Simvastatin with Phenytoin 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 Phenytoin
- Dilantin®
- Phenytek®
- Phenytoin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 10, 2023
Interaction Effect
Loss of simvastatin efficacy
Interaction Summary
Phenytoin may decrease the efficacy of simvastatin, based on a patient with familial hypercholesterolemia who was treated with concurrent medication. Phenytoin is known to induce CYP3A4 enzymes, which are partially responsible for simvastatin metabolism. Total cholesterol values improved considerably when phenytoin was discontinued, and elevated gamma-glutamyl transpeptidase levels returned to normal.
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Patients receiving phenytoin and simvastatin should be monitored for simvastatin efficacy, as measured by total cholesterol and triglycerides.
Mechanism Of Interaction
Induction by phenytoin of CYP3A4-mediated simvastatin metabolism
Literature Reports
A) A 50-year-old woman was receiving simvastatin 10 mg daily for familial hypercholesterolemia and had a total cholesterol level of 9.4 mmol/L and a triglyceride level of 1.87 mmol/L. Other medications included sodium valproate 200 mg three times daily for epilepsy. Her anticonvulsant medication was switched to phenytoin 325 mg daily, and three months later her cholesterol had increased to 15.99 mmol/L. Serum activity of gamma-glutamyl transpeptidase, which was in the normal range (5 Units/L to 50 Units/L) before phenytoin, was also elevated at 175 Units/L. Simvastatin was increased to 40 mg in a step-wise manner, with no resolution. Antilipidemic therapy was switched to fluvastatin 40 mg daily and finally to atorvastatin, starting at 10 mg daily and increasing in a step-wise fashion to 80 mg daily. Her cholesterol stayed in excess of 10 mmol/L throughout these changes, while phenytoin levels remained within the therapeutic range. Phenytoin was slowly discontinued, and her total cholesterol decreased to 6.24 mmol/L while gamma-glutamyl transpeptidase returned to normal values .
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.
Phenytoin Overview
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Phenytoin is used to control certain type of seizures, and to treat and prevent seizures that may begin during or after surgery to the brain or nervous system. Phenytoin is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in the brain.
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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.