Gemfibrozil
Gemfibrozil is an oral **antihyperlipidemic** agent belonging to the fibrate class. > **Clinical Pearl:** While primarily used in human medicine, it is utilized off-label in veterinary medicine for severe hypertriglyceridemia (often >500 mg/dL) in dogs and cats, particularly when dietary management (ultra-low-fat diets) fails. Miniature Schnauzers are a classic breed prone to primary hyperlipidemia that might require this therapy. Key features include: - Used as an **adjunctive therapy** alongside strict dietary fat restriction. - May reduce influenza-related mortality (noted in murine models) and is being investigated as an adjunctive treatment for severe influenza. - Clinical experience in veterinary medicine is highly limited, and efficacy/safety profiles are not fully established.
Mechanism: Gemfibrozil acts primarily as an agonist for the **Peroxisome Proliferator-Activated Receptor-alpha (PPAR-α)**. - **PPAR-α activation** → alters transcription of genes involved in lipid metabolism. - Increases **lipoprotein lipase (LPL)** activity → enhances clearance of triglyceride-rich lipoproteins. - Inhibits lipolysis in adipose tissue → reduces hepatic uptake of plasma free fatty acids → decreases hepatic production of triglycerides. - Inhibits the synthesis of **apolipoprotein B** (the primary carrier protein for VLDL) → reduces VLDL production and the incorporation of long-chain fatty acids into triglycerides.
Dosing by species
- Hypertriglyceridemia (not controlled with diet alone) · 7.5-10 mg/kg · PO · q12h
- Hypertriglyceridemia (not controlled with diet alone) · 10 mg/kg · PO · q12h
- Hypertriglyceridemia (not controlled with diet alone) · 150 mg-300 mg (total dose) · PO · q12h
- Hypertriglyceridemia (not controlled with diet alone) · 200 mg (total dose) · PO · once daily
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Severe hepatic dysfunction
- Severe renal dysfunction
- Known hypersensitivity to gemfibrozil
Adverse effects
- Abdominal pain
- Vomiting
- Diarrhea
- Abnormal liver function tests
- Dyspepsia (human)
- CNS effects: headache, somnolence, dizziness (human)
- Myositis (human)
- Bone marrow depression (rare, human)
Drug interactions
- Thiazide diuretics · May possibly increase triglyceride concentrations
- Beta-blockers · May possibly increase triglyceride concentrations
- Estrogens · May possibly increase triglyceride concentrations
- Ursodiol · May reduce effectiveness of gemfibrozil
- Warfarin · Gemfibrozil may potentiate anticoagulant effects
Monitoring
- Plasma triglycerides (realistic goal for therapy is 400 mg/dL or less)
- Baseline and periodic CBC
- Baseline and periodic liver function tests
- Adverse clinical effects (GI upset, behavior changes)
- Client adherence to prescribed diet and dosing schedule
Overdose
Limited veterinary information is available. The reported LD50 (oral) in rats is 1414 mg/kg. - **Treatment:** Consider gut-emptying protocols for recent large oral ingestions and provide supportive care as required. - **Monitoring:** Monitor for dehydration and electrolyte imbalance if vomiting and/or diarrhea is severe or persists. Monitor liver function tests.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.