Atazanavir with Rifabutin Interaction Details

Brand Names Associated with Atazanavir

Brand Names Associated with Rifabutin

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

Interaction Effect

Increased rifabutin exposure and an increased risk of rifabutin-related adverse effects

Interaction Summary

In 2 small cohort studies of healthy individuals, coadministration of rifabutin and atazanavir resulted in increased rifabutin plasma concentrations due to the inhibition of CYP3A4-mediated rifabutin metabolism by atazanavir[1]. Therefore, a dose reduction of rifabutin to 150 mg daily or 300 mg 3 times per week is recommended when coadministered with ritonavir-boosted atazanavir. Monitoring for rifabutin activity [2] and adverse effects, including neutropenia, is warranted [1].

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concomitant use of ritonavir-boosted atazanavir and rifabutin has resulted in increased rifabutin plasma concentrations. Therefore, a dose reduction of rifabutin to 150 mg once daily or 300 mg three times a week is recommended along with monitoring for rifabutin activity[2] and adverse effects (eg, neutropenia) [1].

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism of rifabutin

Literature Reports

A) In healthy volunteers, the coadministration of atazanavir/ritonavir with rifabutin 150 mg once daily increased the rifabutin AUC by 110% and the metabolite AUC by 2101% compared with rifabutin (300 mg daily) administration alone [2].

B) In a pharmacokinetic study, coadministration of atazanavir and rifabutin was associated with an 18% (95% CI, 0.94 to 1.48%) increase in rifabutin Cmax, a 2.4-fold increase in Cmin, and 1.1-fold increase in AUC. A 7.2-fold increase in Cmax, a 74.6-fold increase in Cmin, and a 21-fold increase in AUC was observed for the rifabutin active metabolite 25-O desacetyl-rifabutin. Rifabutin 300 mg/day was given for 10 days followed by 150 mg/day for 10 more days; atazanavir 600 mg/day was given on days 11 through 20 [1].

C) In a small cohort of healthy subjects (n=7), coadministration of atazanavir and rifabutin increased rifabutin Cmax, Cmin, and AUC by 149%, 40%, and 48%, respectively, and its active metabolite 25-O desacetyl-rifabutin by 6.77-, 10.45-, and 9.9-fold, respectively, compared with rifabutin alone (150 mg/day on days 1 through 10). The AUC for rifabutin plus 25-O desacetyl-rifabutin was increased by 2-fold. Rifabutin 150 mg was given twice weekly on days 1 through 15; atazanavir 300 mg/day plus ritonavir 100 mg was given on days 1 through 17 [1].

D) In a small cohort of healthy subjects (n=7), coadministration of atazanavir and rifabutin was associated with mean increases in rifabutin Cmax, Cmin, and AUC by 34%, 13%, and 15%, respectively. Rifabutin 150 mg/day was given on days 15 through 28; atazanavir 400 mg/day was given on days 1 through 28 [1].

References

1 ) Product Information: REYATAZ(R) oral capsules, oral powder, atazanavir oral capsules, oral powder. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2020.

2 ) Panel on Antiretroviral Guidelines for Adults and Adolescents: Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. AIDSinfo, U.S. Department of Health and Human Services. Rockville, MD. 2013. Available from URL: http://aidsinfo.n... . As accessed 2013-02-12.

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.

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.