>10% Gastrointestinal: Dyspepsia (20%)

1% to 10%:

Central nervous system: Fatigue (4%), vertigo (2%), headache (1%)

Dermatologic: Eczema (2%), rash (2%)

Gastrointestinal: Abdominal pain (10%), diarrhea (7%), nausea/vomiting (3%), constipation (1%)

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

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

Bexarotene's serum concentration is significantly increased; avoid concurrent use.

Chlorpropamide: May increase risk of hypoglycemia.

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

CYP1A2 substrates: Gemfibrozil may increase the levels/effects of CYP1A2 substrates. Example substrates include aminophylline, fluvoxamine, mexiletine, mirtazapine, ropinirole, theophylline, and trifluoperazine.

CYP2C8/9 substrates: Gemfibrozil may increase the levels/effects of CYP2C8/9 substrates. Example substrates include amiodarone, fluoxetine, glimepiride, glipizide, nateglinide, phenytoin, pioglitazone, rosiglitazone, sertraline, and warfarin.

CYP2C19 substrates: Gemfibrozil may increase the levels/effects of CYP2C19 substrates. Example substrates include citalopram, diazepam, methsuximide, phenytoin, propranolol, and sertraline.

Furosemide: Increased blood levels of both in hypoalbuminemia.

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

HMG-CoA reductase inhibitors (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin) may increase the risk of myopathy and rhabdomyolysis. The manufacturer warns against the concurrent use of lovastatin (if unavoidable, limit lovastatin to <20 mg/day). Combination therapy with statins has been used in some patients with resistant hyperlipidemias (with great caution).

Repaglinide: Gemfibrozil may increase the serum concentration of repaglinide (prolonged, severe hypoglycemia has been reported). The addition of itraconazole may augment the effects of gemfibrozil on repaglinide. Consider alternative therapy.

Rifampin: Decreased gemfibrozil blood levels.

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

Onset of action: May require several days

Absorption: Well absorbed

Protein binding: 99%

Metabolism: Hepatic via oxidation to two inactive metabolites; undergoes enterohepatic recycling

Half-life elimination: 1.4 hours

Time to peak, serum: 1-2 hours

Excretion: Urine (70% primarily as unchanged drug)

Hemodialysis: Not removed by hemodialysis; supplemental dose is not necessary

A recent study (VA-HIT) showed that gemfibrozil therapy resulted in a significant reduction in the risk of major cardiovascular events in patients with CHD and isolated low HDL-C 40 mg/dL (average: 32 mg/dL) with LDL-C 140 mg/dL (average: 111 mg/dL) and TGs 300 mg/dL (average: 161 mg/dL) (Rubins, 1999). These findings suggest that the rate of coronary events is reduced by raising HDL-cholesterol levels in patients with isolated low HDL-C levels. The treatment of isolated low HDL-C in the general population is usually reserved for patients at high risk for developing CAD with therapy focused on addressing the other risk factors. At present, minimal if any, data are available on how to use medications in patients with low HDL-C and no risk factors.

Bermingham RP, Whitsitt TB, Smart ML, et al, "Rhabdomyolysis in a Patient Receiving the Combination of Cerivastatin and Gemfibrozil," Am J Health-Syst Pharm, 2000, 57:461-4.

Duell PB, Connor WE, and Illingworth DR, "Rhabdomyolysis After Taking Atorvastatin With Gemfibrozil,"Am J Cardiol, 1998, 81:368-9.

"Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III),"JAMA, 2001, 285(19):2486-97.

Frick MH, Heinonen OP, Huttunen JK, et al, "Efficacy of Gemfibrozil in Dyslipidaemic Subjects With Suspected Heart Disease. An Ancillary Study in the Helsinki Heart Study Frame Population,"Ann Med, 1993, 25(1):41-5.

Mahley RW and Bersot TP, "Drug Therapy for Hypercholesterolemia and Dyslipidemia,"Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th ed, Hardman JE and Limbird LE, eds, New York, NY: McGraw-Hill, 2001, 993-5.

Pierce LR, Wysowski DK, and Gross TP, "Myopathy and Rhabdomyolysis Associated With Lovastatin/Gemfibrozil Combination Therapy,"JAMA, 1990, 264(1):71-5.

Rubins HB, Robbins SJ, Collins D, et al, "Gemfibrozil for the Secondary Prevention of Coronary Heart Disease in Men With Low Levels of High-Density Lipoprotein Cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group,"N Engl J Med, 1999, 341(6):410-8.

Tal A, Rajeshawari M, and Isley W, "Rhabdomyolysis Associated With Simvastatin/Gemfibrozil Therapy,"South Med J, 1997, 90(5):546-7.