Oxybutynin Hydrochloride Tablets 5mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Oxybutynin Hydrochloride Tablets 5mg
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 5mg Oxybutynin Hydrochloride USP.
For excipients, see Section 6.1
3. PHARMACEUTICAL FORM
White uncoated tablets.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Indicated for urinary incontinence, urgency and frequency in unstable bladder conditions due either to idiopathic detrusor instability or neurogenic bladder disorders (detrusor hyperreflexia) in conditions such as spina bifida and multiple sclerosis.
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
Adults: The usual dose is 5mg two or three times daily. This may be increased to a maximum dosage of 5mg four times daily (20mg) to obtain a satisfactory clinical response provided that the side-effects are tolerated.
Elderly: The elimination half-life may be increased in some elderly patients, therefore, dosage should be individually titrated commencing at 5mg twice daily. The final dosage will depend on response and tolerance to side-effects. As with other anticholinergic drugs, caution should be observed in frail and elderly patients.
Children over 5 years of age: Neurogenic bladder disorders: The usual dose is 5mg twice daily. This may be increased to a maximum of 5mg three times daily to obtain a clinical response provided that the side-effects are tolerated. Nocturnal enuresis: The usual dose is 5mg two or three times daily. The last dose should be given before bedtime.
In children the maintenance dose may be achieved by upward titration from an initial dose of 3mg twice daily (an elixir formulation of oxybutynin is available).
Children under 5 years of age: Not recommended.
4.3 Contraindications
• Hypersensitivity to oxybutynin or any of the other ingredients of this formulation
• 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
• Glaucoma (as it may raise intra-ocular pressure. 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 esophagitis.
When oxybutynin is used in high environmental temperatures, this can cause heat prostration due to decreased sweating
Paediatric population
Oxybutynin hydrochloride is not recommended for use in children below age 5 years due to insufficient data on safety and efficacy.
There is limited evidence supporting the use of Oxybutynin in children with monosymptomatic nocturnal enuresis (not related to detrusor overactivity).
In children over 5 years of age, Oxybutynin hydrochloride should be used with caution as they may be more sensitive to the effects of the product, particularly the CNS and psychiatric adverse reactions.
4.5 Interaction with other medicinal products and other forms of interaction
Care should be taken if other anticholinergic agents are administered together with oxybutynin, as potentiation of anticholinergic effects can 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, embryonic/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.
Lactation: when oxybutynin is used during lactation, a small amount is excreted in the mother's milk.
Use of oxybutynin during breast feeding is therefore not recommended.
4.7. Effects on Ability to Drive and Use Machines
As oxybutynin may produce drowsiness or blurred vision, the patient 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: constipation1, nausea1, dry mouth1
Common: diarrhoea2, vomiting
Uncommon: abdominal discomfort1, 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 Uncommon: disorientation2
Not known: agitation, anxiety, hallucinations2, nightmares, paranoia, cognitive disorders in elderly, symptoms of depression, dependance (in patients with history of drug or substance abuse)
Nervous system disorders
Very common: dizziness2, headache2, somnolence, drowsiness2 Uncommon: restlessness2
Not known: cognitive disorders, convulsions2
Cardiac disorders
Not known: palpitations, tachycardia, arrhythmia2
Injury, poisoning and procedural complications Not known: heat stroke
Eye disorders Common: dry eyes
Not known: Angle closure glaucoma, mydriasis, ocular hypertension, vision blurred1
Renal and urinary disorders
Common: urinary retention2, difficulty in micturition1
Vascular disorders
Common: flushing (facial flushing more evident in children)1
Skin and subcutaneous tissue disorders Very common: dry skin2
Uncommon: photosensitivity2
Not known: angioedema2, rash2, urticaria, hypohidrosis Immune system disorders Not known: hypersensitivity.
Antimuscarinic drugs may reduce sweating leading to heat sensations and fainting in hot environments.
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; website: www.mhra.gov.uk/yellowcard
4.9 Overdose
The symptoms of overdosage with oxybutynin progress from intensification of the usual side-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.
Measures to be taken are:
1) immediate gastric lavage
2) physostigmine by slow intravenous injection :
Adults : 0.5 to 2.0 mg i.v. slowly, repeated if necessary, up to a maximum of 5 mg.
Children : 30 pg/kg i.v. slowly, repeated if necessary, up to a maximum of 2 mg.
Fever should be treated symptomatically with tepid sponging or ice packs. In pronounced restlessness or excitation, diazepam 10mg may be given by iv injection. Tachycardia may be treated with iv propranolol and urinary retention managed by bladder catheterisation. In the event of progression of the curare-like effect to paralysis of the respiratory muscles, mechanical ventilation will be required.
5.1. Pharmacodynamic Properties
Oxybutynin is an antimuscarinic agent.
Oxybutynin has two main pharmacological effects, an anticholinergic action and a direct antispasmodic activity. Radio ligand binding studies have shown that oxybutynin binds to the M1 subtype of muscarinic receptors. At low doses, it has little or no antagonistic action at the M2-M5 receptor subtypes and less than 10% of the anticholinergic effects of propantheline. It therefore has few common anticholinergic side-effects such as central nervous system or cardiovascular activity. In vitro studies have demonstrated antispasmodic activity probably due to an inhibition of calcium influx into smooth muscle cells. The concentration at which inhibition of calcium influx into smooth muscle cells occurs is approximately 100 times greater than that of selective M1 blockade. The myorelaxant effects may reduce bladder spasm thus decreasing frequency of micturition. Oxybutynin has weak analgesic effects comparable to dextropropoxyphene.
5.2. Pharmacokinetic Properties
Following oral administration of oxybutynin, peak plasma concentrations are reached within one hour. A half-life of less than 2 hours has been reported. Oxybutynin has been detected in breast milk.
5.3. Pre-clinical Safety Data
Not applicable.
6 PHARMACEUTICAL PARTICULARS
6.1. List of Excipients
Also contains: cellulose, lactose, magnesium stearate, purified talc (E553).
6.2. Incompatibilities
None known.
6.3. Shelf Life
Two years from the date of manufacture.
6.4. Special Precautions for Storage
Shelf Life - After dilution or reconstitution Not applicable.
Shelf Life - After first opening the container Not applicable.
6.5. Nature and Content of Container
The product may also be supplied in blister packs in cartons:
a) Carton: Printed carton manufactured from white folding box board.
b) Blister pack: (i) 250pm white rigid PVC. (ii) Surface printed 20pm hard temper aluminium foil with 5-6g/M2 PVC compatible heat seal lacquer on the reverse side.
Pack sizes: 21s, 28s, 30s, 56s, 60s, 84s, 100s, 120s
6.6. Instructions for Use, Handling and Disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Actavis UK Limited (Trading style: Actavis) Whiddon Valley BARNSTAPLE N Devon EX32 8NS
8. MARKETING AUTHORISATION NUMBER(S)
PL 0142/0394
9. DATE OF FIRST AUTHORISATION/RENEWAL OF
AUTHORISATION
10.7.97
10 DATE OF REVISION OF THE TEXT
26/06/2015
These side effects may be reduced with the reduction of the dose.
Children are at a higher risk of these effects.