Simvastatin with Ketoconazole 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®
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 02, 2023
Interaction Effect
An increased risk of myopathy or rhabdomyolysis
Interaction Summary
The concurrent use of ketoconazole and simvastatin is contraindicated. If coadministration is required, temporarily suspend simvastatin during the duration of ketoconazole treatment. Simvastatin is a CYP3A4 substrate and ketoconazole is a potent inhibitor of CYP3A4 . Myopathy and rhabdomyolysis have been observed in patients treated with simvastatin or another HMG-CoA reductase inhibitor following the initiation of therapy with ketoconazole .
Severity
Contraindicated
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
The concurrent use of ketoconazole and simvastatin is contraindicated. If coadministration is required, temporarily suspend simvastatin during the duration of ketoconazole treatment.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated simvastatin metabolism by ketoconazole
Literature Reports
A) A 73-year-old man was admitted to the hospital with rapid progressive muscle weakness. He had been taking simvastatin 20 mg daily for the previous 7 months for hypercholesterolemia. Three weeks prior to admission, treatment with ketoconazole 200 mg daily was initiated for a generalized pruritic rash which was fungal in origin. Examination showed weakness and tenderness of the lower limbs, upper limbs, and trunk, and the patient was unable to sit or walk alone. The serum creatine phosphokinase (CK) concentration was 43,900 international units/L (normal: 50 to 200 international units/L), and serum aldolase, aspartate aminotransferase, alanine aminotransferase, and lactase dehydrogenase levels were also elevated. His urine was positive for myoglobin, and a diagnosis of rhabdomyolysis and hepatotoxicity was made. Simvastatin and ketoconazole were both discontinued, and the CK returned to normal in 2 months. The patient showed marked improvement and neither the simvastatin nor ketoconazole were reinstituted .
B) Simvastatin and ketoconazole coadministration were thought to precipitate rhabdomyolysis in a 54-year-old woman. She had been receiving therapy with simvastatin 20 mg daily for one year when ketoconazole 400 mg daily was initiated for candida paronychia. Within a few days of cotherapy, she experienced flu-like symptoms and had difficulty climbing stairs and running, although her liver function and blood panel were normal. Four weeks later, she was admitted to the hospital with generalized weakness and muscle pain. Rhabdomyolysis was diagnosed based on a serum creatine phosphokinase level of 31,200 international units/L, serum aldolase level of 121 international units/L, and myoglobin in the urine. Ketoconazole and simvastatin were both discontinued, and over the next week the patient's muscle strength returned to normal and serum levels decreased. A month after hospital discharge, simvastatin was reinstated without a similar adverse effect .
C) Prostate cancer managed by a statin was associated with development of rhabdomyolysis when high-dose ketoconazole was added to the treatment regimen. A 73-year-old man with metastatic prostate cancer was treated with simvastatin for hypercholesterolemia for 8 years. Progressive prostatic cancer developed while the patient was receiving leuprolide and bicalutamide, and treatment was subsequently switched to leuprolide plus ketoconazole and hydrocortisone. The patient began to experience progressive proximal muscle weakness in the arms and legs. Plasma creatine kinase and aspartate aminotransferase were greatly increased, and electromyography demonstrated acute diffuse noninflammatory myopathy. The patient improved after the medications were discontinued .
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.
Ketoconazole Overview
-
Ketoconazole is used to treat fungal infections when other medications are not available or cannot be tolerated. Ketoconazole should not be used to treat fungal meningitis (infection of the membranes surrounding the brain and spinal cord caused by a fungus) or fungal nail infections. Ketoconazole is in a class of antifungals called imidazoles. It works by slowing the growth of fungi that cause infection.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
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.