Atazanavir with Simvastatin Interaction Details

Brand Names Associated with Atazanavir

Brand Names Associated with Simvastatin

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

Interaction Effect

An increased risk of simvastatin toxicity, including an increased risk of myopathy or rhabdomyolysis

Interaction Summary

Concomitant use of atazanavir and simvastatin is contraindicated. Atazanavir is an inhibitor of CYP3A, and coadministration with simvastatin, a CYP3A substrate, may result in increased plasma concentrations of simvastatin, potentially causing myopathy including rhabdomyolysis[1][2].

Severity

Contraindicated

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Coadministration of atazanavir and simvastatin is contraindicated due to the potential for serious reactions such as myopathy, including rhabdomyolysis[1][2].

Mechanism Of Interaction

Inhibition of CYP3A-mediated simvastatin metabolism by atazanavir

Literature Reports

A) Rhabdomyolysis and acute renal failure occurred in a 72-year-old man receiving simvastatin concomitantly with amiodarone. The patient presented with a 4-day history of generalized pain, weakness, and fatigue, and a 3-day history of dark orange urine. He had been on atorvastatin 40 mg daily for 2 years and was switched to simvastatin 80 mg 27 days before current presentation. Additionally, amiodarone 400 mg daily was initiated 19 days prior to current presentation, and then decreased to 200 mg daily after 7 days. His other chronic medications included atazanavir, stavudine, and delavirdine, all taken for 2 years. Laboratory results revealed a creatine kinase level of 66,680 units/liter, nearly 300 times the upper limit of normal. The patient was diagnosed with rhabdomyolysis and oliguric acute renal failure. Simvastatin, amiodarone, and HIV medications were all temporarily discontinued, and the patient was given forced alkaline diuresis and dialysis. He was discharged on day 9 (creatine kinase level, 1695 units/liter), restarted on amiodarone, and outpatient dialysis was continued for one month. His HIV medications were restarted after 6 weeks, but the statin was not initiated. This patient had additional risk factors of advanced age and concomitant use of atazanavir, where atazanavir may have contributed by further decreasing simvastatin's metabolism. The Naranjo adverse drug event probability scale indicated a "probable" rating that the effects were due to an interaction between simvastatin and amiodarone/atazanavir [3].

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: EVOTAZ(R) oral tablets, atazanavir cobicistat oral tablets. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2023.

3 ) Schmidt GA, Hoehns JD, Purcell JL, et al: Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir. J Am Board Fam Med 2007; 20(4):411-416.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.

Simvastatin Overview

• Simvastatin is used together with diet, weight-loss, and exercise to reduce the risk of heart attack and stroke and to decrease the chance that heart surgery will be needed in people who have heart disease or who are at risk of developing heart disease. Simvastatin is also used to decrease the amount of fatty substances such as low-density lipoprotein (LDL) cholesterol (''bad cholesterol'') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol (''good cholesterol'') in the blood. Simvastatin may also be used to decrease the amount of cholesterol and other fatty substances in the blood in children and teenagers 10 to 17 years of age who have familial heterozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally). Simvastatin is in a class of medications called HMG-CoA reductase inhibitors (statins). It works by slowing the production of cholesterol in the body to decrease the amount of cholesterol that may build up on the walls of the arteries and block blood flow to the heart, brain, and other parts of the body.

• Accumulation of cholesterol and fats along the walls of your arteries (a process known as atherosclerosis) decreases blood flow and, therefore, the oxygen supply to your heart, brain, and other parts of your body. Lowering your blood level of cholesterol and fats with simvastatin has been shown to prevent heart disease, angina (chest pain), strokes, and heart attacks.

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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.