Brand name: Lopid
Drug class: Fibric Acid Derivatives
VA class: CV350
Chemical name: 5-(2,5-Dimethylphenoxy)-2,2-dimethylpentanoic acid
Molecular formula: C₁₅H₂₂O₃
CAS number: 25812-30-0

Medically reviewed by Drugs.com on Jul 16, 2024. Written by ASHP.

Introduction

Antilipemic agent; fibric acid derivative.

Uses for Gemfibrozil

Prevention of Cardiovascular Events

Adjunct to dietary therapy to reduce the risk of developing CHD in patients with type IIb hyperlipoproteinemia without clinical evidence of CHD (primary prevention) who have an inadequate response to dietary management, weight loss, exercise, and drugs known to reduce LDL-cholesterol and increase HDL-cholesterol (e.g., bile acid sequestrants, niacin) and who have low HDL-cholesterol concentrations in addition to elevated LDL-cholesterol and triglycerides.

Potential benefit unlikely to outweigh potential risks in patients with type IIa hyperlipoproteinemia and elevations of LDL-cholesterol only (because of toxicity, including malignancy, gallbladder disease, abdominal pain leading to appendectomy and other abdominal surgeries, and increased incidence of noncardiovascular and all-cause mortality, associated with the chemically and pharmacologically similar drug clofibrate [no longer commercially available in US]).

Manufacturer states that gemfibrozil is not indicated for use in the management of patients with low HDL-cholesterol as their only lipid abnormality (isolated low HDL-cholesterol).

Reduction of recurrent coronary events^{† [off-label]}, including death from coronary causes, MI, and stroke in men with clinical evidence of CHD who have low HDL-cholesterol and moderately elevated LDL-cholesterol concentrations.

AHA/ACC cholesterol management guideline states that lifestyle modification is the foundation of cardiovascular risk reduction. If pharmacologic therapy is needed, statins are first-line drugs of choice because of their demonstrated benefits in reducing risk of atherosclerotic cardiovascular disease (ASCVD). Nonstatin drugs may be considered as adjunctive therapy in certain high-risk patients, but other drugs (e.g., ezetimibe) are generally recommended. Although fibrates have mild LDL-lowering effects, randomized controlled studies do not support their use as add-on therapy to statins.

If fibrate therapy is necessary in a statin-treated patient, AHA/ACC states that it is safer to use fenofibrate than gemfibrozil because of lower risk of severe myopathy.

Dyslipidemias

Adjunct to dietary therapy in the management of severe hypertriglyceridemia in patients at risk of developing pancreatitis (typically those with serum triglyceride concentrations >2000 mg/dL and elevated concentrations of VLDL-cholesterol and fasting chylomicrons) who do not respond adequately to dietary management.

Also may be used in patients with triglyceride concentrations of 1000–2000 mg/dL who have a history of pancreatitis or of recurrent abdominal pain typical of pancreatitis; however, efficacy in patients with type IV hyperlipoproteinemia and triglyceride concentrations >1000 mg/dL who exhibit type V patterns subsequent to dietary or alcoholic indiscretion has not been adequately studied.

Manufacturer states that gemfibrozil is not indicated for use in patients with type I hyperlipoproteinemia who have elevated triglyceride and chylomicron concentrations but normal VLDL-cholesterol concentrations.

Effective in a very limited number of patients with type III hyperlipoproteinemia^{† [off-label]} to decrease elevated triglyceride and cholesterol concentrations associated with this disorder.

Gemfibrozil Dosage and Administration

General

• Patients should be placed on a standard lipid-lowering diet before initiation of gemfibrozil therapy and should remain on this diet during treatment with the drug.

Administration

Oral Administration

Administer orally twice daily, 30 minutes before the morning and evening meals.

Dosage

Adults

Prevention of Cardiovascular Events

Oral

600 mg twice daily.

Monitor lipoprotein concentrations periodically. Discontinue therapy in patients who fail to achieve an adequate response after 3 months of therapy.

Dyslipidemias

Oral

600 mg twice daily.

Monitor lipoprotein concentrations periodically. Discontinue therapy in patients who fail to achieve an adequate response after 3 months of therapy.

Cautions for Gemfibrozil

Contraindications

• Hepatic impairment, including primary biliary cirrhosis; severe renal impairment; or preexisting gallbladder disease.

• Known hypersensitivity to gemfibrozil or any ingredient in the formulation.

Warnings/Precautions

Warnings

Cholelithiasis

May increase cholesterol excretion in bile, resulting in cholelithiasis. Cholecystitis and cholelithiasis reported. Discontinue therapy if gallbladder studies indicate the presence of gallstones.

Musculoskeletal Effects

Use may be associated with myositis. Myalgia, myopathy, myasthenia, painful extremities, arthralgia, synovitis, and rhabdomyolysis reported. Myopathy, rhabdomyolysis, and other complications also reported in patients receiving gemfibrozil concomitantly with certain other antilipemic agents.

Monitor creatine kinase (CK, creatine phosphokinase, CPK) concentrations in patients reporting adverse musculoskeletal effects. Discontinue therapy if myositis is suspected or diagnosed.

Effect on Morbidity and Mortality

Effect on cardiovascular mortality not established. Because gemfibrozil is chemically, pharmacologically, and clinically similar to other fibric acid derivatives, some adverse effects of clofibrate (no longer commercially available in the US) such as increased incidence of cholelithiasis, cholecystitis requiring surgery, postcholecystectomy complications, malignancy, pancreatitis, appendectomy, gallbladder disease, and increased overall mortality may also apply to gemfibrozil, and the usual precautions associated with fibrate therapy should be observed.

Cataracts

Possible subcapsular bilateral and unilateral cataracts.

Sensitivity Reactions

Hypersensitivity Reactions

Angioedema, laryngeal edema, urticaria, rash, dermatitis, and pruritus reported.

Major Toxicities

Hematologic Effects

Mild decreases in hemoglobin, hematocrit, and leukocyte counts reported; these counts usually normalize during long-term therapy. Severe anemia, leukopenia, thrombocytopenia, and bone marrow hypoplasia have occurred rarely; eosinophilia also reported.

Monitor blood cell counts periodically during the first 12 months of therapy.

General Precautions

Hepatic Effects

Possible elevations in serum concentrations of aminotransferase (i.e., AST, ALT), LDH, bilirubin, and alkaline phosphatase. Serum aminotransferase concentrations usually return slowly to pretreatment values following discontinuance of gemfibrozil. Cholestatic jaundice reported.

Perform liver function tests periodically. Discontinue therapy if abnormalities persist.

Carcinogenicity

Carcinogenicity (e.g., hepatic tumors, Leydig cell tumors) demonstrated in animals.

Specific Populations

Pregnancy

Category C.

Lactation

Not known if gemfibrozil is distributed into milk. Discontinue nursing or the drug.

Pediatric Use

Safety and efficacy not established.

Renal Impairment

Possible exacerbation of renal insufficiency in patients with baseline S_cr >2 mg/dL. Consider use of alternative antilipemic therapy against the risks and benefits of a lower dose of gemfibrozil.

Common Adverse Effects

GI disturbances (e.g., dyspepsia, abdominal pain, diarrhea, nausea, vomiting, constipation, acute appendicitis, gallbladder surgery), adverse CNS effects (headache, hypesthesia, paresthesias, dizziness, somnolence, peripheral neuritis, depression), fatigue, eczema, vertigo, taste perversion, blurred vision, decreased libido, impotence.

Drug Interactions

Specific Drugs

Gemfibrozil Pharmacokinetics

Absorption

Bioavailability

Rapidly and completely absorbed from the GI tract.

Peak plasma concentrations occur within 1–2 hours. Plasma concentrations do not appear to correlate with therapeutic response.

Food

Rate and extent of absorption increased when administered 30 minutes before meals.

Distribution

Extent

Highest tissue concentrations observed in the liver and kidneys in animals.

Gemfibrozil crosses the placenta; not known if it is distributed into milk.

Plasma Protein Binding

About 95%.

Elimination

Metabolism

Appears to be metabolized in the liver to 4 major metabolites produced via 3 metabolic pathways. A phenol derivative (metabolite I) is pharmacologically active.

Elimination Route

Excreted in urine (70%) in the form of metabolites and in feces (approximately 6%).

Half-life

1.3–1.5 hours.

Stability

Storage

Oral

Tablets

20–25°C. Protect from light and humidity.

Actions and Spectrum

• Decreases serum concentrations of triglycerides, VLDL-cholesterol, and, to a lesser extent, LDL-cholesterol. Increases HDL-cholesterol. Causes a variable reduction in serum total cholesterol, because the decrease in serum cholesterol is a net result of a decrease in VLDL-cholesterol, an increase in HDL-cholesterol, and an increase or decrease in LDL-cholesterol.

• Generally increases LDL-cholesterol in patients with type IV or V hyperlipoproteinemia and decreases LDL-cholesterol in type IIa or IIb disorder.

• Inhibits lipolysis of fat in adipose tissue and decreases hepatic uptake of plasma free fatty acids (i.e., free fatty acid turnover is decreased), thereby reducing hepatic triglyceride production (triglyceride turnover rate is decreased). Also inhibits production and increases clearance of VLDL carrier apolipoprotein B (VLDL-apo B), leading to a decrease in VLDL production, enhanced clearance of VLDL, and, subsequently, a decrease in serum triglyceride concentrations.

Advice to Patients

• Importance of patients informing clinicians of any unexplained muscle pain, tenderness, or weakness.

• Importance of adhering to nondrug therapies and measures, including dietary management, weight control, physical activity, and management of potentially contributory disease (e.g., diabetes mellitus).

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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