Oxybutynin Hydrochloride 2.5mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Oxybutynin hydrochloride 2.5mg Tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Oxybutynin hydrochloride tablets 2.5mg contain 2.5mg of oxybutynin hydrochloride.
3. PHARMACEUTICAL FORM
Oxybutynin hydrochloride tablets are light blue and circular.
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 non-drug therapy, when other treatment has failed.
4.2. Posology and Method of Administration
Oxybutynin hydrochloride tablets are for oral administration. The tablet should be swallowed with plenty of water or other fluid, to ensure passage through the oesophagus.
Adults: The dose is usually one tablet of 2.5 mg or 5 mg given two or three times daily, although this may be increased up to a maximum of 5 mg 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.
Elderly: A dose of 2.5 mg or 5 mg 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 2.5 mg to 5 mg twice daily should be given initially and this can be increased up to 5 mg three times daily to obtain a clinical response. In cases of nocturnal enuresis alone, the usual dose is 5 mg two or three times daily with the last dose given before bedtime.
Children under 5 years of age: The safety and efficacy of oxybutynin hydrochloride 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.
Following initial control, a reduced maintenance dose may be introduced.
4.3. Contra-Indications
Oxybutynin hydrochloride tablets are contra-indicated in patients:
- who have demonstrated hypersensitivity to the product or any component;
- with untreated angle closure glaucoma or with untreated narrow anterior chamber angles since anticholinergic drugs may aggravate these conditions;
- with partial or complete obstruction of the gastrointestinal tract, paralytic ileus, intestinal atony of the elderly or debilitated patient, megacolon, toxic megacolon complicating ulcerative colitis, severe colitis;
- with myasthenia gravis;
- with obstructive uropathy as urinary retention may be precipitated;
- with unstable cardiovascular status in acute haemorrhage;
- who are breast-feeding.
4.4. Special Warnings and Special Precautions for Use
Warnings:
Oxybutynin hydrochloride tablets, when administered in the presence of high environmental temperature, can cause heat prostration (fever and heat stroke due to decreased sweating). Diarrhoea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. In this instance treatment with oxybutynin hydrochloride tablets would be inappropriate and possibly harmful.
Precautions:
Oxybutynin hydrochloride tablets 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, hepatic or renal disease and severe gastro-intestinal motility disorders (also see section 4.3).
The symptoms of hyperthyroidism, coronary artery/heart disease, congestive cardiac failure, cardiac arrhythmias, tachycardias, hypertension and prostatic hypertrophy may be aggravated following the administration of oxybutynin hydrochloride tablets.
Special care should be taken in patients with hiatus hernia associated with reflux oesophagitis, as anticholinergic drugs may aggravate this condition.
If oxybutynin hydrochloride tablets are administered in such patients then this should be accompanied by some clinical monitoring.
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.
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 hydrochloride, as potentiation of anticholinergic effects could occur.
Occasional cases of interaction between anticholinergics and clozapine, phenothiazines, amantadine, butyrophenones- haloperidol, levadopa, digitalis and tricyclic antidepressants have been reported and care should be taken if oxybutynin hydrochloride tablets are administered concurrently with such drugs. Oxybutynin hydrochloride tablets may cause drowsiness. Alcohol or other sedative drugs may enhance this effect.
By reducing gastric motility, oxybutynin may affect the absorption of other drugs.
4.6. Pregnancy and Lactation
Pregnancy:
There are no data relating to the safety of oxybutynin hydrochloride tablets in human pregnancy but in pregnant rats it has been noted that oxybutynin crosses the placenta unchanged. The foetal blood levels reach 50% maternal levels after six hours and decline more slowly than maternal levels. Oxybutynin hydrochloride tablets should therefore not be given to pregnant women unless, in the judgement of the physician, the probable clinical benefits outweigh the potential hazards. No embryotoxicity was observed in animal studies at doses which did not produce maternal toxicity.
Lactation:
Oxybutynin hydrochloride has been detected in breast milk in animal studies (approximately 60% of that found in the maternal blood). These concentrations decline more slowly than in maternal blood so that oxybutynin hydrochloride tablets should not be taken by breast-feeding mothers.
4.7. Effects on Ability to Drive and Use Machines
As oxybutynin hydrochloride tablets may cause drowsiness or blurred vision, the patient should be cautioned regarding activities requiring mental alertness such as driving a motor vehicle, operating machinery or performing hazardous work whilst taking this drug.
4.8. Undesirable Effects
Oxybutynin hydrochloride tablets may produce all the side effects that may be associated with anticholinergic drugs:
Cardiac disorders: palpitations, tachycardia, cardiac arrhythmia
Vascular disorders: vasodilatation and facial flushing which may be more marked in children.
Skin and subcutaneous tissue disorders: decreased sweating, dry skin, allergic reactions such as rash, urticaria, angioedema, photosensitivity.
Gastrointestinal disorders: constipation, diarrhoea, decreased gastrointestinal motility, dry mouth, nausea, abdominal discomfort, vomiting, gastroesophageal reflux,
Renal and urinary disorders: urinary hesitance, difficulty in micturition, and retention.
Metabolism and nutrition disorders: anorexia
Nervous system disorders: headache, dizziness, drowsiness, convulsions
Psychiatric disorders: Agitation, hallucinations, nightmares, insomnia, restlessness, disorientation.
General disorders and administration site conditions: Asthenia
Eye disorders: blurred vision, mydriasis, intraocular hypertension, onset of narrow-angle glaucoma, dry eyes.
Reproductive system and breast disorders: impotence, suppression of lactation.
4.9. Overdose
The symptoms of overdose with oxybutynin hydrochloride tablets progress from an 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.
Measure to be taken are:
1. Immediate gastric lavage and
2. Slow intravenous injection of 1.0 to 2.0mg of physostigmine
Adults: 0.5 to 2.0 mg of physostigmine by slow intravenous administration. Repeat after 5 minutes, if necessary up to a maximum total dose of 5mg.
Children: 30 micrograms/kg of physostigmine by slow intravenous administration. Repeat after 5 minutes, if necessary up to a maximum total dose of 2mg.
Fever should be treated symptomatically with tepid sponging or ice packs.
In pronounced restlessness or excitation, diazepam 10mg may be given by intravenous injection, tachycardia may be treated by intravenous injection of propranolol and urinary retention can be managed by catheterisation.
In the event of progression of the curare- like effect to the 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 in patients 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 gastrointestinal 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 Pre-clinical 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 (100 mg/kg/day).
6 PHARMACEUTICAL PARTICULARS
6.1 List of Excipients
Crospovidone Ph.Eur., microcrystalline cellulose Ph.Eur., lactose monohydrate Ph.Eur., magnesium stearate Ph.Eur., indigo carmine aluminium lake (E132) HSE.
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 Content of Container
Oxybutynin hydrochloride tablets are available in Aluminium / uPVC / PVdC strips in boxes of 20, 28, 30, 56, 60, 84 and 120.
6.6 Special precautions for disposal
No special requirements
7 MARKETING AUTHORISATION HOLDER
Tillomed Laboratories Limited 3 Howard Road Eaton Socon St Neots
CambsPE193ET
8 MARKETING AUTHORISATION NUMBER(S)
PL 11311/0136
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
10 February 1999 / 27/03/2009
10 DATE OF REVISION OF THE TEXT
13/01/2011