Cibinqo Drug Interactions

Potential for other medicines to affect pharmacokinetics of CIBINQO: Abrocitinib is metabolised 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.
Co-administration 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 (see Pharmacology: Pharmacokinetics under Actions) increased by 91% and 155%, respectively, compared with administration alone (see Dosage & Administration).
Co-administration with CYP2C19/CYP2C9 inducers: Administration of CIBINQO 200 mg after multiple doses with rifampin, a strong inducer of CYP enzymes, resulted in reduction of abrocitinib active moiety exposures by approximately 56% (see Dosage & Administration). Based on the results of PBPK analysis, moderate induction of CYP enzymes reduces the exposure of abrocitinib active moiety by 44%.
Co-administration 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.
Co-administration with products which increase gastric pH: The effect of elevating gastric pH on abrocitinib active moiety exposures is not clinically significant and dose adjustment is not needed.
When abrocitinib 200 mg was administered concomitantly with famotidine 40 mg, a H2-receptor antagonist, the peak (C_max) and extent (AUC_inf) of abrocitinib active moiety exposures decreased by approximately 82% and 20% respectively. The effect of elevating gastric pH with antacids, or proton pump inhibitors (omeprazole) on the pharmacokinetics of abrocitinib has not been studied and may reduce the absorption of abrocitinib in a manner similar to that seen with famotidine.
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 oestradiol/levonorgestrel), or with substrates of BCRP and OAT3 (e.g., rosuvastatin), MATE1/2K (e.g., metformin), CYP3A4 (e.g., midazolam), CYP1A2 (e.g., caffeine) and CYP2B6 (e.g., efavirenz). In vitro, abrocitinib is an inhibitor of P-glycoprotein (P-gp). Co-administration 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 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.
In vitro, abrocitinib is an inhibitor of CYP2C19 enzyme. Co-administration of abrocitinib 200 mg once daily with omeprazole 10 mg single dose increased the AUC_inf and C_max of omeprazole by approximately 189% and 134%, respectively, indicating that abrocitinib is a moderate inhibitor of CYP2C19 enzyme. Caution should be exercised when using abrocitinib concomitantly with narrow therapeutic index medicines that are primarily metabolised by CYP2C19 enzyme (e.g., S-mephenytoin, clopidogrel).