Gemfibrozil and Pravastatin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Gemfibrozil
Pravastatin
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
Decreased pravastatin clearance, increased pravastatin exposure, and increased risk of myopathy or rhabdomyolysis
Interaction Deep Dive
Concomitant use of pravastatin and gemfibrozil (an OATP1B1 and OAT3 transporter inhibitor) has resulted in an increase in the exposure and a decrease in the clearance of pravastatin1. The use of fibrates alone may occasionally be associated with the development of myopathy. Therefore, the combined use of pravastatin and gemfibrozil should be avoided. Carefully weigh the benefit/risk ratio of concurrent therapy. If coadministered, monitor the patient for signs and symptoms of myopathy or rhabdomyolysis, and discontinue use if CK levels show a marked increase, or if myopathy or rhabdomyolysis is diagnosed or suspected 2. However, one short-term study and one small, longer-term study found no rhabdomyolysis with this drug combination 43.
Why it happens (mechanism)
Inhibition of OATP1B1- and OAT3-mediated pravastatin transport by gemfibrozil
Literature reports
5 reports — tap to read
a) Concomitant use of pravastatin and gemfibrozil (an OATP1B1 and OAT3 transporter inhibitor) resulted in a 2-fold increase in the AUC of pravastatin 1.
b) Myopathy was not reported in a study involving the concurrent use of pravastatin 40 mg daily and gemfibrozil 1200 mg daily. However, 4 of the 75 subjects had markedly increased creatine phosphokinase (CPK) levels, compared to 1 of 73 subjects who received placebo. There were more frequent CPK elevations and patient withdrawals because of musculoskeletal symptoms in the groups receiving combination therapy than in the groups which received placebo or monotherapy with gemfibrozil or pravastatin 2.
c) A study of pravastatin and gemfibrozil cotherapy followed 32 hyperlipidemic patients for a year on average 3. No cases of myalgia or significant rises in liver enzymes (greater than 3 times normal) occurred. One case of asymptomatic elevation of creatine kinase was reported.
d) A double-blind, randomized, placebo-controlled study (n=290) of a combination regimen of pravastatin 40 mg with gemfibrozil 600 mg was compared to each drug alone and placebo. Researchers found no severe myopathy or rhabdomyolysis after 12 weeks. Severe myopathy was defined in this study as creatine kinase (CK) greater than 10,000 international units/L plus muscle pain and weakness. However, 2 patients on the combination regimen were removed from the study due to asymptomatic increased CK levels. In addition, 14 patients experienced musculoskeletal pain, most of which the investigators judged to be unrelated to the treatment, although one patient also had an increased CK level (950 international units/L). The mean AST level increased significantly from baseline in patients receiving the combination and gemfibrozil-only regimens. It is speculated that the hydrophilic properties of pravastatin may explain the drug's low incidence of myopathy. The drug is more selective for hepatocytes than other tissues. This study does not rule out myopathy after long-term treatment and therefore, advice is against the routine combination therapy with pravastatin and gemfibrozil 4.
e) An increase in pravastatin AUC occurs with concomitant gemfibrozil administration. A randomized, placebo-controlled, crossover study with 2 phases was used to evaluate the effect of concomitant gemfibrozil administration on the AUC of pravastatin. Subjects took gemfibrozil 600 mg or placebo for 3 days. On day 3, pravastatin 40 mg was administered. Gemfibrozil increased the plasma concentrations of pravastatin, as compared with placebo. In the gemfibrozil phase, the AUC (0-24) of pravastatin was 202% (range, 40% to 413%; p less than 0.05) and the Cmax was 181% (range, 27% to 428%; p less than 0.05) of the corresponding value in the placebo phase. The mean renal clearance of pravastatin was reduced from 25 L/hr to 14 L/hr (p less than 0.0001) by gemfibrozil. There was a significant correlation between the increase in AUC (0-24) of pravastatin and the decrease in its renal clearance caused by gemfibrozil (Pearson correlation coefficient, r equal to 0.72; p=0.02). The change in renal clearance was only a minor contributor to the increase in pravastatin AUC. Interference with a transport protein may contribute to the increase in pravastatin AUC from 0 hours to infinity by gemfibrozil. Reduced renal clearance of pravastatin is also a contributing factor 5.
Common questions
Can I take Gemfibrozil and Pravastatin together?
Decreased pravastatin clearance, increased pravastatin exposure, and increased risk of myopathy or rhabdomyolysis Always confirm with your pharmacist or prescriber before making any change.
How serious is the Gemfibrozil and Pravastatin interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
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 Pravastatin 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 (5)
- 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: PRAVACHOL(R) oral tablets, pravastatin sodium oral tablets. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2012. DailyMed
- Rosenson RS & Frauenheim WA: Safety of combined pravastatin-gemfibrozil therapy. Am J Cardiol 1994; 74:499-500. PubMed
- Wiklund O, Angelin B, Bergman M, et al: Pravastatin and gemfibrozil alone and in combination for the treatment of hypercholesterolemia. Am J Med 1993; 94:13-20. PubMed
- Kyrklund C, Backman J, Neuvonen M, et al: Gemfibrozil increases plasma pravastatin concentrations and reduces pravastatin renal clearance. Clin Pharmacol Ther 2003; 73:538-544. PubMed
Keep reading about Gemfibrozil
Keep reading about Pravastatin
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