Clarithromycin with Atazanavir Interaction Details

Brand Names Associated with Clarithromycin

Brand Names Associated with Atazanavir

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Feb 29, 2024

Interaction Effect

Increased clarithromycin/atazanavir exposure and increased risk of cardiotoxicity (QT prolongation)

Interaction Summary

Concomitant administration of atazanavir (a protease inhibitor) and clarithromycin led to significant increases in clarithromycin Cmax and AUC. Both agents are substrates and inhibitors of CYP3A, and a bidirectional interaction has been demonstrated. Inhibition of CYP3A-mediated clarithromycin metabolism by atazanavir may increase the risk of QT prolongation. During coadministration with atazanavir, a dose reduction of clarithromycin by 50% is recommended[1], or reduce the clarithromycin dose by 75% if CrCl is less than 30 mL/min. Consider alternative therapy for indications other than infections due to Mycobacterium avium complex as exposure to the microbiologically-active metabolite, 14-OH clarithromycin, was significantly reduced. Avoid coadministration of clarithromycin at doses greater than 1000 mg/day with protease inhibitors [2]. Additionally, concomitant use may also increase the exposure of atazanavir due to inhibition of CYP3A4 metabolism of atazanavir by clarithromycin [3].

Severity

Major

Onset

Unspecified

Evidence

Established

How To Manage Interaction

Concomitant administration of atazanavir (a protease inhibitor) and clarithromycin may cause QTc prolongation due to increased clarithromycin exposure. Additionally, the coadministration may decrease the efficacy of clarithromycin due to decreased exposure to the microbiologically-active metabolite. Due to the reduction of clarithromycin active metabolite, consider alternative antibacterial therapy for indications other than infections due to Mycobacterium avium complex. If coadministration of atazanavir and clarithromycin is required, reduce the clarithromycin dose by 50%[1] (or reduce the clarithromycin dose by 75% in patients with CrCl of less than 30 mL/min). Do not coadminister clarithromycin doses in excess of 1000 mg/day with protease inhibitors [2]. Additionally, concomitant use may also increase the exposure of atazanavir due to inhibition of CYP3A4 metabolism of atazanavir by clarithromycin [3].

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism of clarithromycin; inhibition of CYP3A4-mediated metabolism of atazanavir; additive QT interval prolongation

Literature Reports

A) In a drug interaction study (n=21), coadministration of clarithromycin in the presence of atazanavir led to a significant increase in clarithromycin Cmax and AUC. In the fed state, subjects received atazanavir 400 mg daily on days 1 to 10, with coadministration of clarithromycin 500 mg twice daily, initiated on day 7 to day 10, and on days 18 to 21. The ratio of clarithromycin pharmacokinetic parameters (PK) with and without atazanavir (ratio 1= no effect) showed an increase in clarithromycin Cmax (ratio, 1.5; 90% confidence interval (CI), 1.32 to 1.71) and AUC (ratio, 1.94; 90% CI, 1.75 to 2.16). Correspondingly, the Cmax and AUC of the active 14-OH clarithromycin metabolite were significantly decreased. A study of atazanavir PK parameters in the presence of clarithromycin led to an increase in atazanavir Cmax and AUC but to a lesser extent (n=29). Using the same dosage regimens as the aforementioned study, the ratio of atazanavir PK parameters with and without clarithromycin showed an increase in atazanavir Cmax (ratio, 1.06; 90% CI, 0.93 to 1.2) and AUC (ratio, 1.28; 90% CI, 1.16 to 1.43) [1].

B) In a drug interaction study, subjects received atazanavir 400 mg daily with coadministration of clarithromycin 500 mg twice daily, clarithromycin exposure increased 94%, the 14-OH clarithromycin active metabolite decreased 70%, and atazanavir exposure increased 28% [2].

References

1 ) Product Information: REYATAZ(R) oral capsules, oral powder, atazanavir oral capsules, oral powder. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2023.

2 ) Product Information: BIAXIN(R) Filmtab(R) oral tablets, clarithromycin oral tablets. Abbott Laboratories (per FDA), North Chicago, IL, 2012.

3 ) Product Information: VOQUEZNA(TM) TRIPLE PAK(TM) oral kit, vonoprazan oral tablets, amoxicillin oral capsules, clarithromycin oral tablets kit. Phathom Pharmaceuticals (per FDA), Buffalo Grove, IL, 2023.

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.

Atazanavir Overview

• Atazanavir is used along with other medications to treat human immunodeficiency virus (HIV) infection in adults and children who are at least 3 months of age and weigh at least 22 lb (10 kg). Atazanavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although atazanavir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Atazanavir must be given with other medications that treat HIV infection to completely treat the infection. Taking these medications along with practicing safer sex and making other lifestyle changes may decrease the risk of transmitting the HIV virus to other people.

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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.