Imipramine and Olanzapine and fluoxetine interaction
Imipramine and Olanzapine and fluoxetine: 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 Imipramine (Imipramine Hydrochloride) label · effective 2026-07-06
Anyone considering the use of imipramine hydrochloride or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.
The plasma concentration of imipramine may increase when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decrease by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), and adjustment of the dosage of imipramine may therefore be necessary.
Imipramine hydrochloride may enhance the CNS depressant effects of alcohol.
Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other.
Imipramine hydrochloride may potentiate the effects of CNS depressant drugs.
From the Olanzapine and fluoxetine label · effective 2026-03-31
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 )
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.
If serotonin syndrome occurs, consider discontinuation of olanzapine and fluoxetine capsules and/or concomitant serotonergic drugs [see Warnings and Precautions ( 5.6 )] .
In 2 fluoxetine studies, previously stable plasma levels of imipramine and desipramine have increased >2- to 10-fold when fluoxetine has been administered in combination.
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 )
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.