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COLOFAC MR MODIFIED RELEASE CAPSULES

Active substance(s): MEBEVERINE HYDROCHLORIDE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Colofac® MR. Modified release capsule.

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Mebeverine hydrochloride 200 mg.
For excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Modified release capsule.
White, opaque, modified release capsule imprinted with “245”

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
For the symptomatic relief of irritable bowel syndrome.

4.2

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
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.

4.3

Contraindications
Hypersensitivity to the active substance or to any of the excipients.

4.4

Special warnings and precautions for use
None

4.5

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.

4.6

Fertility, Pregnancy and lactation
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).

4.7

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.

4.8

Undesirable effects
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.
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:
www.mhra.gov.uk/yellowcard.

4.9

Overdose
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

PHARMACOLOGICAL PROPERTIES

5.1

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

5.2

Pharmacokinetic properties
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 (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%.
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 efficacy and safety of the product has only been evaluated in adults.

5.3

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
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.

6

PHARMACEUTICAL PARTICULARS

6.1

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
triacetate
Capsule shell:
Gelatine, titanium dioxide (E171), printing inks: shellac (E904), black iron
oxide (E172), propylene glycol, concentrated ammonia solution, potassium
hydroxide

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
3 years when stored in the original container.

6.4

Special precautions for storage
Do not store above 30ºC.

Do not refrigerate or freeze.
Store in the original package.

6.5

Nature and contents of container
Boxes containing 10 or 60 capsules in PVC-Al press through strips.

6.6

Special precautions for disposal
None.

7

MARKETING AUTHORISATION HOLDER
BGP Products Ltd.

Abbott House,
Vanwall Business Park,
Vanwall Road, Maidenhead,
SL6 4XE,
UK

8

MARKETING AUTHORISATION NUMBER(S)
PL 43900/0029

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
14th August 1998

10

DATE OF REVISION OF THE TEXT
26/03/2015

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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