Colofac^® MR. Modified release capsule.

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.

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.

Paralytic ileus.

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

Porphyria.

No interaction studies have been performed.

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).

No studies on the effects on the ability to drive and use machines have been performed.

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

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, relieving spasm without affecting normal gut motility.

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).

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.

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.

Not applicable.

3 years when stored in the original container.

Do not store above 30°C.

Do not refrigerate or freeze.

Store in the original package.

Boxes containing 10 or 60 capsules in PVC-Al press through strips.

None.

Abbott Healthcare Products Limited

Mansbridge Road

West End

Southampton

SO18 3JD

PL 00512/0155

14 August 1998/August 2003

19 December 2011

POM