Alprazolam and Pregabalin interaction

Alprazolam and Pregabalin: 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

• Effects on Driving and Operating Machinery: Patients receiving • alprazolam XR should be cautioned against operating machinery or driving a motor vehicle, as well as avoiding concomitant use of alcohol and other central nervous system (CNS) depressant drugs.

Warnings and precautionsby drug classView label on DailyMed
Moderate

For the same reason, patients should be cautioned about the concomitant use of alcohol and other CNS depressant drugs during treatment with alprazolam XR [see Drug Interactions (7.1) ] .

Warnings and precautionsby drug classView label on DailyMed
Moderate

• Use with Other CNS Depressants: Produces additive CNS depressant effects.

Drug interactionsby drug classView label on DailyMed
Minor

Examples Psychotropic medications, anticonvulsants, antihistaminics, ethanol, and other drugs which themselves produce CNS depression.

Drug interactionsby drug classView label on DailyMed

From the Pregabalin (Lyrica CR) label · effective 2026-03-12

Major

• Respiratory Depression : May occur with LYRICA when used with concomitant CNS depressants or in the setting of underlying respiratory impairment.

Warnings and precautionsby drug classView label on DailyMed
Major

Respiratory Depression There is evidence from case reports, human studies, and animal studies associating pregabalin with serious, life-threatening, or fatal respiratory depression when co-administered with central nervous system (CNS) depressants, including opioids, or in the setting of underlying respiratory impairment.

Warnings and precautionsby drug classView label on DailyMed
Major

The management of respiratory depression may include close observation, supportive measures, and reduction or withdrawal of CNS depressants (including LYRICA CR).

Warnings and precautionsby drug classView label on DailyMed
Major

There is more limited evidence from case reports, animal studies, and human studies associating pregabalin with serious respiratory depression, without co-administered CNS depressants or without underlying respiratory impairment.

Warnings and precautionsby drug classView label on DailyMed
Moderate

When the decision is made to co-prescribe LYRICA CR with another CNS depressant, particularly an opioid, or to prescribe LYRICA CR to patients with underlying respiratory impairment, monitor patients for symptoms of respiratory depression and sedation, and consider initiating LYRICA CR at a low dose.

Warnings and precautionsby 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.