Clarithromycin with Pimozide Interaction Details

Brand Names Associated with Clarithromycin

Brand Names Associated with Pimozide

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 08, 2023

Interaction Effect

An increased risk of QT-interval prolongation

Interaction Summary

Concurrent use of clarithromycin and pimozide is contraindicated. Clarithromycin may inhibit the metabolism of pimozide, resulting in increased pimozide exposure. Elevated serum levels of pimozide have been associated with serious or fatal cardiac arrhythmias (eg, QT-interval prolongation, ventricular tachycardia, ventricular fibrillation, torsades de pointes) .

Severity

Contraindicated

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concurrent use of clarithromycin and pimozide is contraindicated due to the potential for serious or fatal cardiotoxicity, including QT-interval prolongation.

Mechanism Of Interaction

Additive prolongation effects on QT interval

Literature Reports

A) A case report describes a 27-year-old male with a history of Tourette syndrome who experienced sudden cardiac death after being co-prescribed pimozide and clarithromycin. The patient was currently taking pimozide 14 mg/day, but due to an increase in the number of tics he was experiencing, it was decided that his dose of pimozide be slowly increased by one 2 mg tablet per day. Two days after the increase in dose, he was diagnosed with bronchopneumonia. Clarithromycin 500 mg per day was prescribed. Four days after he presented to the emergency department he complained of a racing heart and felt a "head rush". He was observed without incident. An ECG showed a corrected QT interval of 0.506 seconds. He was discharged with instructions to follow-up with his neurologist. The following day he was found unconscious, apneic, and unresponsive without the ability to be resuscitated. Blood pimozide concentrations were 50 ng/ml (4-20 ng/ml). Cardiac arrhythmia resulting from an excessive concentration of pimozide was the most likely cause of death .

B) In a randomized, double-blind, placebo-controlled crossover design study, twelve healthy volunteers were given a single oral dose of pimozide 6 mg after five days of pretreatment with placebo or clarithromycin 500 mg twice daily. With respect to cytochrome P450 2D6 (CYP2D6) phenotyping, five study subjects were poor metabolizers and seven were extensive metabolizers. All participants had a corrected QTc shorter than 470 ms prior to inclusion in the study. Clarithromycin pretreatment increased the pimozide maximum concentration (Cmax) from 4.4 ng/mL to 6.1 ng/mL and increased the area under the concentration-time curve (AUC) by 113% (146 ng/mL/hr vs. 310 ng/mL/hr). Pimozide half-life, clearance, and apparent volume of distribution were also significantly increased by clarithromycin. Pimozide prolonged the QT interval in all study subjects, and these increases coincided with plasma concentrations. In the first 20 hours after administration, the clarithromycin group had a more prolonged QTc interval (increased by 15.7 ms) than the placebo group (increased by 13.3 ms). There was no significant effect of CYP2D6 phenotyping or gender on the pharmacodynamics or pharmacokinetics of pimozide. Clarithromycin inhibits cytochrome P450 3A (CYP3A) enzymes, which are responsible for pimozide metabolism. Inhibition of pimozide metabolism leads to cardiotoxicity, which is an effect of the parent drug .

Clarithromycin Overview

• Clarithromycin is used to treat certain bacterial infections, such as pneumonia (a lung infection), bronchitis (infection of the tubes leading to the lungs), and infections of the ears, sinuses, skin, and throat. It also is used to treat and prevent disseminated Mycobacterium avium complex (MAC) infection [a type of lung infection that often affects people with human immunodeficiency virus (HIV)]. It is used in combination with other medications to eliminate H. pylori, a bacterium that causes ulcers. Clarithromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as clarithromycin will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

Pimozide Overview

• Pimozide is used to control motor or verbal tics (an uncontrollable need to repeat certain movements or sounds) caused by Tourette's disorder (condition characterized by motor or verbal tics). Pimozide should only be used to treat people who cannot take other medications or who have taken other medications without good results. Pimozide should only be used to treat severe tics that stop the person from learning, working, or performing daily activities.

• Pimozide is in a class 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.