GEMFIBROZIL
Clinical safety rating: avoid
Contraindicated (not allowed)
Gemfibrozil is a fibric acid derivative that activates peroxisome proliferator-activated receptor alpha (PPARα), leading to increased lipolysis and clearance of triglycerides from plasma, and reduced hepatic VLDL secretion. It also increases HDL cholesterol.
| Metabolism | Gemfibrozil undergoes extensive hepatic metabolism via oxidation and glucuronidation. Major enzyme involved is CYP3A4, though it also inhibits CYP2C8 and CYP2C9. |
| Excretion | Primarily renal (approximately 70% as unchanged drug and glucuronide conjugate) with about 6% fecal elimination. Biliary excretion is minimal. |
| Half-life | Terminal elimination half-life is 1.5 hours. In patients with renal impairment, half-life may be prolonged up to 7-8 hours. |
| Protein binding | Approximately 95-98% bound, primarily to albumin. |
| Volume of Distribution | Apparent Vd is 0.11-0.14 L/kg, indicating limited extravascular distribution (mainly confined to plasma and interstitial fluid). |
| Bioavailability | Oral bioavailability is nearly 100% after administration of the conventional tablet; food may reduce rate but not extent of absorption. |
| Onset of Action | Oral: Onset of lipid-lowering effect is usually within 2-5 days, with maximum effect by 4-12 weeks. |
| Duration of Action | Duration of lipid-lowering effect persists for several weeks after discontinuation due to altered lipoprotein metabolism; clinical effect wanes gradually over 4-6 weeks. |
Oral: 600 mg twice daily, 30 minutes before morning and evening meals.
| Dosage form | TABLET |
| Renal impairment | GFR 30-59 mL/min: 600 mg once daily. GFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class A/B: caution, no specific dose adjustment available. Child-Pugh Class C: contraindicated. |
| Pediatric use | Not recommended in pediatric patients. |
| Geriatric use | No specific dose adjustment; initiate at lower end of dosing range due to age-related renal function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Potentiates the effects of warfarin and increases risk of myopathy with statins Can cause cholelithiasis and myopathy.
| Breastfeeding | Gemfibrozil is excreted into human breast milk in low concentrations; the milk-to-plasma (M/P) ratio is reported as approximately 0.1 to 0.2. Based on limited data, absolute infant dose is estimated to be <1% of maternal weight-adjusted dose. Caution is advised; consider alternatives due to potential for adverse effects in nursing infants (e.g., gastrointestinal upset, effects on lipid metabolism). American Academy of Pediatrics considers gemfibrozil compatible with breastfeeding with caution. |
| Teratogenic Risk | Gemfibrozil is classified as FDA Pregnancy Category C. In animal studies, it has been shown to cause fetal toxicity at doses 0.5 to 3 times the human dose, including increased incidence of skeletal anomalies (e.g., delayed ossification, rib deformities) and reduced fetal weight. First trimester exposure is associated with potential teratogenic effects, though human data are limited. Second and third trimester exposure may lead to fetal growth restriction and possible neonatal complications such as hypoglycemia or hyperbilirubinemia. Use is not recommended during pregnancy, especially in first trimester. |
■ FDA Black Box Warning
There is an increased risk of rhabdomyolysis when gemfibrozil is used in combination with statins, particularly cerivastatin (now withdrawn). Concomitant use with simvastatin is contraindicated.
| Common Effects | Dyspepsia |
| Serious Effects |
["Severe hepatic impairment","Severe renal impairment (creatinine clearance <10 mL/min)","Pre-existing gallbladder disease","Concomitant use with simvastatin or repaglinide","Hypersensitivity to gemfibrozil"]
| Precautions | ["Risk of myopathy/rhabdomyolysis, especially with statins","Cholelithiasis","Hepatic dysfunction","Monitor renal function","May increase glucose levels in diabetics"] |
| Food/Dietary | Take on an empty stomach 30 minutes before meals for optimal absorption. Avoid high-fat meals as they can decrease absorption. Alcohol may exacerbate hypertriglyceridemia and hepatic effects. |
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| Fetal Monitoring | Monitor maternal liver function tests (AST, ALT, alkaline phosphatase) and complete blood count regularly. Assess renal function (serum creatinine, BUN). Perform fetal ultrasound for growth and anatomy if exposure occurs in first trimester. Monitor maternal blood glucose and lipid profile. Watch for signs of myopathy or rhabdomyolysis (muscle pain, weakness, elevated creatine kinase). |
| Fertility Effects | In animal studies, gemfibrozil at high doses caused reduced fertility and increased preimplantation loss. Human data are insufficient; however, based on animal findings, potential for decreased fertility in males and females cannot be excluded. In males, gemfibrozil may affect spermatogenesis (reduced sperm count and motility). Use with caution in patients planning conception. |
| Clinical Pearls | Gemfibrozil is a fibric acid derivative used primarily for hypertriglyceridemia. It increases HDL modestly but has no proven CV mortality benefit. Contraindicated with statins due to increased risk of rhabdomyolysis. Monitor renal function and LFTs. Avoid in severe renal impairment (CrCl <30 mL/min) or gallbladder disease. |
| Patient Advice | Take 30 minutes before morning and evening meals to reduce GI side effects. · Report unexplained muscle pain, tenderness, or weakness immediately, especially if also taking a statin. · Avoid alcohol as it may worsen triglyceride levels and liver effects. · Do not use if you have severe kidney disease or gallstones. · Store at room temperature, protect from light and moisture. |