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What the FDA labels say about taking them together

Fentanyl and mirtazapine

Fentanyl's FDA label of March 6, 2026 names mirtazapine in its drug interactions section, and mirtazapine'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 mirtazapine FDA label on DailyMed (effective August 6, 2025, Organon LLC).

What does the fentanyl label say about mirtazapine?

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. … (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the 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 …

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 mirtazapine label say about fentanyl?

Mirtazapine label, drug interactions

Examples SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, amphetamines, St. John's Wort, tramadol, tryptophan, buspirone Strong CYP3A Inducers Clinical Impact The concomitant use of strong CYP3A inducers with REMERON/REMERONSolTab decreases the plasma concentration of mirtazapine [see Clinical Pharmacology (12.3) ]. Intervention Increase the dose of REMERON/REMERONSolTab if needed with concomitant CYP3A inducer use. Conversely, a decrease in dosage of REMERON/REMERONSolTab may be needed if the CYP3A inducer is discontinued [see Dosage and Administration (2.5) ].

Mirtazapine label, warnings and precautions

The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John's Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications (4), Drug Interactions (7) ].

Source: FDA drug label (REMERON), Organon LLC, effective August 6, 2025 (SPL set 98ad1917-a094-44f5-a28f-a64a8cfcd887), 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
36Mirtazapine generic labelers
FentanylMirtazapine
Labeled forPainDepression
Boxed warningYesYes
Pharmacy cost (NADAC)$1.79 per mL 100 mcg/2 mL vial$0.063 per tablet 15 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)

What next?