Simvastatin with Troglitazone 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
Decreased simvastatin efficacy
Interaction Summary
No significant reductions in total and LDL cholesterol were seen in patients receiving troglitazone when they were converted from pravastatin to simvastatin, whereas an additional 11% reduction was expected. One possible explanation for the reduced lipid-lowering effect of simvastatin in troglitazone patients is that troglitazone induces cytochrome P450 3A4 (CYP3A4) enzymes which are responsible for simvastatin metabolism. Simvastatin did not significantly affect the pharmacokinetics of troglitazone .
Severity
Minor
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Higher doses of simvastatin may be required to compensate for troglitazone metabolic induction and a consequent diminishing of the lipid lowering effects of simvastatin. Additional monitoring of lipid profiles may be necessary.
Mechanism Of Interaction
Induction of cytochrome P450 3A4-mediated simvastatin metabolism
Literature Reports
A) A retrospective analysis was conducted which included 344 patients with diabetes who were divided into two groups. The troglitazone group included 21 patients treated with troglitazone before and after the conversion from similar doses of pravastatin to simvastatin, and the non-troglitazone group was made up of 323 patients. No significant reductions in total and LDL cholesterol were seen in the patients receiving troglitazone when they were converted from pravastatin to simvastatin, whereas an additional 11% reduction was expected .
B) A case report of a patient that developed severe hepatitis and myositis eight weeks after the addition of troglitazone to a previously stable course of simvastatin has been described. A 68-year-old female with type 2 diabetes mellitus and hypercholesterolemia had self-resumed troglitazone 200 mg twice daily for 8 weeks after running out of metformin. She had been treated with simvastatin for three years. Her initial laboratory results were: AST 546 IU/L, ALT 437 IU/L, alkaline phosphatase 109 IU/L, total bilirubin 4.5 mg/dL, albumin 2.5 mg/dL, total protein 7.6 gm/dL, glucose 275 mg/dL, creatine kinase 14,300 IU/L, hemoglobin 12.9 g/dL, platelet 88,000/microliter, prothrombin 18.1 sec, and cholesterol 117 mg/dL. Analysis of ascites fluid demonstrated cirrhosis. Electromyography of the lower extremities revealed muscle inflammation and necrosis. Over a period of 12 weeks the myositis resolved, however, the hepatitis progressed to symptomatic cirrhosis. The author concludes that the underlying pathogenic mechanism is altered mitochondrial metabolism, resulting in combined severe toxicity to both liver and skeletal muscle .
C) Concomitant administration of troglitazone and simvastatin resulted in a modest decrease in both the area under the plasma concentration-time profiles (AUC) and maximum plasma concentrations (Cmax) of HMG-CoA reductase inhibitors by 30% and 40%, respectively. In an open-label, randomized, multiple-dose, two-period crossover study involving 12 subjects, each subject received troglitazone 400 mg daily for 24 days with simvastatin 40 mg on days 15 through 24. Subjects were administered simvastatin 40 mg daily for 10 days in Treatment B. Mean plasma concentrations of simvastatin were significantly higher (p less than 0.05) for simvastatin alone (Treatment B) than those obtained following administration of simvastatin and troglitazone (Treatment A). The AUC and Cmax for active and total HMG-CoA reductase inhibitors were reduced by troglitazone treatment. No significant differences (p equal to 0.677) was observed in plasma troglitazone AUC values with or without simvastatin. Cmax was significantly higher for troglitazone with simvastatin than for troglitazone alone. The authors conclude that these results are consistent with the documented ability of troglitazone to decrease plasma levels of several CYP3A4 substrates via induction of CYP3A4, the enzyme responsible for simvastatin metabolism. Simvastatin did not significantly alter the pharmacokinetics of troglitazone, supporting that simvastatin is not an inhibitor of drug metabolizing enzymes .
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.