Atazanavir with Ranitidine Interaction Details

Brand Names Associated with Atazanavir

Brand Names Associated with Ranitidine

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

Interaction Effect

Reduced atazanavir exposure

Interaction Summary

Concomitant use of atazanavir (alone or with ritonavir) and a H2-blocker, such as raNITIdine, may result in the loss of atazanavir efficacy and development of resistance. In a case series (n=14), concomitant use showed no significant effect on virologic outcome[1]. However, concomitant use of atazanavir and famotidine has resulted in reduced atazanavir exposure. In treatment-naive patients, do not exceed raNITIdine dose equivalent to famotidine 40 mg twice daily and atazanavir 300 mg/ritonavir 100 mg (as a single dose with food) should be given with or at least 10 hrs after raNITIdine dose. When atazanavir is given without ritonavir, do not exceed raNITIdine dose equivalent to famotidine 20 mg/dose or 40 mg/daily, and atazanavir 400 mg (once daily with food) should be given with or at least 2 hrs before and 10 hrs after raNITIdine dose. In treatment-experienced patients, do not exceed raNITIdine dose equivalent to famotidine 20 mg twice daily, and atazanavir 300 mg/ritonavir 100 mg (as a single dose with food) should be given with or at least 10 hrs after raNITIdine dose. When used together with both tenofovir and raNITIdine, atazanavir and ritonavir doses should be 400 mg and 100 mg, respectively (as a single dose with food). For treatment-experienced pregnant women during the second or third trimester, use atazanavir 400 mg and ritonavir 100 mg once daily when given with tenofovir disoproxil fumarate or a H2-blocker; atazanavir is not recommended with both tenofovir and a H2-blocker [2].

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Concomitant use of atazanavir (alone or with ritonavir) and an H2-receptor antagonist, such as raNITIdine, may result in the loss of atazanavir efficacy and development of resistance. For concomitant use in treatment-naive patients, the raNITIdine dose should not exceed a dose equivalent to famotidine 40 mg twice daily and the atazanavir 300 mg/ritonavir 100 mg dose (as a single dose with food) should be given with or at least 10 hours (hrs) after the raNITIdine dose. When atazanavir is administered without ritonavir, the raNITIdine dose should not exceed a dose equivalent to famotidine 20 mg (single dose) or 40 mg (total daily dose) and atazanavir 400 mg (once daily with food) should be given with or at least 2 hrs before and at least 10 hrs after the raNITIdine dose. For concomitant use in treatment-experienced patients, the raNITIdine dose should not exceed a dose equivalent to famotidine 20 mg twice daily, and the atazanavir 300 mg/ritonavir 100 mg dose (as a single dose with food) should be given with or at least 10 hrs after the raNITIdine dose. When used together with both tenofovir and raNITIdine, the atazanavir and ritonavir doses should be 400 mg and 100 mg, respectively (as a single dose with food). For treatment-experienced pregnant women during the second or third trimester, the dosing recommendation when coadministered with tenofovir disoproxil fumarate or an H2-receptor antagonist is atazanavir 400 mg and ritonavir 100 mg once daily; atazanavir is not recommended with both tenofovir and an H2-receptor antagonist in this population[2].

Mechanism Of Interaction

Reduced solubility of atazanavir as pH increases

Literature Reports

A) A case series study involving 14 HIV-positive patients treated with atazanavir and acid-suppressive therapy (proton pump inhibitor (PPI), H2-receptor antagonists raNITIdine 150 mg/day) or buffered didanosine tablets) demonstrated no significant effect on virologic outcome during median of 6 months' follow-up. Eight patients were taking atazanavir 300 mg with ritonavir 100 mg once daily, 5 were taking atazanavir 400 mg without ritonavir, and one was taking atazanavir 400 mg with a second protease inhibitor. None of the patients were receiving other medications that could increase plasma levels of atazanavir. Plasma viral load was undetectable in 7 patients at the time atazanavir-based therapy was initiated; 5 of the remaining 7 with detectable viremia prior to atazanavir attained an undetectable viral load through the last documented follow-up; 1 patient had a reduction in viral load 0.91 log(10) copies/mL through 16 weeks of follow-up, and the other patient had an increase of 0.13 log(10) copies/mL over the same time period. Omeprazole was then discontinued in this last patient, and the viral load results remained unchanged through 40 weeks of atazanavir treatment [1].

B) When ritonavir was not part of the regimen, and famotidine and atazanavir were simultaneously administered, the Cmax, AUC, and minimum concentration (Cmin) of atazanavir were significantly decreased; however, the Cmax, AUC, and Cmin were not altered when atazanavir was administered 10 hrs after or 2 hrs before famotidine. Atazanavir 400 mg once daily administered simultaneously with famotidine 40 mg twice daily in 15 subjects resulted in a significant decline in atazanavir Cmax, AUC and Cmin by 47% (90% confidence interval (CI), 18% to 66%), 41% (90% CI, 13% to 60%), and 42% (90% CI, 11% to 63%), respectively. However, when atazanavir 400 mg once daily was administered 10 hr after and 2 hrs before famotidine 40 mg twice daily (n=14), the Cmax, AUC, and Cmin values were not significantly altered (8% increase (90% CI, 18% decrease to 41% increase), 5% decrease (90% CI, 26% decrease to 21% increase), and 21% decrease (90% CI 40% decrease to 4% increase), respectively [2].

C) When ritonavir was part of the regimen, the Cmax was not altered when atazanavir/ritonavir was simultaneously coadministered with famotidine. Atazanavir 300 mg/ritonavir 100 mg once daily administered simultaneously with famotidine 40 mg twice daily in 14 subjects resulted in no significant change in atazanavir geometric mean Cmax and a 1.79- and 4.46-fold higher AUC and minimum concentration (Cmin), respectively, relative to atazanavir 400 mg once daily without ritonavir. Furthermore, when atazanavir 400 mg/ritonavir 100 mg once daily was administered with famotidine 40 mg twice daily (n=15) , the Cmax, AUC, and Cmin values were not significantly altered (2% increase (90% confidence interval (CI), 13% decrease to 18% increase), 3% increase (90% CI, 14% decrease to 22% increase), and 14% decrease (90% CI ,32% decrease to 8% increase)), respectively [2].

D) In study 1 (n=18), concomitant administration of famotidine 20 mg twice daily plus atazanavir 300 mg/ritonavir 100 mg/tenofovir 300 mg once daily (administered simultaneous with morning famotidine) resulted in a decrease in atazanavir Cmax, AUC, and minimum concentration (Cmin) by 9% (90% confidence interval (CI), 1% to 16%), 10% (90% CI, 2% to 18%), and 19% (90% CI, 6% to 31%), respectively. In study 2 (n=20), atazanavir 300 mg/ritonavir 100 mg/tenofovir 300 mg once daily administered 12 hrs after the evening famotidine 40 mg once-daily dose resulted in a decrease in atazanavir Cmax, AUC, and Cmin by 11% (90% CI, 3% to 19%), 12% (95% CI, 4% to 20%), and 23% (90% CI, 7% to 37%), respectively. In study 3 (n=18), atazanavir 300 mg/ritonavir 100 mg/tenofovir 300 mg once daily administered 10 hrs after the evening famotidine 40-mg dose and 2 hr before the morning famotidine 40 mg dose resulted in a decrease in atazanavir Cmax, AUC, and Cmin by 26% (90% CI, 16% to 34%), 21% (90% CI, 12% to 30%), and 28% (90% CI, 17% to 37%), respectively [2].

References

1 ) Antoniou T, Yoong D, Beique L, et al: Impact of acid-suppressive therapy on virologic response to atazanavir-based regimens in antiretroviral-experienced patients: a case series. J Acquir Immune Defic Syndr 2005; 39(1):126-128.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

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

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.

Ranitidine Overview

• Ranitidine is used to treat ulcers; gastroesophageal reflux disease (GERD), a condition in which backward flow of acid from the stomach causes heartburn and injury of the food pipe (esophagus); and conditions where the stomach produces too much acid, such as Zollinger-Ellison syndrome. Over-the-counter ranitidine is used to prevent and treat symptoms of heartburn associated with acid indigestion and sour stomach. Ranitidine is in a class of medications called H₂ blockers. It decreases the amount of acid made in the stomach.

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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.