4.2 Posology and method of administration
From
Adults (including the elderly):
The capsules should be swallowed with a sufficient amount of water (at least 100 ml water). Do not chew.
One capsule of 200 mg twice daily, to be given one in the morning and one in the evening.
Paediatric Population
Mebeverine 200 mg modified release capsules are not recommended for use in children and adolescents below 18, due to insufficient data on safety and efficacy.
To:
Adults (including the elderly):
The capsules should be swallowed with a sufficient amount of water (at least 100 ml water). They should not be chewed because the coating is intended to ensure a prolonged release mechanism (see 5.2).
One capsule of 200 mg twice daily, to be given one in the morning and one in the evening.
Paediatric Population
Mebeverine 200 mg modified release capsules are not recommended for use in children and adolescents below 18, due to insufficient data on safety and efficacy.
Duration of use is not limited.
If one or more doses are missed, the patient should continue with the next dose as prescribed; the missed dose(s) should not be taken in addition to the regular dose.
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.
4.6 Pregnancy and lactation
From:
No clinical data on exposed pregnancies are available.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3).
Caution should be exercised when prescribing to pregnant women.
There is insufficient information on the excretion of mebeverine in human or animal breast milk. Physico-chemical and available pharmacodynamic data on mebeverine point to excretion in breast milk and a risk to the suckling child cannot be excluded. Mebeverine should not be used during breast-feeding.
To:
Pregnancy
There are no or limited amounts of data from the use of mebeverine in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). mebeverine 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. Mebeverine should not be used during breast-feeding.
Fertility
There are no clinical data on male or female fertility; however, animal studies do not indicate harmful effects of mebeverine (see section 5.3).
4.9 Overdose
From:
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.
No specific antidote is known; gastric lavage and symptomatic treatment is recommended.
To:
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 a neurological and cardiovascular nature.
No specific antidote is known and symptomatic treatment is recommended.
Gastric lavage should only be considered in case of multiple intoxication or if discovered within about one hour. Absorption reducing measures are not necessary.
5.2 Pharmacokinetic properties
From:
Mebeverine is rapidly and completely absorbed after oral administration in the form of tablets or suspension. Mebeverine is not excreted as such, but metabolised completely. The first step in the metabolism is hydrolysis, leading to veratric acid and mebeverine alcohol. Both veratric acid and mebeverine alcohol are excreted into the urine, the latter partly as the corresponding carboxylic acid and partly as the demethylated carboxylic acid.
To:
Absorption:
Mebeverine is rapidly and completely absorbed after oral administration of tablets. 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, initially splitting 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 5.77h. During multiple dosing (200 mg b.i.d.) the Cmax of DMAC is 804 ng/ml and tmax is about 3 hrs. The relative bioavailability of the modified release capsule appears to be optimal with a mean ratio of 97%.
Elimination:
Mebeverine is not excreted as such, but metabolised 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).
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