Atorvastatin with Efavirenz Interaction Details

Brand Names Associated with Atorvastatin

Brand Names Associated with Efavirenz

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

Interaction Effect

Decreased atorvastatin plasma concentrations

Interaction Summary

When 14 HIV-seronegative subjects were given atorvastatin 10 mg/day for 4 days together with efavirenz 600 mg/day for 15 days, the Cmax, AUC, and Cmin of atorvastatin was reduced by 14%, 43%, and 69%, respectively. The Cmax, AUC, and Cmin of the total active (including metabolites) of atorvastatin decreased by 15%, 32%, and 48%, respectively. The pharmacokinetics of efavirenz were not significantly affected[1][2]. Although this did not appear to have detrimental effects on the lipid-lowering ability of atorvastatin, further long-term studies at steady-state concentrations of both drugs are needed. Efavirenz may decrease the effectiveness of atorvastatin necessitating an increase dose, change in therapy, and/or addition of other lipid-lowering agents.

Severity

Moderate

Onset

Rapid

Evidence

Established

How To Manage Interaction

Concomitant administration of atorvastatin and efavirenz in healthy, HIV-seronegative subjects has resulted in decreased atorvastatin plasma concentrations, which may potentially lower atorvastatin efficacy[1]. If these agents are administered concurrently, consider increasing the atorvastatin dose, changing therapy, and/or adding other lipid-lowering agents to achieve the desired lipid-lowering effect.

Mechanism Of Interaction

Induction of CYP3A4-mediated metabolism of atorvastatin by efavirenz

Literature Reports

A) In an open-label pharmacokinetic study, coadministration of atorvastatin and efavirenz in healthy, HIV-seronegative subjects resulted in decreased atorvastatin AUC values. Subjects (n=14) received oral atorvastatin 10 mg every night for 4 days. From days 5 to 18, efavirenz 600 mg was administered every night at bedtime. Atorvastatin was restarted on day 16 through 18. Blood samples were taken to determine the atorvastatin AUC from 0 to 24 hours before and after coadministration of efavirenz. Total (atorvastatin plus 2 active metabolites) AUC values decreased by a median of 34.5%, from 28.1 nanograms (ng) x hr/mL (95% CI, 23.37 to 46.87 ng x hr/mL) on day 3 to 21.42 ng x hr/mL (95% CI, 15.53 to 30.09 ng x hr/mL) on day 18 (p=0.0052). Median Cmax values for atorvastatin were 1.7 nanogram/mL (3.0 nanomol/L) and 1.65 nanogram/mL (2.95 nanomol/L) for days 3 and 18, respectively (p=0.1531). LDL changed by a median of -29 mg/dL (-0.75 mmol/L) with atorvastatin alone. The effect on LDL was attenuated when efavirenz was coadministered for 4 days (-22 mg/dL or -0.57 mmol/L); however, the difference in LDL changes with and without efavirenz was not significantly different (p=0.3479). Atorvastatin did not alter the metabolism of efavirenz. A study limitation was the short duration (4 days) of efavirenz and atorvastatin coadministration, which limits the ability to evaluate the full potential for a pharmacodynamic interaction [2].

References

1 ) Product Information: SUSTIVA(R) oral capsules, tablets, efavirenz oral capsules, tablets. Bristol-Myers Squibb Company, Princeton, NJ, 2008.

2 ) Gerber JG, Rosenkranz SL, Fichtenbaum CJ, et al: Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin, and pravastatin: results of AIDS Clinical Trials Group 5108 Study. J Acquir Immune Defic Syndr 2005; 39(3):307-312.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

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.

Efavirenz Overview

• Efavirenz is used along with other medications to treat human immunodeficiency virus (HIV) infection. Efavirenz is in a class of medications called non-nucleoside reverse transcriptase inhibitors (NNRTIs). It works by decreasing the amount of HIV in the blood. Although efavirenz 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 life-style changes may decrease the risk of transmitting (spreading) 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.