Atazanavir with Tenofovir Disoproxil Fumarate Interaction Details
Brand Names Associated with Atazanavir
- Atazanavir
- ATZ
- Reyataz®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Feb 29, 2024
Interaction Effect
Reduced atazanavir exposure and/or increased tenofovir exposure
Interaction Summary
Concomitant use of atazanavir and tenofovir has resulted in increased tenofovir concentrations and decreased atazanavir concentrations. Atazanavir without ritonavir should not be coadministered with tenofovir. When atazanavir plus ritonavir is coadministered with tenofovir, the recommended doses are atazanavir 300 mg with ritonavir 100 mg and tenofovir 300 mg (all as a single daily dose with food)[1][2]. For a treatment-experienced pregnant woman during the second or third trimester, the dosing recommendation when coadministered with tenofovir is atazanavir 400 mg and ritonavir 100 mg once daily. There are insufficient data to recommend dosing for atazanavir/ritonavir when coadministered with tenofovir and an H2-receptor antagonist in treatment-experienced pregnant women [1]. Because tenofovir levels may be increased, all patients receiving atazanavir with ritonavir plus tenofovir should be monitored for signs of tenofovir-associated adverse effects, including renal disorders [1][2].
Severity
Major
Onset
Unspecified
Evidence
Established
How To Manage Interaction
Concomitant use of atazanavir and tenofovir disoproxil fumarate has resulted in increased tenofovir concentrations and decreased atazanavir minimum concentrations and AUC. When atazanavir is coadministered with tenofovir, administer atazanavir 300 mg with ritonavir 100 mg and tenofovir 300 mg (all as a single daily dose with food)[1][2]. For a treatment-experienced pregnant woman during the second or third trimester, the dosing recommendation when coadministered with tenofovir is atazanavir 400 mg and ritonavir 100 mg once daily. There are insufficient data to recommend dosing for atazanavir/ritonavir when coadministered with tenofovir and an H2-receptor antagonist in treatment-experienced pregnant women [1]. Because tenofovir levels may be increased, monitor all patients receiving atazanavir with ritonavir plus tenofovir for signs of tenofovir-associated adverse effects, including renal disorders [1][2].
Mechanism Of Interaction
Unknown
Literature Reports
A) During a clinical trial, 2.9% of patients treated with atazanavir/cobicistat/tenofovir disoproxil fumarate discontinued treatment due to renal adverse events compared with 3.2% of patients administered atazanavir/ritonavir/tenofovir disoproxil fumarate. Overall, 2% of patients in the both the cobicistat and ritonavir groups had laboratory findings consistent with proximal renal tubulopathy. Discontinuation of cobicistat resulted in improvement in proximal tubulopathy findings; however, complete resolution did not occur. Renal replacement therapy was not required [3].
B) In a study of the effects of atazanavir on tenofovir pharmacokinetic parameters (n=33), concomitant use of atazanavir 400 mg once daily on days 2 through 16 and tenofovir 300 mg once daily on days 9 through 16 and days 24 through 30 resulted in ratios (concomitant therapy vs tenofovir monotherapy) for tenofovir Cmax of 1.14 (90% confidence interval (CI), 1.08 to 1.2), tenofovir AUC of 1.24 (90% CI, 1.21 to 1.28) and tenofovir minimum concentration (Cmin) of 1.22 (90% CI, 1.15 to 1.3). Results were similar when there was 12 hours between atazanavir and tenofovir dosing. In a study of 12 patients, concomitant use (doses separated by 12 hours) of atazanavir 300 mg/ritonavir 100 mg once daily in the morning on days 25 through 34 and tenofovir 300 once daily in the evening on days 1 through 7 and days 25 through 34 resulted in ratios (atazanavir/ritonavir plus tenofovir vs tenofovir monotherapy) for tenofovir Cmax of 1.34 (90% CI, 1.2 to 1.51), tenofovir AUC of 1.37 (90% CI, 1.3 to 1.45) and tenofovir Cmin of 1.29 (90% CI, 1.21 to 1.36) [1][2].
C) In a study of the effects of tenofovir on atazanavir pharmacokinetic parameters (n=34), concomitant use of atazanavir 400 mg once daily on days 2 through 16 and tenofovir 300 mg once daily on days 9 through 16 resulted in ratios (concomitant therapy vs atazanavir monotherapy) for atazanavir Cmax of 0.79 (90% confidence interval (CI), 0.73 to 0.86), atazanavir AUC of 0.75 (90% CI, 0.7 to 0.81) and atazanavir minimum concentration (Cmin) of 0.6 (90% CI, 0.52 to 0.68). In a study of 10 HIV-infected patients, concomitant use of atazanavir 300 mg/ritonavir 100 mg once daily on days 1 through 42 and tenofovir 300 once daily on days 15 through 42 resulted in ratios (atazanavir/ritonavir plus tenofovir vs atazanavir/ritonavir) for atazanavir Cmax of 0.72 (90% CI, 0.5 to 1.05), atazanavir AUC of 0.75 (90% CI, 0.58 to 0.97) and atazanavir Cmin of 0.77 (90% CI, 0.54 to 1.1). Atazanavir exposure was higher when atazanavir 300 mg plus ritonavir 100 mg were administered compared with atazanavir 400 mg. When coadministered with ritonavir and tenofovir, atazanavir geometric mean values for Cmax, AUC, and Cmin were 3190 nanograms (ng)/mL, 34,459 ng x hour/mL, and 491 ng/mL, respectively. In both studies, results were similar when there was 12 hours between atazanavir and tenofovir dosing [1][2].
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 ) Product Information: VIREAD(R) oral tablets, tenofovir disoproxil fumarate oral tablets. Gilead Sciences, Inc., Foster City, CA, 2010.
3 ) Product Information: EVOTAZ(R) oral tablets, atazanavir cobicistat oral tablets. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2023.
Atazanavir Overview
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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.
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Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
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