Clonazepam and Olanzapine and fluoxetine interaction

Clonazepam 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.

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 Clonazepam (Klonopin) label · effective 2025-12-01

Major

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug.

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Moderate

They should also be warned about the concomitant use of alcohol or other CNS-depressant drugs during Klonopin therapy (see PRECAUTIONS: Drug Interactions and PRECAUTIONS: Information for Patients ).

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Moderate

Pharmacodynamic Interactions The CNS-depressant action of the benzodiazepine class of drugs may be potentiated by alcohol, narcotics, barbiturates, nonbarbiturate hypnotics, antianxiety agents, the phenothiazines, thioxanthene and butyrophenone classes of antipsychotic agents, monoamine oxidase inhibitors and the tricyclic antidepressants, and by other anticonvulsant…

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Minor

In a study in which the 2 mg clonazepam orally disintegrating tablet was administered with and without propantheline (an anticholinergic agent with multiple effects on the GI tract) to healthy volunteers, the AUC of clonazepam was 10% lower and the C max of clonazepam was 20% lower when the orally disintegrating tablet was given with propantheline compared to…

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Minor

The selective serotonin reuptake inhibitors sertraline (weak CYP3A4 inducer) and fluoxetine (CYP2D6 inhibitor), and the anti-epileptic drug felbamate (CYP2C19 inhibitor and CYP3A4 inducer) do not affect the pharmacokinetics of clonazepam.

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From the Olanzapine and fluoxetine label · effective 2026-03-31

Moderate

Benzodiazepines : May potentiate orthostatic hypotension and sedation ( 7.6 , 7.7 )

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Moderate

Carbamazepine : Potential for elevated carbamazepine levels and clinical anticonvulsant toxicity ( 7.7 )

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Moderate

Phenytoin : Potential for elevated phenytoin levels and clinical anticonvulsant toxicity ( 7.7 )

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Moderate

Potential for Other Drugs to Affect Olanzapine and Fluoxetine Capsules Benzodiazepines — Co-administration of diazepam with olanzapine potentiated the orthostatic hypotension observed with olanzapine [see Drug Interactions ( 7.7 )] .

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Moderate

Carbamazepine — Patients on stable doses of carbamazepine have developed elevated plasma anticonvulsant concentrations and clinical anticonvulsant toxicity following initiation of concomitant fluoxetine treatment.

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.