One coated tablet contains 100 mg mebeverine hydrochloride.
Excipients with known effect: Lactose monohydrate and Sucrose.
Excipients: Core: Lactose, Potato starch, Povidone, Talc, Magnesium stearate.
Coating: Talc, Sucrose Granulated, Gelatin, Gum Acacia, Carnauba Wax.
Pharmacotherapeutic Group: Synthetic anticholinergics, esters with tertiary amino group. ATC Code: A03AA04.
Pharmacology: Pharmacodynamics: Mechanism of Action and Pharmacodynamic Effects: 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 were evaluated in more than 1500 patients. Considerable improvements in the predominant symptomatology of irritable bowel syndrome (eg, abdominal pain, stool characteristics) were generally observed in reference or baseline-controlled clinical studies.
All formulations of mebeverine were generally safe and well tolerated in the recommended dose regimen.
Pediatric Population: Clinical trials with the tablet or capsule formulations have been performed in adults only. Clinical efficacy and safety data from clinical trials as well as from post-marketing experience with a suspension formulation of mebeverine pamoate in patients >3 years of age have shown that mebeverine is efficacious, safe and well-tolerated.
Clinical studies with mebeverine suspension showed that mebeverine was efficacious in ameliorating the symptoms of irritable bowel syndrome in childhood. Further open, baseline-controlled studies with mebeverine suspension confirmed the efficacy of the drug.
The dosing schedule for the tablet or capsule formulation was calculated based on the consistent safety and favorable tolerability of mebeverine.
Pharmacokinetics: Absorption: Mebeverine is rapidly and completely absorbed after oral administration of tablets or suspension. The modified release formulation permits a twice daily dosing scheme.
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 firstly. 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).
Pediatric 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 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, embryo toxic 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 in 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 and children from 9 years on: 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 diseases.
For oral use.
The coated tablets should be swallowed with a sufficient amount of water (at least 100 mL water). They should not be chewed because of the unpleasant taste.
Adults and children over 10 years: One 100 mg tablet four times daily.
Children aged 9-10 years: One 100 mg tablet three times daily.
Duration of use is not limited.
In case of one or more dose(s) is (are) missed, the patient should continue with the next dose as prescribed; the missed dose(s) is (are) not to be taken in addition to the regular dose.
Mebeverine hydrochloride (Duspatalin) should not be used in children aged below 3 years as no clinical data is available for this age group.
For children from 3-8 years mebeverine 100 mg tablets should not be used due to the high content of active substance.
Special Population: No posology studies in elderly, renal and/or hepatic impaired patients have been performed. No specific risk for elderly, renal and/or hepatic impaired patients could be identified from available post-marketing data. No dosage adjustment is deemed necessary in elderly, renal and/or hepatic impaired patients.
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 in Description.
Since Mebeverine coated tablets contain lactose, patients with rare hereditary problems including galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Since Mebeverine 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 the Ability to Drive or Operate Machinery: 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 effects of mebeverine on the ability to drive or use machines.
Use in pregnancy: There are only a very 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).
Mebeverine hydrochloride (Duspatalin) is not recommended during pregnancy.
Use in 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. Mebeverine hydrochloride (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 Mebeverine hydrochloride (Duspatalin) (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 authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal. 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 Mebeverine hydrochloride (Duspatalin) and ethanol.
Incompatibilities: Not applicable.
Store at temperatures not exceeding 30°C.
Store in the original package. Do not freeze.
Shelf Life: 36 months.
A03AA04 - mebeverine ; Belongs to the class of synthetic anticholinergics, esters with tertiary amino group. Used in the treatment of functional bowel disorders.
Tab 100 mg (round, white, sugar-coated) x 100's.