Simvastatin with Mibefradil Interaction Details
Brand Names Associated with Simvastatin
- Flolipid®
- Juvisync® (as a combination product containing Simvastatin, Sitagliptin)
- Simcor® (as a combination product containing Niacin, Simvastatin)
- Simvastatin
- Vytorin® (as a combination product containing Ezetimibe, Simvastatin)
- Zocor®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 10, 2023
Interaction Effect
An increased risk of myopathy and/or rhabdomyolysis
Interaction Summary
Rhabdomyolysis and myopathy has been observed in patients treated with simvastatin alone and in combination with mibefradil. Simvastatin is dependent on CYP450 3A4 for metabolic clearance, and mibefradil is a potent inhibitor of CYP450 3A4. Therefore, the concurrent administration of simvastatin and mibefradil is contraindicated.
Severity
Contraindicated
Onset
Delayed
Evidence
Probable
How To Manage Interaction
The concurrent use of simvastatin and mibefradil is contraindicated.
Mechanism Of Interaction
Inhibition of cytochrome P450 3A4-mediated simvastatin metabolism by mibefradil
Literature Reports
A) An 83-year-old female was admitted to the hospital one week after the onset of immobilizing myopathy associated with low-back pain and oliguria. Prior to admission, she had been stabilized on simvastatin 20 mg once daily for a year, and mibefradil 50 mg daily was added to therapy four weeks prior to admission for blood pressure control. Upon admission, her creatine phosphokinase (CPK) was 50125 U/L, alanine aminotransferase was 1179 U/L, and her aspartate aminotransferase was 998 U/L. In addition, she was hyperkalemic, and was in severe renal failure. She was diagnosed with rhabdomyolysis, and all medications were discontinued. Within 10 days, she regained the functionality of her legs and her muscle pain disappeared. She was discharged from the hospital four weeks after admission in good physical health .
B) A 47-year-old male kidney transplant recipient treated with simvastatin 40 mg daily and cyclosporine for two weeks experienced rhabdomyolysis one month after mibefradil 50 mg daily was added to therapy. He was admitted to the hospital following complaints of progressive muscle weakness, myalgia, hematuria, and oliguria. Admission laboratory values included CPK 150,698 U/L, LDH 2986 U/L, creatinine 4.8 mg/dL, and SGOT 3101 U/L. On admit, his simvastatin level was measured at 135 ngEq/mL. Four days later, the simvastatin level was still measurable at 6.4 ngEq/mL. Plasma half-life of simvastatin acid is less than two hours, and long-term therapy does not result in the accumulation of simvastatin or simvastatin acid. This patient's rhabdomyolysis was attributed to mibefradil's inhibition of cytochrome P450 3A4-mediated cyclosporine and simvastatin metabolism .
Simvastatin Overview
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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.
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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.
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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:
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.