Ketoconazole and Methadone interaction
Ketoconazole and Methadone: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Ketoconazole label · effective 2026-07-07
QT Prolongation and Drug Interactions Leading to QT Prolongation Coadministration of the following drugs with ketoconazole is contraindicated: dofetilide, quinidine, pimozide, lurasidone, cisapride, methadone, disopyramide, dronedarone, ranolazine.
Additionally, the following other drugs are contraindicated with ketoconazole tablets: methadone, disopyramide, dronedarone, ergot alkaloids such as dihydroergotamine, ergometrine, ergotamine, methylergometrine, irinotecan, lurasidone, oral midazolam, alprazolam, triazolam, felodipine, nisoldipine, ranolazine, tolvaptan, eplerenone, lovastatin, simvastatin and…
Coadministration of the following drugs with ketoconazole is contraindicated: dofetilide, quinidine, pimozide, lurasidone, cisapride, methadone, disopyramide, dronedarone, ranolazine.
This may potentiate and prolong hypnotic and sedative effects, especially with repeated dosing or chronic administration of these agents.
…methadone when coadministered with ketoconazole tablets may increase the risk of serious cardiovascular events including QT prolongation and torsade de pointes, or respiratory or CNS depression [See CONTRAINDICATIONS .] Fentanyl: The potential increase in plasma concentrations of fentanyl when coadministered with ketoconazole tablets may increase the risk of…
From the Methadone (METHADOSE) label · effective 2026-04-27
Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of methadone and CYP3A4, CYP2B6,…
Inhibitors of CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 Clinical Impact: Methadone undergoes hepatic N-demethylation by several cytochrome P450 (CYP) isoforms, including CYP3A4, CYP2B6, CYP2C19, CYP2C9, and CYP2D6.
Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.
Open in the checkerNot medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.