Silibor forte

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT SILIBOR FORTE (SILYBORFORTE)

Composition:

Active substance:

1 capsule contains dry extract of milk thistle (Silybi mariani extractum siccum) (22–27:1, extraction solvent — 95% acetone), equivalent to silymarin — 70 mg;

Excipients: crospovidone; calcium stearate; lactose monohydrate; capsule shell contains titanium dioxide (E 171), sunset yellow FCF (E 110), gelatin.

Pharmaceutical form. Capsules.

Main physicochemical properties: hard gelatin capsules of orange color. The capsule contents — a mixture of granules and powder of light yellow or brownish-yellow color; presence of particle agglomerates is allowed. The manufacturer's trademark — ZT — may be printed on the capsule.

Pharmacotherapeutic group. Agents used in liver diseases, lipotropic agents. Hepatotropic agents. Silymarin. ATC code A05B A03.

Pharmacological Properties.

Pharmacodynamics. The drug belongs to the group of hepatoprotective medicinal agents. It contains the active ingredient silymarin, derived from the fruits of Silybum marianum (milk thistle). Silymarin is a mixture of four isomeric flavonolignans: silybin, isosilybin, silydianin, and silychristin.

The drug exerts hepatoprotective and antitoxic effects.

It has been established that silymarin exhibits antagonistic effects against numerous hepatotoxic substances, including toxins from the death cap mushroom (Amanita phalloides), lanthanides, carbon tetrachloride, galactosamine, thioacetamide, and others. The anti-hepatotoxic action of silymarin is due to its competitive interaction with receptors for these toxins on the hepatocyte membrane, resulting in membrane-stabilizing effects. As a result, the progression of hepatic steatosis and fibrosis is slowed. Silymarin demonstrates metabolic and cell-regulating effects by modulating cell membrane permeability, inhibiting the 5-lipoxygenase pathway—particularly leukotriene B4 (LTB4)—and scavenging free reactive oxygen radicals. Silymarin stimulates the synthesis of proteins (structural and functional) and phospholipids in damaged liver cells (normalizing lipid metabolism), stabilizes their cellular membranes, and binds free radicals (antioxidant effect), thereby protecting liver cells from harmful influences and promoting their regeneration.

The effects of flavonoids, including silymarin, are associated with their antioxidant properties and microcirculation-improving effects. Clinically, these effects manifest as improvement in subjective and objective symptoms and normalization of liver function parameters (reduction in transaminase levels, γ-globulins, and serum bilirubin). This leads to an overall improvement in well-being, reduction in digestive-related complaints, and improved appetite in patients with impaired nutrient absorption due to liver disease.

Pharmacokinetics. Silymarin is slowly absorbed from the gastrointestinal tract (half-absorption time – 2.2 hours). It is extensively distributed throughout the body, with the highest concentrations found in the liver and lower amounts in the kidneys, lungs, heart, and other organs. It is metabolized in the liver via conjugation. Excretion occurs predominantly via bile (approximately 80%) in the form of glucuronides and sulfates, and to a lesser extent via urine (approximately 5%). Up to 40% of silymarin excreted in bile re-enters the enterohepatic circulation. The elimination half-life is 6 hours. It does not accumulate in the body.

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 drug, acute poisoning of various etiologies.

Interaction with other medicinal products and other forms of interaction. When silimarin is used concomitantly at maximum high doses with oral contraceptives or drugs used in estrogen replacement therapy, a possible reduction in the effectiveness of the latter may occur.

Silimarin may enhance the effects of antifungal agents (ketoconazole), antipsychotics (diazepam, alprazolam, lorazepam), hypolipidemic agents (lovastatin), antiallergic drugs (fexofenadine), anticoagulants (clopidogrel, warfarin), and certain anticancer drugs (vinblastine) due to inhibition of the cytochrome P450 system.

Herbal products containing silimarin are widely used as hepatoprotectors in oncological practice concomitantly with cytostatic agents. Clinical studies indicate a low risk of potential pharmacokinetic interactions between silimarin, as an inhibitor of the CYP3A4 and UGT1A1 isoenzymes, and cytostatic drugs which are substrates of these enzymes.

Special precautions for use

Treatment with the drug will be more effective in liver diseases 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 or uterus, prostate cancer). In such cases, medical consultation is required.

The drug contains lactose; therefore, if a patient has been diagnosed with intolerance to certain sugars, medical advice should be sought before taking this medicinal product.

Yellow Sunset FCF (E 110) may cause allergic reactions.

If jaundice develops, medical advice should be sought regarding adjustment of therapy.

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

Ability to influence reaction rate when driving or operating machinery. The drug does not affect the ability to drive or operate machinery; however, patients with pre-existing vestibular disorders should exercise caution until their individual response to the drug is established.

Method of administration and dosage.

Take before meals, without chewing, swallowing with a small amount of water. The recommended dose for adults and children aged 12 years and older is 2 capsules three 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. The drug is not recommended for children under 12 years of age, since the efficacy and safety of the drug in this patient population have not been established.

Overdose.

Cases of overdose have not been reported. In the event of accidental overdose, induce vomiting, perform gastric lavage, and administer activated charcoal. Symptomatic therapy is recommended if necessary. There is no known specific antidote.

Adverse reactions.

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

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

Respiratory system: dyspnea;

Urinary system: increased diuresis;

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

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

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

Shelf life. 5 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. Capsules № 10×2, № 10×4 in blisters in a box.

Availability. Over-the-counter.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA".

LIMITED LIABILITY COMPANY "FARMEKS GROUP".

Manufacturer's address and place of business. Ukraine, 61013, Kharkiv region, city of Kharkiv, Shevchenko Street, building 22.

(LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA")

Ukraine, 08301, Kyiv region, city of Boryspil, Shevchenko Street, building 100.

(LIMITED LIABILITY COMPANY "FARMEKS GROUP")