What the FDA labels say about taking them together
Cyclobenzaprine and tramadol
Cyclobenzaprine's FDA label of February 21, 2025 names tramadol in its warnings section, and tramadol's label names cyclobenzaprine too. The tramadol 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 tramadol FDA label on DailyMed (effective March 5, 2026, Lupin Pharmaceuticals, Inc.).
What does the cyclobenzaprine label say about tramadol?
Cyclobenzaprine label, warningsWARNINGS Serotonin Syndrome The development of a potentially life-threatening serotonin syndrome has been reported with cyclobenzaprine hydrochloride when used in combination with other drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, or MAO inhibitors.
Cyclobenzaprine Hydrochloride label (Teva Pharmaceuticals USA, Inc., May 31, 2024), drug interactionsDRUG INTERACTIONS Based on its structural similarity to tricyclic antidepressants, cyclobenzaprine hydrochloride extended-release capsules may have life-threatening interactions with MAO inhibitors [see Contraindications ( 4 )], may enhance the effects of alcohol, barbiturates, and other CNS depressants, may enhance the seizure risk in patients taking tramadol, or may block the antihypertensive action of guanethidine and similarly acting compounds.
Tonmya label (Tonix Medicines, Inc., August 14, 2026), drug interactionsMAO inhibitors may be life-threatening [see Contraindications (4) ], Alcohol, barbiturates, and other CNS depressants may increase the risk of adverse reactions associated with these drugs, Tramadol may increase the seizure risk, Guanethidine or other similar acting drugs may block the antihypertensive action of these drugs.
Source: FDA drug label (Cyclobenzaprine Hydrochloride, NDA021777), Teva Pharmaceuticals USA, Inc., effective May 31, 2024 (SPL set ca74d27a-f7c6-462d-a913-1cfa061bd8f3), via openFDA
Source: FDA drug label (Tonmya, NDA219428), Tonix Medicines, Inc., effective August 14, 2026 (SPL set 6fa59588-ce9b-48cf-8c5f-725a448f8571), via openFDA
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 tramadol label say about cyclobenzaprine?
Tramadol 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).
Tramadol 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 monoamine oxidase inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) [see Drug Interactions ( 7 )].
Source: FDA drug label (Tramadol Hydrochloride Extended-Release, NDA022370), Trigen Laboratories, LLC, effective January 23, 2026 (SPL set c0bc7218-3fd0-4646-96f4-25355fc84aa9), via openFDA
Source: FDA drug label (Tramadol Hydrochloride, NDA214044), TruPharma, LLC, effective January 25, 2023 (SPL set aea56ff9-94ac-47a8-8f15-8790d538973b), via openFDA
Source: FDA drug label (TRAMADOL HYDROCHLORIDE), Lupin Pharmaceuticals, Inc., effective March 5, 2026 (SPL set 46bb9ae6-3ee8-463c-badb-c7a45a89b84b), 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 | Tramadol | |
|---|---|---|
| Labeled for | Muscle spasms and spasticity, Nerve pain and fibromyalgia | Pain |
| Boxed warning | No | Yes |
| Pharmacy cost (NADAC) | $0.0171 per tablet 10 mg tablet | $0.0248 per tablet 50 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