- Approval Id
- 8882c231741d6ce0
- Drug Approval Emc Name
- Mebeverine hydrochloride 135mg film-coated tablets
- Drug Name
- Mebeverine hydrochloride 135mg film-coated tablets
- Company Name
- Aspire Pharma Ltd
- Company Address
- 4 Rotherbrook Court, Bedford Road, Petersfield, Hampshire, GU32 3QG, UK
- Company Website
- http://www.aspirepharma.co.uk
- Company Telephone
- +44 (0)1730 231148
- Company Medical Info Direct Line
- +44 (0)1730 231148
- Company Customer Care Direct Line
- +44 (0)1730 231148
- Atc Code
- A03AA04
- Legal Category
- Prescription only medicine
- Authorisation Holder
- Aspire Pharma Ltd,
Unit 4, Rotherbrook Court,
Bedford Road,
Petersfield,
Hampshire,
GU32 3QG
United Kingdom
- Authorisation Number
- PL35533/0125
- Authorisation Date
- 14/06/2018
- Instruction Authorisation Holder
- Aspire Pharma Ltd,
Unit 4, Rotherbrook Court,
Bedford Road,
Petersfield,
Hampshire,
GU32 3QG
United Kingdom
- Instruction Authorisation Number
- PL35533/0125
- Instruction Authorisation Date
- 14/06/2018
- Instruction Composition
- Each film-coated tablet contains 135mg mebeverine hydrochloride.
Excipient with known effect:
Each film-coated tablet contains 49.51mg of lactose monohydrate.
For the full list of excipients, see section 6.1
- Instruction Dosage Form
- White coloured round shaped, biconvex film-coated tablets and plain on both sides.
- Instruction Clinical Particulars
- 4.1 Therapeutic indications
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. The medicine 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.4.2 Posology and method of administration
For oral use.
The 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.
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, 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.4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.4.4 Special warnings and precautions for use
Since Mebeverine film-coated tablets contain lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.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.
\*Breastfeeding\*
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 or search for MHRA Yellow Card in the Google Play or Apple App Store.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.
- Instruction Pharmacology
- 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 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 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 efficacy and safety 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.
\*Distribution\*:
No significant accumulation occurs after multiple doses.
\*Biotransformation\*:
Mebeverine hydrochloride is mainly metabolized 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 Cmax of DMAC for the coated tablets with 135 mg is 1670 ng/ml and tmax 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.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.
- Instruction Pharmaceutical Particulars
- 6.1 List of excipients
\*\*Core tablet\*\*
Microcrystalline cellulose
Lactose monohydrate
Sodium starch glycolate type A
Povidone
Magnesium stearate
Talc
\*\*Film coating\*\*
Opadry white (ingredients: hypromellose (E464), titanium dioxide (E171), polyethylene glycol/macrogol and talc)6.2 Incompatibilities
Not applicable.6.3 Shelf life
36 months6.4 Special precautions for storage
This medicine does not require any special storage conditions.6.5 Nature and contents of container
PVC/PVdC – Aluminium blisters in cardboard cartons: 10, 15, 84 or 100 film-coated tablets
Not all pack sizes may be marketed.6.6 Special precautions for disposal and other handling
None.
- Instruction Content
- ## Composition
Each film-coated tablet contains 135mg mebeverine hydrochloride.
Excipient with known effect:
Each film-coated tablet contains 49.51mg of lactose monohydrate.
For the full list of excipients, see section 6.1
## Pharmaceutical Form
White coloured round shaped, biconvex film-coated tablets and plain on both sides.
## Clinical Particulars
4.1 Therapeutic indications
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. The medicine 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.4.2 Posology and method of administration
For oral use.
The 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.
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, 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.4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.4.4 Special warnings and precautions for use
Since Mebeverine film-coated tablets contain lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.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.
\*Breastfeeding\*
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 or search for MHRA Yellow Card in the Google Play or Apple App Store.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.
## 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 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 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 efficacy and safety 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.
\*Distribution\*:
No significant accumulation occurs after multiple doses.
\*Biotransformation\*:
Mebeverine hydrochloride is mainly metabolized 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 Cmax of DMAC for the coated tablets with 135 mg is 1670 ng/ml and tmax 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.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.
## Pharmaceutical Particulars
6.1 List of excipients
\*\*Core tablet\*\*
Microcrystalline cellulose
Lactose monohydrate
Sodium starch glycolate type A
Povidone
Magnesium stearate
Talc
\*\*Film coating\*\*
Opadry white (ingredients: hypromellose (E464), titanium dioxide (E171), polyethylene glycol/macrogol and talc)6.2 Incompatibilities
Not applicable.6.3 Shelf life
36 months6.4 Special precautions for storage
This medicine does not require any special storage conditions.6.5 Nature and contents of container
PVC/PVdC – Aluminium blisters in cardboard cartons: 10, 15, 84 or 100 film-coated tablets
Not all pack sizes may be marketed.6.6 Special precautions for disposal and other handling
None.
