No

Antilipemic Agent (Fibric Acid)

Treatment of hypertriglyceridemia in types IV and V hyperlipidemia for patients who are at greater risk for pancreatitis and who have not responded to dietary intervention

C

Hypersensitivity to gemfibrozil or any component; significant hepatic or renal dysfunction; primary biliary cirrhosis; pre-existing gallbladder disease

Possible increased risk of malignancy and cholelithiasis. No evidence of cardiovascular mortality benefit. Anemia and leukopenia have been reported. Elevations in serum transaminases can be seen. Discontinue if lipid response not seen. Be careful in patient selection; this is not a first- or second-line choice. Other agents may be more suitable. Adjustments in warfarin therapy may be required with concurrent use. Use caution when combining gemfibrozil with HMG-CoA reductase inhibitors (may lead to myopathy, rhabdomyolysis). Renal function deterioration has been seen when used in patients with a serum creatinine >2.0 mg/dL. Safety and efficacy in pediatric patients have not been established.

>10% Gastrointestinal: dyspepsia (19.6%)

1% to 10%:

Central nervous system: Fatigue (3.8%), vertigo (1.5%), headache (1.2%)

Dermatologic: Eczema (1.95), rash (1.7%)

Gastrointestinal: Abdominal pain (9.8%), diarrhea (7.2%), nausea/vomiting (2.5%), constipation (1.4%)

<1% or case reports with probable causation (Limited to important or life-threatening symptoms): Hypoesthesia, paresthesia, taste perversion, cataracts, intracranial hemorrhage, peripheral vascular disease, cholestatic jaundice, dizziness, somnolence, peripheral neuritis, decreased libido, depression, headache, blurred vision, impotence, myopathy, myasthenia, myalgia, arthralgia, synovitis, rhabdomyolysis, increased creatinine phosphokinase, increased bilirubin, increased transaminases, increased alkaline phosphatase, anemia, leukopenia, bone marrow hypoplasia, eosinophilia, angioedema, laryngeal edema, urticaria, exfoliative dermatitis, rash, dermatitis, pruritus, vasculitis, Raynaud's phenomenon, hypokalemia, nephrotoxicity, dermatomyositis/polymyositis

Reports where causal relationship has not been established: Weight loss, extrasystoles, pancreatitis, hepatoma, colitis, confusion, seizures, syncope, retinal edema, decreased fertility (male), renal dysfunction, positive ANA, drug-induced lupus-like syndrome, thrombocytopenia, anaphylaxis, vasculitis, alopecia, photosensitivity.

Symptoms of overdose include abdominal pain, diarrhea, nausea, vomiting

Following GI decontamination, treatment is supportive

CYP3A3/4 enzyme substrate

Chlorpropamide: May increase risk of hypoglycemia.

Cyclosporine's blood levels may be reduced; monitor cyclosporine levels and renal function.

Furosemide: Increased blood levels of both in hypoalbuminemia.

Glyburide (and possibly other sulfonylureas): The hypoglycemic effects may be increased.

HMG-CoA reductase inhibitors (atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, simvastatin) may increase the risk of myopathy and rhabdomyolysis. The manufacturer warns against the concurrent use of lovastatin. However, combination therapy with statins has been used in some patients with resistant hyperlipidemias (with great caution).

Rifampin: Decreased gemfibrozil blood levels.

Warfarin: Hypoprothrombinemic response increased; monitor INRs closely when gemfibrozil is initiated or discontinued.

The exact mechanism of action of gemfibrozil is unknown, however, several theories exist regarding the VLDL effect; it can inhibit lipolysis and decrease subsequent hepatic fatty acid uptake as well as inhibit hepatic secretion of VLDL; together these actions decrease serum VLDL levels; increases HDL cholesterol; the mechanism behind HDL elevation is currently unknown

Onset of effect: May require several days

Absorption: Well absorbed

Protein binding: 99%

Metabolism: In the liver by oxidation to two inactive metabolites

Half-life: 1.4 hours

Time to peak serum concentration: Within 1-2 hours

Elimination: A portion of the drug undergoes enterohepatic recycling; excreted in urine, primarily as unchanged drug (70%)

Adults: Oral: 1200 mg/day in 2 divided doses, 30 minutes before breakfast and dinner

Before initiation of therapy, patients should be placed on a standard cholesterol-lowering diet for 3-6 months and the diet should be continued during drug therapy.

Serum cholesterol, LFTs

Selection of lipid-lowering therapy should be based on the patient's lipid profile, concomitant disease states, and the cost of therapy. Gemfibrozil increases HDL, decreases total cholesterol and triglycerides. A recent study (HIT), showed that gemfibrozil therapy resulted in a significant reduction in the risk of major cardiovascular events in patients with low HDL cholesterol. These findings suggest that the rate of coronary events is reduced by raising HDL cholesterol levels and lowering triglyceride levels. The treatment of low HDL in the general population, is not established.

May cause sedation; may rarely cause depression

None reported

No information available to require special precautions

No effects or complications reported

You must return to provider for assessment of drug effectiveness. Should be taken 30 minutes before meals. Take with milk or meals if GI upset occurs. You may experience loss of appetite and flatulence (frequent small meals may help), muscle aches (mild, temporary pain relievers may be required), dizziness, faintness, or blurred vision (use caution when driving or engaging in tasks that require alertness until response to drug is known). Report severe stomach pain, nausea, vomiting, chills, sore throat, headache, and any vision changes. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Monitor serum cholesterol; abnormal elevation of AST, ALT, LDH, bilirubin and alkaline phosphatase have occurred; if no appreciable triglyceride or cholesterol, lowering effect occurs after 3 months, the drug should be discontinued

Capsule: 300 mg

Tablet, film coated: 600 mg

Ahmad S, "Gemfibrozil Interaction With Warfarin Sodium," Chest, 1990, 98(4):1041-2.

Todd PA and Ward A, "Gemfibrozil: A Review of Its Pharmacodynamic and Pharmacokinetic Properties and Therapeutic Use in Dyslipidaemia," Drugs, 1988, 36(3):314-39.