Duspatalin

Mebeverine hydrochloride.

Duspatalin 135 mg coated tablets are round, white, sugar-coated tablets for oral administration (to be taken by mouth), containing 135 mg mebeverine hydrochloride per tablet.
Excipients/Inactive Ingredients: Core: lactose monohydrate, starch (potato), povidone, talc, magnesium stearate.
Coating: talc, sucrose, gelatine, acacia, carnauba wax.

Pharmacotherapeutic group: Synthetic anticholinergics, esters with tertiary amino group. ATC-Code: A03AA04.
Pharmacology: Pharmacodynamics: Mechanism of action: Mebeverine is a musculotropic antispasmodic with a direct effect on the smooth muscle of the gastrointestinal tract, without affecting normal gut motility.
The exact mechanism of action is not known, but multiple mechanisms, such as a decrease in ion channel permeabilities, blockade of noradrenaline reuptake, a local anesthetic effect, changes in water absorption might contribute to the local effect of mebeverine on the gastrointestinal tract. Via these mechanisms mebeverine has antispasmodic effects leading to normalization of gut motility without exerting a permanent relaxation of smooth muscle cells in the gastrointestinal tract (so called hypotonia). Systemic side-effects as seen with typical anti-cholinergics are absent.
Clinical efficacy and safety: The clinical efficacy and safety of different formulations of mebeverine was evaluated in more than 1500 patients. Considerable improvements in the predominant symptomatology of irritable bowel syndrome (e.g. abdominal pain, stool characteristics) were generally observed in reference or baseline-controlled clinical studies.
Mebeverine were generally safe and well tolerated in the recommended dose regimen.
Paediatric population: Clinical trials with the tablet or capsule formulations have been performed in adults only.
The dosing schedule for the tablet formulation was calculated based on the consistent safety and favourable tolerability of mebeverine.
Pharmacokinetics: Absorption: Mebeverine is rapidly and completely absorbed after oral administration of tablets.
Distribution: No significant accumulation occurs after multiple doses.
Biotransformation: Mebeverine hydrochloride is mainly metabolized by esterases, which split the ester bonds 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 2.45 h. During multiple dosing Cmax of DMAC for the coated tablets with 135 mg is 1670 ng/ml and tmax is 1 h.
Elimination: Mebeverine is not excreted as such, but metabolized completely; the metabolites are excreted nearly 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 pharmacokinetic studies have been conducted in children with any formulation of mebeverine.
Toxicology: Preclinical Safety Data: Effects in repeat-dose studies after oral and parenteral doses were indicative of central nervous involvement excitation with behavioral, 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 400mg/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.

Symptomatic treatment of abdominal pain and cramps, bowel disturbances and intestinal discomfort related to irritable bowel syndrome.
Treatment of gastro-intestinal spasm secondary to organic disease.

Adults: Take one tablet three times daily, approximately 20 minutes before a meal.
Swallow the tablets with at least 100ml water, do not chew.
Always take Duspatalin exactly as doctor has prescribed. If patient has any questions, check with a doctor or pharmacist.
If patient forgets to take tablet(s), do not take a double dose to compensate for it. If patients requires further information, ask a doctor or pharmacist for advice.
Paediatric population: Duspatalin 135mg tablets are not recommended for use in children and adolescents below 18, due to insufficient data on safety and efficacy.

Symptoms: Theoretically, CNS excitability may occur in cases of overdose. In cases where mebeverine was taken in overdose, symptoms were either absent or mild and usually rapidly reversible. Observed symptoms of overdose were of neurological and cardiovascular nature.
Treatment: No specific antidote is known and symptomatic treatment is recommended. Gastric lavage should only be considered in case of multiple intoxication discovered within about one hour. Absorption reducing measures are not necessary.

Hypersensitivity to the active substance or to any of the excipients listed under Description.

Since Duspatalin coated tablets contain lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Since Duspatalin coated tablets contain sucrose, patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed. The pharmacodynamic and pharmacokinetic profile as well as post-marketing experience do not indicate any harmful effect of mebeverine on the ability to drive or to use machines.

Pregnancy: There are no or limited amount of data from the use of Duspatalin in pregnant women.
Animal studies are insufficient with respect to reproductive toxicity (see Pharmacology: Toxicology: Preclinical Safety Data under Actions). Duspatalin is not recommended during pregnancy.
Lactation: It is unknown whether mebeverine or its metabolites are excreted in human milk. The excretion of mebeverine in milk has not been studied in animals. Duspatalin should not be used during breast-feeding.
Fertility: There are no clinical data regarding impact on male or female fertility; however, available animal studies do not indicate harmful effects of trademark (see Pharmacology: Toxicology: Preclinical Safety Data under Actions).

The following adverse events have been reported spontaneously during post-marketing use. A precise frequency cannot be estimated from available data.
Allergic reactions mainly but not exclusively limited to the skin have been observed.
Skin and subcutaneous tissue disorders: Urticaria, angioedema, face edema, exanthema.
Immune system disorders: Hypersensitivity (anaphylactic reactions).
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the local authorities.

No interaction studies have been performed with the exception of alcohol. In vitro and in vivo-studies in animals have demonstrated the absence of any interaction between Duspatalin and ethanol.

Incompatibilities: Not applicable.

This product can be stored for up to 5 years.
Do not store above 30°C.
Store in the original package.
Any unused product or waste material should be disposed of in accordance with local requirements.

Antispasmodics

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

C