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Drug Details

Fenofibrate 267mg Capsules

• Drug Class Description
  Serum Lipid Reducing Agents/Cholesterol and Triglyceride Reducers/Fibrates ATC code: C10A B05
• Generic Name
  fenofibrate
• Presentation
  Capsules, hard Green and caramel, hard gelatin capsules
• Description
  Each capsule contains 267mg fenofibrate
• Indications
  

  Fenofibrate is indicated as an adjunct to diet and other non-pharmacological treatment (e.g. exercise, weight reduction) for the following:

  - Treatment of severe hypertriglyceridaemia with or without low HDL cholesterol.

  - Mixed hyperlipidaemia when a statin is contraindicated or not tolerated.

  Fenofibrate should only be used in patients in whom a full investigation has been performed to define their abnormality. Other risk factors, such as hypertension and smoking, may also require management.

• Adult Dosage
  

  Adults

  The initial recommended dose is one capsule of fenofibrate 200mg taken daily with food. However, in patients with severe dyslipidaemia, an increased dose of 267 mg, is recommended. Fenofibrate should always be taken with food, because it is less well absorbed from an empty stomach. Dietary measures instituted before therapy should be continued.

  Renal impairment

  In patients with renal impairment, the dosage may need to be reduced depending on rate of creatinine clearance.

  Fenofibrate 267mg Capsules is therapeutically equivalent to LIPANTIL^®267 Capsules (micronised fenofibrate) or 400 mg of the standard formulation (non-micronised).

• Child Dosage
  

  This dosage is not recommended in children.

• Elderly Dosage
  

  In elderly patients without renal impairment, the normal adult dose is recommended.

• Contra Indications
  

  Fenofibrate 267mg is contraindicated in children, in patients with severe liver or renal dysfunction, gallbladder disease, biliary cirrhosis and in patients hypersensitive to fenofibrate or any component of this medication, known photoallergy or phototoxic reaction during treatment with fibrates or ketoprofen.

  Use during pregnancy and lactation.

  Chronic or acute pancreatitis with the exception of acute pancreatitis due to severe hypertriglyceridemia

• Special Precautions
  

  Secondary causes of dyslipidaemia, such as uncontrolled type 2 diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemia, obstructive liver disease, pharmacological treatment, alcoholism, should be adequately treated before fenofibrate therapy is initiated.

  Response to therapy should be monitored by determination of serum lipid values (total cholesterol, LDL-C, triglycerides). If an adequate response has not been achieved after several months (e.g. 3 months) complementary or different therapeutic measures should be considered.

  Renal function

  In renal dysfunction the dose of fenofibrate may need to be reduced, depending on the rate of creatinine clearance. Dose reduction should be considered in elderly patients with impaired renal function.

  It is recommended that creatinine is measured during the first three months after initiation of treatment and thereafter periodically. Treatment should be interrupted in case of an increase in creatinine levels> 50% of (upper limit of normal).

  Transaminases

  Moderately elevated levels of serum transaminases may be found in some patients but rarely interfere with treatment. However, it is recommended that serum transaminases should be monitored every three months during the first twelve months of treatment. Treatment should be interrupted in the event of ALAT (SGPT) or ASAT (SGOT) elevations to more than 3 times the upper limit of the normal range or more than one hundred international units.

  Pancreatitis

  Pancreatitis has been reported in patients taking fenofibrate. This occurrence may represent a failure of efficacy in patients with severe hypertriglyceridaemia, a direct drug effect, or a secondary phenomenon mediated through biliary tract stone or sludge formation, resulting in obstruction of the common bile duct.

  Myopathy

  Muscle toxicity, including very rare cases of rhabdomyolysis, has been reported with administration of fibrates and other lipid-lowering agents. The incidence of this disorder increases in cases of hypoalbuminaemia and previous renal insufficiency. Patients with pre-disposing factors for myopathy and/or rhabdomyolysis, including age above 70 years, personal or familial history of hereditary muscular disorders, renal impairment, hypothyroidism and high alcohol intake, may be at an increased risk of developing rhabdomyolysis. For these patients, the putative benefits and risks of fenofibrate therapy should be carefully weighed up.

  Muscle toxicity should be suspected in patients presenting diffuse myalgia, myositis, muscular cramps and weakness and/or marked increases in CPK (levels exceeding 5 times the normal range). In such cases treatment with fenofibrate should be stopped.

  The risk of muscle toxicity may be increased if the drug is administered with another fibrate or an HMG-CoA reductase inhibitor, especially in cases of pre-existing muscular disease. Consequently, the co-prescription of fenofibrate with a statin should be reserved to patients with severe combined dyslipidaemia and high cardiovascular risk without any history of muscular disease. This combination therapy should be used with caution and patients should be monitored closely for signs of muscle toxicity.

  For hyperlipidaemic patients taking oestrogens or contraceptives containing oestrogen it should be ascertained whether the hyperlipidaemia is of primary or secondary nature (possible elevation of lipid values caused by oral oestrogen).

• Interactions
  

  Oral anti-coagulants

  Fenofibrate enhances oral anti-coagulant effect and may increase risk of bleeding. In patients receiving oral anti-coagulant therapy, the dose of anti-coagulant should be reduced by about one-third at the commencement of treatment and then gradually adjusted if necessary according to INR (International Normalised Ratio) monitoring.

  HMG-CoA reductase inhibitors or Other Fibrates

  The risk of serious muscle toxicity is increased if fenofibrate is used concomitantly with HMG-CoA reductase inhibitors or other fibrates. Such combination therapy should he used with caution and patients monitored closely for signs of muscle toxicity.

  There is currently no evidence to suggest that fenofibrate affects the pharmacokinetics of simvastatin.

  Ciclosporin

  Some severe cases of reversible renal function impairment have been reported during concomitant administration of fenofibrate and ciclosporin. The renal function of these patients must therefore be closely monitored and the treatment with fenofibrate stopped in the case of severe alteration of laboratory parameters.

  Other

  No proven clinical interactions of fenofibrate with other drugs have been reported, although in vitro interaction studies suggest displacement of phenylbutazone from plasma protein binding sites. In common with other fibrates, fenofibrate induces microsomal mixed-function oxidases involved in fatty acid metabolism in rodents and may interact with drugs metabolised by these enzymes.

  Cytochrome P450 enzymes: In vitro studies using human liver microsomes indicate that fenofibrate and fenofibric acid are not inhibitors of cytochrome (CYP) P450 isoforms CYP3A4, CYP2D6, CYP2E1, or CYP1A2. They are weak inhibitors of CYP2C19 and CYP2A6, and mild-to-moderate inhibitors of CYP2C9 at therapeutic concentrations.

  Patients co-administered fenofibrate and CYP2C19, CYP2A6, and especially CYP2C9 metabolised drugs with a narrow therapeutic index should be carefully monitored and, if necessary, dose adjustment of these drugs is recommended.

• Adverse Drug Reactions
  

  Fenofibrate is generally well tolerated. Adverse reactions observed during fenofibrate treatment are not very frequent; they are generally minor, transient and do not interfere with treatment.

  The most commonly reported adverse reactions include:

  Gastrointestinal: Digestive, gastric or intestinal disorders (abdominal pain, nausea, vomiting, diarrhoea, and flatulence) moderate in severity.

  Uncommon: Pancreatitis*

  Cardiovascular system

  Uncommon: Thromboembolism (pulmonary embolism, deep vein thrombosis)*

  Skin: Reactions such as rashes, pruritus, urticaria or photosensitivity reactions; in individual cases (even after many months of uncomplicated use) cutaneous photosensitivity may occur with erythema, vesiculation or nodulation on parts of the skin exposed to sunlight or artificial UV light (e.g. sun lamp).

  Neurological disorders: Headache.

  General disorders: Fatigue

  Disorders of the ear: Vertigo

  Less frequently reported adverse reactions:

  Liver: Moderately elevated levels of serum transaminases may be found in some patients but rarely interfere with treatment. Episodes of hepatitis have been reported very rarely. When symptoms (e.g. jaundice, pruritus) indicative of hepatitis occur, laboratory tests are to be conducted for verification and fenofibrate discontinued, if applicable (see Special Warnings). Development of gallstones has been reported.

  Muscle: As with other lipid lowering agents, cases of muscle toxicity (diffuse myalgia, myositis, muscular cramps and weakness) and very rare cases of rhabdomyolysis have been reported. These effects are usually reversible when the drug is withdrawn.

  In rare cases, the following effects are reported:

  Sexual asthenia and alopecia. Increases in serum creatinine and urea, which are generally slight, and also a slight decrease in haemoglobin and leukocytes may be observed.

  Very rare cases of interstitial pneumopathies have been reported.

  * In the FIELD-study, a randomized placebo-controlled trial performed in 9795 patients with type 2 diabetes mellitus, a statistically significant increase in pancreatitis cases was observed in patients receiving fenofibrate versus patients receiving placebo (0.8% versus 0.5%; p = 0.031). In the same study, a statistically significant increase was reported in the incidence of pulmonary embolism (0.7% in the placebo group versus 1.1% in the fenofibrate group; p = 0.022) and a statistically non-significant increase in deep vein thromboses (placebo: 1.0 % [48/4900 patients] versus fenofibrate 1.4% [67/4895 patients]; p = 0.074).