Atazanavir with Famotidine Interaction Details

Brand Names Associated with Atazanavir

Brand Names Associated with Famotidine

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

Interaction Effect

Reduced atazanavir exposure and an increased risk of QT interval prolongation

Interaction Summary

Concomitant use of atazanavir and famotidine resulted in reduced atazanavir exposure resulting in loss of atazanavir efficacy and development of resistance and may prolong the QT interval. For treatment-naive patients, do not exceed famotidine 40 mg twice daily and give atazanavir 300 mg/ritonavir 100 mg dose (single dose with food) with or at least 10 hours after the famotidine dose. When atazanavir is administered without ritonavir, do not exceed famotidine 20 mg/dose or 40 mg/day, and give atazanavir 400 mg (once daily with food) with or at least 2 hours before and at least 10 hours after the famotidine dose. For treatment-experienced patients, do not exceed famotidine 20 mg twice daily, and give atazanavir 300 mg/ritonavir 100 mg dose (single dose with food) with or at least 10 hours after famotidine dose. When used together with both tenofovir and famotidine, give atazanavir 400 mg/ritonavir 100 mg (as a single dose with food)[1]; or if using cobicistat, give atazanavir 400 mg/cobicistat 150 mg [2]. For treatment-experienced pregnant women during second or third trimester, give atazanavir 400 mg/ritonavir 100 mg once daily when coadministered with either tenofovir disoproxil fumarate or famotidine; atazanavir is not recommended with both tenofovir and famotidine in this population [1].

Severity

Major

Onset

Unspecified

Evidence

Established

How To Manage Interaction

Concurrent use of atazanavir (alone or with ritonavir) and famotidine may result in loss of atazanavir efficacy and development of resistance and may prolong the QT interval. For treatment-naive patients, do not exceed famotidine 40 mg twice daily and give atazanavir 300 mg/ritonavir 100 mg dose (as a single dose with food) with or at least 10 hours after the famotidine dose. For atazanavir without ritonavir, do not exceed famotidine 20 mg/dose or 40 mg/day and give atazanavir 400 mg (once daily with food) with or at least 2 hours before and at least 10 hours after the famotidine dose. For treatment-experienced patients, do not exceed famotidine 20 mg twice daily, and give atazanavir 300 mg/ritonavir 100 mg dose (as a single dose with food) with or at least 10 hours after the famotidine dose. When used together with both tenofovir and famotidine, give atazanavir 400 mg/ritonavir 100 mg (as a single dose with food)[1]; or if using cobicistat, give atazanavir 400 mg/cobicistat 150 mg [2]. For treatment-experienced pregnant women during the second or third trimester, use atazanavir 400 mg/ritonavir 100 mg once daily when coadministered with either tenofovir disoproxil fumarate or an H2 blocker; atazanavir is not recommended with both tenofovir and an H2 blocker in this population [1].

Mechanism Of Interaction

Reduced solubility of atazanavir as pH increases; additive QT interval prolongation

Literature Reports

A) In a multiple-dose, sequential study of patients with HIV (n=40) receiving atazanavir 300 mg/ritonavir 100 mg once daily plus 2 or more nucleoside reverse transcriptase inhibitors (with or without tenofovir), the Cmax, AUC, and Cmin of atazanavir significantly decreased following the addition of famotidine. Compared with those receiving atazanavir/ritonavir alone, the Cmax, AUC, and Cmin of atazanavir decreased by 23%, 23%, and 20%, respectively, in patients receiving atazanavir/ritonavir plus famotidine 40 mg twice daily and 20%, 13%, and 1%, respectively, in patients receiving atazanavir/ritonavir plus famotidine 20 mg twice daily. Compared with those receiving atazanavir/ritonavir/tenofovir alone, atazanavir Cmax, AUC, and Cmin decreased by 23%, 24%, and 25%, respectively, in patients receiving atazanavir/ritonavir/tenofovir plus famotidine 40 mg twice daily and 21%, 21%, and 19%, respectively, in patients receiving atazanavir/ritonavir/tenofovir plus famotidine 20 mg twice daily. There were no reports of serious adverse effects during the study and all patients maintained a virologically suppressed level of less than 400 copies/mL. The results confirmed the reduction in atazanavir exposure when administered with famotidine is similar in HIV-infected subjects compared with noninfected subjects [3].

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 hours after or 2 hours 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%, 41%, and 42%, respectively. However, when atazanavir 400 mg once daily was administered 10 hours after and 2 hours before famotidine 40 mg twice daily (n=14), the Cmax, AUC, and Cmin values were not significantly altered [1].

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 change in mean atazanavir Cmax, a 1.79-fold higher AUC, and 4.46-fold higher minimum concentration (Cmin), 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 [1].

D) In study 1 (n=18), coadministration 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%, 10%, and 19%, respectively. In study 2 (n=20), atazanavir 300 mg/ritonavir 100 mg/tenofovir 300 mg once daily administered 12 hours after the evening famotidine 40-mg once-daily dose resulted in a decrease in atazanavir Cmax, AUC, and Cmin by 11%, 12%, and 23%, respectively. In study 3 (n=18), atazanavir 300 mg/ritonavir 100 mg/tenofovir 300 mg once daily administered 10 hours after the evening famotidine 40-mg dose and 2 hours before the morning famotidine 40 mg dose resulted in a decrease in atazanavir Cmax, AUC, and Cmin by 26%, 21%, and 28%, respectively [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 ) Product Information: TYBOST(R) oral tablets, cobicistat oral tablets. Gilead Sciences Inc (per manufacturer), Foster City, CA, 2020.

3 ) Wang X, Boffito M, Zhang J, et al: Effects of the H2-receptor antagonist famotidine on the pharmacokinetics of atazanavir-ritonavir with or without tenofovir in HIV-infected patients. AIDS Patient Care STDS 2011; 25(9):509-515.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

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.

Famotidine Overview

• Prescription famotidine is used to treat ulcers (sores on the lining of the stomach or small intestine); gastroesophageal reflux disease (GERD, a condition in which backward flow of acid from the stomach causes heartburn and injury of the esophagus [tube that connects the mouth and stomach]); and conditions where the stomach produces too much acid, such as Zollinger-Ellison syndrome (tumors in the pancreas or small intestine that cause increased production of stomach acid). Over-the-counter famotidine is used to prevent and treat heartburn due to acid indigestion and sour stomach caused by eating or drinking certain foods or drinks. Famotidine is in a class of medications called H₂ blockers. It works by decreasing 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.