Fluoxetine with Haloperidol Interaction Details

Brand Names Associated with Fluoxetine

Brand Names Associated with Haloperidol

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 11, 2023

Interaction Effect

Increased haloperidol exposure, an increased risk of haloperidol toxicity and an increased risk of QT interval prolongation

Interaction Summary

Use caution with coadministration of FLUoxetine and haloperidol, as concurrent use increases the risk of QT interval prolongation (including torsades de pointes) inherent in both drugs. Coadministration with FLUoxetine may also increase haloperidol plasma concentrations  and increase the risk of haloperidol toxicity . Consider ECG assessment and periodic ECG monitoring if initiating treatment with FLUoxetine in patients with risk factors for QT interval prolongation and ventricular arrhythmia. Discontinue FLUoxetine and obtain a cardiac evaluation if patients develop signs or symptoms consistent with ventricular arrhythmia .

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Use caution with coadministration of FLUoxetine and haloperidol, as concurrent use increases the risk of QT interval prolongation (including torsades de pointes) inherent in both drugs. Coadministration with FLUoxetine may also increase haloperidol plasma concentrations  and increase the risk of haloperidol toxicity . Consider ECG assessment and periodic ECG monitoring if initiating treatment with FLUoxetine in patients with risk factors for QT interval prolongation and ventricular arrhythmia. Discontinue FLUoxetine and obtain a cardiac evaluation if patients develop signs or symptoms consistent with ventricular arrhythmia .

Mechanism Of Interaction

Inhibition of CYP2D6-mediated metabolism of haloperidol by FLUoxetine; additive QT interval prolongation

Literature Reports

A) A 40-year-old man developed urinary retention while taking FLUoxetine and haloperidol. During a recurrence of depression, the patient was treated with FLUoxetine 20 mg/day, ALPRAZolam 1.5 mg per day, and haloperidol 1 mg per day. The patient had previously taken FLUoxetine and ALPRAZolam without incident. Approximately 1 week after beginning therapy, the patient developed difficulty in voiding urine, dilated pupils, dry mouth, palpitations, restlessness, hand tremors, and insomnia. After discontinuation of haloperidol and ALPRAZolam, side effects ceased within 1 week. The authors postulated that the interaction was due to FLUoxetine inhibition of cytochrome CYP2D6, which metabolizes haloperidol .

B) FLUoxetine increased plasma concentrations of haloperidol in 8 outpatients. Patients received FLUoxetine 20 mg daily for 10 days with maintenance doses of haloperidol (average dose, 14 mg per day). After 10 days, mean plasma concentrations of haloperidol had increased by 20%. Extrapyramidal symptom scores did not change appreciably after the addition of FLUoxetine although 1 patient developed mild akathisia and another developed tremors. Extrapyramidal symptoms were expected to increase because of indirect inhibition of dopamine synthesis by FLUoxetine .

C) A 39-year-old man experienced tardive dyskinesia with concomitant FLUoxetine and haloperidol therapy. He was taking FLUoxetine 20 mg daily for 2 months, then haloperidol 2 mg twice daily was started and later lowered to 1 mg per day. Five months later during a routine examination, tardive dyskinesia was diagnosed. The suggested mechanism was the down-regulation of dopamine activity .

D) A 39-year-old woman developed tardive dyskinesia associated with concomitant FLUoxetine and haloperidol therapy. She had been taking haloperidol 2 to 5 mg a day for two years (both with and without benztropine) with occasional mild, reversible extrapyramidal symptoms. Five days before stopping haloperidol, she started taking FLUoxetine, which was increased over several days to 40 mg twice a day. After two weeks of FLUoxetine she took haloperidol 5 mg each on two consecutive days (along with continuation of FLUoxetine). She then experienced severe tongue stiffness, parkinsonism, and akathisia. Both FLUoxetine and haloperidol were withdrawn. During the next 7 days her extrapyramidal symptoms gradually disappeared .

E) Some clinical data suggests a possible pharmacodynamic and/or pharmacokinetic interaction between SSRIs and antipsychotics. Elevation of blood levels of haloperidol has been observed in patients receiving concomitant FLUoxetine .

Fluoxetine Overview

• Fluoxetine is used to treat depression, obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over), some eating disorders, and panic attacks (sudden, unexpected attacks of extreme fear and worry about these attacks). Fluoxetine is also used to relieve the symptoms of premenstrual dysphoric disorder, including mood swings, irritability, bloating, and breast tenderness. It is also used along with olanzapine (Zyprexa) to treat depression that did not respond to other medications and episodes of depression in people with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Fluoxetine is in a class of medications called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance.

Haloperidol Overview

• Haloperidol is used to treat psychotic disorders (conditions that cause difficulty telling the difference between things or ideas that are real and things or ideas that are not real). Haloperidol is also used to control motor tics (uncontrollable need to repeat certain body movements) and verbal tics (uncontrollable need to repeat sounds or words) in adults and children who have Tourette's disorder (condition characterized by motor or verbal tics). Haloperidol is also used to treat severe behavioral problems such as explosive, aggressive behavior or hyperactivity in children who cannot be treated with psychotherapy or with other medications. Haloperidol is in a group of medications called conventional antipsychotics. It works by decreasing abnormal excitement in the brain.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.