Fluoxetine and Iloperidone interaction

Fluoxetine and Iloperidone: 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 Iloperidone (FANAPT) label · effective 2026-05-06

Major

Avoid the use of FANAPT in combination with any other drugs that prolong the QT interval [see Warnings and Precautions (5.3) ] .

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Moderate

…prolong QTc including Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications, antipsychotic medications (e.g., chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone).

Warnings and precautionsby drug classView label on DailyMed
Moderate

Table 7: Clinically Important Drug Interactions with FANAPT Strong CYP2D6 Inhibitors Clinical Impact Coadministration of fluoxetine with iloperidone increased exposure (area under curve, [AUC]) of iloperidone and its metabolite P88, by about 2- to 3- fold, and decreased the AUC of its metabolite P95 by one-half [see Clinical Pharmacology (12.3 , 12.5) ] .

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Moderate

Intervention Reduce the dose of FANAPT by one-half when administered with strong CYP2D6 inhibitors.

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Moderate

When a strong CYP2D6 inhibitor is withdrawn from the combination therapy, the iloperidone dose should be returned to the previous level [see Dosage and Administration (2.4) ] .

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From the Fluoxetine (Prozac) label · effective 2026-01-08

Moderate

Use with caution in combination with other drugs that prolong the QT interval ( 4.2 , 5.11 , 7.7 , 7.8 ) 7.1 Monoamine Oxidase Inhibitors (MAOI) [See Dosage and Administration ( 2.9 , 2.10 ), Contraindications ( 4.1 ), and Warnings and Precautions ( 5.2 )] .

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Moderate

Coadministration of fluoxetine with other drugs that are metabolized by CYP2D6, including certain antidepressants (e.g., TCAs), antipsychotics (e.g., phenothiazines and most atypicals), and antiarrhythmics (e.g., propafenone, flecainide, and others) should be approached with caution.

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Minor

These include specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol,); specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl…

Warnings and precautionsby drug classView label on DailyMed
Minor

Antipsychotics: Potential for elevation of haloperidol and clozapine levels ( 7.7 )

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Minor

Antipsychotics — Some clinical data suggests a possible pharmacodynamic and/or pharmacokinetic interaction between SSRIs and antipsychotics.

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.