Lopid®(gemfibrozil)

INDICATIONS AND USAGE LOPID (gemfibrozil tablets, USP) is 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 2000 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 1000 mg/dL are unlikely to present a risk of pancreatitis. LOPID therapy may be considered for those subjects with triglyceride elevations between 1000 and 2000 mg/dL who have a history of pancreatitis or of recurrent abdominal pain typical of pancreatitis. 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. Drug therapy is not indicated for patients with Type I hyperlipoproteinemia. 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 LIKELY TO OUTWEIGH THE RISKS. LOPID IS ALSO NOT INDICATED FOR THE TREATMENT OF PATIENTS WITH LOW HDL-CHOLESTEROL AS THEIR ONLY LIPID ABNORMALITY.

CONTRAINDICATIONS 1. Hepatic or severe renal dysfunction, including primary biliary cirrhosis. 2. Preexisting gallbladder disease. 3. Hypersensitivity to gemfibrozil. 4. Combination therapy of gemfibrozil with simvastatin. 5. Combination therapy of gemfibrozil with repaglinide. 6. Combination therapy of gemfibrozil with dasabuvir. 7. Combination therapy of gemfibrozil with selexipag.

Major warnings include: chemical, pharmacological, and clinical similarities between gemfibrozil and clofibrate suggest adverse findings with clofibrate may also apply. The WHO study showed a statistically significant 44% higher age-adjusted total mortality in the clofibrate group during the trial period. A gallstone prevalence substudy showed a trend toward greater prevalence of gallstones during treatment (7.5% vs 4.9% for placebo). 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 only be administered to patients described in the indications section. Concomitant anticoagulant therapy requires caution with warfarin dosage reduction. Concomitant therapy with HMG-CoA reductase inhibitors is associated with increased risk of rhabdomyolysis. LOPID is a strong inhibitor of CYP2C8 and may increase exposure of substrates of OATP1B1 and OATP1B3 transporters.

In the Helsinki Heart Study (2046 patients on LOPID for up to 5 years), statistically more frequent adverse reactions in the LOPID group included: gastrointestinal reactions (34.2% vs 23.8%), dyspepsia (19.6% vs 11.9%), abdominal pain (9.8% vs 5.6%), acute appendicitis (1.2% vs 0.6%), and atrial fibrillation (0.7% vs 0.1%). Common reactions without significant group difference: diarrhea (7.2%), fatigue (3.8%), nausea/vomiting (2.5%), eczema (1.9%), rash (1.7%), vertigo (1.5%), constipation (1.4%), headache (1.2%). Gallbladder surgery performed in 0.9% of LOPID vs 0.5% of placebo subjects. Nervous system and special senses reactions (hypesthesia, paresthesias, taste perversion) were more common. Additional reported reactions include cholestatic jaundice, pancreatitis, rhabdomyolysis, exfoliative dermatitis, angioedema, and lupus-like syndrome.

LOPID (gemfibrozil tablets, USP) is a lipid regulating agent. Each tablet contains 600 mg gemfibrozil. Inactive ingredients include calcium stearate, candelilla wax, microcrystalline cellulose, hydroxypropyl cellulose, hypromellose, methylparaben, Opaspray white, polyethylene glycol, polysorbate 80, propylparaben, colloidal silicon dioxide, pregelatinized starch. The chemical name is 5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid. The empirical formula is C15H22O3, molecular weight 250.35. Gemfibrozil is a white solid, stable under ordinary conditions, with a melting point of 58°–61°C.