Generic Name: Gemfibrozil
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

Introduction

Antilipemic agent; fibric acid derivative.2

Uses for Lopid

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.1 67 68 104 105 110 127

Because of potential toxicity, including malignancy, gallbladder disease, abdominal pain leading to appendectomy and other abdominal surgeries, and an increased incidence of noncardiovascular and all-cause mortality associated with the chemically and pharmacologically similar drug, clofibrate (no longer commercially available in the US), the potential benefit of gemfibrozil in treating patients with type IIa hyperlipoproteinemia and elevations of LDL-cholesterol only is unlikely to outweigh the risks of such therapy.1

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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).1

Reduction of recurrent coronary events, 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.137

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.1

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;1 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.1

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.1

Effective in a very limited number of patients with type III hyperlipoproteinemia17 18 37 38 43 45 49 to decrease elevated triglyceride and cholesterol concentrations associated with this disorder.

Lopid 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.1

Administration

Oral Administration

Administer orally twice daily, 30 minutes before the morning and evening meals.1

Dosage

Adults

Prevention of Cardiovascular Events
Oral

600 mg twice daily.1 16 17 18 21 22 24 25 26 27 30 31 91 104 106

Monitor lipoprotein concentrations periodically.1 Discontinue therapy in patients who fail to achieve an adequate response after 3 months of therapy.1

Dyslipidemias
Oral

600 mg twice daily.1 16 17 18 21 22 24 25 26 27 30 31 91 104 106

Monitor lipoprotein concentrations periodically.1 Discontinue therapy in patients who fail to achieve an adequate response after 3 months of therapy.1

Cautions for Lopid

Contraindications

  • Hepatic impairment, including primary biliary cirrhosis; severe renal impairment; or preexisting gallbladder disease.1

  • Known hypersensitivity to gemfibrozil or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Cholelithiasis

May increase cholesterol excretion in bile,1 34 61 resulting in cholelithiasis.1 26 34 Cholecystitis and cholelithiasis reported.1 Discontinue therapy if gallbladder studies indicate the presence of gallstones.1

Musculoskeletal Effects

Use may be associated with myositis.1 Myalgia, myopathy, myasthenia, painful extremities, arthralgia, synovitis, and rhabdomyolysis reported.1 Myopathy, rhabdomyolysis, and other complications also reported in patients receiving gemfibrozil concomitantly with certain other antilipemic agents.1

Monitor creatine kinase (CK, creatine phosphokinase, CPK) concentrations in patients reporting adverse musculoskeletal effects.1 108 116 Discontinue therapy if myositis is suspected or diagnosed.1

Effect on Morbidity and Mortality

Effect on cardiovascular mortality not established.1 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,1 and the usual precautions associated with fibrate therapy should be observed.1

Cataracts

Possible subcapsular bilateral and unilateral cataracts.1

Sensitivity Reactions

Hypersensitivity Reactions

Angioedema, laryngeal edema, urticaria, rash, dermatitis, and pruritus reported.1

Major Toxicities

Hematologic Effects

Mild decreases in hemoglobin,1 2 hematocrit,1 2 38 and leukocyte counts1 2 reported; these counts usually normalize during long-term therapy.1 Severe anemia, leukopenia, thrombocytopenia, and bone marrow hypoplasia have occurred rarely; eosinophilia also reported.1

Monitor blood cell counts periodically during the first 12 months of therapy.1

General Precautions

Hepatic Effects

Possible elevations in serum concentrations of aminotransferase (transaminase) (i.e., AST, ALT),1 2 24 25 47 LDH,1 2 bilirubin,1 and alkaline phosphatase.1 2 15 25 47 Serum aminotransferase concentrations usually return slowly to pretreatment values following discontinuance of gemfibrozil.1 Cholestatic jaundice reported.1

Perform liver function tests periodically.1 Discontinue therapy if abnormalities persist.1

Carcinogenicity

Carcinogenicity (e.g., hepatic, Leydig cell tumors) demonstrated in animals.1

Specific Populations

Pregnancy

Category C.1

Lactation

Not known if gemfibrozil is distributed into milk.1 102 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established.1

Renal Impairment

Possible exacerbation of renal insufficiency in patients with baseline Scr >2 mg/dL.1 Consider use of alternative antilipemic therapy against the risks and benefits of a lower dose of gemfibrozil.1

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.1

Interactions for Lopid

Specific Drugs

Drug

Interaction

Comments

β-Adrenergic blocking agents

Possible increase in serum triglyceride and decreases in HDL-cholesterol concentrations30 74

Anticoagulants, oral (e.g., warfarin)

Potentiation of anticoagulant effects1 102 124

Use with caution.1 Reduce anticoagulant dosage to maintain PT at desired level to prevent bleeding complications; monitor PT frequently until stabilized1

Estrogens

Potential increase in serum triglyceride concentrations73

HMG-CoA reductase inhibitors (Statins)

Increased risk of adverse musculoskeletal effects (e.g., myopathy, rhabdomyolysis)1

Methyldopa

Possible decrease in HDL- and LDL-cholesterol concentrations74

Repaglinide

Increased repaglinide concentrations and half-life, resulting in enhanced and prolonged blood glucose-lowering effects.138 139 Potential for severe hypoglycemia.138

Patients currently receiving gemfibrozil should not initiate therapy with repaglinide, and vice versa.138 139 Monitor blood glucose and reduce repaglinide dosage as required if drugs already used concomitantly.138 Patients receiving gemfibrozil concomitantly with repaglinide should not receive itraconazole.138

Thiazide diuretics

Possible increase in total cholesterol and triglyceride concentrations.74

Lopid Pharmacokinetics

Absorption

Bioavailability

Rapidly and completely absorbed from the GI tract.1 2 7 76

Peak plasma concentrations occur within 1–2 hours.1 2 7 9 Plasma concentrations do not appear to correlate with therapeutic response.29 102

Food

Rate and extent of absorption increased when administered 30 minutes before meals.1

Distribution

Extent

Highest tissue concentrations observed in the liver and kidneys in animals.2

Gemfibrozil crosses the placenta;2 not known if it is distributed into milk.1 102

Plasma Protein Binding

About 95%.2

Elimination

Metabolism

Appears to be metabolized in the liver to 4 major metabolites produced via 3 metabolic pathways.2 7 102 A phenol derivative (metabolite I)2 7 is pharmacologically active.102

Elimination Route

Excreted in urine (70%) in the form of metabolites and in feces (approximately 6%).1

Half-life

1.3–1.5 hours.1 7 9 10

Stability

Storage

Oral

Tablets

20–25°C.1 Protect from light and humidity.1

Actions and Spectrum

Advice to Patients

  • Importance of patients informing clinicians of any unexplained muscle pain, tenderness, or weakness.1

  • 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).1 64 67 70 133 136

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

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

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

Gemfibrozil

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

600 mg*

Gemfibrozil Tablets

Mylan, Sandoz, Teva, Watson

Lopid (with parabens; scored)

Pfizer

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Gemfibrozil 600MG Tablets (CAMBER PHARMACEUTICALS): 60/$22.99 or 90/$29.98

Lopid 600MG Tablets (PFIZER U.S.): 60/$176.29 or 180/$506.33

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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