Fluoxetine and Tramadol interaction
Fluoxetine and Tramadol: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Fluoxetine (Prozac) label · effective 2026-01-08
If concomitant use of PROZAC with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases ( 5.2 )
If concomitant use of PROZAC with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.
The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, meperidine, methadone, buspirone, amphetamines, and St.
Use with caution in combination with other drugs that prolong the QT interval ( 4.2 , 5.11 , 7.7 , 7.8 ) 7.1 Monoamine Oxidase Inhibitors (MAOI) [See Dosage and Administration ( 2.9 , 2.10 ), Contraindications ( 4.1 ), and Warnings and Precautions ( 5.2 )] .
Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including PROZAC, both when taken alone, but especially when co-administered with other serotonergic agents.
From the Tramadol (Tramadol Hydrochloride Extended-Release) label · effective 2026-01-23
The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex.
Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with Tramadol Hydrochloride Extended-Release Capsules requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1.
Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex.
Examples: Quinidine, fluoxetine, paroxetine, and bupropion Inhibitors of CYP3A4 Clinical Impact: The concomitant use of Tramadol Hydrochloride Extended-Release Capsules and CYP3A4 inhibitors can increase the plasma concentration of tramadol and may result in a greater amount of metabolism via CYP2D6 and greater levels of M1.
Serotonin Syndrome Risk: Potentially life-threatening condition could result from use of Tramadol Hydrochloride Extended-Release Capsules, particularly during concomitant use of serotonergic drugs.
Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.
Open in the checkerNot medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.