Drug Interaction Report

ADJUST DOSE: Coadministration with potent inhibitors of organic anion transporter 3 (OAT3) may decrease the renal clearance and increase the plasma concentrations of baricitinib, which has been shown in vitro to be a substrate of the transporter. In healthy study subjects, administration of a single 4 mg dose of baricitinib following treatment with multiple twice daily dosing of 1000 mg probenecid, a potent OAT3 inhibitor, resulted in an approximately 70% decrease in baricitinib renal clearance and 2-fold increase in systemic exposure (AUC), with no effect on peak plasma concentration (Cmax) or time to reach peak plasma concentration (Tmax). No clinical pharmacology study has been conducted with OAT3 inhibitors with less inhibition potential. However, simulations with diclofenac and ibuprofen (less potent OAT3 inhibitors) predicted minimal effect on the pharmacokinetics of baricitinib.

MANAGEMENT: The dosage of baricitinib should be reduced by one-half during coadministration with potent OAT3 inhibitors as follows: (1) If the recommended dosage is 4 mg once daily, reduce to 2 mg once daily; (2) If the recommended dosage is 2 mg once daily, reduce to 1 mg once daily; (3) If the recommended dosage is 1 mg once daily, consider discontinuing the OAT3 inhibitor. Patients should be monitored for adverse effects of baricitinib such as infections, malignancies, thrombosis, hematologic abnormalities, gastrointestinal perforations, hyperlipidemia, and hepatic transaminase elevations.

Probenecid may increase the plasma concentrations and half-lives of penicillins. The mechanism is competitive inhibition by probenecid of the renal tubular secretion of penicillins. While this interaction is often exploited to enhance the antibacterial effect of penicillins, toxicity may occur and should be considered if high penicillin dosages are administered intravenously.

ADJUST DOSING INTERVAL: Certain penicillins may exhibit reduced gastrointestinal absorption in the presence of food. The therapeutic effect of the antimicrobial may be reduced.

MANAGEMENT: The interacting penicillin should be administered one hour before or two hours after meals. Penicillin V and amoxicillin are not affected by food and may be given without regard to meals.