Gemfibrozil with Simvastatin Interaction Details


Brand Names Associated with Gemfibrozil

  • Gemfibrozil
  • Lopid®

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®

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Last updated Nov 25, 2023


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Interaction Effect

Increased exposure of simvastatin acid (active metabolite) and an increased risk of myopathy or rhabdomyolysis


Interaction Summary

Concomitant use of gemfibrozil and simvastatin is contraindicated due to increased risk of myopathy and rhabdomyolysis. Concomitant use of simvastatin and gemfibrozil (an OATP1B1 transporter inhibitor) has resulted in an increase in exposure of simvastatin . Short-term, concurrent administration in a small number of subjects did not result in myopathy or rhabdomyolysis, although there were asymptomatic, transitory elevations of creatine phosphokinase (CPK) levels up to 2.5 times the upper limit normal . There are several case reports of myopathy occurring in patients treated with the combination of simvastatin and gemfibrozil . Gemfibrozil increased plasma concentrations of simvastatin and its metabolite by 35% and 185%, respectively .


Severity

Contraindicated


Onset

Delayed


Evidence

Established


How To Manage Interaction

Concomitant use of gemfibrozil and simvastatin is contraindicated due to increased risk of myopathy and rhabdomyolysis.


Mechanism Of Interaction

Inhibition of OATP1B1-mediated simvastatin acid transport by gemfibrozil


Literature Reports

A) Concomitant use of simvastatin and gemfibrozil (an OATP1B1 transporter inhibitor) resulted in a 2.9-fold increase in simvastatin acid (active metabolite) AUC .

B) In a 30-week outpatient study, 19 adult patients with type III hyperlipoproteinemia were treated with simvastatin (20 mg daily or 40 mg daily) alone or in combination with gemfibrozil (450 mg daily). The six patients who were treated for eight weeks with the combination of simvastatin 40 mg and gemfibrozil 450 mg did not develop myopathy or rhabdomyolysis. However, two patients experienced transitory asymptomatic elevations of creatine phosphokinase (CPK) to a maximum of 2.5 times the upper limit normal. The combination treatment further lowered plasma total cholesterol, very low density lipoprotein cholesterol, and triglycerides, compared to simvastatin 20 mg or 40 mg alone, but the difference was not statistically significant. The authors recommended that combination fibrate-HMG CoA reductase inhibitor treatment should be reserved for patients with severe hyperlipidemia who do not respond sufficiently to monotherapy .

C) In a prospective study of 108 patients taking simvastatin plus gemfibrozil for mixed lipid abnormalities, one episode of myopathy occurred but resolved when combination therapy was stopped .

D) A 62- year-old patient with diabetes treated with various medications including simvastatin and gemfibrozil developed symptoms of rhabdomyolysis including elevated serum creatinine and CPK levels . Once both medications were discontinued and with intensive supportive treatment, the patient's renal function and CPK level returned to normal values. The researchers also report a 50-year-old female patient with diabetes maintained on simvastatin and gemfibrozil for hyperlipidemia. Her dose of simvastatin was gradually increased from 10 mg per day to 80 mg per day. After three months of this regimen the patient presented with fatigue, generalized myalgia and anuria, and the diagnosis of rhabdomyolysis with significant renal deficiency was determined. Myoglobin was present in the urine, and CPK level was 8280 mmol/L. Both drugs were discontinued, resulting in a gradual return of renal function to normal levels.

E) A case report describes a patient treated with gemfibrozil and simvastatin who was hospitalized three weeks later with severe proximal muscle weakness, anorexia, and nausea. Initial serum CK, aldolase, BUN, creatinine, SGOT and SGPT levels were elevated. Myoglobin was present in the urine. Electromyography revealed myositis and significant polyneuropathy of the lower limbs. Simvastatin and gemfibrozil were discontinued and after seven days of supportive treatment with hydration and prednisone, the patient's CK value and renal function returned to normal levels .

F) Plasma concentrations of simvastatin and its active form simvastatin acid are increased by gemfibrozil. A dual phase, double-blind, randomized, crossover study involving ten healthy volunteers was designed to assess the effect of gemfibrozil on the pharmacokinetics of simvastatin. When compared to placebo, gemfibrozil increased the mean total area under the plasma concentration-time curve (AUC) of simvastatin by 35% (p less than 0.01) and the AUC of simvastatin acid by 185% (p less than 0.001). Gemfibrozil also increased the elimination half-life of simvastatin by 74% (p less than 0.05) and simvastatin acid by 51% (p less than 0.01). A 112% (p less than 0.01) increase in peak concentration of simvastatin acid was also observed. The authors suggest that the increased risk of myopathy seen in patients treated with combination therapy may have a pharmacokinetic basis .

Gemfibrozil Overview

  • Gemfibrozil is used with diet changes (restriction of cholesterol and fat intake) to reduce the amount of cholesterol and triglycerides (other fatty substances) in the blood in certain people with very high triglycerides who are at risk of pancreatic disease (conditions affecting the pancreas, a gland that produces fluid to break down food and hormones to control blood sugar). Gemfibrozil is also used in people with a combination of low high-density lipoprotein (HDL; 'good cholesterol') levels and high low-density lipoprotein (LDL; 'bad cholesterol') and triglyceride levels to reduce the risk of heart disease. Gemfibrozil is in a class of lipid-regulating medications called fibrates. It works by reducing the production of triglycerides in the liver.

See More information Regarding Gemfibrozil

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.

See More information Regarding Simvastatin

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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.