- Approval Id
- 86f72f3b2fb68489
- Drug Approval Emc Name
- Aurobeverine MR 200mg modified-release capsules, hard
- Drug Name
- Aurobeverine MR 200mg modified-release capsules, hard
- Company Name
- Aurobindo Pharma - Milpharm Ltd.
- Company Address
- Odyssey Business Park, Ares Block, West End Road, South Ruislip, Middlesex, HA4 6QD
- Company Website
- http://www.aurobindo.com
- Company Telephone
- + 44 (0)208 845 8811
- Company Medical Info Email
- medinfo@aurobindo.com
- Company Customer Care Direct Line
- +44 (0)208 845 8811
- Company Medical Info Fax
- +44 (0)208 845 8795
- Atc Code
- A03AA04
- Legal Category
- Prescription only medicine
- Authorisation Holder
- Milpharm Limited
Ares Block, Odyssey Business Park
West End Road
Ruislip HA4 6QD
United Kingdom
- Authorisation Number
- PL 16363/0492
- Authorisation Date
- 21/12/2021
- Instruction Authorisation Holder
- Milpharm Limited
Ares Block, Odyssey Business Park
West End Road
Ruislip HA4 6QD
United Kingdom
- Instruction Authorisation Number
- PL 16363/0492
- Instruction Authorisation Date
- 21/12/2021
- Instruction Composition
- Each capsule contains 200 mg mebeverine hydrochloride
\*\*Excipient with known effect\*\*:
Each capsule contains up to 23.81 mg sucrose.
For the full list of excipients, see section 6.1.
- Instruction Dosage Form
- Modified-release capsule, hard.
Creamy white body and creamy white cap, hard gelatin capsule (approximately 9.8 mm x 6.9 mm) filled with white to off white spherical pellets.
- Instruction Clinical Particulars
- 4.1 Therapeutic indications
For the symptomatic relief of irritable bowel syndrome in adults.4.2 Posology and method of administration
\*\*Posology\*\*
\*Adults:\*
One capsule of 200 mg twice daily; one in the morning and one in the evening.
There are no safety risks for continued use up to a period of 1 year. However, once the desired effect is achieved after several weeks, the dose can be gradually reduced.
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.
\*Paediatric Population\*
Aurobeverine MR is 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.
\*\*Method of administration\*\*
Aurobeverine MR 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 controlled release (see section 5.2).4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.14.4 Special warnings and precautions for use
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltese insufficiency should not take this medicine.4.5 Interaction with other medicinal products and other forms of interaction
No interactions of mebeverine are known.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.
\*\*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).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.
- Instruction Pharmacology
- 5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Synthetic anticholinergics, esters with tertiary amino group, ATC code: A03A A04
\*\*Mechanism of action and pharmacodynamics effects\*\*
Mebeverine is a musculotropic antispasmodic with a direct action on the smooth muscle of the gastrointestinal tract, relieving spasm without affecting normal gut motility. Since the autonomic nervous system is not involved in this mechanism of action, typical systemic anticholinergic side-effects are absent.
\*\*Clinical efficacy and safety\*\*
All formulations of mebeverine were generally safe and well tolerated in the recommended dose regimen.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 metabolised 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).
\*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 400 mg/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
\*Capsule core:\*
Sugar spheres (sucrose, maize starch)
Povidone
Hypromellose
\*SR coating:\*
Ethylcellulose
Macrogol
Magnesium stearate
\*Capsule shell:\*
Gelatin
Titanium dioxide (E 171)6.2 Incompatibilities
Not applicable.6.3 Shelf life
\*\*For blister packs:\*\* 36 months
\*\*For HDPE container packs\*\*: 36 months
\*\*In use shelf life for HDPE container packs:\*\*
3 months6.4 Special precautions for storage
\*\*Blister Pack:\*\*
Do not store above 30°C. Do not refrigerate or freeze. Store in the original package in order to protect from moisture.
\*\*HDPE container pack:\*\*
Store below 25°C. Store in the original container in order to protect from light and moisture.6.5 Nature and contents of container
\*\*Blister pack:\*\* PVC/PVdC – Aluminium blisters in cartons.
\*\*Pack sizes of blister:\*\* 20, 30, 50, 60, 90 and 100 capsules.
\*\*HDPE container pack:\*\* HDPE bottles fitted with round white screw type continuous thread cap.
\*\*Pack sizes of HDPE container:\*\* 250 capsules.
Not all pack sizes may be marketed.6.6 Special precautions for disposal and other handling
No special requirements for disposal
- Instruction Content
- ## Composition
Each capsule contains 200 mg mebeverine hydrochloride
\*\*Excipient with known effect\*\*:
Each capsule contains up to 23.81 mg sucrose.
For the full list of excipients, see section 6.1.
## Pharmaceutical Form
Modified-release capsule, hard.
Creamy white body and creamy white cap, hard gelatin capsule (approximately 9.8 mm x 6.9 mm) filled with white to off white spherical pellets.
## Clinical Particulars
4.1 Therapeutic indications
For the symptomatic relief of irritable bowel syndrome in adults.4.2 Posology and method of administration
\*\*Posology\*\*
\*Adults:\*
One capsule of 200 mg twice daily; one in the morning and one in the evening.
There are no safety risks for continued use up to a period of 1 year. However, once the desired effect is achieved after several weeks, the dose can be gradually reduced.
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.
\*Paediatric Population\*
Aurobeverine MR is 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.
\*\*Method of administration\*\*
Aurobeverine MR 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 controlled release (see section 5.2).4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.14.4 Special warnings and precautions for use
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltese insufficiency should not take this medicine.4.5 Interaction with other medicinal products and other forms of interaction
No interactions of mebeverine are known.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.
\*\*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).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.
## Pharmacological Properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Synthetic anticholinergics, esters with tertiary amino group, ATC code: A03A A04
\*\*Mechanism of action and pharmacodynamics effects\*\*
Mebeverine is a musculotropic antispasmodic with a direct action on the smooth muscle of the gastrointestinal tract, relieving spasm without affecting normal gut motility. Since the autonomic nervous system is not involved in this mechanism of action, typical systemic anticholinergic side-effects are absent.
\*\*Clinical efficacy and safety\*\*
All formulations of mebeverine were generally safe and well tolerated in the recommended dose regimen.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 metabolised 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).
\*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 400 mg/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
\*Capsule core:\*
Sugar spheres (sucrose, maize starch)
Povidone
Hypromellose
\*SR coating:\*
Ethylcellulose
Macrogol
Magnesium stearate
\*Capsule shell:\*
Gelatin
Titanium dioxide (E 171)6.2 Incompatibilities
Not applicable.6.3 Shelf life
\*\*For blister packs:\*\* 36 months
\*\*For HDPE container packs\*\*: 36 months
\*\*In use shelf life for HDPE container packs:\*\*
3 months6.4 Special precautions for storage
\*\*Blister Pack:\*\*
Do not store above 30°C. Do not refrigerate or freeze. Store in the original package in order to protect from moisture.
\*\*HDPE container pack:\*\*
Store below 25°C. Store in the original container in order to protect from light and moisture.6.5 Nature and contents of container
\*\*Blister pack:\*\* PVC/PVdC – Aluminium blisters in cartons.
\*\*Pack sizes of blister:\*\* 20, 30, 50, 60, 90 and 100 capsules.
\*\*HDPE container pack:\*\* HDPE bottles fitted with round white screw type continuous thread cap.
\*\*Pack sizes of HDPE container:\*\* 250 capsules.
Not all pack sizes may be marketed.6.6 Special precautions for disposal and other handling
No special requirements for disposal
