Simvastatin with Posaconazole Interaction Details

Brand Names Associated with Simvastatin

Brand Names Associated with Posaconazole

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

Interaction Effect

Increased simvastatin plasma concentrations and increased risk of myopathy or rhabdomyolysis

Interaction Summary

The concomitant use of posaconazole (a strong CYP3A4 inhibitor) and simvastatin (a CYP3A4 substrate) is contraindicated. In a clinical trial among healthy volunteers, coadministration of posaconazole and simvastatin increased the simvastatin Cmax and AUC by approximately 10-fold , which may increase the risk of myopathy and rhabdomyolysis. If coadministration is required, temporarily suspend simvastatin during the duration of posaconazole treatment .

Severity

Contraindicated

Onset

Unspecified

Evidence

Established

How To Manage Interaction

Concomitant use of posaconazole and simvastatin is contraindicated due to increase in simvastatin plasma concentrations, which may lead to myopathy and rhabdomyolysis. If coadministration is required, temporarily suspend simvastatin during the duration of posaconazole treatment .

Mechanism Of Interaction

Inhibition of CYP3A4-mediated simvastatin metabolism by posaconazole

Literature Reports

A) In a pharmacokinetic study of healthy volunteers (n=35), the coadministration of posaconazole and simvastatin resulted in significant increases in both simvastatin and simvastatin acid Cmax and AUC. Subjects were randomized to receive 50 mg (n=11), 100 mg (n=12), or 200 mg (n=12) daily doses of oral posaconazole for 13 days. In addition, subjects received single oral doses of simvastatin 40 mg alone and in the presence of posaconazole. Compared with simvastatin alone, mean simvastatin Cmax values increased by 7.4-fold (ratio estimate 743%; 90% CI, 565% to 976%), 9.4-fold (ratio estimate, 941%; 90% CI, 713% to 1244%), and 11.4-fold (ratio estimate, 1141%; 90% CI, 799% to 1629%) with the coadministration of posaconazole 50 mg, 100 mg, and 200 mg, respectively, and corresponding AUC values increased by 5.5-fold (ratio estimate, 565%; 90% CI, 443% to 722%), 10.3-fold (ratio estimate, 1031%; 90% CI, 840% to 1267%), and 10.6-fold (estimate ratio, 1060%; 90% CI, 863% to 1302%), respectively. Coadministration also lead to 5.5-fold (ratio estimate, 552%; 90% CI, 431% to 708%), 9.2-fold (ratio estimate, 917%; 90% CI, 736% to 1143%), and 9.5-fold (ratio estimate, 951%; 90% CI, 815% to 1110%) increases in simvastatin acid Cmax values and 5.4-fold (ratio estimate, 535%; 90% CI, 418% to 684%), 7.3-fold (ratio estimate, 734%; 90% CI, 582% to 925%), and 8.5-fold (ratio estimate 848%; 90% CI, 704% to 1023%) increases in simvastatin acid AUC values, respectively according to posaconazole dosage .

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.

Posaconazole Overview

• Posaconazole is used to prevent serious fungal infections that can spread throughout the body in adults and children 2 years of age and older with a weakened ability to fight infection. Posaconazole delayed-release tablets are used to treat invasive aspergillosis (a serious fungal infection that begins in the lungs and spreads through the bloodstream to other organs) in adults and teenagers 13 years of age and older. Posaconazole oral suspension is also used to treat yeast infections of the mouth and throat including yeast infections in adults and teenagers 13 years of age and older that could not be treated successfully with other medications. Posaconazole is in a class of medications called azole antifungals. It works by slowing the growth of fungi that cause infection.

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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.