Gemfibrozil

Gemfibrozil
	Adult Indications & Dosage
	Pediatric Indications & Dosage
	Contraindications
	Warnings & Precautions
	Adverse Reactions
	Drug Interactions
	Use in Specific Populations
	Administration & Monitoring
	Overdosage
	Pharmacology
	Clinical Studies
	How Supplied
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	Patient Counseling Information
	Precautions with Alcohol
	Brand Names
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];

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Overview

Gemfibrozil is a lipid regulating agent that is FDA approved for the {{{indicationType}}} of Types IV and V hyperlipidemia at risk of pancreatitis and who do not respond adequately to a determined dietary effort to control them, and reducing the risk of developing coronary heart disease only in Type IIb patients without history of or symptoms of existing coronary heart disease who have had an inadequate response to weight loss, dietary therapy, exercise, and other pharmacologic agents (such as bile acid sequestrants and nicotinic acid) and who have the following triad of lipid abnormalities: low HDL-cholesterol levels in addition to elevated LDL-cholesterol and elevated triglycerides. Common adverse reactions include dyspepsia, abdominal pain, acute appendicitis, atrial fibrillation, diarrhea, fatigue, eczema, rash, vertigo, constipation, headache.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Types IV and V hyperlipidemia

Dosing Information

1200 mg administered in two divided doses 30 minutes before the morning and evening meals

Condition 2

Dosing Information

(Dosage)

Off-Label Use and Dosage (Adult)

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Gemfibrozil FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Contraindications

Hepatic or severe renal dysfunction, including primary biliary cirrhosis.
Preexisting gallbladder disease.
Hypersensitivity to gemfibrozil.
Combination therapy of gemfibrozil with repaglinide
Combination therapy of gemfibrozil with simvastatin

Warnings

1. Because of chemical, pharmacological, and clinical similarities between gemfibrozil and clofibrate, the adverse findings with clofibrate in two large clinical studies may also apply to gemfibrozil. In the first of those studies, the Coronary Drug Project, 1000 subjects with previous myocardial infarction were treated for five years with clofibrate. There was no difference in mortality between the clofibrate-treated subjects and 3000 placebo-treated subjects, but twice as many clofibrate-treated subjects developed cholelithiasis and cholecystitis requiring surgery. In the other study, conducted by the World Health Organization (WHO), 5000 subjects without known coronary heart disease were treated with clofibrate for five years and followed one year beyond. There was a statistically significant (44%) higher age-adjusted total mortality in the clofibrate-treated group than in a comparable placebo-treated control group during the trial period. The excess mortality was due to a 33% increase in non-cardiovascular causes, including malignancy, post-cholecystectomy complications, and pancreatitis. The higher risk of clofibrate-treated subjects for gallbladder disease was confirmed.

Because of the more limited size of the Helsinki Heart Study, the observed difference in mortality from any cause between the LOPID and placebo groups is not statistically significantly different from the 29% excess mortality reported in the clofibrate group in the separate WHO study at the nine year follow-up (see CLINICAL PHARMACOLOGY). Noncoronary heart disease related mortality showed an excess in the group originally randomized to LOPID primarily due to cancer deaths observed during the open-label extension.

During the five year primary prevention component of the Helsinki Heart Study, mortality from any cause was 44 (2.2%) in the LOPID group and 43 (2.1%) in the placebo group; including the 3.5 year follow-up period since the trial was completed, cumulative mortality from any cause was 101 (4.9%) in the LOPID group and 83 (4.1%) in the group originally randomized to placebo (hazard ratio 1:20 in favor of placebo). Because of the more limited size of the Helsinki Heart Study, the observed difference in mortality from any cause between the LOPID and placebo groups at Year-5 or at Year-8.5 is not statistically significantly different from the 29% excess mortality reported in the clofibrate group in the separate WHO study at the nine year follow-up. Noncoronary heart disease related mortality showed an excess in the group originally randomized to LOPID at the 8.5 year follow-up (65 LOPID versus 45 placebo noncoronary deaths).

The incidence of cancer (excluding basal cell carcinoma) discovered during the trial and in the 3.5 years after the trial was completed was 51 (2.5%) in both originally randomized groups. In addition, there were 16 basal cell carcinomas in the group originally randomized to LOPID and 9 in the group originally randomized to placebo (p=0.22). There were 30 (1.5%) deaths attributed to cancer in the group originally randomized to LOPID and 18 (0.9%) in the group originally randomized to placebo (p=0.11). Adverse outcomes, including coronary events, were higher in gemfibrozil patients in a corresponding study in men with a history of known or suspected coronary heart disease in the secondary prevention component of the Helsinki Heart Study (see CLINICAL PHARMACOLOGY).

A comparative carcinogenicity study was also done in rats comparing three drugs in this class: fenofibrate (10 and 60 mg/kg; 0.3 and 1.6 times the human dose, respectively), clofibrate (400 mg/kg; 1.6 times the human dose), and gemfibrozil (250 mg/kg; 1.7 times the human dose). Pancreatic acinar adenomas were increased in males and females on fenofibrate; hepatocellular carcinoma and pancreatic acinar adenomas were increased in males and hepatic neoplastic nodules in females treated with clofibrate; hepatic neoplastic nodules were increased in males and females treated with clofibrate; hepatic neoplastic nodules were increased in males and females treated with gemfibrozil while testicular interstitial cell (Leydig cell) tumors were increased in males on all three drugs.

2. A gallstone prevalence substudy of 450 Helsinki Heart Study participants showed a trend toward a greater prevalence of gallstones during the study within the LOPID treatment group (7.5% versus 4.9% for the placebo group, a 55% excess for the gemfibrozil group). A trend toward a greater incidence of gallbladder surgery was observed for the LOPID group (17 versus 11 subjects, a 54% excess). This result did not differ statistically from the increased incidence of cholecystectomy observed in the WHO study in the group treated with clofibrate. Both clofibrate and gemfibrozil may increase cholesterol excretion into the bile, leading to cholelithiasis. If cholelithiasis is suspected, gallbladder studies are indicated. LOPID therapy should be discontinued if gallstones are found. Cases of cholelithiasis have been reported with gemfibrozil therapy.

3. Since a reduction of mortality from coronary heart disease has not been demonstrated and because liver and interstitial cell testicular tumors were increased in rats, LOPID should be administered only to those patients described in the INDICATIONS AND USAGE section. If a significant serum lipid response is not obtained, LOPID should be discontinued.

4. Concomitant Anticoagulants – Caution should be exercised when anticoagulants are given in conjunction with LOPID. The dosage of the anticoagulant should be reduced to maintain the prothrombin time at the desired level to prevent bleeding complications. Frequent prothrombin determinations are advisable until it has been definitely determined that the prothrombin level has stabilized.

5. The concomitant administration of LOPID with simvastatin is contraindicated (see CONTRAINDICATIONS and PRECAUTIONS). Concomitant therapy with LOPID and an HMG-CoA reductase inhibitor is associated with an increased risk of skeletal muscle toxicity manifested as rhabdomyolysis, markedly elevated creatine kinase (CPK) levels, and myoglobinuria, leading in a high proportion of cases to acute renal failure and death. IN PATIENTS WHO HAVE HAD AN UNSATISFACTORY LIPID RESPONSE TO EITHER DRUG ALONE, THE BENEFIT OF COMBINED THERAPY WITH LOPID AND an HMG-CoA REDUCTASE INHIBITOR DOES NOT OUTWEIGH THE RISKS OF SEVERE MYOPATHY, rhabdomyolysis, AND ACUTE RENAL FAILURE (seePRECAUTIONS, Drug Interactions). The use of fibrates alone, including LOPID, may occasionally be associated with myositis. Patients receiving LOPID and complaining of muscle pain, tenderness, or weakness should have prompt medical evaluation for myositis, including serum creatine–kinase level determination. If myositis is suspected or diagnosed, LOPID therapy should be withdrawn.

6. Cataracts – Subcapsular bilateral cataracts occurred in 10%, and unilateral in 6.3%, of male rats treated with gemfibrozil at 10 times the human dose.