Supralip NT 145

Fenofibrate (nanoparticles).

Serum lipid reducing agent/cholesterol and triglycerides reducer/fibrate.
Pharmacology: Pharmacodynamics: Fenofibrate is a fibric acid derivative whose lipid modifying effects reported in humans are mediated via activation of peroxisome proliferator activated receptor type α (PPARα).
Through activation of PPARα, fenofibrate increases the lipolysis and elimination of atherogenic triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein CIII. Activation of PPARα also induces an increase in the synthesis of apoproteins AI and AII.
The previously mentioned effects of fenofibrate on lipoproteins lead to a reduction in very low- and low density fractions (VLDL and LDL) containing apoprotein B and an increase in the high density lipoprotein fraction (HDL) containing AI and AII.
In addition, through modulation of the synthesis and the catabolism of VLDL fractions, fenofibrate increases the LDL clearance and reduces small dense LDL, the levels of which are elevated in the atherogenic lipoprotein phenotype, a common disorder in patients at risk for coronary heart disease.
During clinical trials with fenofibrate, total cholesterol was reduced by 20-25%, triglycerides by 40-55% and HDL cholesterol was increased by 10-30%.
In hypercholesterolemic patients, where LDL cholesterol levels are reduced by 20-35%, the overall effect on cholesterol results in a decrease in the ratios of total cholesterol to HDL cholesterol, LDL cholesterol to HDL cholesterol, or Apo B to Apo AI, all of which are markers of atherogenic risk.
Because of its effect on LDL cholesterol and triglycerides, treatment with fenofibrate should be beneficial in hypercholesterolemic patients with or without hypertriglyceridemia, including secondary hyperlipoproteinemia eg, type 2 diabetes mellitus. At the present time, no results of long-term controlled clinical trials are available to demonstrate the efficacy of fenofibrate in the primary or secondary prevention of atherosclerotic complications.
Extravascular deposits of cholesterol (tendinous and tuberous xanthoma) may be markedly reduced or even entirely eliminated during fenofibrate therapy.
Patients with raised levels of fibrinogen treated with fenofibrate have shown significant reductions in this parameter, as have those with raised levels of Lp(a). Other inflammatory markers eg, C Reactive Protein are reduced with fenofibrate treatment.
The uricosuric effect of fenofibrate leading to reduction in uric acid levels of approximately 25% should be of additional benefit in those dyslipidemic patients with hyperuricemia.
Fenofibrate has been shown to possess anti-aggregatory effect on platelets in animals and in a clinical study, which showed a reduction in platelet aggregation induced by ADP, arachidonic acid and epinephrine.
Pharmacokinetics: Absorption: Maximum plasma concentrations (C_max) occur within 2-4 hrs after oral administration. Plasma concentrations are stable during continuous treatment in any given individual.
In contrast to the other fenofibrate formulations, the maximum plasma concentration and overall exposure of the nanoparticle formulation is independent from food intake. Therefore, Supralip NT 145 may be taken without regard to meals. A food-effect study involving administration of the new 145-mg tablet formulation of fenofibrate to healthy male and female subjects under fasting conditions and with a high fat meal indicated that exposure (AUC and C_max) to fenofibric acid is not affected by food.
Distribution: Fenofibric acid is strongly bound to plasma albumin (>99%).
Metabolism and Excretion: After oral administration, fenofibrate is rapidly hydrolyzed by esterases to the active metabolite fenofibric acid. No unchanged fenofibrate can be detected in the plasma. Fenofibrate is not a substrate for CYP3A4. No hepatic microsomal metabolism is involved.
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. In elderly patients, the fenofibric acid apparent total plasma clearance is not modified.
Kinetic studies following the administration of a single dose and continuous treatment have demonstrated that the drug does not accumulate. Fenofibric acid is not eliminated by hemodialysis.
The plasma elimination half-life of fenofibric acid is approximately 20 hrs.

Treatment of severe hypertriglyceridaemia with or without low HDL cholesterol. Mixed hyperlipidaemia in patients at high cardiovascular risk (eg, dyslipidemia in diabetes mellitus) in addition to a statin when triglycerides and HDL cholesterol are not adequately controlled.

Adults and elderly: 1 tab once daily.
Dosage reduction is required in patients with renal impairment.
Administration: Tablet should be swallowed whole with a glass of water. Supralip NT 145 may be given at any time of the day, with or without food.

No case of overdose has been 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 hemodialysis.

Patients with hepatic or renal insufficiency. Children.
Patients hypersensitive to fenofibrate or to any of the excipients of Supralip NT 145. In case of known photoallergy or phototoxic reaction during treatment with fibrates or ketoprofen, and in gallbladder disease.
Patients allergic to peanut or arachis oil or soya lecithin or related products due to the risk of hypersensitivity reactions.
Use in Pregnancy & Lactation: Supralip NT 145 may not be used during pregnancy and lactation as there are no data in pregnant women and on the excretion of fenofibrate and its metabolites into breast milk.

Secondary cause of hypercholesterolemia eg, uncontrolled type 2 diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemia, obstructive liver disease, pharmacological treatment, alcoholism, should be adequately treated before fenofibrate therapy is initiated.
For hyperlipidemic patients taking estrogens or contraceptives containing estrogens, it should be ascertained whether the hyperlipidemia is of primary or secondary nature (possible elevation of lipid values caused by oral estrogen).
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 be monitored every 3 months during the first 12 months of treatment. Attention should be paid to patients who show increases in transaminase levels and therapy should be discontinued if ASAT and ALAT levels increase to >3 times the upper limit of the normal range or 100 IU.
Pancreatitis have 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 with obstruction of the common bile duct.
Muscle: Muscle toxicity, including very rare cases of rhabdomyolysis, has been reported with administration of fibrates and other lipid-lowering agents. Patients with hypoalbuminemia and renal insufficiency in their personal history have a higher incidence of myotoxicity. 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 upper normal range). In such cases, treatment with fenofibrate should be stopped.
Patients with predisposing factors for myopathy and/or rhabdomyolysis, including patients >70 years, personal or familial history of hereditary muscular disorders, renal impairment, hypoalbuminemia, 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.
The risk of muscle toxicity may be increased if the drug is administered with another fibrate or an HMG-CoA reductase inhibitor (statins), especially in cases of preexisting muscular disease. Consequently, the co-prescription of fenofibrate with a statin should be reserved to patients with severe combined dyslipidemia 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.
Renal Function: Treatment should be interrupted in case of an increase in creatinine levels >50% of ULN (upper limit of normal). It is recommended that creatinine measurement be considered during the first 3 months after initiation of treatment.
Supralip NT 145 contains lactose, therefore, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. It also contains sucrose, therefore, patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Supralip NT 145 may not be used during pregnancy and lactation as there are no data in pregnant women and on the excretion of fenofibrate and its metabolites into breast milk.

The frequencies of adverse events are ranked according to the following: Very common (>1/10); common (>1/100, <1/10); uncommon (>1/1000, <1/100); rare (>1/10,000, <1/1000); very rare (<1/10,000), including isolated reports.
Gastrointestinal Disorders: Common: Digestive, gastric or intestinal disorders (abdominal pain, nausea, vomiting, diarrhoea and flatulence) moderate in severity. Very Rare: Cases of pancreatitis have been reported during treatment with fenofibrate.
Hepatobiliary Disorders: Common: Moderately elevated levels of serum transaminases. Uncommon: Development of gallstones. Very Rare: Episodes of hepatitis. When symptoms (eg, jaundice, pruritus) indicative of hepatitis occur, laboratory tests are to be conducted for verification and fenofibrate discontinued, if applicable.
Skin and Subcutaneous Tissue Disorders: Uncommon: Rashes, pruritus, urticaria or photosensitivity reactions. Rare: Alopecia. Very Rare: Cutaneous photosensitivity with erythema, vesiculation or nodulation on parts of the skin exposed to sunlight or artificial UV light (eg, sunlamp) in individual cases (even after many months of uncomplicated use).
Musculoskeletal, Connective Tissue and Bone Disorders: Rare: Diffuse myalgia, myositis, muscular cramps and weakness. Very Rare: Rhabdomyolysis.
Blood and Lymphatic System Disorders: Rare: Decrease in hemoglobin and leukocytes.
Nervous System Disorders: Rare: Sexual asthenia, headache.
Respiratory, Thoracic and Mediastinal Disorders: Very Rare: Interstitial pneumopathies.
Investigation: Uncommon: Increases in serum creatinine and urea.

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 ⅓ at the start of treatment and then gradually adjusted, if necessary, according to INR (International Normalized Ratio) monitoring. Therefore, this combination is not recommended.
Cyclosporin: Some severe cases of reversible renal function impairment have been reported during concomitant administration of fenofibrate and cyclosporin. 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.
Cytochrome P-450 Enzymes: In vitro studies using human liver microsomes indicate that fenofibrate and fenofibric acid are not inhibitors of cytochrome (CYP) P-450 isoforms CYP3A4, CYP2D6, CYP2E1, or CYP1A2. They are weak inhibitors of CYP2C19 and CYP2A6, and mild to moderate inhibitors of CYP2C9 at therapeutic concentrations.

Store at a temperature below 30°C.

Dyslipidaemic Agents

C10AB05 - fenofibrate ; Belongs to the class of fibrates. Used in the treatment of hyperlipidemia.

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