Alprazolam and Nefazodone interaction

Alprazolam and Nefazodone: 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 Alprazolam (Alprazolam XR) label · effective 2025-02-11

Major

• taking strong cytochrome P450 3A (CYP3A) inhibitors (e.g., ketoconazole, itraconazole), except ritonavir [see Dosage and Administration (2.5) , Warnings and Precautions (5.5) , Drug Interactions (7.1) ] .

Contraindicationsby drug classView label on DailyMed
Major

• Concomitant use with strong cytochrome P450 3A (CYP3A) inhibitors, except ritonavir.

Contraindicationsby drug classView label on DailyMed
Major

Strong CYP3A Inhibitors Alprazolam XR is contraindicated in patients receiving strong inhibitors of CYP3A such as azole antifungal agents [see Contraindications (4) ] .

Warnings and precautionsby drug classView label on DailyMed
Major

Prevention or management Concomitant use of alprazolam XR with a strong CYP3A4 inhibitor (except ritonavir) is contraindicated [see Contraindications (4) , Warnings and Precautions (5.5) ] .

Drug interactionsby drug classView label on DailyMed
Major

Prevention or management Avoid use and consider appropriate dose reduction when alprazolam XR is coadministered with a moderate or weak CYP3A inhibitor [see Warnings and Precautions (5.5) ] .

Drug interactionsby drug classView label on DailyMed

From the Nefazodone (Nefazodone Hydrochloride) label · effective 2025-07-31

Moderate

Interaction with Triazolobenzodiazepines Interaction studies of nefazodone with two triazolobenzodiazepines, i.e., triazolam and alprazolam, metabolized by cytochrome P450 3A4, have revealed substantial and clinically important increases in plasma concentrations of these compounds when administered concomitantly with nefazodone.

Warningsnames AlprazolamView label on DailyMed
Moderate

Alprazolam When alprazolam (1 mg BID) and nefazodone (200 mg BID) were coadministered, steady-state peak concentrations, AUC and half-life values for alprazolam increased by approximately 2 fold.

Warningsnames AlprazolamView label on DailyMed
Moderate

If alprazolam is coadministered with nefazodone, a 50% reduction in the initial alprazolam dosage is recommended.

Warningsnames AlprazolamView label on DailyMed
Minor

Nefazodone plasma concentrations were unaffected by alprazolam.

Warningsnames AlprazolamView label on DailyMed
Minor

Triazolam/Alprazolam – See CONTRAINDICATIONS and WARNINGS .

Drug interactionsnames AlprazolamView 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.