Gemfibrozil and Simvastatin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Gemfibrozil
Simvastatin
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased exposure of simvastatin acid (active metabolite) and an increased risk of myopathy or rhabdomyolysis
Interaction Deep Dive
Concomitant use of gemfibrozil and simvastatin is contraindicated due to increased risk of myopathy and rhabdomyolysis3. Concomitant use of simvastatin and gemfibrozil (an OATP1B1 transporter inhibitor) has resulted in an increase in exposure of simvastatin 1. 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 4. There are several case reports of myopathy occurring in patients treated with the combination of simvastatin and gemfibrozil 9. Concomitant use of ezetimibe/simvastatin with gemfibrozil is also contraindicated 2.
Why it happens (mechanism)
Inhibition of OATP1B1-mediated simvastatin acid transport by gemfibrozil
Literature reports
7 reports — tap to read
a) Concomitant use of simvastatin and gemfibrozil (an OATP1B1 transporter inhibitor) resulted in a 2.9-fold increase in simvastatin acid (active metabolite) AUC 1.
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 4.
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 5.
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 6.
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 7.
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 8.
g) In drug interaction studies, coadministration of gemfibrozil 600 mg BID for 3 days together with simvastatin 40 mg increases the simvastatin and its active metabolite simvastatin acid AUC by 1.35 and 2.85 and increased Cmax by 0.91 and 2.18 respectively 2.
Common questions
Can I take Gemfibrozil and Simvastatin together?
Increased exposure of simvastatin acid (active metabolite) and an increased risk of myopathy or rhabdomyolysis Always confirm with your pharmacist or prescriber before making any change.
How serious is the Gemfibrozil and Simvastatin interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Gemfibrozil or Simvastatin need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (9)
- Tornio A, Neuvonen PJ, Niemi M, et al: Role of gemfibrozil as an inhibitor of CYP2C8 and membrane transporters. Expert Opin Drug Metab Toxicol 2017; 13(1):83-95. PubMed
- Product Information: VYTORIN(R) oral tablets, ezetimibe simvastatin oral tablets. Organon LLC (per FDA), Jersey City, NJ, 2024. DailyMed
- Product Information: ZOCOR(R) oral tablets, simvastatin oral tablets. Organon & Co (per FDA), Jersey City, NJ, 2022. DailyMed
- Feussner G, Eichinger M, & Ziegler R: The influence of simvastatin alone or in combination with gemfibrozil on plasma lipids and lipoproteins in patients with type III hyperlipoproteinemia. Clin Investig 1992; 70:1027-1035. PubMed
- Murdock DK, Murdock AK, Murdock RW, et al: Long-term safety and efficacy of combination gemfibrozil and HMG-CoA reductase inhibitors for the treatment of mixed lipid disorders. Am Heart J 1999; 138(1):151-155. PubMed
- Van Puijenbroek EP, Du Buf-Vereijken PW, Spooren PF, et al: Possible increased risk of rhabdomyolysis during concomitant use of simvastatin and gemfibrozil. J Internal Med 1996; 240:403-404. PubMed
- Tal A, Rajeshawari M, & Isley W: Rhabdomyolysis associated with simvastatin-gemfibrozil therapy. South Med J 1997; 90(5):546-7. PubMed
- Backman JT, Kyrklund C, Kivisto, et al: Plasma concentrations od active simvastatin acid are increased by gemfibrozil. Clin Pharmacol Ther 2000; 68:122-129.
- Van Puijenbroek EP, Du Buf-Vereijken PW, Spooren PF, et al: Possible increased risk of rhabdomyolysis during concomitant use of simvastatin and gemfibrozil. J Intern Med 1996; 240(6):403-4. PubMed
Keep reading about Gemfibrozil
Keep reading about Simvastatin
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