Olanzapine and fluoxetine and Paroxetine interaction

Olanzapine and fluoxetine and Paroxetine: 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 Olanzapine and fluoxetine label · effective 2026-03-31

Major

If concomitant use of olanzapine and fluoxetine capsules 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 ( 5.6 )

Warnings and precautionsby drug classView label on DailyMed
Major

If concomitant use of olanzapine and fluoxetine 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
Moderate

Anticholinergic (antimuscarinic) Effects : Use with caution with other anticholinergic drugs and in patients with urinary retention, prostatic hypertrophy, constipation, history of paralytic ileus or related conditions ( 5.21 )

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, meperidine, methadone, tryptophan, buspirone, amphetamines, and St.

Warnings and precautionsby drug classView label on DailyMed
Moderate

The Effect of Other Drugs on Olanzapine — Fluoxetine, an inhibitor of CYP2D6, decreases olanzapine clearance a small amount [see Clinical Pharmacology ( 12.3 )].

Drug interactionsby drug classView label on DailyMed

From the Paroxetine (PAROXETINE HYDROCHLORIDE) label · effective 2026-09-16

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 Paroxetine HCL CR 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, meperidine, methadone, tryptophan, buspirone, amphetamines, and St.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Other Serotonergic Drugs Clinical Impact The concomitant use of serotonergic drugs with Paroxetine HCL CR increases the risk of serotonin syndrome.

Drug interactionsby drug classView label on DailyMed
Minor

Activation of Mania or Hypomania In patients with bipolar disorder, treating a depressive episode with Paroxetine HCL CR or another antidepressant may precipitate a mixed/manic episode.

Warnings and precautionsby 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.