Simvastatin with Efavirenz Interaction Details

Brand Names Associated with Simvastatin

Brand Names Associated with Efavirenz

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 10, 2023

Interaction Effect

Decreased simvastatin plasma concentrations

Interaction Summary

When 14 patients were given simvastatin 40 mg/day for 4 days together with efavirenz 600 mg/day for 15 days, the Cmax, AUC, and Cmin of simvastatin was reduced by 72%, 68%, and 45%, respectively. The Cmax and AUC of the total active (including metabolites) of simvastatin decreased by 68% and 60%, respectively. In an open-label, multidose pharmacokinetic study, coadministration of efavirenz and simvastatin in healthy, HIV-seronegative volunteers resulted in decreased simvastatin AUC values and Cmax concentrations by approximately 58% and 50%, respectively. Additionally, the lipid-lowering ability of simvastatin was attenuated when coadministered with efavirenz . Efavirenz may potentially decrease the effectiveness of simvastatin necessitating an increase dose, change in therapy, and/or addition of other lipid-lowering agents. Studies with both drugs coadministered for longer durations are needed to determine the extent of the pharmacodynamic interaction.

Severity

Moderate

Onset

Delayed

Evidence

Established

How To Manage Interaction

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

Mechanism Of Interaction

Induction of CYP450 3A4-mediated metabolism of simvastatin by efavirenz

Literature Reports

A) In an open-label pharmacokinetic study, coadministration of efavirenz and simvastatin in healthy, HIV-seronegative subjects resulted in decreased simvastatin AUC values and plasma concentrations. Subjects (n=13) received oral simvastatin 40 mg every night for 4 days. From day 5 to 18, efavirenz 600 mg was administered every night at bedtime. Simvastatin was restarted on day 15 through 18. Blood samples were taken to determine the simvastatin AUC from 0 to 24 hours before and after coadministration of efavirenz. Simvastatin AUC values decreased by a median of 58%, from 36.48 nanograms (ng) x hr/mL (95% CI, 11.63 to 58.34 ng x hr/mL) on day 3 to 14.46 ng x hr/mL (95% CI, 5.34 to 27.02 ng x hr/mL) on day 18 (p=0.0031). Median Cmax values for simvastatin were 3.52 ng/mL (95% CI, 1.21 to 4.59 ng/mL) and 1.63 ng/mL (95% CI, 0.62 to 2.61 ng/mL) for days 3 and 18, respectively (median within-subject change of -50.5%, p=0.0134). LDL changed by a median of -37 mg/dL (95% CI, -64 to -26) with simvastatin alone. The effect on LDL was attenuated when efavirenz was coadministered for 4 days (-32 mg/dL; 95% CI, -37 to -11, p=0.0476). Simvastatin does not alter the metabolism of efavirenz. A study limitation was the short duration (4 days) of efavirenz and simvastatin coadministration, which limits the ability to evaluate the full potential for a pharmacodynamic interaction .

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.

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.