Atazanavir with Rosuvastatin Interaction Details

Brand Names Associated with Atazanavir

Brand Names Associated with Rosuvastatin

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

Interaction Effect

Increased rosuvastatin exposure and an increased risk of myopathy or rhabdomyolysis

Interaction Summary

Concomitant use of atazanavir 300 mg/ritonavir 100 mg with rosuvastatin 10 mg for 8 days resulted in a significant 3-fold and 7-fold increase in rosuvastatin AUC and Cmax, respectively. Increased rosuvastatin exposure could potentially cause myopathy, including rhabdomyolysis[1][2]. In a prospective study of 6 healthy, adult patients, concomitant use of atazanavir/ritonavir with rosuvastatin led to increases in AUC and Cmax values of 213% and 600%, respectively, compared with rosuvastatin use alone. Although the mechanism is not known, it is postulated that greater absorption and/or decreased biliary excretion of rosuvastatin, when coadministered with atazanavir/ritonavir, could account for the considerable increase in the rosuvastatin AUC [3]. Therefore, if concurrent therapy is required, initiate rosuvastatin therapy with 5 mg/day and limit the dose to 10 mg/day [1].

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concomitant use of atazanavir and rosuvastatin has resulted in significantly elevated rosuvastatin plasma concentrations, and may increase the risk of myopathy or rhabdomyolysis. If concurrent therapy of atazanavir and rosuvastatin is required, initiate rosuvastatin therapy at 5 mg daily and limit the rosuvastatin dose to 10 mg once daily[1][2].

Mechanism Of Interaction

Unknown

Literature Reports

A) In a single-center, prospective study, concomitant use of rosuvastatin and atazanavir/ritonavir increased the extent and rate of bioavailability of rosuvastatin and its metabolites compared with rosuvastatin alone. Six healthy adult HIV-seronegative participants each received a single 10-mg oral rosuvastatin dose at baseline (day 0) with blood samples taken at 0, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, and 24 hours after administration followed by a 6-day washout period. On day 7, patients were started on atazanavir/ritonavir 300 mg/100 mg orally each morning. On day 14, patients received a single 10-mg rosuvastatin dose and their final atazanavir/ritonavir dose followed by blood samples taken again at the same intervals as on day 0. An internally validated tandem mass spectrometric method was used to measure plasma concentrations of rosuvastatin and its metabolites, N-desmethyl-rosuvastatin and rosuvastatin-lactone, over 24 hours. With concurrent atazanavir/ritonavir and rosuvastatin use, rosuvastatin AUC and Cmax increased 213% (43.8 vs 14 nanograms (ng) hr/mL; p=0.001) and 600% (13.3 vs 1.9 ng/mL; p=0.002), respectively, from baseline with a shorter Tmax (1.75 vs 2.91 hr; p less than 0.05). Compared with baseline, N-desmethyl-rosuvastatin Cmax was significantly higher (0.899 vs 0.345 ng/mL; p=0.005) with a significantly shorter Tmax (2.16 vs 4.33 hr; p less than 0.0001) with concurrent atazanavir/ritonavir use. The AUC value, although higher, did not increase significantly (4.11 vs 3.07 ng hr/mL; p=0.135). Rosuvastatin-lactone AUC and Cmax were both significantly greater with atazanavir/ritonavir use compared with baseline (8.87 vs 5.45 ng hr/mL; p =0.004 and 1.2 vs 0.442 ng/mL; p=0.001, respectively) with a significantly shorter Tmax (2.25 vs 5 hr; p=0.001) [3].

B) Concomitant use of atazanavir 300 mg/ritonavir 100 mg with rosuvastatin 10 mg for 8 days resulted in a significant 3.1-fold and 7-fold increase in rosuvastatin AUC and Cmax, respectively [1].

References

1 ) Product Information: CRESTOR(R) oral tablets, rosuvastatin calcium oral tablets. AstraZeneca Pharmaceuticals LP (per FDA), Wilmington, DE, 2023.

2 ) Product Information: REYATAZ(R) oral capsules, atazanavir sulfate oral capsules. Bristol-Myers Squibb (per FDA), Princeton, NJ, 2012.

3 ) Busti AJ, Bain AM, Hall RG, et al: Effects of atazanavir/ritonavir or fosamprenavir/ritonavir on the pharmacokinetics of rosuvastatin. J Cardiovasc Pharmacol 2008; 51(6):605-610.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.

Rosuvastatin Overview

• Rosuvastatin 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. Rosuvastatin is also used to decrease the amount of cholesterol 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. Rosuvastatin may also be used together with diet to decrease the amount of cholesterol and other fatty substances in the blood in children and teenagers 8 to 17 years of age who have familial heterozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally). Rosuvastatin is used together with diet, and alone or in combination with other medications, to decrease the amount of cholesterol and other fatty substances in the blood in adults and children and teenagers 7 to 17 years of age who have familial homozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally). Rosuvastatin 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 rosuvastatin 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.