Brexpiprazole and Ketoconazole interaction

Brexpiprazole and Ketoconazole: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

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

Major

This may potentiate and prolong hypnotic and sedative effects, especially with repeated dosing or chronic administration of these agents.

Contraindicationsby drug classView label on DailyMed
Major

…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…

Drug interactionsby drug classView label on DailyMed
Moderate

Antipsychotics, Anxiolytics and Hypnotics Lurasidone, alprazolam, oral midazolam, pimozide, triazolam aripiprazole, buspirone, haloperidol, midazolam IV, quetiapine, ramelteon, risperidone The increase in plasma concentrations of lurasidone when coadministered with ketoconazole tablets may increase the risk of serious side effects (See CONTRAINDICATIONS ).

Drug interactionsby drug classView label on DailyMed

From the Brexpiprazole (Rexulti) label · effective 2026-04-23

Moderate

Strong CYP2D6 REXULTI may be administered without dosage adjustment in patients with MDD when administered with strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine). or CYP3A4 inhibitors Administer half of recommended dosage.

Drug interactionsby drug classView label on DailyMed
Moderate

Strong/moderate CYP2D6 with Strong/moderate CYP3A4 inhibitors Administer a quarter of the recommended dosage.

Drug interactionsby drug classView label on DailyMed
Moderate

Known CYP2D6 poor metabolizers taking strong/moderate CYP3A4 inhibitors Administer a quarter of the recommended dosage.

Drug interactionsby drug classView label on DailyMed
Moderate

Table 12 Clinically Important Drug Interactions with REXULTI Strong CYP3A4 Inhibitors Clinical Impact: Concomitant use of REXULTI with strong CYP3A4 inhibitors increased the exposure of brexpiprazole compared to the use of REXULTI alone [see Clinical Pharmacology (12.3) ] .

Drug interactionsby drug classView label on DailyMed
Moderate

Intervention: With concomitant use of REXULTI with a strong CYP3A4 inhibitor, reduce the REXULTI dosage [see Dosage and Administration (2.7) ] .

Drug interactionsby drug classView label on DailyMed

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Not 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.