Gemfibrozil

FDA Drug Information • Also known as: Gemfibrozil, Lopid

Brand Names: Gemfibrozil, Lopid
Drug Class: Peroxisome Proliferator Receptor alpha Agonist [EPC]
Route: ORAL
Dosage Form: TABLET, FILM COATED
Product Type: HUMAN PRESCRIPTION DRUG

Description

DESCRIPTION Gemfibrozil, USP is a lipid regulating agent. It is available as tablets for oral administration. Each tablet contains 600 mg gemfibrozil. Each tablet also contains the following inactive ingredients: colloidal silicon dioxide, NF; croscarmellose sodium, NF; calcium stearate, NF; microcrystalline cellulose, NF; methylcellulose, USP and opadry white. The chemical name is 5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid, with the following structural formula: The empirical formula is C 15 H 22 O 3 and the molecular weight is 250.35; the solubility in water and acid is 0.0019% and in dilute base it is greater than 1%. The melting point is 58° to 61°C. Gemfibrozil is a white solid which is stable under ordinary conditions. image

What Is Gemfibrozil Used For?

INDICATIONS AND USAGE Gemfibrozil Tablets are indicated as adjunctive therapy to diet for: 1. Treatment of adult patients with very high elevations of serum triglyceride levels (Types IV and V hyperlipidemia) who present a risk of pancreatitis and who do not respond adequately to a determined dietary effort to control them. Patients who present such risk typically have serum triglycerides over 2,000 mg/dL and have elevations of VLDL-cholesterol as well as fasting chylomicrons (Type V hyperlipidemia). Subjects who consistently have total serum or plasma triglycerides below 1,000 mg/dL are unlikely to present a risk of pancreatitis. Gemfibrozil therapy may be considered for those subjects with triglyceride elevations between 1,000 and 2,000 mg/dL who have a history of pancreatitis or of recurrent abdominal pain typical of pancreatitis. It is recognized that some Type IV patients with triglycerides under 1,000 mg/dL may, through dietary or alcoholic indiscretion, convert to a Type V pattern with massive triglyceride elevations accompanying fasting chylomicronemia, but the influence of gemfibrozil therapy on the risk of pancreatitis in such situations has not been adequately studied. Drug therapy is not indicated for patients with Type I hyperlipoproteinemia, who have elevations of chylomicrons and plasma triglycerides, but who have normal levels of very low density lipoprotein (VLDL). Inspection of plasma refrigerated for 14 hours is helpful in distinguishing Types I, IV, and V hyperlipoproteinemia. 2. 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, known to reduce LDL- and raise HDL-cholesterol) and who have the following triad of lipid abnormalities: low HDL-cholesterol levels in addition to elevated LDL-cholesterol and elevated triglycerides (see WARNINGS , PRECAUTIONS , and CLINICAL PHARMACOLOGY ). The National Cholesterol Education Program has defined a serum HDL-cholesterol value that is consistently below 35 mg/dL as constituting an independent risk factor for coronary heart disease. Patients with significantly elevated triglycerides should be closely observed when treated with gemfibrozil. In some patients with high triglyceride levels, treatment with gemfibrozil is associated with a significant increase in LDL-cholesterol. BECAUSE OF POTENTIAL TOXICITY SUCH AS MALIGNANCY, GALLBLADDER DISEASE, ABDOMINAL PAIN LEADING TO APPENDECTOMY AND OTHER ABDOMINAL SURGERIES, AN INCREASED INCIDENCE IN NON-CORONARY MORTALITY, AND THE 44% RELATIVE INCREASE DURING THE TRIAL PERIOD IN AGE-ADJUSTED ALL-CAUSE MORTALITY SEEN WITH THE CHEMICALLY AND PHARMACOLOGICALLY RELATED DRUG, CLOFIBRATE, THE POTENTIAL BENEFIT OF GEMFIBROZIL IN TREATING TYPE IIA PATIENTS WITH ELEVATIONS OF LDL-CHOLESTEROL ONLY IS NOT...

Dosage and Administration

DOSAGE AND ADMINISTRATION The recommended dose for adults is 1,200 mg administered in two divided doses 30 minutes before the morning and evening meals (see CLINICAL PHARMACOLOGY ).

Side Effects (Adverse Reactions)

ADVERSE REACTIONS In the double-blind controlled phase of the primary prevention component of the Helsinki Heart Study, 2,046 patients received gemfibrozil for up to five years. In that study, the following adverse reactions were statistically more frequent in subjects in the gemfibrozil group: GEMFIBROZIL ( N = 2,046 ) PLACEBO ( N = 2,035 ) Frequency in percent of subjects Gastrointestinal reactions 34.2 23.8 Dyspepsia 19.6 11.9 Abdominal pain 9.8 5.6 Acute appendicitis 1.2 0.6 (histologically confirmed in most cases where data were available) Atrial fibrillation 0.7 0.1 Adverse events reported by more than 1% of subjects, but without a significant difference between groups: Diarrhea 7.2 6.5 Fatigue 3.8 3.5 Nausea/Vomiting 2.5 2.1 Eczema 1.9 1.2 Rash 1.7 1.3 Vertigo 1.5 1.3 Constipation 1.4 1.3 Headache 1.2 1.1 Gallbladder surgery was performed in 0.9% of gemfibrozil and 0.5% of placebo subjects in the primary prevention component, a 64% excess, which is not statistically different from the excess of gallbladder surgery observed in the clofibrate group compared to the placebo group of the WHO study. Gallbladder surgery was also performed more frequently in the gemfibrozil group compared to the placebo group (1.9% versus 0.3%, p=0.07) in the secondary prevention component. A statistically significant increase in appendectomy in the gemfibrozil group was seen also in the secondary prevention component (6 on gemfibrozil versus 0 on placebo, p=0.014). Nervous system and special senses adverse reactions were more common in the gemfibrozil group. These included hypesthesia, paresthesias, and taste perversion. Other adverse reactions that were more common among gemfibrozil treatment group subjects but where a causal relationship was not established include cataracts, peripheral vascular disease, and intracerebral hemorrhage. From other studies it seems probable that gemfibrozil is causally related to the occurrence of MUSCULOSKELETAL SYMPTOMS (see WARNINGS ), and to ABNORMAL LIVER FUNCTION TESTS and HEMATOLOGIC CHANGES (see PRECAUTIONS ). Reports of viral and bacterial infections (common cold, cough, urinary tract infections) were more common in gemfibrozil treated patients in other controlled clinical trials of 805 patients. Additional adverse reactions that have been reported for gemfibrozil are listed below by system. These are categorized according to whether a causal relationship to treatment with gemfibrozil is probable or not established: CAUSAL RELATIONSHIP PROBABLE CAUSAL RELATIONSHIP NOT ESTABLISHED General: weight loss Cardiac: extrasystoles Gastrointestinal: cholestatic jaundice pancreatitis hepatoma colitis Central Nervous System: dizziness somnolence paresthesiaperipheral neuritisdecreased libidodepression headache confusion convulsions syncope Eye: blurred vision retinal edema Genitourinary: impotence decreased male fertility renal dysfunction Musculoskeletal: myopathy myasthenia myalgia painful extremities arthralgia synovitis rhabdomyolysis (see WARNINGS and Drug Interactions under PRECAUTIONS ) Clinical Laboratory: increased creatine phosphokinase increased bilirubin increased liver transaminases (AST, ALT) increased alkaline phosphatase positive antinuclear antibody Hematopoietic: anemia leukopenia bone marrow hypoplasia eosinophilia thrombocytopenia Immunologic: angicedema laryngeal edema urticaria anaphylaxis Lupus-like syndrome vasculitis Integumentary: exfoliative dermatitis rash dermatitis pruritus alopecia photosensitivity Additional adverse reactions that have been reported include cholecystitis and cholelithiasis ( see WARNINGS ).

Warnings and Precautions

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, 1,000 subjects with previous myocardial infarction were treated for five years with clofibrate. There was no difference in mortality between the clofibrate-treated subjects and 3,000 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), 5,000 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 gemfibrozil 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 gemfibrozil 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 gemfibrozil 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 gemfibrozil 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 gemfibrozil 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 gemfibrozil at the 8.5 year follow-up (65 gemfibrozil 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 gemfibrozil and 9 in...

Contraindications

CONTRAINDICATIONS Hepatic or severe renal dysfunction, including primary biliary cirrhosis. Preexisting gallbladder disease (see WARNINGS ). Hypersensitivity to gemfibrozil. Combination therapy of gemfibrozil with simvastatin (see WARNINGS and PRECAUTIONS ). Combination therapy of gemfibrozil with repaglinide (see PRECAUTIONS ). Combination therapy of gemfibrozil with dasabuvir (see PRECAUTIONS ). Combination therapy of gemfibrozil with selexipag (see PRECAUTIONS ).

Overdosage

OVERDOSAGE There have been reported cases of overdosage with gemfibrozil. In one case, a 7-year-old child recovered after ingesting up to 9 grams of gemfibrozil. Symptoms reported with overdosage were abdominal cramps, abnormal liver function tests, diarrhea, increased CPK, joint and muscle pain, nausea and vomiting. Symptomatic supportive measures should be taken, should an overdose occur.

How Supplied

HOW SUPPLIED Gemfibrozil Tablets, USP Supplied as White film-coated, capsule shaped, biconvex tablets de-bossed with I on the left side of bisect and G on the right side of bisect on one side and 225 on the other. NDC 51655-143-52: Bottles of 30 NDC 51655-143-25: Bottles of 60 NDC 51655-143-26: Bottles of 90 NDC 51655-143-83: Bottles of 180 Store at controlled room temperature 20° - 25°C (68° - 77°F) [see USP]. Protect from light and humidity. Preserve in tight containers. Manufactured by: InvaGen Pharmaceuticals, Inc. (a subsidiary of Cipla Ltd.) Hauppauge, NY 11788 Manufactured for: Cipla USA, Inc. 10 Independence Boulevard, Suite 300 Warren, NJ 07059 Revised:01/2021 To report SUSPECTED ADVERSE REACTIONS, contact Cipla Ltd. at 1-866-604-3268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.