Lipanthyl Penta 145

White, oblong, film-coated tablets engraved "145" on one side and the "
Click on icon to see table/diagram/image
" logo on the other side.
One film-coated tablet contains 145.0 mg fenofibrate as nanoparticles.
Excipients with known effect: Each film-coated tablet contains 132.00 mg lactose monohydrate; 145.00 mg sucrose; 0.50 mg soybean lecithin.
Excipients/Inactive Ingredients: Core: Sucrose, Lactose monohydrate, microcrystalline cellulose and colloidal silica anhydrous, Crospovidone, Hypromellose, Sodium lauril sulfate, Docusate sodium, Magnesium stearate.
Coating: Polyvinyl alcohol, Titanium dioxide (E171), Talc, Soybean lecithin, Xanthan gum.

Pharmacotherapeutic group: lipid lowering agents/cholesterol and triglyceride lowering products/fibrates. ATC code: C10AB05.
Pharmacology: Pharmacodynamics: Fenofibrate is a fibric acid derivative whose lipid-regulating effects in humans are mediated via activation of PPARα (peroxisome proliferator activated receptor type alpha).
Activation of PPARα increases the activity of lipoprotein lipase and reduces the production of apoliprotein CIII. Via this mechanism, fenofibrate raises lipolysis and elimination of atherogenic, triglyceride-rich particles from the plasma. Activation of PPARα also induces an increase in the synthesis of apoproteins AI and AII.
The previously mentioned effects of fenofibrate lead to a reduction in very-low-density and low-density lipoproteins (VLDL and LDL) containing apolipoprotein B and an increase in the high-density lipoproteins (HDL) due to increased production of apoproteins AI and AII.
Patients with an elevated CHD (coronary heart disease) risk commonly express an atherogenic liporotein phenotype characterized by an increased fraction of small dense LDL particles. By regulating the synthesis and catabolism of VLDL, fenofibrate lowers the levels of small dense LDL and increases LDL clearance.
During clinical trials with fenofibrate, total cholesterol was reduced by 20 to 25%, triglycerides by 40 to 55% and HDL cholesterol was increased by 10 to 30%.
In hypercholesterolemic patients, where LDL cholesterol levels are reduced by 20 to 35%, the overall effect on cholesterol (LDL, HDL) 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.
There is evidence that treatment with fibrates may reduce coronary heart disease events but it has not been shown to decrease all-cause mortality in the primary or secondary prevention of cardiovascular disease.
The Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial was a randomized placebo-controlled study in 5518 patients with type 2 diabetes mellitus treated with fenofibrate in addition to simvastatin. Treatment with fenofibrate plus simvastatin did not show significant differences in the composite primary endpoint of non-fatal myocardial infarction, non-fatal stroke and cardiovascular deaths compared to simvastatin monotherapy (hazard ratio [HR] 0.92; 95% Cl: 0.79 to 1.08; p=0.32; absolute risk reduction: 0.74%). In the pre-specified subgroup of dyslipidemic patients, defined as those in the lowest tertile of HDL-C (≤34 mg/dL or 0.88 mmol/L) and highest tertile of TG (≥204 mg/dL or 2.3 mmol/L), fenofibrate plus simvastatin therapy demonstrated a 31% relative risk reduction compared to simvastatin monotherapy for the composite primary outcome criterion (Hazard Ratio [HR] 0.69; 95% Cl 0.49 to 0.97; p=0.03; absolute risk reduction: 4.95%). Another pre-specified subgroup analysis identified a statistically significant treatment-by-gender interaction (p=0.01) indicating a possible treatment benefit of combination therapy in men (p=0.037) but a potentially higher risk for the primary endpoint in women treated with combination therapy compared to simvastatin monotherapy (p=0.069). This was not observed in the previously mentioned subgroup of patients with dyslipidemia, but there was also no clear evidence of benefit in dyslipidaemic women treated with fenofibrate plus simvastatin, and a possible harmful effect in this subgroup could not be excluded.
Extravascular deposits of cholesterol (tendinous and tuberous xanthomas) may be markedly reduced or even entirely eliminated during fenofibrate therapy.
In patients with elevated baseline Lp(a) or fibrinogen levels, treatment with fenofibrate produced a significant lowering of Lp(a) or fibrinogen concentrations. Other inflammatory markers such as C-reactive protein are reduced with fenofibrate treatment.
Fenofibrate produces an approximately 25% reduction of uric acid levels. This is of additional benefit in dyslipidaemic patients with hyperuricaemia.
In animal studies and a clinical trial, fenofibrate inhibited platelete aggregation induced by ADP, arachidonic acid and epinephrine.
Pharmacokinetics: LIPANTHYL PENTA 145 contains 145 mg of fenofibrate as nanoparticles in the form of a film-coated tablet.
Absorption: Maximum plasma concentrations (C_max) occur within 2-4 hours after oral administration. Plasma concentrations remain constant in any given individual following repeated administration.
Contrarily to previous fenofibrate formulations, the maximum plasma concentration and overall exposure of the nanoparticle formation is independent from food intake. Therefore, the medicinal product may be taken without regard to meals.
A study involving 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. Plasma clearance of fenofibric acid is unchanged in the elderly patients.
Pharmacokinetic studies with single and repeated dosing have demonstrated that the active substance does not accumulate. Fenofibric acid is not eliminated by haemodialysis.
The plasma elimination half-life of fenofibric acid is approximately 20 hours.
Toxicology: Preclinical safety data: In a three-month, oral, non-clinical study in rats with fenofibric acid, the active metabolite of fenofibrate, toxicity for the skeletal muscles (particularly those rich in type I fibres) and heart failure, anaemia and decreased body weight were seen. No skeletal toxicity was noted at doses up to 30 mg/kg [approximately 17 times the maximum recommended human dose (MRHD)]. No signs of cardiac toxicity were noted at approximately three times the MRHD.
Reversible ulcers and erosions in the gastrointestinal tract occurred in dogs treated for three months. No gastrointestinal lesions were noted in this study at approximately five times the MRHD.
Studies on mutagenicity of fenofibrate have been negative.
In rats and mice, liver tumors have been found at high dosages, which are attributable to peroxisome proliferation. These changes are specific to small rodents and have not been observed in other animal species. This is of no relevance to therapeutic use in humans.
Studies in mice, rats and rabbits did not reveal any teratogenic effect. Embryotoxic effects were observed at doses in the range of maternal toxicity. Prolongation of the gestation period and difficulties during delivery were observed at high doses. Reversible hypospermia, testicular vasculation and immaturity of the ovaries were observed in a repeat-dose study with fenofibric acid in young dogs. However, no effect on fertility were detected in preclinical reproductive studies with fenofibrate.

LIPANTHYL PENTA 145 is indicated as an adjunct to diet and other non-pharmacological treatment (e.g. exercise, weight reduction) for the following conditions: Severe hypertriglyceridemia 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.

The diet should be continued during treatment with this medicinal product. Response to treatment should be monitored by recording serum lipid levels. If an adequate lipid-lowering response has not been achieved after several months of treatment with fenofibrate (e.g. 3 months), complementary or different therapeutic measures should be considered.
Posology: Adults: Recommended daily dose: 1 film-coated tablet (containing 145 mg fenofibrate) daily.
Patients currently taking fenofibrate 200 mg or 160 mg once daily can be changed to LIPANTHYL PENTA 145 (1 film-coated tablet daily) without further dose adjustment.
Elderly patients (>65 years old): No dose adjustment is necessary. The usual dose is recommended except for decreased renal function with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m² (see Patients with renal impairment as follows).
Patients with renal impairment: Fenofibrate should not be used if severe renal impairment, defined as eGFR <30 ml/min/1.73 m², is present.
If eGFR is between 30 and 59 ml/min/1.73 m², the daily dose should not exceed 100 mg fenofibrate (standard) or 67 mg micronised.
If, during follow-up, the eGFR decreases persistently to <30 ml/min/1.73 m², fenofibrate should be discontinued.
Hepatic impairment: LIPANTHYL PENTA 145 is not recommended for patients with hepatic impairment due to the lack of data.
Children and adolescents: The safety and efficacy of fenofibrate have not been sufficiently established in children and adolescents below the age of 18. No studies are available. Therefore, the use of fenofibrate is not recommended in children and adolescents under 18 years.
Method of administration: The medicinal product may be given at any time of the day, with or without food (see Pharmacology: Pharmacokinetics under Actions).
The film-coated tablet should be swallowed whole with a glass of water.

Only isolated reports of fenofibrate overdose have been received to date. In the majority of cases no overdose symptoms were reported. There is no specific antidote. If an overdose is suspected, symptomatic treatment should be initiated and suitable supportive measures taken. Fenofibrate cannot be eliminated by hemodialysis.

Hepatic insufficiency (including biliary cirrhosis and unexplained persistent liver function abnormality).
Known gallbladder disease.
Severe renal insufficiency (estimated glomerular filtration rate <30 ml/min/1.73 m²).
Chronic or acute pancreatitis with the exception of acute pancreatitis due to severe hypertriglyceridaemia.
Known photoallergy or phototoxic reaction during treatment with fibrates or ketoprofen.
Hypersensitivity to the active substance or to any of the excipients listed in Description.
LIPANTHYL PENTA 145 should not be taken by patients allergic to peanuts, arachis oil, soya lecithin (3-sn-phosphatidyl choline) or related products due to the risk of hypersensitivity reactions.

Secondary cause of hypercholesterolemia such as uncontrolled type 2 diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemia, obstructive liver disease or alcoholism should be treated before LIPANTHYL PENTA 145 therapy is considered.
Secondary causes of hyperlipidaemia may occur during pharmacological treatment with diuretics, beta-blockers, oestrogens, gestagens, combined oral contraceptives, immunosuppressants and protease inhibitors. In these cases, tests should be carried out to establish whether primary or secondary hyperlipidaemia is involved (these medicinal products may trigger a rise in lipid values).
Liver: As with other lipid-lowering drugs, increases have been reported in transaminase levels in some patients whilst taking fenofibrate. In the majority of the observed cases, the elevations were temporary, minor and asymptomatic. It is recommended that transaminase levels are monitored every 3 months during the first 12 months of treatment and regularly thereafter.
Patients displaying elevated transaminase levels should be closely monitored. Treatment should be discontinued if ASAT (SGOT) and ALAT (SGPT) levels increase to more than 3 times the upper limit of normal range. 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 (see Contraindications and Adverse Reactions). In patients with severe hypertriglyceridemia, this may be due to insufficient efficacy of the medicinal product, a direct drug effect or a secondary phenomenon mediated through cholelithiasis with obstruction of the common bile duct.
Muscle: Muscle toxicity including rare cases of rhabdomyolysis, with or without renal failure, has been reported with the administration of fibrates and other lipid-lowering agents. The incidence of this disorder increases in case of hypoalbuminaemia and previous renal insufficiency.
Patients with predisposing factors for myopathy and/or rhabdomyolysis, including age above 70 years, personal or family history of hereditary muscular disorders, renal impairment, hypothyroidism and high alcohol intake, may be at increased risk of developing rhabdomyolysis. For these patients, the 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 creatine phosphokinase (CPK) (levels exceeding five times the upper normal range). In such cases, the medicinal product should be stopped.
The risk of muscle toxicity may be elevated if this medicinal product is combined with another fibrate or with an HMG-CoA reductase inhibitor, especially in cases of pre-existing muscle disease. Consequently, the combination of fenofibrate with an HMG-CoA reductase inhibitor or another fibrate should be reserved to patients with severe combined hyperlipidemia and high cardiovascular risk without any history of muscle disease and with close monitoring of potential muscle toxicity.
Renal function: LIPANTHYL PENTA 145 is contraindicated in severe renal impairment (see Contraindications).
LIPANTHYL PENTA 145 should be used with caution in patients with mild to moderate renal insufficiency. Dose adjustment is required in patients with an eGFR between 30 and 59 ml/min/1.73 m² (see Dosage & Administration).
Reversible elevations in serum creatinine have been reported in patients receiving fenofibrate monotherapy or co-administered with statins. Elevations in serum creatinine were generally stable over time with no evidence of continued increase with long-term therapy. A return to baseline values was observed following discontinuation of treatment.
During clinical trials, 10% of patients had a creatinine increase from baseline greater than 30 μmol with co-administered fenofibrate and simvastatin versus 4.4% with statin monotherapy. 0.3% of patients receiving co-administration had clinically relevant increases in creatinine to values >200 μmol/l.
Treatment should be interrupted when the creatinine levels is 50% above the upper limit of normal. It is recommended that creatinine is measured during the first 3 months after initiation of treatment and periodically thereafter.
Excipients: This medicinal product contains lactose, patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
This medicinal product contains sucrose, patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product.
Fenofibrate was not shown to reduce coronary heart disease morbidity and mortality in 2 large, randomized controlled trials (the ACCORD lipid trial and FIELD study) in patients with type 2 diabetes mellitus.
Effects on the ability to drive and use machines: LIPANTHYL PENTA 145 has no or negligible effect on the ability to drive and use machines.

Pregnancy: There are no adequate data on the use of fenofibrate during pregnancy. Animal studies have not demonstrated any teratogenic effects. Embryotoxic effects were observed at doses in the range of maternal toxicity (see Pharmacology: Toxicology: Preclinical safety data under Actions). The potential risk for humans is unknown. Therefore, LIPANTHYL PENTA 145 should only be used during pregnancy after a careful benefit/risk assessment.
Lactation: It is unknown whether fenofibrate and/or its metabolites are excreted in human milk. A risk to the suckling child cannot be excluded. Consequently, LIPANTHYL PENTA 145 should not be used during breast-feeding.
Fertility: Reversible effects on fertility have been observed in animal studies (see Pharmacology: Toxicology: Preclinical safety data under Actions).
There are no clinical data on fertility from the use of LIPANTHYL PENTA 145.

The most commonly reported adverse effects during fenofibrate therapy are digestive or gastrointestinal disorders.
The following undesirable effects have been observed during placebo-controlled clinical trials (n=2344) and post-marketing with the frequencies indicated as follows: See table.

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Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is very important. It allows continued monitoring of the benefit/risk ratio of the medicinal product.
Healthcare professionals are asked to report any suspected adverse reactions to the Drug Office, Department of Health.Website: http://www.drugoffice.gov.hk/eps/do/en/healthcare_providers/adr_reporting/index.html

Oral anticoagulants: Fenofibrate may enhance the oral anticoagulant effect and thus may increase the 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 - whilst monitoring coagulation parameters (International Normalized Ratio).
Cyclosporine: Isolated cases of severe albeit reversible, impairment of renal function have been reported during concomitant administration of fibrate-containing medicinal products and cyclosporin. The renal function of these patients must therefore be closely monitored and the treatment with fenofibrate discontinued in the case of significant changes in diagnostic laboratory parameters.
HMG-CoA reductase inhibitors and other fibrates: The risk of serious muscle damage is increased if fenofibrate is used concomitantly with HMG-CoA reductase inhibitors or other fibrates. Such combination therapy should be used with caution, and patients monitored for signs of muscle damage (see Precautions).
Glitazones: Some cases of reversible paradoxical reduction of HDL-cholesterol have been reported during concomitant administration of fenofibrate and glitazones. Therefore, it is recommended to monitor HDL-cholesterol if one of these components is added to the other. Either therapy should be discontinued if HDL cholesterol is too low.
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 moderate inhibitors of CYP2C9 at therapeutic concentrations.
Patients coadministered 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.

Instructions for use and handling: No special requirements.
Incompatibilities: Not applicable.

Store in the original package, at a temperature not exceeding 30°C.
Shelf-life: 3 years.

Dyslipidaemic Agents

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

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