Cibinqo Drug Interactions

Potential for other medicines to affect pharmacokinetics of CIBINQO: Abrocitinib is metabolized predominantly by CYP2C19 and CYP2C9 enzymes and to a lesser extent by CYP3A4 and CYP2B6 enzymes, and its active metabolites are renally excreted and are substrates of the organic anion transporter 3 (OAT3). Therefore, exposures of abrocitinib and/or its active metabolites may be affected by medicinal products that strongly inhibit or induce CYP2C19 or CYP2C9 or inhibit the OAT3 transporter. Dose adjustments, as appropriate, based on these results are outlined in Dosage & Administration.
Coadministration with CYP2C19/CYP2C9 inhibitors: When CIBINQO 100 mg was administered concomitantly with fluvoxamine (a strong CYP2C19 and moderate CYP3A inhibitor) or fluconazole (a strong CYP2C19, moderate CYP2C9 and CYP3A inhibitor), the extent of exposure of abrocitinib active moiety increased by 91% and 155%, respectively, compared with administration alone.
Coadministration with CYP2C19/CYP2C9 inducers: Administration of CIBINQO 200 mg after multiple dosing with rifampin, a strong inducer of CYP enzymes, resulted in reduction of abrocitinib active moiety exposures by approximately 56%.
Coadministration with OAT3 inhibitors: When CIBINQO 200 mg was administered concomitantly with probenecid, an OAT3 inhibitor, abrocitinib active moiety exposures increased by approximately 66%. This is not clinically significant, and a dose adjustment is not needed.
Potential for CIBINQO to affect pharmacokinetics of other medicines: No clinically significant effects of CIBINQO were observed in drug interaction studies with oral contraceptives (e.g., ethinyl estradiol/levonorgestrel), or with substrates of BCRP and OAT3 (e.g., rosuvastatin), MATE1/2K (e.g., metformin) and CYP3A4 (e.g., midazolam). In vitro abrocitinib is an inhibitor of P-glycoprotein (P-gp). Coadministration of dabigatran etexilate (a P-gp substrate), with a single dose of CIBINQO 200 mg increased dabigatran AUC_inf and C_max by approximately 53% and 40%, respectively, compared with administration alone. Caution should be exercised for concomitant use of abrocitinib with dabigatran. The effect of abrocitinib on the pharmacokinetics of other P-gp substrates has not been evaluated. Caution should be exercised as the levels of P-gp substrates with a narrow therapeutic index, such as digoxin, may increase.