LOPID

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LOPID (LOPID).

How it works

Lopid (gemfibrozil) is a fibric acid derivative that activates peroxisome proliferator-activated receptor alpha (PPARα), leading to increased lipoprotein lipase activity, reduced hepatic triglyceride secretion, and enhanced clearance of very-low-density lipoproteins (VLDL). It also increases high-density lipoprotein (HDL) cholesterol.

What the body does with it

Metabolism	Gemfibrozil is metabolized in the liver via oxidation of the methyl group to form hydroxymethyl and carboxyl metabolites, primarily by CYP3A4 (minor). It undergoes glucuronidation by UGT2B7.
Excretion	Primarily hepatic metabolism and renal excretion; approximately 70% of a dose is excreted in urine as unchanged drug and glucuronide conjugates, with ~30% excreted in feces via biliary elimination.
Half-life	Terminal elimination half-life is approximately 1.5 hours in patients with normal renal function; clinical context: short half-life requires twice-daily dosing to maintain therapeutic levels; may be prolonged in renal impairment.
Protein binding	97-99% bound to plasma proteins, primarily albumin.
Volume of Distribution	0.6-1.0 L/kg; indicates distribution primarily into extracellular fluid and tissues, with limited CNS penetration.
Bioavailability	Oral bioavailability is 85-95%; slightly reduced with food but not clinically significant.
Onset of Action	Oral administration: clinical effect on triglyceride reduction begins within 2-5 days; maximal lipid changes observed after 4-8 weeks.
Duration of Action	Duration of effect persists for 24 hours after a single dose; clinical note: steady-state concentrations achieved after 3-7 days of twice-daily dosing.

Classification & Brands

Action Class	PPAR alpha agonists (Fibrate)
Brand Substitutes	Gempar 300mg Capsule, Lipigem 300 Capsule, Lipizyl 300mg Capsule, Triglyd 300mg Capsule, GEMPAR 300 MG CAPSULE, Triglyd 600mg Tablet

Dosing & administration

600 mg orally twice daily, 30 minutes before morning and evening meals; maximum dose 1200 mg/day.

Dosage form	TABLET
Renal impairment	Contraindicated in severe renal impairment (GFR < 30 mL/min). For GFR 30-80 mL/min, reduce dose to 600 mg once daily. No adjustment for GFR >80 mL/min.
Liver impairment	Contraindicated in Child-Pugh class B or C. For Child-Pugh class A, use with caution at 600 mg once daily; monitor liver function.
Pediatric use	Not approved for pediatric use. Limited data: 10-20 mg/kg/day divided twice daily, max 1200 mg/day, only if benefits outweigh risks.
Geriatric use	Start at 600 mg once daily; titrate slowly due to increased risk of renal impairment and biliary disease. Monitor renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LOPID (LOPID).

Breastfeeding	Excreted in rat milk; unknown in human milk. M/P ratio not established. Caution advised due to potential for serious adverse reactions in nursing infants. Consider alternative therapy or discontinue nursing.
Teratogenic Risk	Pregnancy Category C. No adequate studies in pregnant women. In animal studies, fetal skeletal variations and delayed ossification were observed at doses 0.6 to 5 times the human exposure. Use only if potential benefit justifies risk. First trimester: limited data, theoretical risk. Second/third trimesters: no specific malformation pattern, but may affect fetal lipid metabolism.

Warnings & precautions

■ FDA Black Box Warning

Hepatic tumorigenicity: Gemfibrozil increased the incidence of benign liver tumors (hepatic adenomas) in male rats at doses 10 times the human dose. No evidence of hepatic tumors in humans has been reported.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Severe hepatic or renal dysfunction (including primary biliary cirrhosis)","Preexisting gallbladder disease","Concurrent use with simvastatin (due to increased risk of myopathy/rhabdomyolysis)","Hypersensitivity to gemfibrozil"]

Clinical Precautions

Precautions

["Cholelithiasis: Gemfibrozil increases cholesterol excretion into bile, leading to a risk of gallstones.","Myopathy/rhabdomyolysis: Risk is increased when used with statins (especially simvastatin) and in renal impairment.","Hypoglycemia: May occur in diabetic patients.","Hematologic abnormalities: Monitor hemoglobin and white blood cell counts initially and periodically.","Hepatic effects: Monitor liver function tests; discontinue if significant elevations occur."]

Clinical Tips & Counseling

Drug interactions

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LOPID

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LOPID (LOPID).

How it works

What the body does with it

Metabolism	Gemfibrozil is metabolized in the liver via oxidation of the methyl group to form hydroxymethyl and carboxyl metabolites, primarily by CYP3A4 (minor). It undergoes glucuronidation by UGT2B7.
Excretion	Primarily hepatic metabolism and renal excretion; approximately 70% of a dose is excreted in urine as unchanged drug and glucuronide conjugates, with ~30% excreted in feces via biliary elimination.
Half-life	Terminal elimination half-life is approximately 1.5 hours in patients with normal renal function; clinical context: short half-life requires twice-daily dosing to maintain therapeutic levels; may be prolonged in renal impairment.
Protein binding	97-99% bound to plasma proteins, primarily albumin.
Volume of Distribution	0.6-1.0 L/kg; indicates distribution primarily into extracellular fluid and tissues, with limited CNS penetration.
Bioavailability	Oral bioavailability is 85-95%; slightly reduced with food but not clinically significant.
Onset of Action	Oral administration: clinical effect on triglyceride reduction begins within 2-5 days; maximal lipid changes observed after 4-8 weeks.
Duration of Action	Duration of effect persists for 24 hours after a single dose; clinical note: steady-state concentrations achieved after 3-7 days of twice-daily dosing.

Classification & Brands

Action Class	PPAR alpha agonists (Fibrate)
Brand Substitutes	Gempar 300mg Capsule, Lipigem 300 Capsule, Lipizyl 300mg Capsule, Triglyd 300mg Capsule, GEMPAR 300 MG CAPSULE, Triglyd 600mg Tablet

Dosing & administration

600 mg orally twice daily, 30 minutes before morning and evening meals; maximum dose 1200 mg/day.

Dosage form	TABLET
Renal impairment	Contraindicated in severe renal impairment (GFR < 30 mL/min). For GFR 30-80 mL/min, reduce dose to 600 mg once daily. No adjustment for GFR >80 mL/min.
Liver impairment	Contraindicated in Child-Pugh class B or C. For Child-Pugh class A, use with caution at 600 mg once daily; monitor liver function.
Pediatric use	Not approved for pediatric use. Limited data: 10-20 mg/kg/day divided twice daily, max 1200 mg/day, only if benefits outweigh risks.
Geriatric use	Start at 600 mg once daily; titrate slowly due to increased risk of renal impairment and biliary disease. Monitor renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LOPID (LOPID).

Breastfeeding	Excreted in rat milk; unknown in human milk. M/P ratio not established. Caution advised due to potential for serious adverse reactions in nursing infants. Consider alternative therapy or discontinue nursing.
Teratogenic Risk	Pregnancy Category C. No adequate studies in pregnant women. In animal studies, fetal skeletal variations and delayed ossification were observed at doses 0.6 to 5 times the human exposure. Use only if potential benefit justifies risk. First trimester: limited data, theoretical risk. Second/third trimesters: no specific malformation pattern, but may affect fetal lipid metabolism.