Clarithromycin with Rifabutin Interaction Details

Brand Names Associated with Clarithromycin

Brand Names Associated with Rifabutin

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

Interaction Effect

Reduced clarithromycin exposure and increased risk of uveitis; increased rifabutin exposure

Interaction Summary

Coadministration of clarithromycin (a CYP3A inhibitor and substrate) with rifabutin (a CYP3A inducer and substrate) may decreased the efficacy of clarithromycin and increase the exposure and risk of rifabutin-associated adverse events including uveitis. In a study of 12 HIV-infected patients with Mycobacterium avium complex, the AUC of clarithromycin decreased by 50% while the AUC of rifabutin increased by 75% with concurrent use. An alternative to clarithromycin should be considered. If concurrent use is required, decrease the rifabutin dose. A study of rifabutin toxicity recommends reducing the rifabutin dose to 300 mg/day when combining therapy with a macrolide antibiotic . Carefully monitor for uveitis when rifabutin is coadministered with clarithromycin or other macrolides. Refer to an ophthalmologist if uveitis is suspected and suspend rifabutin treatment if warranted .

Severity

Major

Onset

Unspecified

Evidence

Established

How To Manage Interaction

Coadministration of clarithromycin (a CYP3A inhibitor and substrate) with rifabutin (a CYP3A inducer and substrate) may decreased the efficacy of clarithromycin and increase the risk of rifabutin-associated adverse events including uveitis. An alternative to clarithromycin should be considered. If concurrent use is required, decrease the rifabutin dose. Carefully monitor for uveitis when rifabutin is coadministered with clarithromycin or other macrolides. Refer to an ophthalmologist if uveitis is suspected and suspend rifabutin treatment if warranted.

Mechanism Of Interaction

Induction of CYP3A-mediated clarithromycin metabolism; inhibition of CYP3A-mediated rifabutin metabolism

Literature Reports

A) The AUC of clarithromycin decreased by 50% while the AUC of rifabutin increased by 75% when rifabutin 300 mg/day and clarithromycin 500 mg every 12 hours were coadministered to HIV-infected patients with Mycobacterium avium complex (N=12) .

B) In a study of HIV-infected patients (N=10), rifabutin AUC increased by 76% over 7 days at doses of 300 mg/day with coadministration of either clarithromycin 500 mg/day or fluconazole 200 mg/day. Rifabutin AUC increased 152% with coadministration of both drugs over 7 days. The Cmax of rifabutin increased by 85% when given with clarithromycin, by 91% when given with fluconazole, and by 149% when given with both drugs .

C) In a study of 26 HIV-infected volunteers with CD4 counts of less than 200 cells/mm(3), clarithromycin AUC decreased by 44% and Cmax by 41% over 4 weeks when rifabutin 300 mg/day was added to a 2-week clarithromycin 500 mg twice-daily regimen. Among patients treated for 2 weeks with rifabutin 300 mg/day monotherapy, rifabutin AUC increased from 4 mcg/hr/mL to 7.1 mcg/hr/mL and Cmax increased by 69% when coadministered with clarithromycin for 4 weeks .

D) Increased rifabutin plasma concentrations, thrombocytopenia, and severe neutropenia occurred within 9 days of clarithromycin and rifabutin coadministration in a study of 30 healthy volunteers. The drug regimen of the first volunteer to develop neutropenia was rifabutin 300 mg/day with clarithromycin 500 mg twice daily. The patient was admitted for inpatient treatment with an absolute neutrophil count of 0.8 x 10(9) on day 9 of the study. Bone marrow aspirates taken on day 10 revealed hypoplastic bone marrow consistent with drug injury. A total of 3 volunteers received inpatient care for neutropenia, and 5 patients were treated with granulocyte colony stimulating factor (G-CSF). Patients coadministered clarithromycin and rifabutin also experienced a mean 43% decrease in platelet counts .

E) Steady-state peak serum concentrations of clarithromycin decreased from 5.4 mcg/mL to 2 mcg/mL over 4.1 months when patients were switched from clarithromycin 1000 mg/day monotherapy to coadministration with rifabutin 600 mg/day .

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.

Rifabutin Overview

• Rifabutin helps to prevent or slow the spread of Mycobacterium avium complex disease (MAC; a bacterial infection that may cause serious symptoms) in patients with human immunodeficiency virus (HIV) infection. It is also used in combination with other medications to eliminate H. pylori, a bacteria that causes ulcers. Rifabutin is in a class of medications called antimycobacterials. It works by killing the bacteria that cause infection.

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

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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.