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What the FDA labels say about taking them together

Fentanyl and metaxalone

Fentanyl's FDA label of March 6, 2026 names metaxalone in its drug interactions section, and metaxalone's label names fentanyl too. The fentanyl label: “The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome [see.”

Check it at the source: the fentanyl FDA label on DailyMed (effective March 6, 2026, Hikma Pharmaceuticals USA Inc.); the metaxalone FDA label on DailyMed (effective January 11, 2023, Amneal Pharmaceuticals of New York LLC).

What does the fentanyl label say about metaxalone?

Fentanyl 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 [see. … 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).

Fentanyl 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, trazadone, 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) ].

Source: FDA drug label (Fentanyl Citrate, NDA019115), Hospira, Inc., effective August 24, 2026 (SPL set bfa8018a-4cbc-434b-e09e-782872b0340a), via openFDA

Source: FDA drug label (Fentanyl Citrate), Hikma Pharmaceuticals USA Inc., effective March 6, 2026 (SPL set ce5db1c2-feb1-4ad2-847a-d02e865bd47e), via openFDA; the full label on DailyMed

What does the metaxalone label say about fentanyl?

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

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

6Fentanyl generic labelers
33Metaxalone generic labelers
FentanylMetaxalone
Labeled forPainMuscle spasms and spasticity
Boxed warningYesNo
Pharmacy cost (NADAC)$1.79 per mL 100 mcg/2 mL vial$0.452 per tablet 800 mg tablet
Shortage nowIn shortageNo current entry

Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)

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