0.2, 0.3 or 0.4 mg moxonidine.

Lipanthyl 160 MR: Film-coated modified release tablets Box of 30.

Lipanthyl 200 M: Capsules: Box of 30.

 

Lipanthyl 160 MR: Each tablet contains Fenofibrate 160 mg. Excipients: sodium laurilsulfate, lactose mono¬hydrate, povidone, crospovidone, microcrystallinece¬lose, silica colloidal anhydrous, sodium steam fumarate.

Lipanthyl 200 M: Each capsule contains: Fenofibrate micronised: 200 mg.

 

Fenofibrate is a fibric acid derivative whose lipid modifying effects reported in humans are mediated via activation of Peroxisome Proliferator Activated Receptor type alpha (PPARa). Through activation of PP.ARs. 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 PPARa also induces an increase in the synthesis of apoproteins Al and All. The above stated effects of Fenofibrate on lipoproteins lead to a reduction in very low- and low density fractions (VLDL and LDL) containing apoprotein B and an in¬crease in the high density lipoprotein fraction (HDL) containing apoprotein AI and All. 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 cornmon disorder in patients at risk for coronary heart disease. 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 hypercholesterolaemic patients, where LDL cholesterol levels are reduced by 20 to 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 Al, all of which are markers of atherogenic risk. Because of its significant effect on LDL cholesterol and triglycerides, treatment with Fenofibrate should be beneficial in hypercholesterolaemic patients with or without hypertriglyceridaemia including secondary hyperlipoproteinaemia such as 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 prima 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 such as 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 these dyslipidaemic patients with hype¬ruricaemia. Fenofibrate has been shown to possess an 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.

Preclinical safety data: Chronic toxicity studies have yielded no relevant information about specific toxicity of Fenofibrate. Studies on mutagenicity of Fenofibrate have been negative. In rats and mice, liver tumours have been found at high dosages, which are attribut¬table 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 man. Studies in mice, rats and rabbits did not reveal any teratogenic effect. Embryotoxic effects were observed at doses in the range of maternal toxic¬ity. Prolongation of the gestation period and difficulties during delivery were observed at high doses. No sign of any effect on fertility has been detected.

 

Lipanthyl 160 MR: Lipanthyl 160 mg is a film-coated tablet with modified release containing 160 mg of mi¬cronised Fenofibrate and is suprabioavailable (larger bioavailability) compared to the previous formulations. Maximum plasma concentrations (Cmax) occur within 4-5 hrs after oral administration. Plasma concentrations are stable during continuous treatment in any given individual. The absorption of Fenofibrate is increased when administered with food.. Fenofibric acid is strongly bound to plasma albumin (more than 99%). Plasma half-life: The plasma elimination half-life of fenofibric acid is approximately 20 hrs. No unchanged Fenofi¬brate can be detected in the plasma where the prnccal metabolite is fenofibric acid. 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 fabric acid and its glucuronide conjugate. In eld¬erly patients, the fenofibric acid apparent total plasma clearance is not modified. Kinetic studies following the administration of a single dose and continuous treat¬ment have demonstrated that the drug does not accu¬mulate. Fenofibric acid is not eliminated by haemodi¬alysis

Lipanthyl 200 M: In plasma, no metabolised form of Fenofibrate is found. The major plasma metabolite is fenofibric acid. Peak plasma concentration is achieved in about 5 hrs after ingestion of the product. The mean plasma concentration is about 15 µg/ml for a dose of 200 mg/day Fenofibrate. This level is stable in continu¬ous treatments. Fenofibric acid is bound to plasma albumin and might reduces the protein binding of antivi¬tamins K and potentiate their anticoagulant effect. The elimination half-life of fenofibric acid is about 20 hrs. Excretion is mainly by urine: 70% in 24 hrs, 88% in 6 days, and 93% urine and faeces. Fenofibrate is mainly excreted as fenofibric acid and its glucuroconjuguated derivative. Kinetic studies, after continuous treatment, show that there is no accumulation of Fenofibrate. Fenofibric acid is not excreted during hemodialysis.

 

Lipanthyl 160 MR: Hypercholesterolaemia and hyper¬triglyceridaemia alone or combined (types IIa, IIb, IV dyslipidaemias, as well as types III and V dyslipidae¬mias although only a few patients have been treated during clinical trials) in patients unresponsive to dietary and other non-drug therapeutic measures (e.g. weight reduction or increased physical activity), particularly when there is evidence of associated risk factors. The treatment of secondary hyperlipoproteinaemias is indi¬cated if the hyperlipoproteinaemia persists despite effective treatment of the underlying disease (e.g. dyslipidaemia in diabetes mellitus). Dietary measures initiated before therapy should be continued.

Lipanthyl 200 M: Hypercholesterolemia (type IIa) and endogen hypertriglyceridemia of adult, isolated (type IV) or associated (types IIb and III), when a diet focusing on calorie restriction is insufficient. At the present time, no results of long term controlled clinical trials are available and demonstrate the efficacy of Fenofibrate in Primary or secondary prevention of atherosclerosis complications.

 

Hepatic insufficiency (including biliary cirrhosis). Renal insufficiency. Children. Hypersensitivity to Fenofibrate or any component of this medication, Known photoal¬lergy or phototoxic reaction during treatment with fi¬brates or ketoprofen, Gallbladder disease. Use during Pregnancy and lactation.

 

Liver function: As with other lipid lowering agents, in¬creases have been reported in transaminase levels in some patients. In the majority of cases these elevations were transient, minor and asymptomatic. It is recom¬mended that transaminase levels be monitored every 3 months during the first 12 months of treatment. Atten¬tion should be paid to patients who develop increase in transaminase levels and therapy should be discontin¬ued if ASAT and ALAT levels increase to more than 3 times the upper limit of the normal range or 100 IU.

Muscle: Muscle toxicity, including very rare cases of rhabdomyolysis, has been reported with administration of fibrates and other lipid-lowering agents. The inci¬dence of this disorder increases in cases of hypoalbu¬minaemia and previous renal insufficiency. Muscle toxicity should be suspected in patients presenting diffuse myalgia, myositis, muscular cramps and weak¬ness and/or marked increases in CPK (levels exceed¬ing 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 com¬bined dyslipidaemia and high cardiovascular risk with¬out 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 estrogens or con¬traceptives containing oestrogens it should be ascer¬tained whether the hypertipidaemia is of primary or secondary nature (possible elevation of lipid values caused by oral oestrogen).

Ability to drive and use machines: No effect noted.

Pregnancy and lactation: There are no adequate data from the use of Fenofibrate in pregnant women. Animal studies have not demonstrated any teratogenic effects. Embryotoxic effects have been shown at doses in the range of maternal toxicity. The potential risk for humans is unknown. There are no data on the excretion of Fenofibrate and/or its metabolites into breast milk.

 

Oral anticoagulants: Fenofibrate enhances oral antico¬agulant effect and may increase risk of bleeding. It is recommended that the dose of anticoagulants is re¬duced by about one third at the start of treatment and then gradually adjusted if necessary according to INR (International Normalised Ratio) monitoring.

Cyclosporin: Some severe cases of reversible renal function impairment have been reported during con¬comitant 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.

 

The most- commonly reported adverse reactions in¬clude:

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

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. sunlamp).

Less frequently reported adverse reactions:

Liver: Moderately elevated levels of serum transami¬nases may be found in some patients. Episodes of hepatitis have been reported very rarely. When symp¬toms (e.g. jaundice, pruritus) indicative of hepatitis occur, laboratory tests are to be conducted for verifica¬tion and Fenofibrate discontinued, if applicable.

Muscle: As with other lipid lowering agents, cases of muscle toxicity (diffuse myalgia, myositis, muscular cramps and weakness) and very rare cases of rhabdo¬myolysis have been reported. These effects are usually reversible when the drug is withdrawn. In rare cases, the following effects are reported: gallstones (but any causal relationship remains inconclu¬sive), 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.

 

Lipanthyl 160 MR:

Adults: The recommended dose is one tablet containing 160 mg Fenofibrate taken once daily.

Patients currently taking one Lipanthyl 200 mg capsule can be changed to one 160 mg tablet without further dose adjustment.

Children: The use of the 160 mg dosage form is contra¬indicated in children.

Elderly patients: The usual adult dose is recommended.

Patients with renal impairment: Dosage reduction is required in patients with renal impairment. The use of dosage forms containing a lower dose of active ingredi¬ent (67 mg micronised Fenofibrate capsules or 100 mg standard Fenofibrate capsules) is recommended in these patients.

Hepatic disease: Patients with hepatic disease have not been studied.

Dietary measures initiated before therapy should be continued, if after several months of Fenofibrate ad¬ministration (e.g. 3 months) serum lipid levels have not been reduced satisfactorily, complementary or different therapeutic measures should be considered.

Method of administration: Tablet should be swallowed whole during a meal.

Lipanthyl 200 M:

In association with a diet, this medication constitute a long term symptomatic treatment, and its efficacy must be regularly controlled.

Capsules of Micronised Lipanthyl 200 must be pre¬scribed as one capsule daily with the main meal.

 

No case of overdosage 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 elimi¬nated by haemodialysis.

 

Store in the original package. Do not store above 30°C