Duspatalin® retard 200

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DUSPATALIN® RETARD 200 (DUSPATALIN® RETARD 200)

Composition:

Active substance: mebeverine hydrochloride;

1 capsule contains mebeverine hydrochloride 200 mg;

Excipients: magnesium stearate, methacrylic acid copolymer dispersion, talc, hypromellose, polyacrylate dispersion, glycerol triacetate;

Hard gelatin capsule (size № 1): titanium dioxide (E 171), gelatin.

Pharmaceutical form. Prolonged-release hard capsules.

Main physicochemical properties: opaque white hard gelatin capsules of size № 1 with appropriate marking "245", containing granules of white to almost white color.

Pharmacotherapeutic group. Drugs used in functional gastrointestinal disorders. Synthetic anticholinergic agents, esterified tertiary amines. Mebeverine. ATC code A03A A04.

Pharmacological Properties.

Pharmacodynamics.

Mechanism of action and pharmacodynamic effects.

Mebeverine is a myotropic spasmolytic 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 side 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 (such as abdominal pain, altered bowel habits) was generally observed in reference and baseline-controlled clinical trials.

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

Children.

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

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

The dosage regimen for the drug in tablet or capsule form has been established 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 Duospatalin® Retard 200, no significant accumulation occurs.

Biotransformation.

Mebeverine hydrochloride is mainly metabolized by esterases, which in the first stage of metabolism cleave the ester bonds, forming veratric acid and mebeverine alcohol. In plasma, demethylcarboxylic acid (DMCA) is the main metabolite. The elimination half-life of DMCA at steady state is 5.77 hours. With repeated administration of capsules (200 mg twice daily), the Cmax for DMCA 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 partially excreted by the kidneys as the corresponding carboxylic acid (CA) and partially as demethylcarboxylic acid (DMCA).

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 discomfort in the intestinal area associated with irritable bowel syndrome;
• treatment of secondary gastrointestinal spasms caused by organic diseases.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients listed in the section "Composition".

Interaction with other medicinal products and other forms of interaction.

Interaction studies have not been performed, except for interaction with alcohol. In vitro and in vivo studies in animals have demonstrated no interaction between Duspatalin® Retard 200 and ethanol.

Special precautions for use.

None.

Use during pregnancy or breastfeeding.

Pregnancy

There are only very limited data on the use of mebeverine in pregnant women. Reproductive toxicity studies conducted in animals are insufficient. Duospatalin® Retard 200 is not recommended during pregnancy.

Breastfeeding

It is unknown whether mebeverine or its metabolites are excreted in human breast milk. Excretion of mebeverine into the breast milk of animals has not been studied. Duospatalin® Retard 200 should not be used during breastfeeding.

Fertility

There are no clinical data on the effect on male or female fertility; however, available animal studies do not indicate any harmful effect of Duospatalin® Retard 200 on fertility.

Ability to affect reaction speed when driving or operating machinery.

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

Dosage and Administration.

For oral use.

Swallow the capsules with sufficient amount of water (not less than 100 mL). Chewing is not recommended due to the capsule coating designed to ensure a prolonged-release mechanism.

For adults and children aged 10 years and older: take 1 capsule twice daily (in the morning and evening).

Duration of use is not limited. If one or more doses are missed, the patient should take the next dose as prescribed. Missed dose(s) should not be compensated by taking additional doses along with the regular dose.

Special populations.

Dosage studies in elderly patients and 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 patients with impaired renal and/or hepatic function. Dose adjustment in the above-mentioned patient groups is not considered necessary.

Children.

Duspatalin® Retard 200 should not be used in children under 3 years of age due to lack of clinical data in this age group. Duspatalin® Retard 200, 200 mg capsules, should not be used in children aged 3 to 10 years due to the high content of active substance.

Overdose.

Symptoms. Theoretically, in case of overdose, central nervous system stimulation may occur. In reported cases of overdose, symptoms were either absent or mild and generally resolved quickly. Observed overdose symptoms were of neurological or cardiovascular origin.

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

Side effects.

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

Allergic reactions were observed predominantly, but not exclusively, affecting the skin.

Disorders of the skin and subcutaneous tissue:

urticaria, angioneurotic edema, facial swelling, rash.

Immune system disorders:

hypersensitivity (anaphylactic reactions).

Shelf life. 3 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Do not store at temperatures below 5 °C. Keep out of reach and sight of children.

Packaging. 10 capsules per blister, 3 blisters per cardboard box; or 15 capsules per blister, 1, 2, or 4 blisters per cardboard box.

Prescription status. Prescription only.

Manufacturer. Mylan Laboratories SAS.

Manufacturer's address and location of operations.
Route de Belleville, Lieu dit Maillard, 01400, Chatillon-sur-Chalaronne, France.