Alunbrig Drug Interactions

Agents that May Increase Brigatinib Plasma Concentrations: CYP3A Inhibitors: The concomitant use of strong CYP3A inhibitors with brigatinib, including but not limited to certain antivirals (e.g., indinavir, nelfinavir, ritonavir, saquinavir), macrolide antibiotics (e.g., clarithromycin, telithromycin, troleandomycin), antifungals (e.g., ketoconazole, voriconazole), and nefazodone should be avoided. If concomitant use of strong CYP3A inhibitors cannot be avoided, the dose of brigatinib should be reduced by approximately 50% (i.e., from 180 mg to 90 mg, or from 90 mg to 60 mg). After discontinuation of a strong CYP3A inhibitor, brigatinib should be resumed at the dose that was tolerated prior to the initiation of the strong CYP3A inhibitor.
The concomitant use of moderate CYP3A inhibitors (e.g., diltiazem and verapamil) with brigatinib should be avoided. If concomitant use of moderate CYP3A inhibitors cannot be avoided, the dose of brigatinib should be reduced by approximately 40% (i.e., from 180 mg to 120 mg, 120 mg to 90 mg, or from 90 mg to 60 mg). After discontinuation of a moderate CYP3A inhibitor, brigatinib should be resumed at the dose that was tolerated prior to the initiation of the moderate CYP3A inhibitor.
Grapefruit or grapefruit juice may also increase plasma concentrations of brigatinib and should be avoided.
CYP2C8 Inhibitors: No dose adjustment is required for brigatinib during coadministration with strong CYP2C8 inhibitors.
P-gp and BCRP Inhibitors: No dose adjustment is required for brigatinib during coadministration with P-gp and BCRP inhibitors.
Agents that May Decrease Brigatinib Plasma Concentrations: CYP3A Inducers: The concomitant use of strong CYP3A inducers with brigatinib, including but not limited to rifampin, carbamazepine, phenytoin, rifabutin, phenobarbital, and St. John's Wort should be avoided.
The concomitant use of moderate CYP3A inducers with brigatinib, including but not limited to efavirenz, modafinil, bosentan, etravirine, and nafcillin should be avoided. If concomitant use of moderate CYP3A inducers cannot be avoided, the dose of brigatinib may be increased in 30 mg increments after 7 days of treatment with the current brigatinib dose as tolerated, up to a maximum of twice the brigatinib dose that was tolerated prior to the initiation of the moderate CYP3A inducer. After discontinuation of a moderate CYP3A inducer, brigatinib should be resumed at the dose that was tolerated prior to the initiation of the moderate CYP3A inducer.
Agents that May Have Their Plasma Concentrations Altered by Brigatinib: CYP3A Substrates: Brigatinib reduces plasma concentrations of coadministered medications that are predominantly metabolized by CYP3A.
Brigatinib may also induce other enzymes and transporters (e.g., CYP2C, P-gp) via the same mechanisms responsible for induction of CYP3A (e.g., pregnane X receptor activation).
Transporter Substrates: Brigatinib is an inhibitor of P-gp, BCRP, OCT1, MATE1, and MATE2K in vitro. Coadministration of brigatinib with substrates of P-gp (e.g. digoxin, dabigatran, colchicine, pravastatin), BCRP (e.g., methotrexate, rosuvastatin, sulfasalazine), OCT1, MATE1, and MATE2K may increase their plasma concentrations.