Duspatalin Retard

Opaque white, hard gelatin capsule, size no. 1, with standard imprint 245.
One hard controlled-release capsule contains 200 mg mebeverine hydrochloride.

Pharmacotherapeutic group: synthetic anticholinergics, esters with tertiary amino group. ATC code: A03AA04.
Pharmacology: Pharmacodynamics: Mechanism of action and pharmacodynamic effects: Mebeverine is a musculotropic spasmolytic agent with a direct effect on the smooth muscles of the gastro-intestinal tract without affecting the normal intestinal motility. Because this effect is not brought about via the autonomic nervous system, the typical anticholinergic adverse effects do not occur.
Pharmacokinetics: Absorption: Mebeverine is quickly and fully absorbed after oral administration of tablets. The formulation with controlled release allows for a twice daily dosage scheme.
Distribution: No significant accumulation occurs after multidosage use.
Biotransformation: Mebeverine hydrochloride is mainly metabolized by esterases, which first split the ester compounds into veratric acid and mebeverine alcohol. The main metabolite in plasma is DMAC (demethylated carboxylic acid). The steady state elimination half life of DMAC is 5.77 hours. During multidosage use (200 mg twice daily) the C_max of DMAC is 804 ng/ml and the t_max is about 3 hours. The relative biological availability of the controlled-release capsule appears to be optimal with an average ratio of 97%.
Elimination: Mebeverine is not excreted as such but excreted fully metabolized; the metabolites are excreted almost completely. Veratric acid is excreted into the urine; mebeverine alcohol is also excreted into the urine, partly as the corresponding carboxylic acid (MAC) and partly as the demethylated carboxylic acid (DMAC).
Paediatric population: No clinical investigations in children have taken place with any form of mebeverine.
Toxicology: Preclinical safety data: Effects in repeat-dose studies after oral and parenteral doses were indicative of central nervous involvement with behavioral excitation, mainly tremor and convulsions. In the dog, the most sensitive species, these effects were seen at oral doses equivalent to 3 times the maximum recommended clinical dose of 400 mg/day based on body surface area (mg/m²) comparisons.
The reproductive toxicity of mebeverine was not sufficiently investigated in animal studies. There was no indication of teratogenic potential in rats and rabbits. However, embryotoxic effects (reduction in litter size, increased incidence of resorption) were noticed in rats at doses equivalent to twice the maximum daily clinical dose. This effect was not observed in rabbits. No effects on male or female fertility were noted in rats at doses equivalent to the maximum clinical dose.
In conventional in vitro and in vivo genotoxicity tests mebeverine was devoid of genotoxic effects. No carcinogenicity studies have been performed.

Adults over the age of 18 years: Symptomatic treatment of irritable bowel syndrome.

For oral use.
The capsules must be taken with a sufficient quantity of water (at least 100 ml). They must not be chewed because the coating is designed for a controlled release mechanism (see Pharmacology: Pharmacokinetics under Actions).
Adults over the age of 18 years: Twice daily 1 capsule of 200 mg, one in the morning and one in the evening.
There are no safety risks for a duration of use up to 1 year. However, when the desired effect has been achieved after a few weeks, the dose may be reduced gradually.
If one or more doses have not been taken, the patient must continue with the next dose as prescribed; the missed dose should not be taken on top of the usual dose.
Pediatric population: Duspatalin Retard should not be used in children and adolescents below the age of 18 years because the safety and efficacy have not been established in this group.
Elderly patients and patients with kidney and/or liver disorders: No dose studies have been performed in elderly patients and patients with kidney and/or liver disorders.

Very little is reported in the literature about symptoms after mebeverine overdose. In cases of mebeverine overdose, the symptoms were either absent or mild and usually quickly reversible. Observed symptoms of overdose were of neurological nature. There is no known specific antidote and symptomatic treatment is recommended. Measures to decrease absorption are not necessary.

Do not take this medicine if the patient is allergic (hypersensitive) to the active substance or to any of the excipients.

Not applicable.
Effects on ability to drive and use machines: No studies have been carried out into the effect on the ability to drive and use machines. Neither the pharmacodynamic and pharmacokinetic profile, nor the post-marketing experience indicate an adverse effect of mebeverine on the ability to drive and use machines.

Pregnancy: There are no or limited amount of data from the use of mebeverine in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see Pharmacology: Toxicology: Preclinical safety data under Actions). Use of Duspatalin retard is advised against during pregnancy.
Breast-feeding: It is unknown whether mebeverine or one of its metabolites is excreted in human milk. Excretion of mebeverine in breast milk has not been investigated in animals. Duspatalin Retard should not be used during breast-feeding.
Fertility: No clinical data are available on the fertility in men or women; however, animal studies do not indicate damaging effects from Duspatalin Retard (see Pharmacology: Toxicology: Preclinical safety data under Actions).

The following undesirable effects have been reported spontaneously during post-marketing use. No exact frequency can be determined from the available data.
The observed allergic reactions mainly, but not exclusively, limited to the skin.
Skin and subcutaneous tissue disorders: Urticaria, angioedema, facial oedema, exanthem.
Immune system disorders: Hypersensitivity (anaphylactic reactions).

As far as known, mebeverine has no interactions with other medicinal products.

Special precautions for disposal and other handling: Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: Not applicable.

Do not store above 30°C or below 5°C.
Store in the original package.

Antispasmodics

A03AA04 - mebeverine ; Belongs to the class of synthetic anticholinergics, esters with tertiary amino group. Used in the treatment of functional bowel disorders.

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