Adult: Standard micronised formulation: Initially, 67 mg tid or 200 mg once daily. May reduce to 67 mg bid, or increase to 67 mg 4 times daily, or 267 mg once daily according to response. Non-micronised formulation: Initially, 200-300 mg daily given in divided doses, then may be adjusted to 200-400 mg daily according to response. Improved bioavailability formulation: 40-160 mg once daily.
Oral Mixed hyperlipidaemia
Adult: In patients at high CV risk in addition to a statin, or when a statin is contraindicated or not tolerated: Standard micronised formulation: Initially, 67 mg tid or 200 mg once daily. May reduce to 67 mg bid or increase to 67 mg 4 times daily or 267 mg once daily according to response. Non-micronised formulation: Initially, 200-300 mg daily given in divided doses, then may be adjusted to 200-400 mg daily according to response. Improved bioavailability formulation: 40-160 mg once daily.
GFR 30-59 mL/min/1.73 m2: Micronised formulation: 67 mg once daily. GFR <30 mL/min/1.73 m2: Contraindicated.
Should be taken with food.
Active liver disease including primary biliary cirrhosis, unexplained persistent liver function abnormality, severe renal impairment (GFR <30 mL/min/1.73 m2), pre-existing gallbladder disease, pancreatitis (with the exception of acute pancreatitis due to severe hypertriglyceridaemia, known photoallergy or phototoxic reaction during treatment with fibrates or ketoprofen). Lactation.
Patients with pre-disposing factors for myopathy and/or rhabdomyolysis (diabetes mellitus, personal or familial history of hereditary muscular disorders, hypoalbuminaemia, hypothyroidism, high alcohol intake, concomitant use with HMG-CoA reductase inhibitors), risk factors for venous thromboembolism. Mild to moderate renal impairment. Elderly. Pregnancy.
Significant: Cholelithiasis, agranulocytosis, thrombocytopenia, hypersensitivity, myopathy, rhabdomyolysis, pancreatitis, venous thromboembolism, elevated level of serum transaminase. Blood and lymphatic system disorders: Decreased haemoglobin and leukocytes. Gastrointestinal disorders: Nausea, vomiting, abdominal pain, diarrhoea, flatulence. Investigations: Increased serum creatinine, urea. Musculoskeletal and connective tissue disorders: Diffuse myalgia, myopathy, muscular cramps and weakness. Nervous system disorders: Headache, dizziness. Respiratory, thoracic and mediastinal disorders: Nasopharyngitis, sinusitis, rhinitis. Skin and subcutaneous tissue disorders: Rash, pruritus. urticaria, alopecia, photosensitivity.
Monitor blood counts, lipid profile, LFT during therapy and periodically thereafter.
May increase risk of ciclosporin-induced nephrotoxicity. May increase risk of bleeding with oral anticoagulants (e.g. warfarin). Increased risk of myopathy and rhabdomyolysis with colchicine, HMG-CoA reductase inhibitors, and other fibrates. May enhance adverse effects of ezetimibe. May decrease absorption with bile acid sequestrants (except colesevelam).
Increased rate of absorption with food.
Description: Fenofibrate, a fibric acid derivative, reduces total plasma triglycerides by the activation of peroxisome proliferator-activated receptor-α (PPAR-α) and lipoprotein lipase, thereby leading to a reduced production of apoprotein CIII, and an increased synthesis of apoproteins AI and AII, and fatty acid transport protein. Thus, resulting to an increased VLDL catabolism, fatty acid oxidation, and elimination of atherogenic triglyceride-rich particles; as a result of a decrease in VLDL and LDL and an increase in HDL levels. Pharmacokinetics: Absorption: Readily absorbed from the gastrointestinal tract. Increased absorption with food except when given as choline salt. Bioavailability: Approx 81% (fenofibric acid). Time to peak plasma concentration: 2-8 hours. Distribution: Widely distributed to most tissues. Plasma protein binding: Approx 99% mainly to plasma albumin (fenofibric acid). Metabolism: Rapidly metabolised in the tissue and plasma via esterases to its active metabolite, fenofibric acid, then undergoes hepatic or renal inactivation via glucuronidation. Excretion: Mainly via urine (approx 60% as metabolite); faeces (25%). Elimination half-life: Approx 20 hours (fenofibric acid).