Carsil^® Forte (Capsules) Instructions for Use

Marketing Authorization Holder

Sopharma, JSC (Bulgaria)

ATC Code

A05BA03 (Silymarin)

Active Substance

Silibinin (Rec.INN registered by WHO)

Dosage Form

Carsil® Forte

Capsules 90 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin No. 0, light brown in color; the capsule contents are a powdery mass from light yellow to yellow-brown in color with agglomerates.

Excipients: lactose monohydrate, microcrystalline cellulose, wheat starch, povidone, polysorbate-80, colloidal anhydrous silicon dioxide, mannitol, crospovidone, sodium bicarbonate, magnesium stearate.

Shell composition iron oxide black – 0.02%, iron oxide red – 0.03%, titanium dioxide – 0.6666%, iron oxide yellow – 0.35%, gelatin – up to 100%.

6 pcs. – blisters (5) – cardboard packs.

Clinical-Pharmacological Group

Hepatoprotective agent

Pharmacotherapeutic Group

Means for the treatment of diseases of the liver and biliary tract; agents for the treatment of liver diseases, lipotropic agents

Pharmacological Action

A herbal remedy, a hepatoprotector. Contains an extract of Silybum marianum fruit, the main active substances of which are a mixture of 6 flavonolignan isomers (silymarin): silibinin A and B, iso-silibinin A and B, silydianin and silychristin. Silibinin is the most active among them. The mechanism of hepatoprotective action is not fully understood; existing data prove the presence of several main mechanisms of action.

Antioxidant action. Silymarin interacts with free radicals in the liver and converts them into less toxic compounds, interrupting the process of lipid peroxidation, prevents the destruction of cellular structures by binding with free radicals and regulating intracellular glutathione content. Depending on the concentration, it suppresses microsomal peroxidation induced by NADPH-Fe²⁺-ADP. It affects enzyme systems associated with glutathione and superoxide dismutase. Components of silymarin suppress the peroxidation of linoleic acid catalyzed by lipoxygenase and protect hepatic mitochondria and microsomes from the formation of lipid peroxides induced by various agents.

Membrane-stabilizing action. Silymarin stabilizes cell membranes and regulates their permeability, thereby preventing the entry of hepatotoxic agents into hepatocytes. It has been established that the membrane-stabilizing action of silymarin is due to its competitive interaction with receptors for corresponding toxins on the hepatocyte membrane. The effect of silymarin on membrane permeability is associated with qualitative and quantitative changes in membrane lipids – cholesterol and phospholipids.

Silymarin stimulates regenerative processes in the liver (restoration of damaged hepatocytes) as a result of activating the synthesis of structural and functional proteins (ribosomal synthesis of RNA, protein and DNA) and phospholipids. It has been experimentally established that silymarin also suppresses the transformation of hepatic stellate cells into myofibroblasts, a process responsible for the deposition of collagen fibers.

Anti-inflammatory action. According to the results of experimental studies, it has been shown that Silibinin at a certain concentration is capable of inhibiting the synthesis of leukotriene B4 (leukotriene B4/LTB₄) in isolated Kupffer cells of animals. Silymarin, Silibinin, silydianin and silychristin inhibit the activity of lipoxygenase and prostaglandin synthase in vitro. In in vitro studies on human polymorphonuclear leukocytes, it has been shown that one of the mechanisms for the realization of the anti-inflammatory action of silibinin is the suppression of hydrogen peroxide formation.

Clinically, the pharmacodynamic properties of silymarin are expressed in the improvement of subjective and objective symptoms and normalization of indicators of the functional state of the liver (transaminases, gamma-globulin, bilirubin).

Pharmacokinetics

Absorption

After oral administration, silymarin is incompletely absorbed from the gastrointestinal tract (up to 23-47%). C_max in plasma is reached 4-6 hours after a single oral dose.

Distribution

In studies with ¹⁴C-labeled silibinin, the highest concentrations are found in the liver, lungs, stomach, and pancreas, and in small amounts in the kidneys, heart, and other organs.

Metabolism

It undergoes enterohepatic recirculation. It is metabolized in the liver by conjugation with sulfates and glucuronic acid. Glucuronides and sulfates have been found in bile as metabolites.

Excretion

T_1/2 is 1-3 hours for unchanged silymarin and 6-8 hours for its metabolites. It is excreted mainly with bile (about 80%) in the form of glucuronides and sulfates, to a small extent (about 5%) by the kidneys unchanged. Does not accumulate.

Indications

As part of complex therapy

• Toxic liver damage;
• Conditions after acute hepatitis;
• Chronic hepatitis of non-viral etiology;
• Liver steatosis (non-alcoholic and alcoholic);
• Liver cirrhosis;
• Prevention of liver damage during long-term use of medications, alcohol, in chronic intoxication (including occupational).

ICD codes

Dosage Regimen

Capsules are taken orally with a sufficient amount of water.

Adults and children over 12 years

Treatment of severe liver lesions begins with a dose of 1 capsule 3 times/day. In milder and moderate cases, the dose is 1 capsule 1-2 times a day.

For the prevention of chemical intoxications – 1-2 capsules per day. The course of treatment continues for at least 3 months.

Children under 12 years of age

There is insufficient clinical data on use in children.

Adverse Reactions

From the immune system: very rarely – skin allergic reactions – itching, rash; with unknown frequency – anaphylactic shock.

From the hearing organ and labyrinthine disorders: rarely – intensification of existing vestibular disorders.

From the gastrointestinal tract: rarely – diarrhea as a result of enhanced function of the liver and gallbladder; with unknown frequency – nausea, vomiting, dyspepsia, decreased appetite, flatulence.

Contraindications

• Hypersensitivity to the active substance or any of the excipients included in the used drug;
• Children under 12 years of age;
• Lactase deficiency, galactosemia or glucose/galactose malabsorption syndrome (due to the presence of lactose in the composition).
• Celiac disease (gluten enteropathy) (due to the presence of wheat starch in the composition).

With caution

Patients with hormonal disorders (endometriosis, uterine fibroids, carcinoma of the breast, ovaries and uterus, prostate carcinoma) due to the possible manifestation of the estrogen-like effect of silymarin.

Use in Pregnancy and Lactation

Not recommended for use during pregnancy and breastfeeding.

Pediatric Use

Contraindicated in children under 12 years of age.

Special Precautions

Effect on ability to drive vehicles and mechanisms

The use of the drug as monotherapy does not affect the ability to drive vehicles and work with mechanisms.

Drug Interactions

Pharmacodynamic drug interaction

Silymarin does not have a significant effect on the pharmacodynamics of other drugs.

When used concomitantly with oral contraceptives and drugs used for hormone replacement therapy, a decrease in the effects of the latter is possible.

Pharmacokinetic drug interaction

Since silymarin has an inhibitory effect on the cytochrome P450 system, an increase in the plasma concentration of drugs such as diazepam, alprazolam, ketoconazole, lovastatin, vinblastine is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

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.