Gemfibrozil !

A fibrate that lowers triglycerides. Famous for interactions: it raises statin and repaglinide levels and must not be combined with simvastatin.

Updated 2026-11-01

Class: Fibrates
Receptor: PPARα (nuclear receptor)
ATC code: C10AB04

PPARα (nuclear receptor)Gemfibrozil

The figure shows fenofibric acid, another fibrate, in the ligand-binding domain of human PPARα; gemfibrozil acts on the same receptor.

Target in 3D: PPARα (nuclear receptor). PDB structure 6LX4 (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Gemfibrozil activates PPARα, increasing lipoprotein lipase activity and fatty acid oxidation and lowering VLDL production, so triglycerides fall and HDL rises modestly. Separately, gemfibrozil strongly inhibits the hepatic uptake transporter OATP1B1 and the enzyme CYP2C8, which explains its many drug interactions.

Activates PPARα in liver and muscle
Lipoprotein lipase up, VLDL production down
Triglycerides fall; HDL rises modestly
Also blocks OATP1B1 and CYP2C8: many interactions

Pharmacokinetics

Absorption: Oral, completely absorbed; peak levels 1 to 2 hours after a dose.
Distribution: Highly bound to plasma albumin.
Metabolism: Oxidation in the liver; excreted mostly in urine as glucuronide conjugates.
Half-life: Short, about an hour (the shortest among the fibrates).

Indications

Very high triglycerides (types IV and V) with risk of pancreatitis, when diet is not enough Familial hypertriglyceridaemia →
Reduction of coronary risk in selected type IIb patients without coronary disease who did not respond to other measures Atherosclerosis and dyslipidaemia →

Adverse effects

Common

Dyspepsia, abdominal pain, diarrhea
Fatigue
Raised liver enzymes

Contraindications

Liver or severe kidney dysfunction, including primary biliary cholangitis
Pre-existing gallbladder disease
Combination with simvastatin, repaglinide, dasabuvir or selexipag
Hypersensitivity to gemfibrozil

Key interactions

Simvastatin and other statins: Raises statin acid levels and the risk of rhabdomyolysis; contraindicated with simvastatin and avoided with the others.
Repaglinide: Large rise in repaglinide levels and severe hypoglycemia; contraindicated.
Warfarin: Potentiates the anticoagulant; the dose is reduced and the INR checked often.
Bile acid resins: Lower gemfibrozil absorption; the doses are given at least 2 hours apart.

What is monitored

Lipid panel, especially triglycerides
Liver tests and blood count periodically
INR if on warfarin
Symptoms of gallstones and muscle pain

Administration and safety

Oral, usually twice daily before the morning and evening meals.
Before dispensing, the medication list is screened for statins, repaglinide and warfarin.
Separated in time from bile acid resins.

Nursing care

Before: lipid panel, liver tests, blood count, gallbladder history, full medication list.
Teach to report muscle pain, weakness or dark urine immediately.
Teach the signs of gallstones (upper right abdominal pain after meals).
Check the INR closely in patients on warfarin.

Pregnancy and breastfeeding

No adequate human studies; used in pregnancy only if clearly needed, such as severe hypertriglyceridemia with pancreatitis risk.

Test yourself

Think of the answer, then tap the question to see it.

Why does gemfibrozil raise statin levels?

It inhibits OATP1B1-mediated uptake of statins into hepatocytes and interferes with their glucuronidation, raising statin acid levels.

Which glucose-lowering drug is contraindicated with gemfibrozil?

Repaglinide: gemfibrozil (through CYP2C8 and OATP1B1) raises its levels many-fold and can cause severe hypoglycemia.

A patient needs a fibrate plus a statin. Which fibrate is preferred?

Fenofibrate, because gemfibrozil has the strongest interaction with statins.

Add to my cards (3)

← Back to the class: Fibrates

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Gemfibrozil: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); DailyMed - GEMFIBROZIL tablet (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 37 (McGraw Hill, 2023); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.