Skip to main content

What the FDA labels say about taking them together

Metaxalone and tramadol

Metaxalone's FDA label of January 11, 2023 names tramadol in its drug interactions section, and tramadol's label names metaxalone 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 metaxalone FDA label on DailyMed (effective January 11, 2023, Amneal Pharmaceuticals of New York LLC); the tramadol FDA label on DailyMed (effective March 5, 2026, Lupin Pharmaceuticals, Inc.).

What does the metaxalone label say about tramadol?

Metaxalone label, drug interactions

Discontinue 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, warnings

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 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 tramadol label say about metaxalone?

Tramadol label, drug interactions

Serotonergic 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).

Tramadol label, warnings and precautions

Serotonergic 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

33Metaxalone generic labelers
39Tramadol generic labelers
MetaxaloneTramadol
Labeled forMuscle spasms and spasticityPain
Boxed warningNoYes
Pharmacy cost (NADAC)$0.452 per tablet 800 mg tablet$0.0248 per tablet 50 mg tablet
Shortage nowNo current entryNo 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?