Potential for other medicines to affect pharmacokinetics of abrocitinib: 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).
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 with antacids, H2-receptor antagonists (famotidine), or proton pump inhibitors (omeprazole) on the pharmacokinetics of abrocitinib has not been studied and may reduce the absorption of abrocitinib due to the low solubility of abrocitinib at pH above 4.
Other in vitro interactions: In vitro, abrocitinib or its metabolites were not significant inhibitors or inducers of CYP enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) or of uridine diphosphate-glucuronyltransferases (UGTs) (UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7). Abrocitinib or its metabolites at clinically meaningful concentrations are not inhibitors of organic anion transporter (OAT)3, organic cation transporter (OCT)1, multidrug and toxin compound extrusion protein (MATE)1/2K and breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1/1B3, bile salt export pump (BSEP), OAT1 or OCT2.
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). 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 AUCinf and Cmax by approximately 53% and 40%, respectively, compared with administration alone. The effect of abrocitinib on pharmacokinetics of digoxin, a P-gp substrate with a narrow therapeutic index, has not been evaluated. Caution should be exercised as the levels of digoxin may increase.