Simvastatin with Carbamazepine Interaction Details

Brand Names Associated with Simvastatin

Brand Names Associated with Carbamazepine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 25, 2023

Interaction Effect

Reduced simvastatin exposure

Interaction Summary

Concurrent administration of carbamazepine with simvastatin significantly reduced maximum serum concentration, serum half-life, and area under the concentration-time curve for both simvastatin and its active metabolite simvastatin acid.

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Monitor cholesterol levels in patients receiving concomitant therapy with carbamazepine and simvastatin. Simvastatin dose may need to be adjusted.

Mechanism Of Interaction

Induction of CYP3A4-mediated first-pass metabolism of simvastatin by carbamazepine

Literature Reports

A) Concurrent administration of carbamazepine with simvastatin significantly reduced simvastatin exposure. In a randomized, crossover study with a 2-week wash out period, healthy subjects (n=12) received either no drug or carbamazepine 200 milligrams (mg) once daily for 2 days, after which the active drug group received carbamazepine 300 mg twice daily for the next 12 days. On day 15 (12 hours after the last carbamazepine dose), subjects fasted for 2 hours prior to receiving a single dose of simvastatin 80 mg. Serial blood samples were obtained immediately prior to and for 24 hours after simvastatin administration. Carbamazepine co-administration significantly reduced the mean maximum serum concentration for both simvastatin and its active metabolite simvastatin acid (from 18.7 nanograms/milliliter (ng/mL) to 6.0 ng/mL and from 3.5 ng/mL to 1.1 ng/mL, respectively; p less than 0.01, both values). Simvastatin and simvastatin acid mean areas under the concentration-time curves (AUC, 0-infinity) declined from 88.8 ng/mL x hour to 22.6 ng/mL x hour and from 33.5 ng/mL x hour to 6.8 ng/mL x hour, respectively (p less than 0.001, both values). Concurrent administration with carbamazepine also significantly reduced simvastatin acid serum mean half-life (from 5.9 hours to 3.7 hours, p less than 0.01) .

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.

Carbamazepine Overview

• Carbamazepine is used alone or in combination with other medications to control certain types of seizures in people with epilepsy. It is also used to treat trigeminal neuralgia (a condition that causes facial nerve pain). Carbamazepine extended-release capsules (Equetro brand only) are also used to treat episodes of mania (frenzied, abnormally excited or irritated mood) or mixed episodes (symptoms of mania and depression that happen at the same time) in patients with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Carbamazepine is in a class of medications called anticonvulsants. It works by reducing abnormal electrical activity in the brain.

Return To Our Drug Interaction Homepage

Feedback, Question Or Comment About This Information?

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.