Mebeverine 135 mg film-coated tablets:

For the symptomatic treatment of irritable bowel syndrome and other conditions usually included in this grouping such as: chronic irritable colon, spastic constipation, mucous colitis, spastic colitis. Mebeverine is effectively used to treat the symptoms of these conditions such as: colicky abdominal pain and cramps, persistent, non-specific diarrhoea (with or without alternating constipation) and flatulence.

Mylan IBS Relief Tablets:

For the symptomatic relief of irritable bowel syndrome.

Mebeverine 135 mg Film-Coated tablets:

Posology

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.

Adults (including the elderly):

One tablet three times a day, preferably 20 minutes before meals. After a period of several weeks, when the desired effect has been obtained, the dosage may be gradually reduced.

Paediatric population:

Mebeverine 135 mg film-coated tablets are not recommended for use in children and adolescents below 18 years, due to insufficient data on safety and efficacy.

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

For oral use.

The film-coated tablets should be swallowed with a sufficient amount of water (at least 100 ml water). Tablets should not be chewed because of the unpleasant taste.

Mylan IBS Relief Tablets:

Posology

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.

Adults (including the elderly):

One tablet three times a day, preferably 20 minutes before meals. If symptoms persist for more than 2 weeks, consult your doctor. Maximum daily dose of 405 mg.

Warning: Do not exceed the stated dose.

Paediatric population:

Mebeverine 135 mg tablets are not recommended for use in children and adolescents below 18 years, due to insufficient data on safety and efficacy.

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

For oral use.

The film-coated tablets should be swallowed with a sufficient amount of water (at least 100 ml water). They should not be chewed because of the unpleasant taste.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Mylan IBS Relief Tablets:

For medicines which are available over-the-counter for pharmacy only [P] or general sales list [GSL] supply.

Additional warnings (to be included in the patient information leaflet):

If this is the first time you have had these symptoms talk to your doctor before using this medicine. This is to make sure it is suitable for you.

Do not use this medicine without talking to your doctor if you:

- are over 40 years of age

- have passed blood in your stools or motions

- are feeling sick or being sick

- have lost your appetite or lost weight

- look pale and feel tired

- are very constipated

- have a fever

- have recently travelled abroad

- are or may be pregnant

- have abnormal vaginal bleeding or discharge

- have difficulty or pain passing water

Talk to your doctor if you get new symptoms, your symptoms get worse or if they do not improve after 2 weeks of treatment.

Excipients:

Mebeverine contains lactose

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Mebeverine contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per each hard capsule, that is to say essentially 'sodium-free'.

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.

Breast-feeding

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 known 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 reported.

Immune system disorders:

Hypersensitivity (anaphylactic reactions)

Skin and subcutaneous tissue disorders:

Urticaria, angioedema, face oedema and 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.

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: A03A A04

Mebeverine is a musculotropic antispasmodic drug 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 anti-muscarinergic 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 safety and efficacy of the product has only been evaluated in adults.

Absorption:

Mebeverine is rapidly and completely absorbed after oral administration of tablets.

Distribution:

No significant accumulation occurs after multiple doses.

Biotransformation:

Mebeverine hydrochloride is mainly metabolised by esterases, which split the ester bonds into veratric acid and mebeverine alcohol firstly.

The main metabolite in plasma is DMAC (demethylated carboxylic acid).

The steady state elimination half-life of DMAC is 2.45 h. During multiple dosing C_max of DMAC for the film-coated tablets with 135 mg is 1670 ng/ml and t_max is 1 h.

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.

Mebeverine 135 mg film-coated tablets contain:

Core tablet

Lactose monohydrate

Cellulose, microcrystalline

Povidone

Sodium Starch Glycolate

Talc

Magnesium Stearate

Water purified

Film-coating

Opadry white Y-1-7000 containing the following;

Hydroxypropyl Methylcellulose (E464)

Titanium Dioxide (E171)

Polyethylene Glycol

None known.

5 years

Store in a dry place, at a temperature not greater than 30° C. Protect from light.

Polypropylene containers with polyethylene caps (with optional polyethylene ullage filler) and PVC/PVDC-Aluminium or Clear PVC-Aluminium blister packs.

Pack sizes: 12, 15, 18, 20, 21, 28, 30, 56, 60, 84, 90 and 100 tablets.

Not all pack sizes may be marketed.

There are no special instructions for the handling of Mebeverine 135 mg film-coated tablets.