What the FDA labels say about taking them together
Amitriptyline and fluoxetine
Amitriptyline's FDA label of September 8, 2026 names fluoxetine in its drug interactions section; fluoxetine's label does not name amitriptyline itself but warns about its class (Tricyclic antidepressants). The amitriptyline label: “While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition.”
Check it at the source: the amitriptyline FDA label on DailyMed (effective September 8, 2026, Sun Pharmaceutical Industries, Inc.); the fluoxetine FDA label on DailyMed (effective January 8, 2026, Dista Products Company).
What does the amitriptyline label say about fluoxetine?
Amitriptyline label, drug interactionsWhile all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition.
Source: FDA drug label (Amitriptyline Hydrochloride), Sun Pharmaceutical Industries, Inc., effective September 8, 2026 (SPL set 4e520c63-1cf6-40f6-a51c-3f9b0e181342), via openFDA; the full label on DailyMed
What does the fluoxetine label say about amitriptyline?
Fluoxetine's label does not name amitriptyline itself; it warns about its class (Tricyclic antidepressants):
Fluoxetine label, drug interactionsThe concomitant use of serotonergic drugs (including other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St. John's Wort) with PROZAC increases the risk of serotonin syndrome.
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
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
| Amitriptyline | Fluoxetine | |
|---|---|---|
| Labeled for | Depression | Depression, Anxiety, Bipolar disorder |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | $0.03 per tablet 10 mg tablet | $0.0519 per capsule 40 mg capsule |
| 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