Metaxalone and Zolpidem interaction
Metaxalone and Zolpidem: 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 Metaxalone label · effective 2026-02-03
If concomitant use with another CNS depressant is warranted, closely monitor for signs of respiratory depression and sedation, particularly during treatment initiation and dosage increases.
If concomitant use of metaxalone and another CNS depressant is warranted, closely monitor for signs of respiratory depression and sedation, particularly during treatment initiation and dosage increases.
Depressants If concomitant use of Metaxalone Tablets, 640 mg and another CNS depressant is warranted, closely monitor for signs of respiratory depression and sedation, particularly during treatment initiation and dosage modification.
Due to the additive pharmacologic effect, concomitant use of Metaxalone Tablets, 640 mg with other CNS depressants may increase the risk of sedation and respiratory depression [see Warnings and Precautions (5.2) ].
Central Nervous System (CNS) Depression : Metaxalone Tablets, 640 mg may impair mental and/or physical abilities required for the performance of hazardous tasks, such as operating machinery or driving a motor vehicle, and may enhance the effects of other CNS depressants including alcohol.
From the Zolpidem (zolpidem tartrate) label · effective 2025-11-19
The use of Zolpidem Tartrate with other sedative-hypnotics (including other zolpidem products) at bedtime or the middle of the night is not recommended.
CNS-Depressant Effects: Impaired alertness and motor coordination, including risk of morning impairment.
Risk increases with dose and use with other CNS depressants and alcohol.
Postmarketing reports have shown that complex sleep behaviors may occur with Zolpidem Tartrate alone at recommended doses, with or without the concomitant use of alcohol or other central nervous system (CNS) depressants [see Drug Interactions (7.1) ] .
Additive effects occur with concomitant use of other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol), including daytime use [see Drug Interactions (7.1) ] .
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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.