Colofac MR

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). 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.

4.3 Contraindications

Paralytic ileus.

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

4.4 Special Warnings And Precautions For Use

Porphyria.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No interaction studies have been performed.

4.6 Pregnancy And Lactation

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.

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.

4.8 Undesirable Effects

Allergic reactions mainly but not exclusively limited to the skin have been observed (A frequency cannot be estimated from the available data)

Immune system disorders:

Hypersensitivity

Skin and subcutaneous tissue disorders:

Urticaria, angioedema, erythematous rash

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.

No specific antidote is known; gastric lavage and symptomatic treatment is recommended.

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, relieving spasm without affecting normal gut motility.

5.2 Pharmacokinetic Properties

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.

5.3 Preclinical Safety Data

During its development phase the entity mebeverine was extensively tested in several animal species in acute, (sub) chronic and reproduction investigations.

The oral LD50 ranged from 902 - 1995 mg/kg.

The main symptoms in the animals, after very high oral and parenteral doses, were indicative of central nervous involvement with behavioural excitation.

The dosages used in animal studies exceeded several times the dosages used for humans (40 mg/kg for animal dosing versus 6 mg/kg for humans).

No mutagenic or clastogenic effects were found in in vitro and in vivo studies with mebeverine.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Capsule content Modified release granules:

Magnesium stearate, copolymer of ethyl acrylate and methyl methacrylate, talc, hypromellose, methacrylic acid – ethyl acrylate copolymer (1:1), glycerol triacetate

Capsule shell:

Gelatine, titanium dioxide (E171), printing inks: shellac (E904), black iron oxide (E172), soya lecithin (E322) Antifoam DC.

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 30°C.

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 And Other Handling

None.

7. Marketing Authorisation Holder

Abbott Healthcare Products Limited

Mansbridge Road

West End

Southampton

SO18 3JD

8. Marketing Authorisation Number(S)

PL 00512/0155

9. Date Of First Authorisation/Renewal Of The Authorisation

14 August 1998/August 2003

10. Date Of Revision Of The Text

28^th February 2011

LEGAL CATEGORY

POM