Barbiturates: [P] Increased metabolism of itraconazole, ketoconazole, voriconazole. Benzodiazepines: [P] Decreased metabolism of alprazolam, midazolam, triazolam. Calcium channel blockers: [P] Decreased calcium channel blocker metabolism. Carbamazepine: [P] Decreased carbamazepine metabolism. Potential increased metabolism of itraconazole, ketoconazole, and voriconazole. Cisapride: [NP] Decreased metabolism of cisapride. Colchicine: [P] Decreased metabolism and transport of colchicine. Cyclosporine: [P] Decreased elimination of cyclosporine. Digoxin: [NE] Increased plasma concentrations of digoxin with itraconazole, posaconazole, and ketoconazole.
E, Expected; HP, Highly predictable. Interaction occurs in almost all patients receiving the interacting combination; P, Predictable. Interaction occurs in most patients receiving the combination; NP, Not predictable. Interaction occurs only in some patients receiving the combination; NE, Not established. Insufficient data available on which to base estimate of predictability.
TABLE 66–1 Important drug interactions.
Barbiturates Induction of hepatic microsomal drug metabolizing enzymes and P-glycoprotein. Additive central nervous system depression with other central nervous system depressants.
Antivirals: Increased metabolism of antivirals amprenavir, atazanavir, boceprevir, darunavir, delavirdine, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, simeprevir, and telaprevir with barbiturates.
Beta-adrenoceptor blockers: [P] Increased β-blocker metabolism. Calcium channel blockers: [P] Increased calcium channel blocker metabolism. Central nervous system depressants: [HP] Additive central nervous system depression. Corticosteroids: [P] Increased corticosteroid metabolism. Cyclosporine: [NE] Increased cyclosporine metabolism. Doxycycline: [P] Increased doxycycline metabolism. Estrogens: [P] Increased estrogen metabolism. Kinase inhibitors: [P] Increased metabolism of axitinib, bosutinib, ceritinib, cabozantinib, cobimetinib, crizotinib, dabrafenib, dasatinib, erlotinib, gefitinib, ibrutinib, idelalisib, imatinib, ixazomib, lapatinib, nilotinib, nintedanib, olaparib, osimertinib, palbociclib, pazopanib, ponatinib, regorafenib, ruxolitinib, sunitinib, tofacitinib, vandetanib, vemurafenib.
Methadone: [NE] Increased methadone metabolism.
Opioid analgesics: [P] Increased elimination of alfentanil, fentanyl, methadone, oxycodone, and sufentanil. Phenothiazine: [P] Increased phenothiazine metabolism. Phenytoin: [P] Increased phenytoin metabolism. Quinidine: [P] Increased quinidine metabolism. Sirolimus: [NE] Increased sirolimus metabolism. Tacrolimus: [NE] Increased tacrolimus metabolism. Theophylline: [NE] Increased theophylline metabolism. Valproic acid: [P] Decreased phenobarbital metabolism. See also Anticoagulants, oral; Antidepressants, tricyclic.