For the symptomatic relief of irritable bowel syndrome.

Posology
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.
Method of administration
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).

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or
sucrose-isomaltese insufficiency should not take this medicine.

No interaction studies have been performed, except with alcohol. In vitro and in vivo studies in
animals have demonstrated the absence of any interaction between mebeverine hydrochloride and
ethanol.

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.
Breastfeeding
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).

No studies on the effects on the ability to drive and use machines have been performed. The
pharmacodynamic and pharmacokinetic profile as well as postmarketing experience do not
indicate any harmful effect of mebeverine on the ability to drive or to use machines.

The following adverse reactions have been reported spontaneously during postmarketing use. A
precise frequency cannot be estimated from available data.
Allergic reactions mainly but not exclusively limited to the skin have been observed.
Immune system disorders:
Hypersensitivity (anaphylactic reactions)
Skin and subcutaneous tissue disorders:
Urticaria, angioedema, face oedema, exanthema.

To reports any side effect(s):
• Saudi Arabia
-The National Pharmacovigilance and Drug Safety Centre (NPC)
Fax: +966-11-205-7662
Call NPC at +966-11-2038222, Exts: 2317--2356-2340.
Toll free phone: 19999
E-mail: npc.drug@sfda.gov.sa
Website: www.sfda.gov.sa/npc
• Other GCC States:
Please contact the relevant competent authority.

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.

Pharmacotherapeutic group: Synthetic anticholinergics, esters with tertiary amino group,
ATC-Code: A03AA04
Mebeverine is a musculotropic antispasmodic with a direct action 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 as well as weak antimuscarinergic
and phosphodiesterase inhibitory effect might contribute to the local effect of
mebeverine on the gastrointestinal tract. Systemic side-effects as seen with typical anticholinergics
are absent.
Clinical efficacy and safety
All formulations of mebeverine were generally safe and well tolerated in the recommended dose
regimen.
Paediatric population
The efficacy and safety of the product has only been evaluated in adults.

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).
Paediatric population
The safety and efficacy of the product has only been evaluated in adults.

Effects in repeat-dose toxicity studies, after oral and parenteral doses, were indicative of central
nervous involvement with behavioural 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 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.

Drug Coating
Mebeverine Hydrochloride
Core Pellets
Sugar spheres (35#40)
Binder Preparation
Povidone (PVPK-30)
Hypromellose (Pharmacoat-606)
Iso Propyl Alcohol
Purified water
SR Coating
Ethyl Cellulose-N-45
Macrogol-6000 (Polyethylene Glycol)
Magnesium Stearate
Iso Propyl Alcohol
Purified water

Not applicable.

Do not store above 30°C.

Alu-PVC / PVDC Blister

Keep out of the reach and sight of children.