COLOFAC MR MODIFIED RELEASE CAPSULES
Active substance(s): MEBEVERINE HYDROCHLORIDE / MEBEVERINE HYDROCHLORIDE / MEBEVERINE HYDROCHLORIDE
NAME OF THE MEDICINAL PRODUCT
Colofac® MR. Modified release capsule.
QUALITATIVE AND QUANTITATIVE COMPOSITION
Mebeverine hydrochloride 200 mg.
For excipients, see section 6.1.
Modified release capsule.
White, opaque, modified release capsule imprinted with “245”
For the symptomatic relief of irritable bowel syndrome.
Posology and 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).
One capsule of 200 mg twice daily, to be given one in the morning and one in
Mebeverine 200 mg modified release capsules are not recommended for use in
children and adolescents below 18, due to insufficient data on safety and
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
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
Hypersensitivity to the active substance or to any of the excipients.
Special warnings and precautions for use
Interaction with other medicinal products and other forms of interaction
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.
Fertility, Pregnancy and lactation
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.
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.
There are no clinical data on male or female fertility; however, animal studies
do not indicate harmful effects of mebeverine (see section 5.3).
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
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
Allergic reactions mainly but not exclusively limited to the skin have been
Immune system disorders:
Hypersensitivity (anaphylactic reactions)
Skin and subcutaneous tissue disorders:
Urticaria, angioedema, face oedema, exanthema.
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 Yellow Card Scheme at:
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
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 anti-cholinergics are absent.
Clinical efficacy and safety
All formulations of mebeverine were generally safe and well tolerated in the
recommended dose regimen.
The safety and efficacy of the product has only been evaluated in adults.
Mebeverine is rapidly and completely absorbed after oral administration of
tablets. The modified release formulation permits a twice daily dosing scheme.
No significant accumulation occurs after multiple doses.
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 (200mg
b.i.d.) the Cmax of DMAC is 804ng/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%.
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).
The efficacy and safety of the product has only been evaluated in adults.
Preclinical safety data
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
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.
List of excipients
Capsule content Modified release granules:
Magnesium stearate, polyacrylate dispersion 30%, talc, hypromellose,
methacrylic acid – ethyl acrylate copolymer (1:1) dispersion 30%, glycerol
Gelatine, titanium dioxide (E171), printing inks: shellac (E904), black iron
oxide (E172), propylene glycol, concentrated ammonia solution, potassium
3 years when stored in the original container.
Special precautions for storage
Do not store above 30ºC.
Do not refrigerate or freeze.
Store in the original package.
Nature and contents of container
Boxes containing 10 or 60 capsules in PVC-Al press through strips.
Special precautions for disposal
MARKETING AUTHORISATION HOLDER
BGP Products Ltd.
Vanwall Business Park,
Vanwall Road, Maidenhead,
MARKETING AUTHORISATION NUMBER(S)
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
14th August 1998
DATE OF REVISION OF THE TEXT
Source: Medicines and Healthcare Products Regulatory Agency
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