LIPIDIL

What it is

Fenofibrate is a fibric acid derivative. Lipidil is available as 48 mg and 145 mg tablets containing fenofibrate nanoparticles.

Approved indications —

Hypercholesterolaemia. — Types II, III, IV and V dyslipidaemia. — Dyslipidaemia associated with type 2 diabetes. — Reduction in the progression of diabetic retinopathy in patients with Type 2 diabetes and existing diabetic retinopathy.

Dosing overview

The usual dose of fenofibrate is 1 × 145 mg tablet. The 48 mg tablets are only recommended when a decreased dosage is required. Patients should never be administered any combination of the 48 mg tablet and the 145 mg tablet of fenofibrate. In moderate renal dysfunction (eGFR between 30 and 60 mL/min/1.73m²), start with one Fenofibrate 48 mg tablet once daily, with the dose able to be increased to two tablets daily after evaluation of renal function and lipid levels. Tablets may be given at any time of the day, with or without food, but should be taken at the same time each day.

Key safety warnings

Elevations in serum creatinine have been reported in patients on fenofibrate, though these elevations tend to return to baseline following discontinuation. Creatinine should be measured during the first 3 months after initiation of treatment and periodically thereafter, with monitoring particularly considered for elderly patients and those with diabetes. Increased liver function test abnormalities have been observed during fenofibrate therapy, and clinically significant liver injury has been reported rarely, including hepatocellular, chronic active and cholestatic hepatitis after exposures of weeks to several years. Baseline and ongoing monitoring of liver function should be performed every 3 months during the first 12 months of treatment and thereafter periodically, and therapy should be discontinued if AST and ALT levels increase to more than 3 times the upper limit of the normal range. There have been reports of elevations of creatine phosphokinase, myositis and myopathy associated with fibrates, and rhabdomyolysis has been reported rarely. Patients complaining of muscle pain, tenderness or weakness should have prompt medical evaluation for myositis, and if myositis is suspected or if CPK rises to ≥5 times the upper limit of normal, fenofibrate therapy should be withdrawn. Patients with pre-disposing factors including age above 70 years, personal or familial history of hereditary muscular disorders, renal impairment, hypoalbuminaemia, hypothyroidism and high alcohol intake may be at increased risk. In the FIELD trial, pulmonary embolus and deep vein thrombosis were observed at higher rates in the fenofibrate group than the placebo group, with 67 DVT events (1.4%) in the fenofibrate group compared to 48 events (1%) in placebo, and 53 PE events (1.1%) in fenofibrate compared to 32 events (0.7%) in placebo.

Contraindications

Fenofibrate is contraindicated in children; patients with liver dysfunction, including primary biliary cirrhosis and unexplained persistent liver function abnormality; patients with severe renal dysfunction (eGFR <30 mL/min/1.73m²); patients with existing gallbladder disease; co-administration with another fibrate; patients hypersensitive to fenofibrate and in cases of known photoallergy or phototoxic reactions during treatment with fibrates or ketoprofen; and chronic or acute pancreatitis with the exception of acute pancreatitis due to severe hypertriglyceridaemia.

Regulatory history

Lipidil fenofibrate tablets (145 mg and 48 mg) were first listed on the Australian Register of Therapeutic Goods on 2 June 2006. The TGA approved an extension of indications on 8 October 2013 to include reduction in the progression of diabetic retinopathy in patients with Type 2 diabetes and existing diabetic retinopathy, based on clinical data demonstrating benefit in this specific patient population.