What the FDA labels say about taking them together
Fluoxetine and methadone
Fluoxetine's FDA label of January 8, 2026 names methadone in its drug interactions section; methadone's label does not name fluoxetine itself but warns about its class (serotonin reuptake inhibitors). The fluoxetine label: “The risk is increased with concomitant use of other serotonergic drugs and with drugs that impair metabolism of serotonin, i.e., MAOIs.”
Check it at the source: the fluoxetine FDA label on DailyMed (effective January 8, 2026, Dista Products Company); the methadone FDA label on DailyMed (effective December 8, 2025, Epic Pharma, LLC).
What does the fluoxetine label say about methadone?
Fluoxetine label, drug interactionsClass III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus).
Fluoxetine label, warnings and precautionsThe risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, meperidine, methadone, buspirone, amphetamines, and St. John's Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications ( 4 ), Drug Interactions ( 7.1 )].
Source: FDA drug label (Prozac), NDA018936 (Eli Lilly And Co), as published by Dista Products Company, effective January 8, 2026 (SPL set c88f33ed-6dfb-4c5e-bc01-d8e36dd97299), via openFDA; the full label on DailyMed
What does the methadone label say about fluoxetine?
Methadone's label does not name fluoxetine itself; it warns about its class (serotonin reuptake inhibitors):
Methadone label, warnings and precautionsSyndrome with Concomitant Use of Serotonergic Drugs Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of methadone hydrochloride tablets 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 …
Methadone label, warnings and precautionsSyndrome with Concomitant Use of Serotonergic Drugs Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of DISKETS 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, trazodone, tramadol), certain …
Source: FDA drug label (Methadone Hydrochloride), Epic Pharma, LLC, effective December 8, 2025 (SPL set 6da7501b-b881-4bc7-891a-74214a00a3ac), 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
| Fluoxetine | Methadone | |
|---|---|---|
| Labeled for | Depression, Anxiety, Bipolar disorder | Pain, Opioid use disorder |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | $0.0519 per capsule 40 mg capsule | $0.177 per tablet 10 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