Atazanavir with Lopinavir Interaction Details
Brand Names Associated with Atazanavir
- Atazanavir
- ATZ
- Reyataz®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Feb 29, 2024
Interaction Effect
Increased or reduced antiretroviral exposure and an increased risk of PR interval prolongation
Interaction Summary
Both atazanavir and lopinavir can prolong the PR interval in patients[1]. ECG monitoring should be considered in patients taking drugs that may prolong the PR interval concomitantly [2]. Coadministration of atazanavir/ritonavir and an additional protease inhibitor is not recommended due to potential for increased exposure to the other protease inhibitor [3]. Atazanavir/cobicistat is not recommended in combination with other antiretroviral drugs that require CYP3A inhibition to achieve adequate exposures (e.g., other HIV protease inhibitors) because dosing recommendations for such combinations have not been established and coadministration may result in decreased exposure of antiretroviral agents, leading to loss of therapeutic effect and development of resistance [4].
Severity
Major
Onset
Unspecified
Evidence
Established
How To Manage Interaction
Due to the potential for additive effects on the PR interval, ECG monitoring should be considered in patients taking other drugs that may prolong the PR interval[3], especially when additional risk factors for altered cardiac conduction are present [5]. Coadministration of atazanavir with ritonavir and an additional protease inhibitor is not recommended due to potential for increased exposure to the other protease inhibitor [3]. Atazanavir/cobicistat is not recommended in combination with other antiretroviral drugs that require CYP3A inhibition to achieve adequate exposures (e.g., other HIV protease inhibitors or elvitegravir) because dosing recommendations for such combinations have not been established and coadministration may result in decreased plasma concentrations of the antiretroviral agents, leading to loss of therapeutic effect and development of resistance [4].
Mechanism Of Interaction
Unknown; additive PR interval prolongation
Literature Reports
A) In an open-label, single-center, parallel-arm, pharmacokinetic study, coadministration of atazanavir and lopinavir/ritonavir in HIV-positive adults (n=10) revealed prolonged PR and QRS intervals. Patients were assigned to either study arm A or B based on which protease inhibitor they were currently receiving as standard care. Patients in arm A received atazanavir 300 mg/ritonavir 100 mg per day on days 1 through 6, atazanavir 300 mg/day and lopinavir 400 mg/ ritonavir 100 mg twice daily on days 7 through 16, and atazanavir 300 mg/day and lopinavir 800 mg/ ritonavir 200 mg once daily on days 17 through 20. Patients in arm B received lopinavir 400 mg/ritonavir 100 mg twice daily on days 1 through 6, and atazanavir 300 mg/day and lopinavir 400 mg/ritonavir 100 mg twice daily on days 7 through 12. Both study arms continued their preexisting nucleoside reverse transcriptase inhibitors. In the 10 patients, ECG monitoring showed increases in mean PR and QRS intervals with concomitant administration of atazanavir and lopinavir/ritonavir. The mean PR interval increased from 149 +/- 18 milliseconds (msec) at baseline to 165 +/-28 msec at day 12 (arm B)/day 16 (arm A) (p less than or equal to 0.01) and the mean QRS interval increased from baseline at 95 +/- 11 msec to 102 +/- 17 at day 12/day 16 (p=not significant). However, upon excluding 2 patients who had a family history of coronary artery disease and developed arrhythmias, the mean increase seen in the QRS interval was statistically significant (5 msec; p less than 0.01). There were no changes in QTc interval, or in atazanavir and lopinavir pharmacokinetics [5].
References
1 ) Product Information: KALETRA(R) film coated oral tablets, oral solution, lopinavir and ritonavir film coated oral tablets, oral solution. Abbott Laboratories, North Chicago, IL, 2009.
2 ) Product Information: REYATAZ(R) oral capsules, atazanavir sulfate oral capsules. Bristol-Myers Squibb Company, Princeton, NJ, 2009.
3 ) Product Information: REYATAZ(R) oral capsules, oral powder, atazanavir oral capsules, oral powder. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2020.
4 ) Product Information: EVOTAZ(R) oral tablets, atazanavir cobicistat oral tablets. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2023.
5 ) Rathbun CR, Liedtke MD, Blevins SM, et al: Electrocardiogram abnormalities with atazanavir and lopinavir/ritonavir. HIV Clin Trials 2009; 10(5):328-336.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...
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.
Where Does Our Information Come From?
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.
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.