Lorlak Drug Interactions

Lorlatinib is primarily metabolized by CYP3A4 and uridine diphosphate-glucuronosyltransferase (UGT) 1A4, with minor contributions from CYP2C8, CYP2C19, CYP3A5, and UGT1A3. CYP3A inhibitors: boceprevir, cobicistat, conivaptan, itraconazole, ketoconazole, posaconazole, telaprevir, troleandomycin, voriconazole, ritonavir, paritaprevir in combination with ritonavir and ombitasvir and/or dasabuvir, and ritonavir in combination with either danoprevir, elvitegravir, indinavir, lopinavir, saquinavir, or tipranavir; grapefruit products. CYP3A inducers: rifampin, carbamazepine, enzalutamide, mitotane, phenytoin, and St. John’s wort. Proton-Pump inhibitors, H2-receptor antagonists, or locally-acting antacids. Drugs whose plasma concentrations may be altered by lorlatinib. CYP3A substrates: hormonal contraceptives, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. CYP2B6 substrates: bupropion. CYP2C9 substrates: tolbutamide, coumarin anticoagulants. UGT substrates: acetaminophen. P-glycoprotein substrates: fexofenadine, digoxin, dabigatran etexilate.