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Appendix C – Drug Companion Document – Fibric Acids

Gemfibrozil, Fenofibrate and Fenofibrate Micronized

Efficacy

•    Triglycerides are reduced 30%-50%, HDL-cholesterol increases 10%-20%. Total cholesterol is only modestly reduced 5%-20% in patients without elevated triglycerides.  Effect on LDL-cholesterol is variable: fenofibrate may lower LDL-cholesterol more than gemfibrozil but it is less effective than statins (dependent on baseline triglyceride level). 

•    Good for severe hypertrigylceridemia in patients at risk for pancreatitis, for prevention of CHD (not proven for fenofibrate) when patient has an abnormal lipid triad of depressed HDL-cholesterol, elevated LDL-cholesterol and elevated triglycerides. May be particularly useful in diabetics with mixed hyperlipidemia and for patients with dysbetalipoproteinemia.

•    The VA-HIT trial utilizing gemfibrozil showed a 22% reduction in CHD death and non-fatal MI in patients with documented CHD and low HDL-cholesterol as their primary lipid abnormality.
 

Safety

•    Myositis has occurred rarely in patients. Risk of myopathy and possibly rhabdomyolysis appears increased when taken with statins.
 
There have been several studies with small numbers of carefully selected patients that have shown fibrates (including gemfibrozil) can be used safely with statins (incidence of myopathy was approximately 0.12%). There may be a potential difference in risk of myopathy between gemfibrozil and fenofibrate when combined with statins. Gemfibrozil has been shown to increase plasma levels of simvastatin acid, lovastatin and rosuvastatin, while fenofibrate had no effect on plasma levels of rosuvastatin. Simvastatin, lovastatin and rosuvastatin all have labeled dose restrictions when combined with gemfibrozil.

•    Cholelithiasis and cholecystitis can occur (0.3%-1% incidence) due to increased cholesterol excreted in the bile. Fibric acids are contraindicated in patients with pre-existing gallbladder disease.
 
•    Use with caution in patients with a history of liver disease. Fibric acids are contraindicated in patients with hepatic or severe renal impairment, including primary biliary cirrhosis.
 
•    Hematologic adverse reactions are rare.

•    Warfarin's anticoagulant effect may be potentiated; INR should be monitored closely.
 

Dosing

Gemfibrozil

•    Usual dose is 600 mg twice daily. The manufacturer recommends taking this 30 minutes before morning and evening meals, but all
      clinical trials were conducted without regard to meals, and efficacy has never been linked to specific blood levels.  If patients have
      stomach upset, taking it with the meal may diminish this.
 

Fenofibrate 

•    Usual starting dose and maximum dose are 145 mg per day with a meal. In the elderly and in patients with impaired renal function, therapy should be initiated with 48 mg per day, increasing only after reviewing effect on lipids and renal function.
 

Fenofibrate micronized 

•    Usual starting dose and maximum dose are 200 mg per day. In the elderly and in patients with impaired renal function, therapy should be initiated with 67 mg per day, increasing only after reviewing effect on lipids and renal function.
 

Fenofibric acid 

•    Usual starting dose and maximum dose are 135 mg per day.  In the elderly and in patients with impaired renal function, therapy should be  initiated with 45 mg per day, increasing only after reviewing effect on lipids and renal function.
 
•    Please consult manufacturer's product labeling insert, or PDR for full prescribing information (Guay, 1999 [R]; HIT Trial [A]; McKenney, 2001b [R]; National Cholesterol Education Program, 2001 [R]).