gemfibrozil (Rx)

>10%

Dyspepsia (20%)

1-10%

Abdominal pain (10%)

Atrial fibrillation (1%)

Diarrhea (7%)

Fatigue (4%)

N/V (3%)

Eczema (2%)

Rash (2%)

Vertigo (2%)

Constipation (1%)

Headache (1%)

<1%

Myalgia

Rhabdomyolysis (especially with admin with statin)

Acute appendicitis

Cholelithiasis

Angioedema

Hypokalemia

Eosinophilia

Myopathy

Synovitis

Taste disturbance

Xerostomia

Flatulence

Rash

Contraindications

Hypersensitivity

Severe liver/renal disease

Primary biliary cirrhosis

Preexisting gallbladder disease

Coadministration with repaglinide, simvastatin, selexipag, or dasabuvir

Cautions

If response inadequate after 3 months, discontinue gemfibrozil

Risk for myopathy/rhabdomyolysis increases with renal impairment

Risk for myopathy/rhabdomyolysis increases with concurrent HMG-CoA reductase inhibitors use (eg, atorvastatin, pravastatin)

If coadministered with anticoagulants, reduce anticoagulant dose and monitor prothrombin time until stabilized

Coadministration with bile acid resin binding agents decreases gemfibrozil AUC by 30%

May increase risk of malignancy

Rule out secondary causes of hyperlipidemia prior to initiating therapy; discontinue if lipid response not seen

Use with caution in patients taking warfarin; adjustments in warfarin may be required

Cases of cholelithiasis reported with gemfibrozil therapy; gemfibrozil may increase cholesterol excretion into bile; if cholelithiasis suspected, perform gallbladder studies; discontinue therapy if gallstones found

Coadministration with repaglinide shown to increase repaglinide plasma concentrations (8-fold increase); prolongs hypoglycemic effect; may result in severe hypoglycemia

Gemfibrozil inhibits CYP2C8 enzyme activity; may increase exposure of CYP2C8 substrates; consider dose reduction of CYP2C8 substrates when administered concomitantly

Gemfibrozil may increase exposure of OATP1B1 drug substrates when administered concomitantly; consider dose reduction of OATP1B1 substrates when administered concomitantly

Myopathy, including rhabdomyolysis, reported with chronic administration of colchicine at therapeutic doses; use caution, especially in the elderly and patients with renal dysfunction

Rarely, severe anemia, leukopenia, thrombocytopenia, and bone marrow hypoplasia reported; periodic blood counts are recommended during first 12 months of therapy

Elevations in serum transaminases seen with use; periodic liver function studies recommended; therapy should be terminated if abnormalities persist

Worsening renal insufficiency upon addition of therapy in individuals with baseline plasma creatinine >2.0 mg/dL reported; in such patients, consider the use of alternative therapy against risks and benefits of a lower dose of metformin

Gemfibrozil may increase enzalutamide levels when administered concomitantly, which may increase risk of seizures; if coadministration necessary, reduce enzalutamide dose

Pregnancy

There are no adequate and well-controlled studies in pregnant women; drug should be used during pregnancy only if potential benefit justifies potential risk to fetus

Drug has shown to produce adverse effects in rats and rabbits at doses between 0.5 and 3 times the human dose (based on surface area); administration to female rats at 2 times human dose (based on surface area) before and throughout gestation caused a dose-related decrease in conception rate, an increase in stillborns, and a slight reduction in pup weight during lactation; there were also dose-related increased skeletal variations; anophthalmia occurred, but rarely

Administration of 0.6 and 2 times the human dose (based on surface area) of LOPID to female rats from gestation day 15 through weaning caused dose-related decreases in birth weight and suppressions of pup growth during lactation

Administration of 1 and 3 times the human dose (based on surface area) to female rabbits during organogenesis caused a dose-related decrease in litter size and, at high dose, an increased incidence of parietal bone variations

Lactation

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

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Inhibits peripheral lipolysis; decreases hepatic uptake of free fatty acids, which may in turn inhibit secretion of VLDL; may increase HDL-cholesterol (mechanism unknown)

Absorption

Peak serum time: 1-2 hr

Distribution

Protein bound: 99%

Metabolism

Enterohepatic circulation

Elimination

Half-life: 1.5 hr

Excretion: Urine (70%); feces (6%)