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What the FDA labels say about taking them together

Fentanyl and nortriptyline

Nortriptyline's FDA label of December 4, 2024 names fentanyl in its warnings section; fentanyl's label does not name nortriptyline itself but warns about its class (Tricyclic antidepressants). The nortriptyline label: “Serotonin Syndrome The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including Pamelor, alone but particularly with concomitant use of other serotonergic drugs …”

Check it at the source: the fentanyl FDA label on DailyMed (effective March 6, 2026, Hikma Pharmaceuticals USA Inc.); the nortriptyline FDA label on DailyMed (effective December 4, 2024).

What does the fentanyl label say about nortriptyline?

Fentanyl's label does not name nortriptyline itself; it warns about its class (Tricyclic antidepressants):

Fentanyl label, warnings and precautions

If ‎a patient is suspected to be experiencing OIH, carefully consider appropriately ‎decreasing the dose of the current opioid analgesic or opioid rotation (safely ‎switching the patient to a different opioid moiety) [see Dosage and ‎Administration (2), Warnings and Precautions (5.7) ] .‎ 5.8 Serotonin Syndrome with Concomitant Use of Serotonergic Drugs Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of fentanyl with serotonergic drugs. …

Fentanyl label, warnings and precautions

Syndrome with Concomitant Use of Serotonergic Drugs Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of fentanyl with serotonergic drugs. 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 …

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 nortriptyline label say about fentanyl?

Nortriptyline label, warnings

Serotonin Syndrome The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including Pamelor, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).

Source: FDA drug label (PAMELOR), SpecGx LLC, effective December 4, 2024 (SPL set e17dc299-f52d-414d-ab6e-e809bd6f8acb), 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
25Nortriptyline generic labelers
FentanylNortriptyline
Labeled forPainDepression
Boxed warningYesYes
Pharmacy cost (NADAC)$1.79 per mL 100 mcg/2 mL vial$0.113 per capsule 10 mg capsule
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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