Silibor 35

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT SILYBOR 35 (SILYBOR 35)

Composition:

Active ingredient: silymarin;

One tablet contains 35 mg of dry extract of Silybum marianum (22–27:1, extracted with 95% acetone), equivalent to 35 mg of silymarin;

Excipients: potato starch; sodium starch glycolate (type A); calcium stearate; lactose monohydrate; hypromellose; titanium dioxide (E 171); sunset yellow FCF (E 110).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: film-coated tablets, from orange to brownish-orange in colour, with a biconvex surface. Specks on the tablet surface are permissible. A cross-section reveals two layers.

Pharmacotherapeutic group. Drugs used in liver diseases, lipotropic agents. Hepatotropic agents. ATC code A05BA03.

Pharmacological properties.

Pharmacodynamics.

The drug belongs to the group of hepatoprotective medicinal agents. The drug contains the active ingredient silymarin, obtained from the fruits of Silybum marianum (milk thistle). Silymarin is a mixture of four flavonolignan isomers: silybin, isosilybin, silydianin, and silychristin. The medicinal product exerts hepatoprotective and antitoxic effects.

The drug inhibits the penetration of toxins into liver cells (demonstrated in poisoning with Amanita phalloides), and also induces physicochemical stabilization of hepatocyte cell membranes, thereby limiting or preventing the loss of soluble cellular components (including transaminases) from liver cells.

The antioxidant effect of the drug is due to the interaction of silybin with free radicals in the liver, converting them into less toxic compounds. Thus, the process of lipid peroxidation is interrupted, preventing further destruction of cellular structures; toxins are neutralized via physiological pathways.

Silymarin stimulates the synthesis of proteins (structural and functional) and phospholipids in damaged liver cells (normalizing lipid metabolism), stabilizes their cell membranes, binds free radicals (antioxidant effect), thereby protecting liver cells from harmful influences and promoting their regeneration. Clinical effects of the drug are manifested in improvement of the general condition of patients with liver diseases and reduction of subjective symptoms (such as weakness, feeling of heaviness in the right hypochondrium, loss of appetite, skin pruritus, vomiting).

Laboratory parameters improve: decreased activity of transaminases, gamma-glutamyl transferase, alkaline phosphatase, and reduced bilirubin levels in blood plasma. Long-term use of the drug significantly increases survival rates in patients suffering from liver cirrhosis.

Pharmacokinetics.

After oral administration, silymarin is slowly absorbed from the gastrointestinal tract. It undergoes enterohepatic circulation. It does not accumulate.

It is intensively distributed throughout the body. In studies using 14C-labeled silybin, the highest concentrations of the substance were found in the liver, and only negligible amounts in the kidneys, lungs, heart, and other organs.

Silymarin is metabolized in the liver via conjugation. Metabolites such as glucuronides and sulfates have been detected in bile.

The elimination half-life of silymarin is 6 hours. It is excreted mainly in bile (approximately 80%) in the form of glucuronides and sulfates, and to a minor extent (approximately 5%) in urine.

Clinical characteristics.

Indications.

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

Contraindications.

Hypersensitivity to the components of the medicinal product. Acute poisonings of various etiologies.

Interaction with other medicinal products and other types of interactions.

When silimarin is used concomitantly with oral contraceptives and drugs used in estrogen replacement therapy, a decrease in the efficacy of the latter is possible.

Silimarin may enhance the effects of such medicinal products as diazepam, alprazolam, lorazepam, ketoconazole, lovastatin, vinblastine, antihistamines (fexofenadine), anticoagulants (clopidogrel, warfarin), atorvastatin, due to inhibition of the cytochrome P450 system.

Herbal products containing silimarin are widely used as hepatoprotectors in oncology practice, administered concomitantly with cytostatics. There is a low risk of possible pharmacokinetic interactions between silimarin, as an inhibitor of CYP3A4 and UGT1A1 isoenzymes, and cytostatics that are substrates of these enzymes.

Special precautions for use

Treatment with this medicinal product will be effective in patients with liver disorders only if a proper diet is followed and alcohol consumption is avoided.

Due to the possible estrogen-like effect of silimarins, caution should be exercised when administering it to patients with hormonal disorders (endometriosis, uterine fibroids, carcinoma of the breast, ovaries or uterus, prostate cancer). In such cases, medical advice is necessary.

If a patient has known intolerance to certain sugars, medical advice should be sought before taking this medicinal product.

If jaundice develops (skin color changes from light yellow to dark yellow, yellowing of the eye sclera), medical advice must be sought to adjust the treatment regimen.

Yellow FCF (E 110) may cause allergic reactions.

If a patient has known intolerance to certain sugars, medical advice should be sought before taking this medicinal product.

Use during pregnancy or breastfeeding

There are no data available on the safety and efficacy of using this medicinal product during pregnancy or breastfeeding; therefore, it should not be administered during these periods.

Ability to influence reaction speed when driving or operating machinery

This medicinal product does not affect the ability to drive vehicles or operate machinery.

Patients with vestibular disorders should exercise caution when driving vehicles or operating machinery while taking this medicinal product.

Method of Administration and Dosage

The medicinal product should be administered orally to adults and children aged 12 years and older, without chewing, swallowing with a small amount of water.

For adults and children aged 12 years and older, the recommended dose is 1–2 tablets 3 times daily.

The duration of treatment is determined individually by a physician depending on the nature and course of the disease.

The average duration of treatment is 3 months.

Children.

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

Overdose.

There have been no reports of overdose.

Treatment: in case of overdose (intake at a dose several times higher than the therapeutic dose), induce vomiting, perform gastric lavage, administer activated charcoal, and apply symptomatic treatment as prescribed by a physician.

Adverse reactions.

The drug is usually well tolerated.

Rarely, in individual cases and in the presence of individual hypersensitivity, the following adverse effects may occur:

Gastrointestinal system: nausea, dyspepsia, diarrhea, vomiting, heartburn;

Skin and skin appendages: in isolated cases, skin allergic reactions are possible—itching, rash, urticaria, increased alopecia;

Other: very rarely, exacerbation of existing vestibular disorders, increased diuresis, dyspnea may occur.

Adverse effects are transient and disappear after discontinuation of the drug without requiring special interventions.

Shelf life. 2 years.

Storage conditions.

Store in original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging. Tablets № 10×3 in blisters in a box.

Availability category. Over-the-counter.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVYA".

Limited Liability Company "FARMEKS GROUP".

Manufacturer's address and location of business activity.

22 Shevchenka Street, Kharkiv, Kharkiv Region, 61013, Ukraine.

(LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVYA")

100 Shevchenka Street, Boryspil, Kyiv Region, 08301, Ukraine.

(Limited Liability Company "FARMEKS GROUP")