Gemfibrozil

Prescription ·Exploratory record · not publication-reviewed ·Updated July 13, 2026

Gemfibrozil is a fibric acid derivative used primarily to lower very high triglyceride levels and to reduce the risk of pancreatitis in patients with severe hypertriglyceridemia. It also modestly raises HDL cholesterol and was shown in the Helsinki Heart Study and VA-HIT to reduce coronary events in selected dyslipidemic patients. It is a potent inhibitor of several drug-metabolizing and transport pathways, which gives it a high potential for clinically important drug interactions.

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Publication status

Exploratory record, not a reviewed medical publication.

See the editorial and medical-review policies for the publication gate.

This generated database record has not completed a claim-level review by a qualified human medical reviewer. Bibliography links and evidence labels are not approval. The page remains available for reference and is excluded from search indexing.

In short

What the research says.

A quick, data-only summary. The full evidence, dosing, and sources are below.

Gemfibrozil is a fibric acid derivative used primarily to lower very high triglyceride levels and to reduce the risk of pancreatitis in patients with severe hypertriglyceridemia. NutriStack rates the supporting evidence as strong. Common adult dosing is 1200 mg per day, taken as 600 mg twice daily 30 minutes before the morning and evening meals., though a prescriber sets the actual dose. With long-term use it can deplete coenzyme q10, folate. This profile indexes 4 sources.

What it's good for

Treatment of severe hypertriglyceridemia (Fredrickson types IV and V) to reduce pancreatitis risk³
Treatment of mixed dyslipidemia / type IIb hyperlipidemia²
Reduction of coronary heart disease risk in selected patients with low HDL and elevated triglycerides who do not respond adequately to diet^1,2

What to watch for

Dyspepsia, abdominal pain, nausea, and diarrhea
Cholelithiasis (gallstones) and cholecystitis due to increased biliary cholesterol excretion
Myopathy and myalgia, with rare rhabdomyolysis especially when combined with statins
Hepatic impairment or active liver disease³
Severe renal impairment³

The bottom line

Evidence rating strong. Most-documented uses: treatment of severe hypertriglyceridemia (fredrickson types iv and v) to reduce pancreatitis risk, treatment of mixed dyslipidemia / type iib hyperlipidemia, reduction of coronary heart disease risk in selected patients with low hdl and elevated triglycerides who do not respond adequately to diet. 4 sources indexed (1987–2019), with 0 interaction records on file.

The science

How it works, mechanistically.

Core mechanism

Gemfibrozil activates peroxisome proliferator-activated receptor alpha (PPAR-alpha), a nuclear transcription factor that regulates lipid metabolism. PPAR-alpha activation increases expression of lipoprotein lipase and reduces apolipoprotein C-III, thereby enhancing the lipolysis and clearance of triglyceride-rich very-low-density lipoproteins (VLDL). It also decreases hepatic VLDL triglyceride synthesis and secretion and increases production of apolipoproteins A-I and A-II, modestly raising HDL. Separately, gemfibrozil and its glucuronide metabolite strongly inhibit CYP2C8, the organic anion transporting polypeptide OATP1B1 (SLCO1B1), and UGT-mediated glucuronidation, which underlies its major interactions with statins and other drugs.^1,2

Class

Fibrate (fibric acid derivative)

Absorption

Best on an empty stomach

Dosing

Dosing & protocol.

Common range

1200 mg per day, taken as 600 mg twice daily 30 minutes before the morning and evening meals.

Recommended form

Oral tablet (600 mg)

Well absorbed orally; bioavailability is optimized when taken about 30 minutes before meals. Administration with food can reduce bioavailability. Although gemfibrozil itself is not fat-soluble, fibrate therapy can reduce absorption of fat-soluble nutrients and, by altering bile composition, increase the risk of cholesterol gallstones; bile-acid sequestrants taken concurrently should be separated by at least 2 hours to avoid binding.³

Depletions

What it depletes.

Nutrients this medication can lower over time, and what to replace.

Coenzyme Q10

Mild

Fibrates lower circulating cholesterol and lipoproteins, which serve as the principal transport vehicles for the lipophilic, cholesterol-pathway-derived molecule coenzyme Q10. Reduced lipoprotein carriers lower measured serum/plasma CoQ10 concentrations. Like statins, fibrates may also modestly reduce endogenous synthesis through effects on the mevalonate/isoprenoid pathway, and the proposed CoQ10 decline is one hypothesized contributor to fibrate-associated myopathy, particularly when combined with a statin.

Replace Coenzyme Q10 (ubiquinone)Monitor Plasma coenzyme Q10 level (interpret relative to total cholesterol/LDL, as CoQ10 tracks with lipoprotein concentration); creatine kinase if myopathy is suspectedOnset Weeks to a few months of continued therapy

Folate

Mild

Fibrate therapy is associated with an increase in plasma total homocysteine, an effect attributed largely to altered renal handling/creatinine and possibly to interference with folate-dependent remethylation of homocysteine. The rise in homocysteine reflects a relative functional drain on folate (and other B vitamins) used in the methionine cycle. This effect is most robustly documented for fenofibrate and bezafibrate; data specific to gemfibrozil are more limited, so the depletion is best regarded as a possible class effect of modest magnitude.

Replace Folic acid (or L-methylfolate)Monitor Plasma total homocysteine; serum/red blood cell folateOnset Within the first weeks to months of therapy

Full Gemfibrozil depletion and interaction guide →

Safety

Full safety detail.

Side effects

Dyspepsia, abdominal pain, nausea, and diarrhea
Cholelithiasis (gallstones) and cholecystitis due to increased biliary cholesterol excretion
Myopathy and myalgia, with rare rhabdomyolysis especially when combined with statins
Elevated liver transaminases
Headache, dizziness, and fatigue
Eczema, rash, and pruritus
Modest decreases in hemoglobin, hematocrit, and white blood cell count early in therapy

Contraindications

Hepatic impairment or active liver disease³
Severe renal impairment³
Preexisting gallbladder disease or cholelithiasis^3,1
Concomitant use with repaglinide (markedly increased plasma concentrations and hypoglycemia risk)^3,4
Concomitant use with simvastatin (markedly increased rhabdomyolysis risk)^4,3
Concomitant use with dasabuvir and selexipag³
Known hypersensitivity to gemfibrozil^1,2

Sources

Sources, by evidence tier.

Numbered references. Citations throughout the page link here.

Randomized controlled trials

1Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol (VA-HIT)PMIDRubins HB, Robins SJ, Collins D, et al. · New England Journal of Medicine · 1999
In men with coronary disease and low HDL, gemfibrozil reduced the combined risk of nonfatal myocardial infarction and coronary death by about 22% without significantly lowering LDL.
2Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemiaPMIDFrick MH, Elo O, Haapa K, et al. · New England Journal of Medicine · 1987
Over 5 years gemfibrozil reduced the incidence of coronary heart disease by approximately 34% compared with placebo, driven by reductions in triglycerides and LDL and an increase in HDL.

Reference material

3Lopid (gemfibrozil) US Prescribing InformationParke-Davis / Pfizer · FDA prescribing information · 2019
The recommended dose is 1200 mg daily in two divided doses 30 minutes before the morning and evening meals; contraindicated with simvastatin, repaglinide, dasabuvir, and in patients with hepatic, severe renal, or gallbladder disease.
4Mechanisms of the gemfibrozil-statin interaction and the risk of myopathyBackman JT, Kyrklund C, Neuvonen M, Neuvonen PJ · Clinical Pharmacology and Therapeutics · 2002
Gemfibrozil and its glucuronide inhibit CYP2C8, OATP1B1, and glucuronidation, raising plasma concentrations of statins such as simvastatin acid and cerivastatin and increasing myopathy and rhabdomyolysis risk.

FAQ

Common questions.

Quick answers about Gemfibrozil, drawn from the data on this page.

What is Gemfibrozil?

What is Gemfibrozil used for?

Commonly cited benefits of Gemfibrozil include: Treatment of severe hypertriglyceridemia (Fredrickson types IV and V) to reduce pancreatitis risk; Treatment of mixed dyslipidemia / type IIb hyperlipidemia; Reduction of coronary heart disease risk in selected patients with low HDL and elevated triglycerides who do not respond adequately to diet. NutriStack rates the overall evidence as strong.

What is a typical dose of Gemfibrozil?

A typical adult dose of Gemfibrozil is 1200 mg per day, taken as 600 mg twice daily 30 minutes before the morning and evening meals.. The commonly recommended form is Oral tablet (600 mg). These are general ranges, not personalized advice; confirm the right dose with a clinician.

What are the side effects of Gemfibrozil?

Reported side effects include dyspepsia, abdominal pain, nausea, and diarrhea, cholelithiasis (gallstones) and cholecystitis due to increased biliary cholesterol excretion, myopathy and myalgia, with rare rhabdomyolysis especially when combined with statins, elevated liver transaminases, headache, dizziness, and fatigue, eczema, rash, and pruritus. This is educational information; check with a healthcare professional before use.

How strong is the evidence for Gemfibrozil?

NutriStack rates this as Strong, meaning multiple high-quality meta-analyses or systematic reviews converge on the same finding. Full tier criteria are at https://nutristackapp.com/methodology/evidence-tiers.

Use this with your stack

Gemfibrozil in NutriStack.

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