What the FDA labels say about taking them together
Metaxalone and methadone
Metaxalone's FDA label of January 11, 2023 names methadone in its drug interactions section, and methadone's label names metaxalone too. The methadone label: “The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.”
Check it at the source: the metaxalone FDA label on DailyMed (effective January 11, 2023, Amneal Pharmaceuticals of New York LLC); the methadone FDA label on DailyMed (effective December 8, 2025, Epic Pharma, LLC).
What does the metaxalone label say about methadone?
Metaxalone label, drug interactionsDiscontinue metaxalone if serotonin syndrome is suspected. Examples of serotonergic drugs include: selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, opioids (particularly fentanyl, meperidine, and methadone), drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
Metaxalone label, warningsSerotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, opioids (particularly fentanyl, meperidine, and methadone), drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including monoamine oxidase (MAO) inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) (see PRECAUTIONS:
Source: FDA drug label (Metaxalone, NDA022503), INA Pharmaceutics Inc, effective February 3, 2026 (SPL set fc6de1a6-26aa-47ac-a5d2-bf127a6ca563), via openFDA
Source: FDA drug label (Metaxalone), Amneal Pharmaceuticals of New York LLC, effective January 11, 2023 (SPL set f06f2b96-3684-483c-89f7-6c9201fd4664), via openFDA; the full label on DailyMed
What does the methadone label say about metaxalone?
Methadone label, drug interactionsSerotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. … neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
Methadone label, warnings and precautionsSerotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) [see Drug Interactions (7) ].
Diskets label (Hikma Pharmaceuticals USA Inc., December 1, 2025), drug interactionsSerotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. … neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
Source: FDA drug label (Diskets, NDA017058), Hikma Pharmaceuticals USA Inc., effective December 1, 2025 (SPL set e6af84de-cbfc-4a3b-bd73-6bcf77337168), via openFDA
Source: FDA drug label (Methadone Hydrochloride, NDA021624), Mylan Institutional LLC, effective December 31, 2025 (SPL set 092d78eb-6423-495c-bf0d-e6532bea7138), via openFDA
Source: FDA drug label (Methadone Hydrochloride), Epic Pharma, LLC, effective December 8, 2025 (SPL set 6da7501b-b881-4bc7-891a-74214a00a3ac), via openFDA; the full label on DailyMed
These are the labels' own sentences. PlainMeds does not grade interactions; a pharmacist or prescriber can say what they mean for one person's medicines.
Both medicines on the record
| Metaxalone | Methadone | |
|---|---|---|
| Labeled for | Muscle spasms and spasticity | Pain, Opioid use disorder |
| Boxed warning | No | Yes |
| Pharmacy cost (NADAC) | $0.452 per tablet 800 mg tablet | $0.177 per tablet 10 mg tablet |
| Shortage now | No current entry | No current entry |
Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)
What next?
- Check more medicines together
- up to five at once