What the FDA labels say about taking them together
Cyclobenzaprine and methadone
Methadone's FDA label of December 8, 2025 names cyclobenzaprine in its drug interactions section; the cyclobenzaprine labels PlainMeds reads (3) do not name methadone. 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 cyclobenzaprine FDA label on DailyMed (effective February 21, 2025, Jubilant Cadista Pharmaceuticals Inc.); the methadone FDA label on DailyMed (effective December 8, 2025, Epic Pharma, LLC).
What does the cyclobenzaprine label say about methadone?
Cyclobenzaprine's label (effective February 21, 2025) and its 2 other brand-application labels do not name methadone in these sections. A label lists what its studies and reports found; it is not a complete list.
Source: FDA drug label (Cyclobenzaprine Hydrochloride), Jubilant Cadista Pharmaceuticals Inc., effective February 21, 2025 (SPL set 592871f6-0eb2-4624-9e10-bd8bf767c002), via openFDA; the full label on DailyMed
What does the methadone label say about cyclobenzaprine?
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. … serotonin 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. … serotonin 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
| Cyclobenzaprine | Methadone | |
|---|---|---|
| Labeled for | Muscle spasms and spasticity, Nerve pain and fibromyalgia | Pain, Opioid use disorder |
| Boxed warning | No | Yes |
| Pharmacy cost (NADAC) | $0.0171 per tablet 10 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