Drugs Affecting the Metabolism of Itraconazole: Interaction studies have been performed with rifampicin, rifabutin and phenytoin. Since the bioavailability of itraconazole and hydroxy-itraconazole was decreased in these studies to such an extent that efficacy may be largely reduced, the combination of itraconazole with these potent enzyme inducers is not recommended. No formal study data are available for other enzyme inducers eg, carbamazepine, phenobarbital and isoniazid but similar effects should be anticipated.
As itraconazole is mainly metabolised through CYP3A4, potent inhibitors of this enzyme may increase the bioavailability of itraconazole eg, ritonavir, indinavir, clarithromycin and erythromycin.
Effects of Itraconazole on the Metabolism of Other Drugs: Itraconazole can inhibit the metabolism of drugs metabolised by the cytochrome 3A family. This can result in an increase and/or prolongation of their effects, including side effects. After stopping treatment, itraconazole plasma levels decline gradually, depending on the dose and duration of treatment (see Pharmacokinetics under Actions). This should be taken into account when the inhibitory effect of itraconazole on co-medicated drugs is considered.
Drugs which should not be used during treatment with itraconazole: Terfenadine, astemizole, mizolastine, cisapride, triazolam, oral midazolam, difetilide, quinidine, pimozide. CYP3A4 metabolised HMG-CoA reductase inhibitors eg, simvastatin and lovastatin.
Calcium-channel blockers can have negative inotropic effects which may be additive to those of itraconazole; itraconazole can inhibit the metabolism of calcium-channel blockers. Therefore, caution should be used when co-administering itraconazole and calcium-channel blockers.
Drugs whose plasma levels, effects or side effects should be monitored (Their dosage, if co-administered with itraconazole, should be reduced if necessary): Oral anticoagulants; HIV protease inhibitors eg, ritonavir, indinavir, saquinavir; certain antineoplastic agents eg, vinca alkaloids, busulphan, docetaxel and trimetrexate; CYP3A4 metabolised calcium-channel blockers eg, dihydropyridines and verapamil; certain immunosuppressive agents eg, cyclosporine, tacrolimus, rapamycin; others eg, digoxin, carbamazepine, buspirone, alfentanil, alprazolam, midazolam IV, rifabutin, methylprednisolone.
No interaction of itraconazole with zidovudine (AZT) and fluvastatine has been observed.
No inducing effects of itraconazole on the metabolism of ethinylestradiol and norethisterone were observed.
Effects on Protein-Binding: In vitro studies have shown that there are no interactions on the plasma protein-binding between itraconazole and imipramine, propranolol, diazepam, cimetidine, indomethacin, tolbutamide and sulfamethazine.