LEGALON® 140

INSTRUCTIONS FOR MEDICINAL USE OF LEGALON® 140 (LEGALON® 140)

Composition:

Active substance: dry extract from fruits of milk thistle (Silybum marianum);

One capsule contains 173–186.7 mg of dry extract from fruits of milk thistle (Silybum marianum) [36-44:1], corresponding to 140 mg of silymarin (DNPH), or 108.2 mg of silymarin (HPLC/DAB), calculated as silibinin (solvent – ethyl acetate);

Excipients: microcrystalline cellulose, maize starch, sodium starch glycolate (type A), sodium lauryl sulfate, magnesium stearate, iron oxide red E 172, iron oxide black E 172, titanium dioxide E 171, gelatin.

Medicinal form. Capsules.

Main physicochemical properties: hard gelatin capsule size 1. Brown cap without marking, brown body without marking. Capsule contents – homogeneous, compacted powder of brownish-yellow color.

Pharmacotherapeutic group. Agents used in the treatment of liver diseases. Hepatotropic agents.

ATC code A05BA03.

Pharmacological properties.

Pharmacodynamics.

The ability of silymarin to bind free radicals provides its antioxidant activity. Thus, the pathophysiological process of lipid peroxidation, responsible for the destruction of cellular membranes, is interrupted or prevented. In damaged hepatocytes, silymarin stimulates protein synthesis and normalizes phospholipid metabolism, resulting in stabilization of cellular membranes and limitation or prevention of the loss of soluble cellular components (particularly transaminases) from liver cells. Silymarin inhibits the penetration of certain hepatotoxic substances (e.g., toxins from Amanita phalloides) into the cell. Silymarin enhances protein synthesis through specific stimulation of RNA polymerase A, a nuclear enzyme. This leads to increased formation of ribosomal RNA and, consequently, to stimulation of synthesis of structural and functional proteins (enzymes). As a result, regenerative capacity is improved and liver cell regeneration is accelerated.

Pharmacokinetics.

Absorption is low and slow (half-absorption period – 2.2 hours), undergoes hepatic metabolism via conjugation, elimination half-life – 6.3 hours. Excreted predominantly in bile in the form of glucuronides and sulfates. Does not accumulate in the body. Enterohepatic circulation is observed.

Clinical characteristics.

Indications. Toxic liver damage: for supportive treatment of patients with chronic inflammatory liver diseases or liver cirrhosis.

Contraindications. Hypersensitivity to fruits of Silybum marianum (milk thistle), to other components of the drug or to any of the excipients; acute poisoning of various etiologies.

Interaction with other medicinal products and other forms of interaction.

When silimarins are used concomitantly at maximum high doses with oral contraceptives or drugs used in estrogen replacement therapy, a possible reduction in efficacy of the latter may occur. Due to inhibition of the cytochrome P450 system, silimarins thereby enhance the effect of certain medicinal products, namely: antiallergic agents (fexofenadine); hypocholesterolemic agents (lovastatin); anticoagulants (clopidogrel, warfarin); antipsychotic agents (alprazolam, diazepam, lorazepam); antifungal agents (ketoconazole); some anticancer drugs (vinblastine).

Special precautions for use.

Treatment with the drug for liver diseases will be more effective if a proper diet is followed and alcohol consumption is avoided.

Due to the possible estrogen-like effect of silymarin at very high doses, it should be used with caution in patients with hormonal disorders (endometriosis, uterine fibroids, carcinoma of the breast, ovaries and uterus, prostate carcinoma). In such cases, medical consultation is required.

If symptoms of jaundice appear (skin discoloration ranging from light yellow to dark yellow, yellowing of the eye whites), medical advice must be sought.

Use during pregnancy or breast-feeding.

Data on the efficacy and safety of the drug during pregnancy or breast-feeding are lacking; therefore, it should not be administered during these periods.

Ability to affect reaction speed when driving vehicles or operating machinery.

Not reported. However, if any vestibular disturbances occur in a patient during treatment, the patient should refrain from driving vehicles or operating machinery.

Method of Administration and Dosage.

For adults and children aged 12 years and older: take 1 capsule three times daily. The capsules should be swallowed whole, without chewing, with sufficient amount of liquid. The duration of treatment is determined individually by a physician, depending on the nature and course of the disease.

Children. There is insufficient data regarding the use of this medication in children; therefore, it should not be administered to children under 12 years of age.

Overdose.

Signs and symptoms of intoxication have not been observed. The adverse reactions described below may be intensified.

No specific antidote is known. Symptomatic treatment is recommended.

Adverse reactions.

Criteria for assessing the frequency of adverse drug reaction:

The medicinal product is well tolerated. Rarely, in individual cases and in the presence of individual hypersensitivity, the following adverse effects may occur:

Gastrointestinal tract: nausea, vomiting, dyspepsia, heartburn, mild diarrhea;

Respiratory system: dyspnea;

Urinary system: increased diuresis;

Skin and skin appendages: exacerbation of alopecia; in isolated cases, hypersensitivity reactions including skin rashes and pruritus may occur;

Other: very rarely, exacerbation of pre-existing vestibular disorders may be observed.

Adverse reactions are temporary and disappear after discontinuation of the drug without the need for special interventions.

Shelf life.

5 years.

Storage conditions.

Store at a temperature not exceeding 30 °C in a place inaccessible to children.

Packaging.

10 capsules per blister; 2, 3, or 6 blisters per cardboard box.

Availability. Over-the-counter (without prescription).

Manufacturer.

MADAUS GmbH.

Manufacturer's address.

Lutticher Strasse 5, 53842 Troisdorf, Germany.

Marketing Authorization Holder.

MEDA Pharma GmbH & Co. KG.

Address of the Marketing Authorization Holder.

Benzstrasse 1, 61352 Bad Homburg, Germany.