (a potent CYP3A inducer) resulted in no clinically meaningful changes in baricitinib exposure.
Elevation of gastric pH using omeprazole had no clinically significant effect on baricitinib exposure.
In vitro, at clinically relevant concentrations, baricitinib is not an inhibitor of OAT1, OAT2, OAT3, organic cation transporter 2 (OCT2), OATP1B1, OATP1B3, BCRP, multidrug resistance protein 1 (MDR1), or MATE2-K. Baricitinib may be a clinically relevant inhibitor of organic cation transporter 1 (OCT1); however, there are currently no known selective OCT1 substrates for which clinically significant interactions can be predicted. In clinical pharmacology studies, concomitant administration of baricitinib with digoxin (a P-gp substrate) or methotrexate (a substrate of multiple transporters) had no clinically meaningful effect on their exposure.
In clinical pharmacology studies, concomitant administration of baricitinib with the CYP3A substrates simvastatin, ethinylestradiol, or levonorgestrel resulted in no clinically meaningful changes in the pharmacokinetics of these drugs.
FDA，2025.01
