Mebeverine-SZ (Tablets) Instructions for Use

Marketing Authorization Holder

Severnaya Zvezda NAO (Russia)

Contact Information

SEVERNAYA ZVEZDA NAO (Russia)

ATC Code

A03AA04 (Mebeverine)

Active Substance

Mebeverine (Rec.INN registered by WHO)

Dosage Form

Mebeverine-SZ

Film-coated tablets, 135 mg: 20, 30, 40, 50, or 60 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets yellow in color, round, biconvex; the tablet core on the cross-section is white or almost white.

Excipients : tablet core lactose monohydrate (milk sugar), potato starch, povidone K30 (medium molecular weight polyvinylpyrrolidone), talc, magnesium stearate; tablet coating hypromellose, talc, polysorbate-80 (tween-80), aluminum lake based on quinoline yellow dye, titanium dioxide (E171).

10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (4) – cardboard packs.
10 pcs. – blister packs (5) – cardboard packs.
10 pcs. – blister packs (6) – cardboard packs.
30 pcs. – polymer jars (1) – cardboard packs.
30 pcs. – polymer bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Myotropic antispasmodic

Pharmacotherapeutic Group

Drugs for the treatment of functional gastrointestinal disorders; synthetic anticholinergic agents, esters with a tertiary amino group

Pharmacological Action

Mechanism of action

A myotropic-acting antispasmodic, it has a direct effect on the smooth muscles of the gastrointestinal tract without affecting normal intestinal peristalsis.

Multiple mechanisms, such as reducing ion channel permeability, blocking norepinephrine reuptake, local anesthetic action, and altering water absorption may cause the local effect of mebeverine on the gastrointestinal tract, but the exact mechanism of action is unknown. Through these mechanisms, Mebeverine has an antispasmodic effect, normalizing intestinal peristalsis and not causing persistent relaxation of gastrointestinal smooth muscle cells (hypotonia).

Pharmacodynamic effects

Systemic adverse reactions, including anticholinergic ones, are absent.

The duration of mebeverine use is not limited. A sustained improvement in symptoms is noted during the first 2-4 weeks of therapy. The most pronounced efficacy may be observed after 6-8 weeks of therapy. When choosing the duration of the treatment course, individual characteristics of the disease course and severity of symptoms should be taken into account.

To further improve the symptoms of the disease, continuation of treatment under medical supervision for 12 months with a continuous therapy regimen or for 6 months with “on-demand” therapy is recommended.

Clinical efficacy and safety

Results of clinical studies confirmed improvement in gastrointestinal symptoms and patients’ quality of life within 2-4 weeks with subsequent improvement upon prolongation of treatment up to 6-8 weeks.

Pharmacokinetics

Absorption

Mebeverine is rapidly and completely absorbed after oral administration.

Distribution

Significant accumulation does not occur upon repeated dosing of the drug.

Metabolism

Mebeverine hydrochloride is mainly metabolized by esterases, which in the first stage cleave the ester into veratric acid and mebeverine alcohol. The main metabolite circulating in plasma is the demethylated carboxylic acid. The T_1/2 at steady state of the demethylated carboxylic acid is approximately 2.45 h. Upon repeated dosing, the C_max of the demethylated carboxylic acid in blood is 1670 ng/ml, the T_max of the demethylated carboxylic acid in blood is 1 h.

Excretion

Mebeverine as such is not excreted from the body but is completely metabolized; its metabolites are almost completely eliminated from the body. Veratric acid is excreted by the kidneys. Mebeverine alcohol is also excreted by the kidneys, partly as carboxylic acid and partly as demethylated carboxylic acid.

Indications

Adults aged 18 years and older

• Symptomatic treatment of pain, spasms, dysfunction and discomfort in the intestinal area associated with irritable bowel syndrome.

Symptoms may include: abdominal pain, cramps, feeling of bloating and flatulence, change in stool frequency (diarrhea, constipation, or alternating diarrhea and constipation), change in stool consistency.

ICD codes

Dosage Regimen

The drug is taken orally. The tablets must be swallowed without chewing, with a sufficient amount of water (at least 100 ml).

It is recommended to take 1 tab. 3 times/day, approximately 20 minutes before meals. At the beginning of drug use, the duration of therapy should be at least 6-8 weeks in order to adequately assess the effectiveness of treatment.

The duration of drug administration is not limited.

If the patient forgot to take one or more doses, the drug should be continued with the next dose. One or more missed doses should not be taken in addition to the regular dose.

Special patient groups

Studies of the dosage regimen in elderly patients, patients with renal and/or hepatic impairment have not been conducted. Available data from post-marketing use of the drug have not revealed specific risk factors for its use in these patient groups. Changes in the dosage regimen in elderly patients and patients with renal and/or hepatic impairment are not required.

Children

The safety and efficacy of the drug Mebeverine-SZ in children under 18 years of age have not been established at this time. Data are not available.

Adverse Reactions

Reports of the listed adverse reactions were spontaneous, and there is insufficient data for an accurate assessment of the frequency of cases.

Allergic reactions were observed mainly from the skin, but other manifestations of allergy were also noted.

From the immune system hypersensitivity reactions (anaphylactic reactions, which may include difficulty breathing, rapid pulse, sharp decrease in blood pressure (weakness and dizziness), sweating).

From the skin and subcutaneous tissues urticaria (allergic rash), angioedema (serious allergic reaction that may include difficulty breathing, swelling of the face, neck, lips, tongue, throat), facial edema, exanthema (skin rash).

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after drug registration in order to ensure continuous monitoring of the drug’s benefit-risk ratio. Healthcare professionals are recommended to report any suspected adverse drug reactions through the national adverse reaction reporting system of the member states of the Eurasian Economic Union.

Contraindications

• Hypersensitivity to any component of the drug;
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
• Pregnancy;
• Breastfeeding period;
• Age under 18 years.

Use in Pregnancy and Lactation

Pregnancy

There are only very limited data on the use of mebeverine in pregnant women. Data from animal studies are insufficient to assess reproductive toxicity. It is not recommended to use the drug Mebeverine-SZ during pregnancy.

Breastfeeding period

Information on the excretion of mebeverine or its metabolites into breast milk is insufficient. Studies on the excretion of mebeverine into milk in animals have not been conducted. The drug Mebeverine-SZ should not be taken while breastfeeding.

Fertility

Clinical data on the effect of the drug on fertility in men or women are lacking, however, known animal studies have not demonstrated adverse effects of the drug Mebeverine-SZ.

Use in Hepatic Impairment

Changes in the dosage regimen in patients with hepatic impairment are not required.

Use in Renal Impairment

Changes in the dosage regimen in patients with renal impairment are not required.

Pediatric Use

The use of the drug is contraindicated under 18 years of age.

Geriatric Use

Changes in the dosage regimen in elderly patients are not required.

Special Precautions

Before taking the drug Mebeverine-SZ, the patient should consult a doctor, in case

• If the symptoms of the disease have occurred for the first time;
• Of unintentional and unexplained weight loss;
• Anemia;
• Rectal bleeding or blood in the stool;
• Fever;
• If someone in the patient’s family has been diagnosed with colon cancer, celiac disease, or inflammatory bowel disease;
• If the patient is over 50 years old and if the symptoms of the disease have occurred for the first time;
• Of recent antibiotic use.

The patient should consult a doctor if the condition worsens while taking the drug or if there is no improvement in symptoms after 2 weeks of use.

Excipients

The drug Mebeverine-SZ contains lactose monohydrate (milk sugar). Patients with rare hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this drug.

Effect on ability to drive vehicles and mechanisms

Studies of the effect of the drug on the ability to drive a car and other mechanisms have not been conducted. The pharmacological properties of the drug, as well as the experience of its use, do not indicate any adverse effect of mebeverine on the ability to drive a car and other mechanisms.

Overdose

In case of an overdose of the drug Mebeverine-SZ, the patient should immediately consult a doctor.

Symptoms theoretically, in case of overdose, an increase in CNS excitability is possible. In cases of mebeverine overdose, symptoms were either absent or minor and, as a rule, quickly reversible. The observed overdose symptoms were neurological and cardiovascular in nature.

Treatment a specific antidote is unknown. Symptomatic treatment is recommended. Gastric lavage is necessary only if intoxication is detected within approximately 1 hour after taking several doses of the drug. Measures to reduce the level of absorption are not required.

Drug Interactions

Only studies on the interaction of this drug with ethanol have been conducted. Animal studies have demonstrated no interaction between the drug Mebeverine-SZ and ethyl alcohol.

Storage Conditions

The drug should be stored out of the reach of children, protected from light, at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 3 years. Do not use after the expiration date printed on the package.

Dispensing Status

The drug is dispensed without a prescription.

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.