Atorvastatin with Ritonavir Interaction Details

Brand Names Associated with Atorvastatin

Brand Names Associated with Ritonavir

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 04, 2024

Interaction Effect

Increased atorvastatin exposure and an increased risk of myopathy, including rhabdomyolysis

Interaction Summary

Coadministration of ritonavir (a CYP3A4 inhibitor[1][2]) with atorvastatin (a CYP3A4 substrate [3]) may increase serum concentrations of atorvastatin and increase the risk of myopathy, including rhabdomyolysis. If concomitant therapy is required, initiate atorvastatin at the lowest possible dose and carefully titrate. Monitor for signs and symptoms of myopathy (e.g., muscle pain, tenderness, or weakness) [1][2]. The concomitant use of atorvastatin and dasabuvir/ombitasvir/paritaprevir/ritonavir is contraindicated [4]. Concomitant use of atorvastatin with tipranavir/ritonavir should be avoided due to an increased risk of myopathy/rhabdomyolysis. In patients taking lopinavir plus ritonavir, consider the risk/benefit of concomitant use with atorvastatin. If atorvastatin is used concomitantly in patients taking saquinavir plus ritonavir, darunavir plus ritonavir or fosamprenavir plus ritonavir, do not exceed a atorvastatin dose of 20 mg/day [5].

Severity

Contraindicated

Onset

Delayed

Evidence

Established

How To Manage Interaction

Coadministration of atorvastatin and ritonavir may increase plasma levels of atorvastatin and increase the risk of myopathy, including rhabdomyolysis. If concurrent therapy is required, initiate with the lowest possible dose of atorvastatin and carefully titrate. Additionally, monitor for atorvastatin adverse effects during therapy (e.g., muscle pain, tenderness, or weakness)[1][2]. The concomitant use of atorvastatin and dasabuvir/ombitasvir/paritaprevir/ritonavir is contraindicated [4]. Concomitant use of atorvastatin with tipranavir/ritonavir should be avoided due to an increased risk of myopathy/rhabdomyolysis. In patients taking lopinavir plus ritonavir, consider the risk/benefit of concomitant use with atorvastatin. If atorvastatin is used concomitantly in patients taking saquinavir plus ritonavir, darunavir plus ritonavir or fosamprenavir plus ritonavir, do not exceed a atorvastatin dose of 20 mg/day [5].

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism of atorvastatin

Literature Reports

A) In a pharmacokinetic study (n=16), concomitant use of fosamprenavir and atorvastatin significantly increased the Cmax and AUC of atorvastatin. When fosamprenavir 1400 mg twice daily for 2 weeks was coadministered with atorvastatin 10 mg once daily for 4 days, the Cmax and AUC of atorvastatin were increased by 304% and 130%, respectively. The Cmax and AUC of amprenavir were decreased by 18% and 27%, respectively. When fosamprenavir 700 mg twice daily plus ritonavir 100 mg twice daily for 2 weeks were coadministered with atorvastatin 10 mg once daily for 4 days, the Cmax and AUC of atorvastatin were increased by 184% and 153%, respectively. The Cmax and AUC of amprenavir did not change (increased or decreased less than or equal to 10%) [6].

B) Coadministration of tipranavir 500 mg/ritonavir 200 mg twice daily with atorvastatin 10 mg once daily for 7 days increased the atorvastatin AUC by 9.36-fold and Cmax by 8.58-fold compared with atorvastatin alone [5].

C) Coadministration of fosamprenavir 700 mg/ritonavir 100 mg twice daily with atorvastatin 10 mg once daily for 4 days increased the atorvastatin AUC by 2.53-fold and Cmax by 2.84-fold compared with atorvastatin alone [5].

D) Coadministration of atorvastatin 40 mg once daily for 4 days with ritonavir-boosted saquinavir 400 mg twice daily for 15 days led to a 3.93-fold increase in atorvastatin AUC and a 4.31-fold increase in Cmax [3][5].

E) Subjects receiving atorvastatin 10 mg daily for 4 days who were coadministered darunavir 300 mg/ritonavir 100 mg twice daily for 9 days had a 3.45-fold increase in atorvastatin AUC and a 2.25-fold increase in Cmax [3][5].

References

1 ) Product Information: NORVIR(R) oral tablets, oral solution, ritonavir oral tablets, oral solution. Abbott Laboratories (per Manufacturer), North Chicago, IL, 2012.

2 ) Product Information: NORVIR(R) oral capsules, oral solution, ritonavir oral capsules, oral solution. Abbott Laboratories (per manufacturer), North Chicago, IL, 2012.

3 ) Product Information: LIPITOR(R) oral tablets, atorvastatin calcium oral tablets. Pfizer (Per FDA), New York, NY, 2012.

4 ) Product Information: VIEKIRA PAK oral tablets, ombitasvir, paritaprevir, ritonavir, dasabuvir oral tablets. AbbVie Inc (per FDA), North Chicago, IL, 2017.

5 ) Product Information: ATORVALIQ(R) oral suspension, atorvastatin calcium oral suspension. CMP Pharma Inc (per FDA), Farmville, NC, 2023.

6 ) Product Information: LEXIVA(R) oral tablets, oral suspension, fosamprenavir calcium oral tablets, oral suspension. ViiV Healthcare and Vertex Pharmaceuticals Incorporated (per FDA), Research Triangle Park, NC, 2012.

Atorvastatin Overview

• Atorvastatin 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. Atorvastatin 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. Atorvastatin 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). Atorvastatin 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 atorvastatin has been shown to prevent heart disease, angina (chest pain), strokes, and heart attacks.

Ritonavir Overview

• Ritonavir is used along with other medications to treat human immunodeficiency virus (HIV) infection. Ritonavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although ritonavir 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. 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:

• 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.