- LIPID - LOWERING DRUGS
- CARDIOVASCULAR DRUGS
- Pharmaceutical Form : Tablets
- Composition : Fenofibrate 160 mg/ Tab
- Active Substance : Fenofibrate
Fenofibrate is a fibric acid derivative whose lipid modifying effects reported in humans are mediated via activation of Peroxisome Proliferators Activated Receptor type α (PPARα). Through activation of PPARα, fenofibrate increases lipolysis and elimination of atherogenic triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of Apoprotein C-III. Activation of PPARα also induces an increase in the synthesis of Apoproteins A-I and A-II.
Absorption: Maximum plasma concentrations (Cmax) occur within 4 to 5 hours after oral administration. Plasma concentrations are stable during continuous treatment in any given individual. The absorption of fenofibrate is increased when administered with food.
Distribution: Fenofibric acid is strongly bound to plasma albumin (more than 99%).
Metabolism and excretion: The drug is excreted mainly in the urine. Practically all the drug is eliminated within 6 days. Fenofibrate is mainly excreted in the form of fenofibric acid and its glucuronide conjugate .Fenofibric acid is not eliminated by haemodialysis. The plasma elimination half-life of fenofibric acid is approximately 20 hours.
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 hyperlipidemia when a statin is contraindicated or not tolerated.
– Mixed hyperlipidemia in patients at high cardiovascular risk in addition to a statin when triglycerides and HDL cholesterol are not adequately controlled (except for 267 mg strength ).
-Hepatic insufficiency (including biliary cirrhosis and unexplained persistent liver function abnormality.
-Known gallbladder disease.
-Severe renal dysfunction.
-Chronic or acute pancreatitis with the exception of acute pancreatitis due to severe hypertriglyceridemia.
-Known photoallergy or phototoxic reaction during treatment with fibrates or ketoprofen.
-Hypersensitivity to the active substance or to any of the excipients.
Secondary causes of hyperlipidemia: Secondary causes of hyperlipidemia, such as uncontrolled type 2 diabetes mellitus, hypothyroidism, nephritic syndrome, dysproteinemia, obstructive liver disease, pharmacological treatment, alcoholism, should be adequately treated before fenofibrate therapy is considered.
It should be ascertained whether the hyperlipidaemia is of primary or secondary nature (possible elevation of lipid values caused by these therapeutic agents).
Liver function: As with other lipid lowering agents, increases have been reported in transaminase levels in some patients. In the majority of cases these elevations were transient, minor and asymptomatic. It is recommended that transaminase levels are monitored every 3 months during the first 12 months of treatment and thereafter periodically. When symptoms indicative of hepatitis occur (e.g. jaundice, pruritus), and diagnosis is confirmed by laboratory testing, fenofibrate therapy should be discontinued.
Pancreas: Pancreatitis has been reported in patients taking fenofibrate. This occurrence may represent a failure of efficacy in patients with severe hypertriglyceridemia, a direct drug effect, or a secondary phenomenon mediated through biliary tract stone or sludge formation, resulting in the obstruction of the common bile duct.
Muscle: Muscle toxicity, including rare cases of rhabdomyolysis, with or without renal failure, 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.
Renal function: Treatment should be interrupted in case of an increase in creatinine levels> 50% ULN (upper limit of normal). It is recommended that creatinine is measured during the first 3 months after initiation of treatment and thereafter periodically.
There are no adequate data from the use of fenofibrate in pregnant women. It should only be used during pregnancy after a careful benefit/risk assessment.
It is unknown whether fenofibrate and/or its metabolites are excreted in human milk. A risk to the suckling child cannot be excluded. Therefore fenofibrate should not be used during breast-feeding.
Headache, Thromboembolism (pulmonary embolism, deep vein thrombosis), abdominal pain, nausea, vomiting, diarrhea, flatulence , Pancreatitis, Transaminases increased , Cholelithiasis, Cutaneous hypersensitivity(e.g. Rashes, pruritus, urticaria), Muscle disorder (e.g. myalgia, myositis, muscular spasms and weakness), Sexual dysfunction, Blood creatinine increased.
Oral anticoagulants: Fenofibrate enhances oral anticoagulant effect and may increase risk of bleeding.
It is recommended that the dose of anticoagulants is reduced by about one third at the start of treatment and then gradually adjusted if necessary according to INR (International Normalised Ratio) monitoring.
Ciclosporin: Some severe cases of reversible renal function impairment have been reported during concomitant administration of fenofibrate and cyclosporine. 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.
HMG-CoA reductase inhibitors and other fibrates: The risk of serious muscle toxicity is increased if a fibrate is used concomitantly with HMG-CoA reductase inhibitors or other fibrates. Such combination therapy should be used with caution and patients monitored closely for signs of muscle toxicity.
Glitazones: Some cases of reversible paradoxical reduction of HDL-cholesterol have been reported during concomitant administration of fenofibrate and glitazones.
Cytochrome P450 enzymes: 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.
Dosage and method of administration:
Capsules and tablets should be swallowed whole during a meal.
Standard micronised formulations of fenofibrate are available as 67-mg capsules to be taken several times daily, or as 200- or 267-mg capsules for once daily dosage.
Non-micronised formulations may also be available and are given in an initial dose of 200 to 300 mg daily in divided doses, adjusted according to response to between 200 and 400 mg daily; 100 mg of non-micronised fenofibrate is therapeutically equivalent to 67 mg of the standard micronised form.
Adults: The recommended dose is:
- One tablet containing 160 mg fenofibrate taken once daily.
- Patients currently taking one fenofibrate 200 mg capsule can be changed to one fenofibrate 160 mg tablet without further dose adjustment.
Elderly patients: without renal impairment, the usual adult dose is recommended.
Patients with renal impairment: Dosage reduction is required in patients with renal impairment.
In patients with severe chronic kidney disease, fenofibrate is not recommended.
Pediatric population: The use of fenofibrate is not recommended in paediatric subjects under 18 years.
Hepatic impairment: Patients with hepatic disease have not been studied.
Only anecdotal cases of fenofibrate overdosage have been received. In the majority of cases no overdose symptoms were reported.
No specific antidote is known. If an overdose is suspected, treat symptomatically and institute appropriate supportive measures as required. Fenofibrate cannot be eliminated by haemodialysis.
STORAGE CONDITIONS: Do not store above 25˚c
PACKAGING: Pack contains 20 tablets.