Clarithromycin with Carbamazepine Interaction Details

Brand Names Associated with Clarithromycin

Brand Names Associated with Carbamazepine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 25, 2023

Interaction Effect

Decreased exposure of clarithromycin; increased exposure of carbamazepine

Interaction Summary

Coadministration of carbamazepine (a CYP3A4 inducer and substrate) and clarithromycin (a CYP3A4 inhibitor and substrate) may result in an increase the exposure of carbamazepine and a decrease in clarithromycin exposure. When clarithromycin was given concurrently with carbamazepine to 12 healthy volunteers in a randomized, double-blind study, the mean AUC of carbamazepine was increased and the formation of the 10,11-epoxide metabolite was significantly reduced . If used concomitantly, closely monitor carbamazepine levels and consider dose adjustments of clarithromycin and/or carbamazepine .

Severity

Major

Onset

Rapid

Evidence

Established

How To Manage Interaction

Coadministration of carbamazepine (a CYP3A4 inducer and substrate) and clarithromycin (a CYP3A4 inhibitor and substrate) may result in an increase the exposure of carbamazepine and a decrease in clarithromycin exposure. If used concomitantly, closely monitor carbamazepine levels and consider dose adjustments of clarithromycin and/or carbamazepine.

Mechanism Of Interaction

Inhibition of CYP3A4-mediated carbamazepine metabolism by clarithromycin; induction of CYP3A4-mediated clarithromycin metabolism by carbamazepine

Literature Reports

A) Carbamazepine toxicity with an increase in serum level associated with the addition of clarithromycin was reported in a 35-year-old woman diagnosed with complex partial seizures. She was maintained on carbamazepine 200 mg 3 times daily with an approximate steady-state level of 8.3 mcg/mL. With development of an upper respiratory infection, clarithromycin 500 mg 2 times daily was initiated. Symptoms of lethargy, fatigue, blurred vision, nausea, "muddled thoughts", and ataxia occurred within a few hours of the first dose. A carbamazepine serum level of 15.5 mcg/mL was obtained 26 hours after the first clarithromycin dose. The symptoms of toxicity resolved rapidly and the level returned to baseline within 36 hours of discontinuing carbamazepine and clarithromycin .

B) A 29 year-old man was diagnosed with simple partial seizures since the age of 11 years and was maintained on carbamazepine 400 mg 2 times daily with an approximate steady-state level of 8 mcg/mL. The addition of clarithromycin increased the serum level to 12.7 mcg/mL, measured at the end of the clarithromycin therapy, despite decreasing carbamazepine (300 mg twice daily); yet, he did not notice any adverse symptoms from an elevated serum level. Upon completion of the therapy, he was placed on the previous carbamazepine dose. Within 1 week, the level returned to baseline .

C) Clarithromycin 500 mg was given concurrently with either oral carbamazepine 400 mg or placebo twice daily to 12 healthy volunteers in a randomized, double-blind study. The mean AUC of carbamazepine was increased and the formation of the 10,11-epoxide metabolite was significantly reduced, indicating a significant change in carbamazepine pharmacokinetics .

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.

Carbamazepine Overview

• Carbamazepine is used alone or in combination with other medications to control certain types of seizures in people with epilepsy. It is also used to treat trigeminal neuralgia (a condition that causes facial nerve pain). Carbamazepine extended-release capsules (Equetro brand only) are also used to treat episodes of mania (frenzied, abnormally excited or irritated mood) or mixed episodes (symptoms of mania and depression that happen at the same time) in patients with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Carbamazepine is in a class of medications called anticonvulsants. It works by reducing abnormal electrical activity 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.