Metaxalone and Pregabalin interaction
Metaxalone 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.
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 Pregabalin (Lyrica CR) label · effective 2026-03-12
• Respiratory Depression : May occur with LYRICA when used with concomitant CNS depressants or in the setting of underlying respiratory impairment.
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.
The management of respiratory depression may include close observation, supportive measures, and reduction or withdrawal of CNS depressants (including LYRICA CR).
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.
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.
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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.