Mebisin retard®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MEBSYN RETARD® (MEBSYN RETARD®)

Composition:

Active substance: mebeverine hydrochloride (mebeverine);

1 capsule contains 200.0 mg of mebeverine hydrochloride in the form of prolonged-release pellets;

Excipients: spherical sugar, sucrose, ethylcellulose, magnesium stearate, povidone, polyethylene glycol (macrogol), hypromellose (hydroxypropylmethylcellulose).

Pharmaceutical form. Capsules.

Main physical and chemical properties: hard gelatin capsules size № 1, body orange-colored, cap white-colored, with the imprint "S" on both parts of the capsule, containing white-colored pellets.

Pharmacotherapeutic group.

Agents used in functional gastrointestinal disorders. Synthetic anticholinergic agents, esterified tertiary amines. ATC code A03AA04.

Pharmacological Properties

Pharmacodynamics

Mechanism of Action and Pharmacodynamic Effects

Mebeverine is a myotropic spasmolytic agent with selective action on the smooth muscles of the gastrointestinal tract. It relieves spasms without suppressing normal intestinal motility. Since this action is not mediated via the autonomic nervous system, typical anticholinergic adverse effects do not occur.

Clinical Efficacy and Safety

The clinical efficacy and safety of various dosage forms of mebeverine have been studied in over 1500 patients. Significant relief of predominant symptoms of irritable bowel syndrome (e.g., abdominal pain, characteristics of bowel movements) was generally observed in reference and controlled clinical trials with primary endpoints.

All dosage forms of mebeverine were generally safe and well tolerated under the recommended dosing regimen.

Children

Clinical studies with mebeverine tablets or capsules have been conducted only in adults. Data on clinical efficacy and safety, as well as post-marketing experience with the use of mebeverine suspension in patients aged 3 years and older, have demonstrated that mebeverine is an effective, safe medicinal product that is well tolerated.

Clinical studies of mebeverine suspension have shown that it is effective in relieving symptoms of irritable bowel syndrome in children. Further open-label, baseline-controlled studies of mebeverine suspension have confirmed the efficacy of the drug.

The dosing regimen for tablets or capsules is based on the safety and tolerability of mebeverine.

Pharmacokinetics

Absorption

Mebeverine is rapidly and completely absorbed after oral administration in tablet form. Due to the prolonged release of the drug from the capsule, it can be administered twice daily.

Distribution

With repeated administration of Mebsin Retard®, no significant accumulation occurs.

Metabolism

Mebeverine hydrochloride is mainly metabolized by esterases, which in the first step of metabolism cleave the ester bonds, forming veratric acid and mebeverine alcohol. In plasma, demethylcarboxylic acid is the main metabolite. The elimination half-life of demethylcarboxylic acid at steady state is 5.77 hours. With repeated administration of capsules (200 mg twice daily), the Cmax of demethylcarboxylic acid was 804 ng/mL, and tmax was approximately 3 hours. The relative bioavailability of the prolonged-release capsules was found to be optimal, with a mean ratio of 97%.

Elimination

Mebeverine is not excreted unchanged; it is completely metabolized, and metabolites are almost entirely eliminated. Veratric acid is excreted in urine. Mebeverine alcohol is also excreted by the kidneys as carboxylic or demethylcarboxylic acid.

Children

Pharmacokinetic studies in children have not been conducted.

Clinical characteristics.

Indications.

Adults and children aged 10 years and older:

• symptomatic treatment of abdominal pain and spasms, intestinal disorders and sensation of discomfort in the intestinal area in irritable bowel syndrome;
• treatment of secondary gastrointestinal spasms caused by organic diseases.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

Studies on interaction were conducted only with alcohol. In vitro and in vivo studies demonstrated absence of any interaction between the drug and ethanol.

Special precautions for use.

Since the drug contains sugar, it should not be taken by patients with rare hereditary conditions such as galactose or fructose intolerance, lactase deficiency, glucose-galactose malabsorption, or sucrase-isomaltase deficiency.

Use during pregnancy or breastfeeding.

Mebcin Retard® is not recommended for use during pregnancy or breastfeeding.

Ability to influence the reaction rate when driving or operating machinery.

Studies on the effect on the ability to drive or operate machinery have not been conducted. However, the pharmacodynamic and pharmacokinetic profile, as well as post-marketing experience, do not indicate any harmful effect on the ability to drive or operate machinery.

Method of Administration and Dosage

The medication is intended for oral administration.

Capsules should be taken with an adequate amount of water (not less than 100 ml). Chewing the capsules is not recommended, as the capsule coating is designed for prolonged release of the active substance.

For adults and children aged 10 years and older, the recommended dose is 1 capsule twice daily (in the morning and in the evening).

Duration of treatment is not limited. If one or more doses are missed, the patient should take the next dose as prescribed. A missed dose should not be taken additionally before the next scheduled dose.

Special Patient Groups

Dosage studies in elderly patients and in patients with impaired renal and/or hepatic function have not been conducted. However, based on available post-marketing data, no specific risk has been identified in elderly patients or in patients with impaired renal and/or hepatic function. Dose adjustment in the above-mentioned patient groups is not required.

Children

Not recommended for children under 10 years of age due to the high content of active substance in Mebesin Retard®.

Overdose

In cases of overdose, central nervous system stimulation may theoretically occur. In reported cases of mebeverine overdose, symptoms were either absent or mild and rapidly resolved. Observed overdose symptoms were of neurological or cardiovascular origin.

Treatment: No specific antidote is known. Symptomatic treatment is recommended. Gastric lavage is indicated only in cases of intoxication with multiple drugs, diagnosed within 1 hour after drug intake. Measures to reduce absorption are not necessary.

Adverse reactions.

The following adverse reactions have been reported spontaneously during post-marketing surveillance. The frequency cannot be precisely determined based on available data.

Allergic reactions, primarily affecting the skin, have been observed.

Skin and subcutaneous tissue disorders: urticaria, angioneurotic edema, facial swelling, hyperemia, skin rash, including hemorrhagic rash.

Nervous system disorders: headache, dizziness, depression.

Gastrointestinal disorders: diarrhea or constipation.

General disorders: hypersensitivity (anaphylactic reactions).

Reporting of adverse reactions after drug registration is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy 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.

Keep out of reach of children.

Store in the original packaging at a temperature not exceeding 30 °C.

Packaging.

10 capsules in a blister pack. 3 blisters in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

Evertogen Life Sciences Limited.

Manufacturer's address and location of operations.

Plot No: S-8, S-9, S-13/P & S-14/P TSIIC, Pharma SEZ, Green Industrial Park, Polepally (V), Jadcherla (M), Mahabubnagar, Telangana, IN-509 301, India.