Simvastatin with Alitretinoin Interaction Details

Brand Names Associated with Simvastatin

Brand Names Associated with Alitretinoin

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

Interaction Effect

Decreased simvastatin plasma concentrations

Interaction Summary

Concomitant use of alitretinoin and simvastatin may lead to a slight decrease in simvastatin plasma concentrations. An analysis of 18 patients in a drug interaction study demonstrated that concomitant administration of alitretinoin and simvastatin yielded a modest but statistically significant decrease in the AUC and Cmax of simvastatin by 16% and 23%, respectively. Monitor patients for loss of simvastatin’s lipid-lowering effect, making dosage adjustments or therapy modifications as necessary.

Severity

Moderate

Onset

Delayed

Evidence

Established

How To Manage Interaction

Concomitant use of alitretinoin and simvastatin may lead a slight decrease in simvastatin plasma concentrations. Monitor patients for loss of simvastatin’s lipid-lowering effect, making dosage adjustments or therapy modifications as necessary.

Mechanism Of Interaction

Competitive inhibition of CYP3A4-mediated metabolism of simvastatin

Literature Reports

A) In a randomized, crossover, drug interaction equivalence study comparing the pharmacokinetics (PK) of simvastatin, ketoconazole, and cyclosporine in the presence of alitretinoin (n=54; age range, 18 to 45 years), an analysis of 18 patients revealed simvastatin AUC and Cmax fell outside the margin of equivalence, with a modest but statistically significant decrease by 16% and 23%, respectively, in the presence of alitretinoin compared with administration of simvastatin alone. The study also examined the effects of simvastatin, ketoconazole, and cyclosporine administration on alitretinoin pharmacokinetics. Subjects received single and multiple doses of alitretinoin 30 mg or simvastatin 40 mg alone and in combination. To deem the PK parameters equivalent (showing no interaction), the 90% confidence interval (CI) around the geometric mean ratio (GMR) comparing alitretinoin and simvastatin AUC and Cmax alone and with coadministration had to fall within 0.8 to 1.25. Following multiple doses, alitretinoin AUC (GMR, 1.071; 90% CI, 0.920 to 1.247) was equivalent when administered with simvastatin and without; however, the simvastatin AUC and Cmax fell outside the equivalence margins when given with alitretinoin compared with administration alone, showing a slight but significant decrease in AUC (GMR, 0.862; 90% CI, 0.782 to 0.952) and Cmax (GMR, 0.757; 90% CI, 0.643 to 0.890) .

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.

Alitretinoin Overview

• Alitretinoin is used to treat skin lesions associated with Kaposi's sarcoma. It helps stop the growth of Kaposi's sarcoma cells.

• This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

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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.