Lipanthyl^® 200 M (Capsules) Instructions for Use

Marketing Authorization Holder

Abbott Laboratories, GmbH (Germany)

Manufactured By

Recipharm Fontaine (France)

ATC Code

C10AB05 (Fenofibrate)

Active Substance

Fenofibrate (Rec.INN registered by WHO)

Dosage Form

Lipanthyl® 200 M

Capsules 200 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin, size No. 1, light brown in color; capsule contents are a white or almost white powder.

Excipients: sodium lauryl sulfate – 7 mg, lactose monohydrate – 101 mg, pregelatinized starch – 30 mg, crospovidone – 7 mg, magnesium stearate – 5 mg.

Capsule shell composition: titanium dioxide (E171) – 1 mg, iron oxide dye (E172) – 0.83 mg, gelatin – up to 75 mg.

10 pcs. – blisters (3) – cardboard packs.
15 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

Hypolipidemic agent

Pharmacotherapeutic Group

Hypolipidemic agent – fibrate

Pharmacological Action

Hypolipidemic agent from the group of fibric acid derivatives.

By activating PPAR-alpha (peroxisome proliferator-activated receptor alpha), Fenofibrate enhances lipolysis and the removal of atherogenic lipoproteins with high triglyceride concentrations from the blood plasma by activating lipoprotein lipase and reducing the synthesis of apoprotein CIII. Activation of PPAR-alpha also leads to increased synthesis of apoproteins AI and AII.

Fenofibrate is a fibric acid derivative, the ability of which to alter lipid concentrations in the human body is mediated by the activation of PPAR-alpha. The effects of fenofibrate on lipoproteins described above lead to a decrease in the concentration of LDL and VLDL, which include apoprotein B, and an increase in the concentration of HDL, which include apoproteins AI and AII.

Furthermore, by correcting disorders in the synthesis and catabolism of VLDL, Fenofibrate increases LDL clearance and reduces the concentration of dense, small-sized LDL particles, an increase of which is observed in patients with an atherogenic lipid phenotype, a common disorder in patients at risk for coronary artery disease.

Fenofibrate reduces platelet aggregation, lowers elevated plasma fibrinogen levels, can slightly reduce blood glucose levels in patients with diabetes mellitus; reduces blood uric acid levels.

Pharmacokinetics

After oral administration, Fenofibrate is rapidly hydrolyzed by esterases. Only the main active metabolite of fenofibrate, fenofibric acid, is detected in the blood plasma. Fenofibrate is not a substrate for the CYP3A4 isoenzyme and does not participate in microsomal metabolism. The original Fenofibrate is not detected in the blood plasma. C_max in the blood plasma is reached 2-4 hours after oral administration. With long-term use, the concentration in the blood plasma remains stable regardless of the patient’s individual characteristics. Plasma protein (albumin) binding is high – more than 99%. It is excreted mainly by the kidneys in the form of fenofibric acid and a glucuronide conjugate. Within 6 days, Fenofibrate is excreted almost completely.

Indications

Hypercholesterolemia and hypertriglyceridemia, isolated or mixed (dyslipidemia type IIa, IIb, III, IV, V according to the Fredrickson classification) in patients for whom diet or other non-drug therapeutic measures (e.g., weight loss or increased physical activity) are ineffective, especially in the presence of dyslipidemia-related risk factors such as arterial hypertension and smoking.

For the treatment of secondary hyperlipoproteinemia, the drug is used in cases where hyperlipoproteinemia persists despite effective treatment of the underlying disease (e.g., dyslipidemia in diabetes mellitus).

ICD codes

Dosage Regimen

Before starting and during treatment, the patient must follow a hypocholesterolemic diet.

Take orally once a day.

The dose depends on the dosage form used.

Treatment is long-term. The effectiveness of therapy should be assessed by the concentration of lipids (total cholesterol, LDL, triglycerides) in the blood serum. If there is no therapeutic effect after several months of therapy (usually after 3 months), the advisability of prescribing concomitant or alternative therapy should be considered.

Adverse Reactions

Blood and lymphatic system disorders rarely – decrease in hemoglobin and leukocytes.

Immune system disorders rarely – hypersensitivity reactions.

Nervous system disorders uncommon – headache.

Vascular disorders uncommon – thromboembolism (pulmonary embolism and deep vein thrombosis of the lower extremities).

Gastrointestinal disorders common – abdominal pain, nausea, vomiting, diarrhea, flatulence, increased activity of liver transaminases; uncommon – pancreatitis, cholelithiasis; rarely – hepatitis.

Skin and subcutaneous tissue disorders rarely – alopecia, photosensitivity reactions.

Allergic reactions uncommon – skin rash, skin itching, urticaria.

Musculoskeletal and connective tissue disorders uncommon – muscle lesions, including diffuse myalgia, myositis, muscle spasm and muscle weakness.

Reproductive system and breast disorders uncommon – erectile dysfunction.

Investigations very common – increased blood homocysteine concentration; uncommon – increased serum creatinine concentration; rarely – increased serum urea nitrogen concentration.

Contraindications

Hypersensitivity to fenofibrate; severe liver dysfunction – class C according to the Child-Pugh scale (including biliary cirrhosis and persistent liver dysfunction of unknown etiology); history of gallbladder disease; severe and moderate renal impairment (CrCl<60 ml/min); chronic or acute pancreatitis, except for cases of acute pancreatitis due to severe hypertriglyceridemia; history of photosensitivity or phototoxicity during treatment with fibrates or ketoprofen; breastfeeding period; age under 18 years.

With caution

In patients with factors predisposing to the development of myopathy and/or rhabdomyolysis, including age over 70 years, history of hereditary muscle diseases, hypothyroidism and alcohol abuse; use during pregnancy; with simultaneous use of oral anticoagulants, HMG-CoA reductase inhibitors

Use in Pregnancy and Lactation

Potential risk to humans is unknown, therefore use during pregnancy is possible only after careful assessment of the expected benefit of therapy for the mother versus the potential risk to the fetus.

Fenofibrate is contraindicated for use during breastfeeding.

Use in Hepatic Impairment

Contraindicated in severe liver dysfunction – class C according to the Child-Pugh scale (including biliary cirrhosis and persistent liver dysfunction of unknown etiology).

Use in Renal Impairment

Contraindicated in severe and moderate renal impairment (CrCl<60 ml/min).

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Use with caution in patients over 70 years of age.

Special Precautions

Before starting fenofibrate, treatment of conditions that may cause secondary hypercholesterolemia should be carried out, including: uncontrolled type 2 diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemia, obstructive liver diseases, consequences of drug therapy, alcoholism.

In patients with hyperlipidemia taking estrogens or hormonal contraceptives containing estrogens, it is necessary to determine whether the hyperlipidemia is primary or secondary. In such cases, the increase in lipid concentrations may be caused by the intake of estrogens.

It is recommended to monitor ALT, AST activity every 3 months during the first 12 months and periodically during further treatment. Patients whose liver transaminase activity increases during treatment require attention, and if ALT and AST activity increases more than 3 times the upper limit of normal (ULN), fenofibrate should be discontinued. If symptoms of hepatitis (jaundice, skin itching) appear, laboratory tests should be performed and, if the diagnosis of hepatitis is confirmed, Fenofibrate should be discontinued.

The risk of developing rhabdomyolysis may be increased in patients with a predisposition to myopathy and/or rhabdomyolysis, including age over 70 years, history of hereditary muscle diseases, hypothyroidism, alcohol abuse. In such patients, Fenofibrate should be used only if the expected benefit outweighs the possible risk of rhabdomyolysis.

If the creatinine concentration increases by more than 50% above the ULN, treatment should be suspended. It is recommended to determine the creatinine concentration during the first 3 months and periodically during further treatment.

During the first twelve months from the start of fenofibrate therapy, periodic monitoring of erythrocyte and leukocyte counts is recommended.

If signs or symptoms of immediate hypersensitivity are observed, it is necessary to immediately consult a doctor and discontinue the use of fenofibrate.

Drug Interactions

Fenofibrate enhances the effect of oral anticoagulants and may increase the risk of bleeding, which is associated with the displacement of the anticoagulant from plasma protein binding sites.

Several severe cases of reversible renal function impairment during simultaneous treatment with fenofibrate and cyclosporine have been described. Therefore, it is necessary to carefully monitor renal function in such patients and discontinue Fenofibrate in case of serious changes in laboratory parameters.

When taking fenofibrate simultaneously with HMG-CoA reductase inhibitors or other fibrates, the risk of serious toxic effects on muscle fibers increases. Such combination therapy should be carried out with caution and patients should be carefully monitored for signs of toxic effects on muscle tissue.

When fenofibrate and glitazones were used concomitantly, several cases of reversible paradoxical decrease in HDL cholesterol concentration were reported. Therefore, during concomitant therapy, monitoring of HDL cholesterol concentration is recommended, and in case of a pronounced decrease in HDL cholesterol concentration, the drugs should be discontinued.

Patients using Fenofibrate concomitantly with drugs metabolized by the CYP2C19, CYP2A6 and especially CYP2C9 isoenzymes with a narrow therapeutic index should be under close observation and, if necessary, adjustment of the doses of these drugs is recommended.

Storage Conditions

Store at 15°C (59°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.