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).

(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. 

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.

It is recognized that some Type IV patients with triglycerides under 1000 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 LOPID 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.

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 likely to outweigh the risks.

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.

LOPID is also not indicated for the treatment of patients with low HDL-cholesterol as their only lipid abnormality.

If a significant serum lipid response is not obtained, LOPID should be discontinued.

Rarely, severe anemia, leukopenia, thrombocytopenia, and bone marrow hypoplasia have been reported. Therefore, periodic blood counts are recommended during the first 12 months of LOPID administration.

Abnormal liver function tests have been observed occasionally during LOPID administration, including elevations of AST, ALT, LDH, bilirubin, and alkaline phosphatase.

There have been reports of worsening renal insufficiency upon the addition of LOPID therapy in individuals with baseline plasma creatinine >2.0 mg/dL. In such patients, the use of alternative therapy should be considered against the risks and benefits of a lower dose of LOPID.

Nervous system and special senses adverse reactions were more common in the LOPID group. These included hypesthesia, paresthesias, and taste perversion.

LOPID is contraindicated in patients with:

• Hepatic or severe renal dysfunction, including primary biliary cirrhosis
• Preexisting gallbladder disease
• Combination therapy of gemfibrozil with simvastatin 
• Combination therapy of gemfibrozil with repaglinide
• Combination therapy of gemfibrozil with dasabuvir
• Combination therapy of gemfibrozil with selexipag

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.

Myopathy, including rhabdomyolysis, has been reported with chronic administration of colchicine at therapeutic doses. Concomitant use of LOPID may potentiate the development of myopathy. Patients with renal dysfunction and elderly patients are at increased risk. Caution should be exercised when prescribing LOPID with colchicine, especially in elderly patients or patients with renal dysfunction.

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.

Caution should be exercised when warfarin is given in conjunction with LOPID. The dosage of warfarin 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.

Concomitant therapy with enzalutamide increases enzalutamide exposure and may increase the risk of seizures. If co-administration is considered necessary, the dose of enzalutamide should be reduced.

Gemfibrozil is a strong inhibitor of CYP2C8 and may increase exposure of drugs mainly metabolized by CYP2C8 (e.g., dabrafenib, enzalutamide, loperamide, montelukast, paclitaxel, pioglitazone, rosiglitazone). Therefore, dosing reduction of drugs that are mainly metabolized by CYP2C8 enzyme may be required when gemfibrozil is used concomitantly.

Gemfibrozil is an inhibitor of OATP1B1 transporter and may increase exposure of drugs that are substrates of OATP1B1 (e.g., atrasentan, atorvastatin, bosentan, ezetimibe, fluvastatin, glyburide, SN-38 [active metabolite of irinotecan], rosuvastatin, pitavastatin, pravastatin, rifampin, valsartan, olmesartan). Therefore, dosing reductions of drugs that are substrates of OATP1B1 may be required when gemfibrozil is used concomitantly.

Gemfibrozil is an inhibitor of CYP1A2, CYP2C8, CYP2C9, CYP2C19, OATP1B1, and UDP glucuronosyltransferase (UGT) 1A1 and 1A3.

Gemfibrozil AUC was reduced by 30% when gemfibrozil was given (600 mg) simultaneously with resin-granule drugs such as colestipol (5 g). Administration of the drugs two hours or more apart is recommended because gemfibrozil exposure was not significantly affected when it was administered two hours apart from colestipol.

There are no adequate and well-controlled studies in pregnant women. Animal studies: adverse effects including stillborns, skeletal variations and decreased weight.

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for tumorigenicity shown for LOPID in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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• Patients under the age of 18. GoToSource

• Type I hyperlipoproteinemia, with elevations of chylomicrons and plasma triglycerides, but normal levels of very low density lipoprotein. GoToSource

• Tobacco addiction. GoToSource

• Diabetes type 2. GoToSource

• Predementia alzheimer’s disease. GoToSource

• Promote remyelination in the CNS of patients with demyelinating disorders. GoToSource

• Atopic dermatitis, allergic contact dermatitis and hyperproliferative skin diseases including skin malignancies. GoToSource

Myopathy (disorder of skeletal muscles). GoToSource

Myositis (inflammation of muscles). GoToSource

Rhabdomyolysis and kidney failure. GoToSource

Increased risk of gallstone formation. GoToSource 

Hepatitis (liver inflammation). GoToSource

Exacerbation of psoriasis. GoToSource

Erythema multiforme (inflammatory skin eruption). GoToSource

Inhibition of taste cells. GoToSource

Venous thrombosis. GoToSource

Sexual dysfunction. GoToSource

Eosinophilic gastroenteritis (inflammatory disease). GoToSource

Cholestatic jaundice (bile excreted by the liver is reduced or blocked and retained in the bloodstream). GoToSource

Pancreatitis (inflammation of pancreas). GoToSource

Peripheral neuropathy (damage to nerves in the peripheral nervous system). GoToSource

Anemia (low number of red blood cells) and leukopenia (low white blood cell count). GoToSource

Rash, vertigo, atrial fibrillation (irregular heartbeat), eczema, abdominal pain, constipation, angioedema (swelling in deep layers of skin), hypokalemia (low blood potassium level), eosinophilia (high level of eosinophils, a type of white blood cell) and xerostomia (dry mouth). GoToSource

Gout (form of inflammatory arthritis). GoToSource

Lawsuits filed for myositis and rhabdomyolysis.