Clozapine and Olanzapine and fluoxetine interaction
Clozapine 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 Clozapine (Clozaril) label · effective 2025-06-06
Proportion of Adult Subjects in Schizophrenia Studies with Weight Gain ≥7% Relative to Baseline Body Weight Weight change CLOZARIL Olanzapine Chlorpromazine N 669 442 155 ≥7% (inclusive) 236 (35%) 203 (46%) 13 (8%) 5.11 Neuroleptic Malignant Syndrome Antipsychotic drugs including CLOZARIL can cause a potentially fatal symptom complex referred to as Neuroleptic…
When possible, avoid concomitant use, with other anticholinergic medications because the risk for anticholinergic toxicity or severe gastrointestinal adverse reactions is increased [see Warnings and Precautions ( 5.7 ), Drug Interactions ( 7.1 )].
CYP2D6 and CYP3A4 Inhibitors Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology ( 12.3 )] .
• Anticholinergic Toxicity : When possible, avoid use with other anticholinergic drugs and use with caution in patients with a current diagnosis or prior history of constipation, urinary retention, clinically significant prostatic hypertrophy, or other conditions in which anticholinergic effects can lead to significant adverse reactions.
Use with caution in patients with a current diagnosis or prior history of constipation, urinary retention, clinically significant prostatic hypertrophy, or other conditions in which anticholinergic effects can lead to significant adverse reactions.
From the Olanzapine and fluoxetine label · effective 2026-03-31
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 )
Use olanzapine and fluoxetine capsules with caution in combination with other drugs that prolong the QT interval ( 4.2 , 5.20 , 7.7 , 7.8 ) 7.1 Monoamine Oxidase Inhibitors (MAOIs) [See Dosage and Administration ( 2.4 , 2.5 ), Contraindications ( 4.1 ), and Warnings and Precautions ( 5.6 )] .
Clozapine : May elevate clozapine levels ( 7.7 )
Clozapine — Elevation of blood levels of clozapine has been observed in patients receiving concomitant fluoxetine.
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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.