Oxybutynin Hydrochloride Tablets 5mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Oxybutynin Hydrochloride Tablets 5mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
The tablets contain 5mg of oxybutynin hydrochloride.
Excipient with known effect: Lactose Monohydrate 118.9mg For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablets
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Oxybutynin hydrochloride has antispasmodic/anticholinergic actions.
Its uses are:
Adults: Urinary incontinence, frequency and urgency in patients with an unstable bladder (urge syndrome).
Neurogenic bladder disorders causing detrusor hyperreflexia in conditions such as multiple sclerosis and spina bifida.
Paediatric population :
Oxybutynin hydrochloride is indicated in children over 5 years of age for:
- Urinary incontinence, urgency and frequency in unstable bladder conditions due to idiopathic overactive bladder or neurogenic bladder disorders (detrusor overactivity)
- Nocturnal enuresis associated with detrusor overactivity, in conjunction with nondrug therapy, when other treatment has failed.
4.2 Posology and method of administration Posology
Adults: The dose is usually one tablet of either 2.5mg of 5mg given two or three times daily, although this may be increased up to a maximum of 5mg four times daily if required to obtain a clinical response, providing that the side effects are tolerated. It is usually wise to institute treatment slowly to minimise the anticholinergic side effects especially that of a dry mouth.
Older people: A dose of 2.5mg of 5mg twice daily is likely to be adequate for the elderly (over 80 years) since the elimination time is doubled as compared to healthy young volunteers. In the elderly peak plasma concentrations have also been shown to be greater than in healthy young volunteers.
Children 5 years of age and over: A dose of 2.5mg to 5mg twice daily should be given initially and this can be increased up to 5mg three times daily to obtain a clinical response. In cases of nocturnal enuresis alone, the usual dose is 5mg two or three times daily with the last dose given before bedtime.
Children under 5 years of age: The safety and efficacy of the tablets have been demonstrated for children 5 years of age and older. There is insufficient clinical data for children under the age of 5 years so that it is not recommended for this age group.
Method of administration
The tablets are for oral administration. The tablets should be swallowed with plenty of water or other fluid, to ensure passage through the oesophagus.
Following initial control, a reduced maintenance dose may be introduced.
4.3 Contraindications
• Hypersensitivity to oxybutynin or any of the excipients listed in section 6.1
• Patients with bladder outflow obstruction where urinary retention may be precipitated
• Gastro-intestinal obstructive disorders, intestinal atony or paralytic ileus
• Toxic megacolon
• Severe ulcerative colitis
• Myasthenia gravis
• Narrow-angle glaucoma or shallow anterior chamber
4.4 Special warnings and precautions for use
Oxybutynin should be used with caution in the frail elderly and children who may be more sensitive to the effects of the product and in patients with autonomic neuropathy (such as those with Parkinson’s disease), severe gastrointestinal motility disorders, hepatic or renal impairment.
Anticholinergics should be used with caution in elderly patients due to the risk of cognitive impairment.
Gastrointestinal disorders: Anticholinergic medicinal products may decrease gastrointestinal motility and should be used with caution in patients with gastrointestinal obstructive disorders, intestinal atony and ulcerative colitis.
Oxybutynin may aggravate tachycardia (and thus hyperthyroidism, congestive heart failure, cardiac arrhythmia, coronary heart disease, hypertension), cognitive disorders and symptoms of prostatic hypertrophy.
Anticholinergic CNS effects (e.g. hallucinations, agitation, confusion, somnolence) have been reported; monitoring recommended especially in first few months after initiating therapy or increasing the dose; consider discontinuing therapy or reducing the dose if anticholinergic CNS effects develop.
Since oxybutynin can cause narrow-angle glaucoma, patients should be advised to contact a physician immediately if they are aware of a sudden loss of visual acuity or ocular pain.
Oxybutynin may reduce salivary secretions which could result in dental caries, parodontosis or oral candidiasis.
Anticholinergic medicinal products should be used with caution in patients who have hiatus hernia/gastro-oesophageal reflux and/or who are concurrently taking medicinal products (such as bisphosphonates) that can cause or exacerbate oesophagitis.
When oxybutynin is used in high environmental temperatures, this can cause heat prostration due to decreased sweating.
Paediatric population
The use of oxybutynin in children under 5 years of age is not recommended; it has not been established whether oxybutynin can be safely used in this age group.
4.5 Interaction with other medicinal products and other forms of interaction
Care should be taken if other anticholinergic agents are used together with oxybutynin, as a potentiation of anticholinergic effects may occur.
The anticholinergic activity of oxybutynin is increased by concurrent use of other anticholinergics or medicinal products with anticholinergic activity, such as amantadine and other anticholinergic antiparkinsonian medicinal products (e.g. biperiden, levodopa), antihistamines, antipsychotics (e.g. phenothiazines, butyrophenones, clozapine), quinidine, digitalis, tricyclic antidepressants, atropine and related compounds like atropinic antispasmodics and dipyridamole.
By reducing gastric motility, oxybutynin may affect the absorption of other drugs.
Oxybutynin is metabolised by cytochrome P 450 isoenzyme CYP 3A4. Concomitant administration with a CYP3A4 inhibitor can inhibit oxybutynin metabolism and increase oxybutynin exposure. Oxybutynin may antagonize prokinetic therapies.
Concomitant use with cholinesterase inhibitors may result in reduced cholinesterase inhibitor efficacy.
Patients should be informed that alcohol may enhance the drowsiness caused by anticholinergic agents such as oxybutynin (see section 4.7).
4.6 Fertility, pregnancy and lactation
Pregnancy: there are no adequate data from the use of oxybutynin in pregnant women. Animal studies are insufficient with respect to effects on pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). The potential risk for humans is unknown. Oxybutynin should not be used during pregnancy unless clearly necessary.
Breast-feeding: when oxybutynin is used during lactation, a small amount is excreted in mother's milk. Use of oxybutynin during breast feeding is therefore not recommended.
4.7 Effects on ability to drive and use machines
Oxybutynin may cause drowsiness or blurred vision. Patients should be cautioned regarding activities requiring mental alertness such as driving, operating machinery or performing hazardous work while taking this drug.
4.8 Undesirable effects
Classification of expected frequencies:
Very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1,000 to <1/100); rare (>1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).
• Infections and infestations Not known: urinary tract infection
• Gastro-intestinal disorders
Very Common: constipation, nausea, dry mouth
Common: diarrhea, vomiting
Uncommon: abdominal discomfort, anorexia, decreased appetite, dysphagia
Not known: gastroesophageal reflux disease, pseudo-obstruction in patients at risk (elderly or patients with constipation and treated with other medicinal products that decrease intestinal motility)
• Psychiatric disorders Common: confusional state
Not known: agitation, anxiety, hallucinations, nightmares, paranoia, cognitive disorders in elderly, symptoms of depression, dependence (in patients with history of drug or substance abuse)
• Nervous system disorders
Very common: dizziness, headache, somnolence
Not known: cognitive disorders, convulsions
Cardiac disorders
• Injury, poisoning and proceduralcomplications Not known: heat stroke • Eye disorders Common: dry eyes
Not known: Angle closure glaucoma, mydriasis, ocular hypertension, vision blurred • Renal and urinary disorders Common: urinary retention • Vascular disorders Common: flushing • Skin and subcutaneous tissue disorders Very common: dry skin
Not known: angioedema, rash, urticaria, hypohidrosis • Immune system disorders Not known: hypersensitivity
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 ,/vellowcard
4.9 Overdose Symptoms
The symptoms of overdosage with oxybutynin progress from an intensification of the usual adverse effects of CNS disturbances (from restlessness and excitement to psychotic behaviour), circulatory changes (flushing, fall in blood pressure, circulatory failure etc.), respiratory failure, paralysis and coma.
Management
Measures to be taken are:
1) immediate gastric lavage
2) physostigmine by slow intravenous injection:
Adults: 0.5 to 2.0mg i.v. slowly, repeated if necessary, up to a maximum of 5mg.
Children: 30pg/kg i.v. slowly, repeated if necessary, up to a maximum of 2mg. Fever should be treated symptomatically.
In pronounced restlessness or excitation, diazepam 10mg may be given by intravenous injection. Tachycardia may be treated with intravenous propranolol and urinary retention managed by bladder catheterisation.
In the event of progression of curare-like effects to paralysis of the respiratory muscles, mechanical ventilation will be required.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Oxybutynin hydrochloride has direct antispasmodic action on the smooth muscle of the bladder detrusor as well as anticholinergic action in blocking the muscarinic effects of acetylcholine on smooth muscle.
These properties cause relaxation of the detrusor muscle of the bladder and inpatients with an unstable bladder, oxybutynin hydrochloride increases bladder capacity and reduces the incidence of spontaneous contraction of the detrusor muscle.
The optimal dose required to bring about the desired effect is in the range 3 -15mg daily.
5.2 Pharmacokinetic properties
Following oral administration, oxybutynin hydrochloride undergoes extensive first-pass metabolism in the liver. This shows considerable inter-subject variability, with maximum plasma concentrations differing by as much as four- or five-fold amongst individuals. However, this does not significantly affect the pharmacological actions of oxybutynin hydrochloride as much of the oral dose (approximately 90%) is metabolised to desethyloxybutynin. This is the major metabolite which is pharmacologically active with similar potency and efficacy to the parent compound.
Oxybutynin hydrochloride is rapidly and well absorbed from the gastro-intestinal tract. In the bioequivalence study peak plasma concentrations for oxybutynin were reached in 0.5 to 1.25 hours with a mean of 0.7 hours. Peak plasma concentrations for desethyloxybutynin were reached in 0.5 to 1.5 hours with a mean of 0.9 hours. Mean elimination half-life for oxybutynin and desethyloxybutynin were 1.4 hours and 2.1 hours respectively.
In man oxybutynin hydrochloride is 83-85% bound to plasma albumin. It is distributed throughout most of the body, with high concentrations in the stomach, intestines and liver, but only very small amounts are found in the central nervous system. It is estimated that only 0.01% of the dose will enter the cerebrospinal fluid. In rats the concentrations achieved in breast milk and in the foetus are approximately 50-60% of those found in the maternal blood. Distribution of the drug in the foetus is similar to that in the mother.
The elimination of oxybutynin hydrochloride is rapid with a short plasma elimination half-life so that repeated administration of oxybutynin hydrochloride results in little accumulation. Very little oxybutynin hydrochloride is excreted unchanged in the urine - more is excreted in the faeces (approximately 23% compared with 8%).
5.3 Preclinical safety data
There was no evidence of genotoxic or carcinogenic potential. High doses of oxybutynin increased the incidence of extra thoracolumbar ribs in rat foetuses as well as mortality of neonates. However, these effects on the reproductive processes occurred only at doses associated with maternal toxicity (100mg/kg/day).
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Crospovidone
Microcrystalline cellulose
Lactose monohydrate
Magnesium stearate
Indigo carmine aluminium lake (E132)
6.2 Incompatibilities
None stated
6.3 Shelf life
Three years
Do not use after the ‘Use Before’ date given on the pack.
6.4 Special precautions for storage
Store below 25°C in a dry place.
6.5 Nature and contents of container
The tablets are available in Aluminium/pPVC/PVdC strips in boxes of 20, 28, 30, 56, 60, 84 and 120.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements
MARKETING AUTHORISATION HOLDER
7
Niche Generics Limited
1 The Cam Centre
Wilbury Way
Hitchin
Hertfordshire
SG4 0TW
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 19611/0027
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
20/01/2003
10 DATE OF REVISION OF THE TEXT
26/06/2015