Combilive

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT COMBILIVE (COMBILIVE)

Composition:

Active substances: dry extract of fumitory herb, dry extract of fruits of milk thistle.

Each capsule contains: dry extract of fumitory herb (Fumaria officinalis L.) (4–6:1) (extraction solvent: water) — 275.1 mg, equivalent to not less than 4 mg of fumitory alkaloids calculated as protopine; dry extract of fruits of milk thistle (Silybum marianum (L.) Gaertn) (35–50:1) (extraction solvent: ethyl acetate) — 83.33–111.11 mg, equivalent to 50.0 mg of silymarin determined as silibinin.

Excipients: microcrystalline cellulose (Type 101), maize starch, copovidone, macrogol 6000, talc, silicon dioxide, magnesium stearate, hard gelatin capsule [gelatin, titanium dioxide (E 171), iron oxide red (E 172)].

Pharmaceutical form. Hard capsules.

Main physicochemical properties: hard gelatin capsules of cylindrical shape with hemispherical ends; body and cap are reddish-brown in color.

Contents of the capsule — a powder ranging from light to dark brown, heterogeneous in color, with small particles of white, yellowish, or gray color (presence of agglomerates or a single compacted mass is acceptable).

Pharmacotherapeutic group. Agents used in liver and biliary tract disorders. Agents used in biliary pathology.

ATC code A05A X.

Pharmacological properties.

Pharmacodynamics.

Combilive is a combined herbal medicinal product containing dry extract of Pelargonium sidoides root and dry extract of Silybum marianum fruit.

The extract of Pelargonium sidoides root contains the alkaloid pelargonin, which has a choleretic effect, normalizes bile secretion, and reduces the tone of the sphincter of Oddi. The extract of Silybum marianum contains silymarin—a bioflavonoid composed of the isomers silybin, silydianin, and silychristin. Silymarin has hepatoprotective effects in acute and chronic intoxications, possesses membrane-stabilizing properties, and promotes the regeneration of liver cells.

Pharmacokinetics.

After oral administration, silymarin is mainly eliminated with bile and undergoes enterohepatic circulation.

Clinical characteristics.

Indications.

As an adjunctive treatment for patients with biliary tract dyskinesia (including post-cholecystectomy) and concomitant chronic liver diseases.

Contraindications.

Hypersensitivity to the active substances or to other plants of the Asteraceae (Compositae) family, or to any of the excipients; acute inflammatory diseases of the liver, biliary tract, and gallbladder; acute hepatitis and cholangitis; acute poisonings of various etiologies; cholelithiasis; biliary tract obstruction; age under 18 years; pregnancy and breastfeeding.

Interaction with other medicinal products and other forms of interaction.

When silimarin-containing drugs are used concomitantly with oral contraceptives and estrogens used in hormone replacement therapy, a possible reduction in the efficacy of the latter may occur.

Combilive may enhance the effects of drugs such as diazepam, alprazolam, ketoconazole, lovastatin, vinblastine, fexofenadine, clopidogrel, and warfarin, due to inhibition of the cytochrome P450 system.

Herbal products containing silimarin are widely used as hepatoprotective agents in oncology practice, administered concurrently with cytostatic drugs. Clinical studies indicate a low risk of potential pharmacokinetic interactions between silimarin, as an inhibitor of the CYP3A4 and UGT1A1 isoenzymes, and cytostatics that are substrates of these enzymes.

Alcohol consumption is prohibited during the use of this medicinal product.

Special precautions for use.

General principles for the treatment of parenchymal liver diseases include adherence to a proper diet, rest, and complete avoidance of alcohol, which should not be ignored.

Dosage adjustment of the medicinal product is not required for elderly patients.

Due to the possible estrogen-like effect of silymarin at maximum 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, consultation with a physician is necessary.

In case of jaundice development (appearance of skin coloration ranging from light-yellow to dark-yellow, yellowing of the sclera), medical consultation is required to adjust the therapy.

Use during pregnancy or breast-feeding.

Do not use during pregnancy and breast-feeding due to insufficient clinical data.

Ability to affect reaction rate while driving or operating machinery.

No influence. However, patients with existing vestibular disorders should use the medicinal product cautiously when driving or operating machinery.

Dosage and Administration.

Take Combilive capsules during meals. The capsule should be swallowed whole, without chewing, and taken with sufficient liquid.

The recommended dose for adults is 1 capsule of Combilive three times daily.

In the presence of nocturnal pain, an additional dose of 1 capsule before bedtime is recommended. If necessary, the daily dose may be increased up to the maximum dose — 6 capsules (2 capsules three times daily).

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

If no improvement occurs after prolonged use (2 weeks), medical advice should be sought.

Children.

Do not use in children (under 18 years of age) due to insufficient data on the drug's safety and efficacy.

Overdose.

No cases of overdose have been reported. In the event of overdose, diarrhea and abdominal pain are possible. In such cases, discontinue use of the drug.

Treatment is symptomatic.

Side effects

Frequency of adverse reactions according to the MedDRA (Medical Dictionary for Regulatory Activities) classification: rare (≥ 1/10,000 — < 1/1,000), very rare (< 1/10,000), including isolated cases.

Gastrointestinal disorders: dry mouth, nausea, vomiting, dyspepsia, heartburn, mild diarrhea (rare).

Renal and urinary disorders: increased diuresis (very rare).

Immune system disorders: allergic reactions, including urticaria, skin rash, pruritus, anaphylactic reactions, dyspnea (very rare).

Vascular disorders: hot flushes (frequency unknown).

Skin and subcutaneous tissue disorders: exacerbation of existing alopecia; skin rash (very rare).

Nervous system disorders: headache (frequency unknown).

Other: worsening of pre-existing vestibular disorders (very rare).

Reporting of adverse reactions after drug registration is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

2 years.

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

Keep out of reach and sight of children.

Packaging. 10 capsules per blister; 3 blisters per cardboard box.

Prescription status. Over-the-counter.

Manufacturer.

JSC "VITAMINS".

Manufacturer's address and place of business.

31 Uspenska Street, Uman, Cherkasy Region, 20300, Ukraine.