Gemfibrozil

Lipid-lowering agent of the fibrate class

ATC code: C10AB04

Brand names: Lopid

Updated 24 Sep 2026 · Methodology

Indications

Severe hypertriglyceridaemia

Second line

Gemfibrozil is a fibrate that lowers triglycerides. It is prescribed for very high hypertriglyceridemia when diet fails and acute pancreatitis becomes a threat. The label defines that group precisely: triglycerides above 2000 mg/dL, and between 1000 and 2000 mg/dL the drug is considered for people with prior pancreatitis. Below 1000 mg/dL pancreatitis risk is generally absent and the drug is not needed. The 2019 guidelines place fibrates in the same position: they cut pancreatitis risk, not myocardial infarction risk. Spanish authors Lahoz and Mostaza describe the same approach for familial and polygenic hypertriglyceridemia in Clin Investig Arterioscler 2021. Diet, alcohol avoidance and diabetes control remain the first step, and the drug delivers little without them. Gemfibrozil carries a feature fenofibrate lacks: it raises statin concentrations sharply, and the label prohibits combining it with simvastatin.

Sources

ICD-10: E78.1 · ICD-11: 5C80.1

Dyslipidemia

Third line

For mixed dyslipidemia, where low comes together with elevated and triglycerides, the label permits gemfibrozil to reduce coronary heart disease risk. That entry rests on the Helsinki Heart Study (N Engl J Med 1987): over five years, middle-aged men without coronary disease had 34 percent fewer coronary events. The label sets strict conditions: only in people without established coronary disease, and only after weight loss, diet, exercise and other drugs have failed. The picture has shifted over the decades. Statins became first line for this lipid profile, and the 2019 guidelines leave fibrates the role of an add-on for residual hypertriglyceridemia. Combination with simvastatin is prohibited and rosuvastatin is capped at 10 mg daily when given together: gemfibrozil blocks the OATP1B1 transporter, statin concentrations rise and rhabdomyolysis risk rises with them.

Sources

ICD-10: E78 · ICD-11: 5C80

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Dyslipidemia, primary CV prevention

Not recommended

Fibrates are marketed as a way to «clean the arteries» and as an add-on to statins for anyone with high cholesterol. There is no evidence base for that use in preventing heart attacks and strokes. The ACCORD-Lipid trial (N Engl J Med 2010) added a fibrate to simvastatin in 5518 patients with type 2 diabetes: over five years the rate of myocardial infarction, stroke and cardiovascular death did not change. The FIELD trial in 9795 patients (Lancet 2005) produced the same result on its primary endpoint. The 2019 guidelines build primary prevention on statins, not fibrates. Adding gemfibrozil to a statin is more dangerous than adding other fibrates: it raises statin concentrations through CYP2C8 and OATP1B1, and the label explicitly prohibits the simvastatin combination because of rhabdomyolysis. If gemfibrozil was offered «for prevention» or to «clean the arteries» in ordinary dyslipidemia, consider seeking a second opinion.

Sources

ICD-10: E78.5 · ICD-11: 5C80

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

Fibrate, an agonist of the nuclear PPAR-alpha receptor. Receptor activation drives lipolysis: lipoprotein lipase activity rises, the liver secretes less VLDL and plasma triglycerides fall. The liver simultaneously increases synthesis of apolipoproteins A-I and A-II, raising cholesterol. The effect on is weak and unpredictable, and in some patients LDL rises. Absorption is complete, peak plasma levels occur within 1 to 2 hours and the elimination half-life runs 1.3 to 1.5 hours. Glucuronidation carries the main elimination route: about 70 percent of the dose leaves in urine, almost entirely as the glucuronide conjugate, with under 2 percent excreted unchanged. The gemfibrozil glucuronide blocks CYP2C8 and the OATP1B1 transporter, which is why the classifies gemfibrozil as a strong CYP2C8 inhibitor.

Safety

Contraindications

Hepatic dysfunction, including primary biliary cholangitis
Severe renal dysfunction
Gallbladder disease, including gallstones
Hypersensitivity to gemfibrozil
Concomitant simvastatin
Concomitant repaglinide
Concomitant dasabuvir
Concomitant selexipag

Serious adverse effects

Rhabdomyolysis, particularly with concomitant statins
Cholelithiasis
Severe hypoglycemia when combined with repaglinide
Cholestatic jaundice and raised transaminases
Anemia, leukopenia, thrombocytopenia
Acute appendicitis: 1.2 percent versus 0.6 percent on placebo in the Helsinki Heart Study
Atrial fibrillation: 0.7 percent versus 0.1 percent on placebo in the Helsinki Heart Study

Common adverse effects

Dyspepsia
Abdominal pain
Diarrhea
Nausea and vomiting
Fatigue
Vertigo
Eczema and rash

Pregnancy: can you take Gemfibrozil?

AEMPS summary of product characteristics (section 4.6): there are no adequate data on gemfibrozil in pregnant women, and animal studies are insufficient to draw clear conclusions on pregnancy and fetal development. The risk to humans is unknown. Gemfibrozil is used during pregnancy only if clearly necessary.

Breastfeeding: can you take Gemfibrozil?

Whether gemfibrozil passes into breast milk has not been studied. The label offers a choice of two options: stop breastfeeding or stop the drug, weighing how much the mother needs it.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Drug–drug interactions

6 pairs found. Sorted from critical to minor.

CriticalRepaglinideMeglitinide – short-acting oral insulin secretagogue

Mechanism

Repaglinide is metabolised by CYP2C8 and taken up by the liver through OATP1B1. Gemfibrozil blocks both routes at once and repaglinide clearance falls. In healthy volunteers, gemfibrozil 600 mg twice daily for 3 days raised repaglinide AUC 8.1-fold and the plasma concentration 7 hours post-dose 28.6-fold.

Symptoms

Severe hypoglycemia: cold sweat, tremor, confusion, seizures, loss of consciousness. The episode arrives later than usual and lasts longer, because repaglinide is cleared many times more slowly. Nocturnal hypoglycemia carries the greatest danger: the person does not wake at the first signs.

Management

The label prohibits this combination, and no dose-reduction workaround exists. If both drugs are already prescribed, repaglinide is switched to an agent with a different metabolic route rather than dose-reduced. During the switch, blood glucose is self-monitored frequently for the first days: CYP2C8 inhibition by the gemfibrozil glucuronide is irreversible and resolves as the enzyme is replaced, not within hours.

Sources

Pair details →Repaglinide →

CriticalSimvastatinHMG-CoA reductase inhibitors (statins)

Mechanism

Simvastatin enters the liver through the OATP1B1 transporter, which gemfibrozil blocks. Statin concentrations in muscle rise, and the fibrate's own myotoxic effect adds to that. The label states it plainly: in patients with an unsatisfactory lipid response to either drug alone, the benefit of combined therapy does not outweigh the risks of severe myopathy, rhabdomyolysis and acute renal failure.

Symptoms

Muscle pain and weakness, most often in the thighs and shoulders, with tenderness on pressure. Then dark tea-coloured urine, a sharp rise in creatine kinase and myoglobinuria. In a proportion of cases acute renal failure develops and ends fatally.

Management

The label prohibits this combination. When both triglyceride lowering and a statin are needed, gemfibrozil is switched to fenofibrate, which does not block OATP1B1 to the same degree and is not prohibited with simvastatin. The 2019 guidelines hold the same line: gemfibrozil is not combined with statins.

Sources

Pair details →Simvastatin →

MajorAtorvastatinHMG-CoA reductase inhibitors (statins)

Mechanism

The label lists atorvastatin among OATP1B1 substrates whose exposure rises with gemfibrozil. The class-wide warning adds to that: combining a fibrate with any HMG-CoA reductase inhibitor raises the risk of skeletal muscle injury.

Symptoms

Muscle pain, weakness and tenderness, dark urine, rising creatine kinase up to rhabdomyolysis with renal failure.

Management

The combination is avoided. When both a statin and triglyceride lowering are needed, fenofibrate replaces gemfibrozil. If joint use still goes ahead, the atorvastatin dose is kept minimal and muscle complaints and creatine kinase are monitored.

Sources

Pair details →Atorvastatin →

MajorPioglitazoneThiazolidinedione (PPAR-γ agonist), oral antidiabetic

Mechanism

Pioglitazone is metabolised mainly by CYP2C8, and gemfibrozil is a strong inhibitor of that enzyme. Pioglitazone exposure rises, and its dose-dependent effects intensify with it: fluid retention and weight gain.

Symptoms

Ankle oedema, rapid weight gain, breathlessness on exertion and when lying down as a sign of decompensating heart failure. Hypoglycemia is possible when pioglitazone is taken with insulin or a sulfonylurea.

Management

The pioglitazone dose is reduced, as the label's general rule for CYP2C8 substrates requires. Weight and oedema are monitored from the first weeks of joint use. The combination is not used in heart failure.

Sources

Pair details →Pioglitazone →

MajorRosuvastatinHMG-CoA reductase inhibitors (statins)

Mechanism

Rosuvastatin is an OATP1B1 substrate and gemfibrozil blocks that transporter. Statin exposure rises, and with it the risk of myopathy and rhabdomyolysis, as with other HMG-CoA reductase inhibitors.

Symptoms

Muscle pain and weakness, muscle tenderness, darkening urine, rising creatine kinase. Rhabdomyolysis brings acute renal failure with it.

Management

Spanish SmPCs for gemfibrozil and rosuvastatin contraindicate gemfibrozil with rosuvastatin 40 mg. At lower doses the combination is not recommended either: the gemfibrozil SmPC requires avoiding gemfibrozil with any statin and allows only low rosuvastatin doses when the benefit outweighs the risk, and the rosuvastatin SmPC does not recommend the combination. If it cannot be avoided, rosuvastatin is started at 5 mg once daily (rosuvastatin SmPC). The US Food and Drug Administration () labels of both drugs cap rosuvastatin at 10 mg once daily. Ask the patient to report unexplained muscle pain, weakness or cramps promptly. Check creatine kinase if they occur, and stop treatment if it is more than 5 times the upper limit of normal (gemfibrozil and rosuvastatin SmPCs). Myopathy and rhabdomyolysis have occurred as early as 3 weeks and as late as several months into combined use, and routine creatine kinase checks do not guarantee that severe muscle and kidney damage will be prevented (gemfibrozil FDA label).

Sources

Pair details →Rosuvastatin →

MajorWarfarinVitamin K antagonist anticoagulants

Mechanism

Gemfibrozil is highly bound to plasma proteins and displaces warfarin from that binding; in vitro studies additionally show inhibition of CYP2C9, the enzyme that metabolises warfarin. Anticoagulant effect intensifies.

Symptoms

Bleeding gums, nosebleeds, bruising after minor knocks, blood in urine and stool. Intracranial haemorrhage carries the greatest danger: sudden headache, limb weakness, speech disturbance.

Management

The label requires reducing the warfarin dose and keeping prothrombin time at the target level. INR is measured frequently until it stabilises, and monitoring repeats with every change in the gemfibrozil dose.

Sources

Pair details →Warfarin →

Label mentions41 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

CriticalRepaglinide
«Uso concomitante de repaglinida, dasabuvir, selexipag (ver sección 4.5) simvastatina o rosuvastatina 40 mg (ver secciones 4.4 y 4.5).»
AEMPS, section 4.3 · Open on CIMA
CriticalRepaglinide
«CONTRAINDICATIONS: Combination therapy of gemfibrozil with repaglinide (see PRECAUTIONS ).»
FDA, section 4 · Open on DailyMed
CriticalSimvastatin
«Uso concomitante de repaglinida, dasabuvir, selexipag (ver sección 4.5) simvastatina o rosuvastatina 40 mg (ver secciones 4.4 y 4.5).»
AEMPS, section 4.3 · Open on CIMA
CriticalSimvastatin
«CONTRAINDICATIONS: Combination therapy of gemfibrozil with simvastatin (see WARNINGS and PRECAUTIONS ).»
FDA, section 4 · Open on DailyMed
Majorestatinasclass named in the label
«Inhibidores de la HMG CoA reductasa: Está contraindicada la administración concomitante de gemfibrozilo y simvastatina, al igual que con rosuvastatina 40 mg (ver secciones 4.3 y 4.4). Debe evitarse…»
AEMPS, section 4.5 · Open on CIMA
MajorGlimepiride
«El perfil de interacciones de gemfibrozilo es complejo. Los estudios in vivo indican que gemfibrozilo y su metabolito gemfibrozilo 1-O-β-glucurónido son potentes inhibidores de CYP2C8 (un enzima…»
AEMPS, section 4.5 · Open on CIMA
MajorPioglitazone
«El perfil de interacciones de gemfibrozilo es complejo. Los estudios in vivo indican que gemfibrozilo y su metabolito gemfibrozilo 1-O-β-glucurónido son potentes inhibidores de CYP2C8 (un enzima…»
AEMPS, section 4.5 · Open on CIMA
MajorRosuvastatin
«Uso concomitante de repaglinida, dasabuvir, selexipag (ver sección 4.5) simvastatina o rosuvastatina 40 mg (ver secciones 4.4 y 4.5).»
AEMPS, section 4.3 · Open on CIMA
MajorWarfarin
«El perfil de interacciones de gemfibrozilo es complejo. Los estudios in vivo indican que gemfibrozilo y su metabolito gemfibrozilo 1-O-β-glucurónido son potentes inhibidores de CYP2C8 (un enzima…»
AEMPS, section 4.5 · Open on CIMA
Moderateanticoagulantesclass named in the label
«Anticoagulantes concomitantes: Gemfibrozilo puede potenciar los efectos de los anticoagulantes antagonistas de la vitamina K tipo cumarina tales como warfarina, acenocumarol o femprocumon. La…»
AEMPS, section 4.4 · Open on CIMA
ModerateColchicine
«Colchicina: El riesgo de miopatía y rabdomiólisis puede incrementarse con la administración concomitante de colchicina y gemfibrozilo. Dicho riesgo puede aumentar en el caso de pacientes de edad…»
AEMPS, section 4.5 · Open on CIMA
ModerateLoperamide
«El perfil de interacciones de gemfibrozilo es complejo. Los estudios in vivo indican que gemfibrozilo y su metabolito gemfibrozilo 1-O-β-glucurónido son potentes inhibidores de CYP2C8 (un enzima…»
AEMPS, section 4.5 · Open on CIMA
ModerateMontelukast
«El perfil de interacciones de gemfibrozilo es complejo. Los estudios in vivo indican que gemfibrozilo y su metabolito gemfibrozilo 1-O-β-glucurónido son potentes inhibidores de CYP2C8 (un enzima…»
AEMPS, section 4.5 · Open on CIMA
Atorvastatin
«Inhibidores de la HMG CoA reductasa: También se ha comunicado que gemfibrozilo afecta la farmacocinética de simvastatina, lovastatina, pravastatina, rosuvastatina y atorvastatina. Gemfibrozilo…»
AEMPS, section 4.5 · Open on CIMA
Lovastatin
«Inhibidores de la HMG CoA reductasa: También se ha comunicado que gemfibrozilo afecta la farmacocinética de simvastatina, lovastatina, pravastatina, rosuvastatina y atorvastatina. Gemfibrozilo…»
AEMPS, section 4.5 · Open on CIMA
Pravastatin
«Inhibidores de la HMG CoA reductasa: También se ha comunicado que gemfibrozilo afecta la farmacocinética de simvastatina, lovastatina, pravastatina, rosuvastatina y atorvastatina. Gemfibrozilo…»
AEMPS, section 4.5 · Open on CIMA

From other drugs’ labels

CriticalRepaglinide
«Uso concomitante de gemfibrozilo (ver sección 4.5).»
AEMPS, section 4.3 · Open on CIMA
CriticalRepaglinide
«CONTRAINDICATIONS: Concomitant use of gemfibrozil [see Drug Interactions (7) ]»
FDA, section 4 · Open on DailyMed
CriticalSimvastatin
«-Administración concomitante de gemfibrozilo, ciclosporina o danazol (ver secciones 4.4 y 4.5)»
AEMPS, section 4.3 · Open on CIMA
CriticalSimvastatin
«CONTRAINDICATIONS: Concomitant use of cyclosporine, danazol or gemfibrozil [see DRUG INTERACTIONS ( 7.1 )].»
FDA, section 4 · Open on DailyMed
MajorAtorvastatin
«Gemfibrozilo/derivados del ácido fíbrico: El uso de fibratos se ha asociado ocasionalmente con acontecimientos relacionados con el músculo, incluyendo rabdomiólisis. El riesgo estos acontecimientos…»
AEMPS, section 4.5 · Open on CIMA
MajorAtorvastatin
«DRUG INTERACTIONS: Intervention: Concomitant use of cyclosporine or gemfibrozil with atorvastatin calcium is not recommended.»
FDA, section 7 · Open on DailyMed
MajorFluvastatin
«Gemfibrozil: Due to an increased risk of myopathy/rhabdomyolysis when HMG-CoA reductase inhibitors are coadministered with gemfibrozil, concomitant administration of fluvastatin sodium with…»
FDA, section 7 · Open on DailyMed
MajorLovastatin
«Mientras dure el tratamiento: La dosis de lovastatina no debe superar los 20mg al día en pacientes que reciben medicación concomitante con ciclosporina, danazol, gemfibrozilo, o dosis hipolipemiantes…»
AEMPS, section 4.4 · Open on CIMA
MajorPioglitazone
«Strong CYP2C8 Inhibitors: An inhibitor of CYP2C8 (e.g., gemfibrozil) significantly increases the exposure (area under the serum concentration-time curve or AUC) and half-life (t 1/2 ) of…»
FDA, section 7 · Open on DailyMed
MajorPitavastatin
«DRUG INTERACTIONS: Intervention: Avoid concomitant use of gemfibrozil with pitavastatin tablets.»
FDA, section 7 · Open on DailyMed
MajorPravastatin
«Fibratos: El uso de fibratos solos se asocia ocasionalmente con la aparición de miopatía. Se ha notificado un aumento del riesgo de reacciones adversas musculares, incluyendo rabdomiolisis, cuando…»
AEMPS, section 4.5 · Open on CIMA
MajorPravastatin
«DRUG INTERACTIONS: Intervention: Avoid concomitant use of gemfibrozil with pravastatin sodium.»
FDA, section 7 · Open on DailyMed
MajorRosuvastatin
«De acuerdo con los resultados de los estudios de interacción específica no se espera ninguna interacción farmacocinética significativa con el fenofibrato, sin embargo, sí podría darse una interacción…»
AEMPS, section 4.5 · Open on CIMA
ModerateColchicine
«Table 4. Other Potentially Significant Drug Interactions Concomitant Drug Class or Food Noted or Anticipated Outcome Clinical Comment HMG-Co A Reductase Inhibitors: atorvastatin, fluvastatin…»
FDA, section 7 · Open on DailyMed
ModerateFluvastatin
«Fibratos y niacina: La administración concomitante de fluvastatina con bezafibrato, gemfibrozilo, ciprofibrato o niacina (ácido nicotínico) no ejerce un efecto clínicamente relevante sobre la…»
AEMPS, section 4.5 · Open on CIMA
ModerateLoperamide
«Drug Interactions: Concomitant use of loperamide hydrochloride capsules with inhibitors of CYP3A4 (e.g., itraconazole) or CYP2C8 (e.g., gemfibrozil) or inhibitors of P-glycoprotein (e.g., quinidine…»
FDA, section 7 · Open on DailyMed
ModerateMontelukast
«Estudios in vitro han demostrado que montelukast es un sustrato de CYP 2C8, y en menor medida, de 2C9 y 3A4. En un estudio de interacción farmacológica que incluía montelukast y gemfibrozilo (un…»
AEMPS, section 4.5 · Open on CIMA
ModeratePioglitazone
«La administración conjunta de pioglitazona y gemfibrozilo (un inhibidor del citocromo P450 2C8) produjo un incremento de tres veces el área bajo la curva de pioglitazona. Debido a que existe la…»
AEMPS, section 4.5 · Open on CIMA
ModeratePitavastatin
«Gemfibrozilo y otros fibratos: El uso de fibratos solos se asocia ocasionalmente a miopatía. La coadministración de fibratos con estatinas se ha asociado a un aumento de miopatía y rabdomiólisis…»
AEMPS, section 4.5 · Open on CIMA
Colchicine
«El uso concomitante de atorvastatina, simvastatina, pravastatina, fluvastatina, gemfibrozilo, fenofibrato, ácido fenofíbrico o bezafibrato (por ellos mismos asociados a miotoxicidad) puede potenciar…»
AEMPS, section 4.5 · Open on CIMA
Empagliflozin
«Un estudio de interacción con gemfibrozilo, un inhibidor in vitro de los transportadores OAT3 y OATP1B1/1B3, mostró que la C max de empagliflozina aumentaba en un 15 % y el AUC aumentaba en un 59 %…»
AEMPS, section 4.5 · Open on CIMA
Ezetimibe
«Fibratos: La administración concomitante con fenofibrato o gemfibrozilo aumenta la concentración total de ezetimiba (aproximadamente 1,5 y 1,7 veces respectivamente).»
AEMPS, section 4.5 · Open on CIMA
Loperamide
«La administración concomitante de hidrocloruro de loperamida (dosis única de 4 mg) e itraconazol, un inhibidor de la CYP3A4 y la glucoproteína P, causó un aumento que triplicó o cuadruplicó las…»
AEMPS, section 4.5 · Open on CIMA
Montelukast
«DRUG INTERACTIONS: No dose adjustment is needed when montelukast sodium is co-administered with theophylline, prednisone, prednisolone, oral contraceptives, fexofenadine, digoxin, warfarin…»
FDA, section 7 · Open on DailyMed

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Frequently asked

What is Gemfibrozil used for?

Gemfibrozil is evaluated for the following indications with varying evidence strength: Severe hypertriglyceridaemia (evidence tier B), Dyslipidemia (evidence tier C), Dyslipidemia, primary CV prevention (evidence tier D). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Gemfibrozil?

Common side effects of Gemfibrozil (≥ 1 in 100): Dyspepsia, Abdominal pain, Diarrhea, Nausea and vomiting, Fatigue, Vertigo. See the Safety section for uncommon and serious reactions.

Is Gemfibrozil safe during pregnancy?

Is Gemfibrozil compatible with breastfeeding?

Whether gemfibrozil passes into breast milk has not been studied. The label offers a choice of two options: stop breastfeeding or stop the drug, weighing how much the mother needs it.

Who should not take Gemfibrozil?

Gemfibrozil is contraindicated in: Hepatic dysfunction, including primary biliary cholangitis; Severe renal dysfunction; Gallbladder disease, including gallstones; Hypersensitivity to gemfibrozil; Concomitant simvastatin. Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMALabel dated 05/09/2025
FDA / DailyMedLabel dated 07/08/2026

Other drugs in this group

Krill oil, Lovastatin, Omega-3 triglycerides (EPA and DHA), Pitavastatin, Rosuvastatin, Simvastatin + Ezetimibe, Cod liver oil, Pravastatin