Fluoxetine and Sertraline interaction

Fluoxetine and Sertraline: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

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

Major

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 )

Warnings and precautionsby drug classView label on DailyMed
Major

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.

Warnings and precautionsby drug classView label on DailyMed
Moderate

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.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Clinical studies of pimozide with other antidepressants demonstrate an increase in drug interaction or QT prolongation.

Drug interactionsby drug classView label on DailyMed
Minor

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.

Warnings and precautionsby drug classView label on DailyMed

From the Sertraline (sertraline hydrochloride) label · effective 2025-08-06

Major

Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone.

Warnings and precautionsby drug classView label on DailyMed
Major

If concomitant use of sertraline hydrochloride capsules with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.

Warnings and precautionsby drug classView label on DailyMed
Major

Avoid the concomitant use of drugs known to prolong the QTc interval.

Drug interactionsby drug classView label on DailyMed
Moderate

The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Drugs that Prolong the QTc Interval Clinical Impact: The risk of QTc prolongation and/or ventricular arrhythmias (e.g., TdP) is increased with concomitant use of sertraline hydrochloride capsules with other drugs which prolong the QTc interval [see Warnings and Precautions ( 5.10 ), Clinical Pharmacology ( 12.2 )] .

Drug interactionsby drug classView label on DailyMed

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Not 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.