Ketoconazole and Phenobarbital interaction
Ketoconazole and Phenobarbital: 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
This may potentiate and prolong hypnotic and sedative effects, especially with repeated dosing or chronic administration of these agents.
Therefore, administration of potent enzyme inducers of CYP3A4 with ketoconazole tablets is not recommended.
…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…
Coadministration of ketoconazole tablets with potent enzyme inducers of CYP3A4 may decrease the bioavailability of ketoconazole to such an extent that efficacy may be reduced.
Anticonvulsants: carbamazepine (see also under 'Drugs that may have their plasma concentrations increased'), phenytoin.
From the Phenobarbital (SEZABY) label · effective 2025-12-23
Drugs that Prolong the QT Interval : Avoid concomitant use.
QT Prolongation SEZABY may prolong the QT interval [see Clinical Pharmacology (12.2)] .
Drugs that Prolong QT Interval SEZABY may prolong the QT interval [see Warnings and Precautions (5.10) and Clinical Pharmacology (12.2)] .
Other products that may also prolong the QTc interval may have additive effects, and products that may increase concentrations of phenobarbital [see Drug Interactions (7.1)] may increase the QT prolongation risk; therefore, avoid concomitant use of SEZABY and these products.
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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.