Oxybutynin Hydrochloride 3 Mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Oxybutynin hydrochloride 3 mg tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 3 mg of oxybutynin hydrochloride.
Excipient: each tablet contains 71.40 mg lactose monohydrate.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablet.
White circular, flat, beveled edged tablet, scored on one side, diameter 6.5 mm, thickness 2.3 -2.7 mm.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Oxybutynin hydrochloride is indicated for urinary incontinence, urgency and frequency in unstable bladder, whether due to neurogenic bladder disorders (detrusor hyperreflexia) in conditions such as multiple sclerosis and spina bifida, or to idiopathic detrusor instability (motor urge incontinence).
Paediatric population
Oxybutynin hydrochloride in 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).
4.2 Posology and method of administration
Adults:
The usual dose is 5mg two or three times a day. This may be increased to a maximum of 5mg four times a day to obtain a clinical response provided that the side effects are tolerated.
Elderly:
The elimination half-life may be increased in some elderly people. Therefore, the dose must be set individually, starting with 2.5 mg twice a day. Afterwards the lowest effective dose has to be chosen.
Children (under 5 years of age): not recommended
Children over 5 years:
Neurogenic bladder instability: the usual dose is 2.5mg twice a day. This dose may be titrated upwards to 5mg two or three times a day to obtain a clinical response provided the side effects are well tolerated. Nocturnal enuresis: the usual dose is 2.5 mg twice a day. This dose may be titrated upwards to 5mg two or three times a day to obtain a clinical response provided the side effects are tolerated. The last dose should be given before bedtime.
The tablets have to be swallowed with plenty of fluid and may be taken on an empty stomach. If gastric irritation occurs the tablets may also be taken during meals or with some milk.
4.3 Contraindications
Hypersensitivity to oxybutynin or one of the other ingredients of the tablet Narrow-angle glaucoma or shallow anterior chamber Myasthenia gravis
Obstruction of the gastro-intestinal tract, paralytic ileus, intestinal atony Micturition problems caused by either obstructive uropathy or prostate hypertrophy Severe ulcerative colitis Toxic megacolon
4.4 Special warnings and precautions for use
Care is essential with frail elderly patients and children who may be more sensitive to the effects of oxybutynin and in patients with autonomic neuropathy, hiatus hernia with reflux oesophagitis or other serious gastrointestinal diseases and decreased hepatic or renal function.
The symptoms of hyperthyroidism, congestive cardiac failure, coronary heart disease, cardiac arrhythmias, tachycardias, hypertension and prostate hypertrophy may be aggravated during the treatment with oxybutynin.
Oxybutynin can cause decreased sweating: in high environmental temperatures this can lead to heat prostration.
Special care should be taken in patients with hiatus hernia associated with reflux oesophagitis, as anticholinergic drugs can aggravate this condition.
Prolonged use may contribute in the development of caries, periodontal disease, oral candidiasis and discomfort due to decrease of inhibition of the salivary flow.
If a urinary tract infection is present an appropriate antibacterial therapy should be started.
Oxybutynin hydrochloride should be used with caution in patients with pollakisuria and nocturia due either to heart disease or renal disease.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose - galactose malabsorption should not take this medicine.
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 safety used in this age group.
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 can occur.
Potentiation of the effects could occur during administration of atropine and other parasympatholytic acting agents.
By the decrease of the gastro-intestinal motility oxybutynin can influence the absorption of other medicines.
Occasional cases of interaction between anticholinergics and clozapine phenothiazines, amantadine, butyrophenones, levodopa, digitalis, quinidine and tricyclic antidepressants have been reported, and care should be taken if oxybutynin is administered concurrently with such drugs.
Since oxybutynin is metabolised by cytochrome P450 isoenzyme 3A4, interactions with drugs that inhibit this isoenzyme can not be excluded. This should be considered when oxybutynin is used concomitantly with antimycotics of the azole-group (e.g. ketoconazole) or macrolide antibiotics (e.g erythromycin). Itraconazole has been demonstrated to inhibit oxybutynin metabolism. This led to doubling of the oxybutynin plasma levels, but only to a 10 % increase for the active metabolite. Because the metabolite is responsible for about 90 % of the antimuscarinic activity, the changes appear to be of minor clinical importance.
Care should be taken if prokinetic agents are taken concurrently with Oxybutynin hydrochloride as decrease of the effect may occur.
4.6 Fertility, pregnancy and lactation
Fertility: Studies in animals have shown impaired fertility in females (see section 5.3).
Pregnancy: There are no data from the use of oxybutynin in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown.
Oxybutynin hydrochloride should not be used during pregnancy unless clearly necessary.
Lactation: It is not known whether oxybutynin is excreted in human breast milk. Oxybutynin is excreted in milk of rats. Use of oxybutynin is not recommended during breast-feeding because there are no data with respect to the effect of oxybutynin on the infant.
4.7 Effects on ability to drive and use machines
Oxybutynin hydrochloride has minor or moderate influence on the ability to drive and use machines. As oxybutynin hydrochloride may cause dizziness, drowsiness or blurred vision, especially in combination with alcohol, 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
Oxybutynin hydrochloride tablets may produce all the side effects that may be associated with anticholinergic drugs:
|
very common (>1/10) |
common (>1/100, <1/10) |
uncommon (>1/1000, <1/100) |
rare (>1/10000, <1/1000) |
very rare, (<1/10000) |
not known | |
|
Psychiatric disorders |
restlessness, disorientation, confusion |
impotence |
agitation, anxiety, hallucination s, nightmares, paranoia, cognitive disorders in elderly, symptoms of depression, dependence (in patients with history of drug or substance abuse) | |||
|
Nervous system disorders: |
dizziness, drowsiness |
headache |
convulsions (children may be more liable to such effects). | |||
|
Eye disorders: |
blurred vision, widened pupils |
decreased Lacrimation / dry eyes |
acute glaucoma (narrow- angle glaucoma) | |||
|
Cardiac disorders: |
tachycardi a, arrhythmia s, palpitation s. | |||||
|
Vascular Disorders: |
Facial flushing | |||||
|
Gastrointestinal disorders: |
dry mouth |
constipation, nausea, abdominal discomfort/p ain |
anorexia, diarrhoea, vomiting |
gastroesopha geal reflux disease, pseudoobstruction in patients at risk (elderly or patients with constipation |
|
and treated with other medicinal products that decrease intestinal motility) | ||||||
|
Skin and subcutaneous tissue disorders: |
decreased sweating/dry skin, |
skin reactions including rash |
angioedema, photosensiti vity | |||
|
Renal and urinary disorders: |
micturition problems |
urinary retention. | ||||
|
General disorders and administration site conditions: |
fatigue |
Heatstroke |
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
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 national reporting system using the Yellow Card Scheme, Website: www.mhra.gov .uk/yellowcard.
4.9 Overdose
Symptoms:
An overdose of oxybutynin is characterised by an intensification of the parasympatholytic adverse effects such as CNS disturbances (from restlessness and excitement to psychotic behaviour), circulatory changes (flushing, fall in blood pressure, circulatory failure, etc.), respiratory failure, paralysis and coma.
Treatment:
Measures to be taken are:
Immediate gastric lavage
Slow intravenous injection of physostigmine (only in severe cases):
Adults: 0.5 - 2 mg, repeat after 5 minutes when necessary, until max. 5 mg totally. Children: 30 pg/kg body-weight, repeated when necessary until max. 2 mg totally
Fever should be treated symptomatically with tepid sponging or ice packs. In pronounced restlessness or excitation, diazepam 10 mg may be given by intravenous injection.
Tachycardia may be treated with intravenous propranolol, and urinary retention managed by bladder catheterization.
In the event of progression of the muscle relaxant effect to paralysis of the respiratory muscles, mechanical ventilation will be required.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Urinary antispasmodics, ATC code: G04BD04
Oxybutynin hydrochloride is a synthetic tertiary amine with a direct spasmolytic and anticholinergic action on the smooth musculature of the detrusor muscle of the bladder. It increases bladder capacity, reduces the frequency of uninhibited detrusor contractions, and delays the first urge to urinate.
5.2 Pharmacokinetic properties
Absorption
Oxybutynin hydrochloride is rapidly absorbed from the gastro-intestinal tract following oral administration.
Because of an extensive hepatic first pass effect, less than 10 % of the dose administered reaches the general circulation unchanged. The maximum plasma level occurs after 1 - 1.5 hours.
Metabolism
N-desethyloxybutynin is an active metabolite that reaches higher plasma levels than the unchanged oxybutynin.
Oxybutynin is extensively metabolised by the liver, primarily by the cytochrome P450 enzyme system, particularly CYP3A4.
Elimination
Elimination mainly takes place by metabolic changes in the liver, i. e. hydrolysis and demethylation. The metabolites are excreted in the urine. Unchanged oxybutynin is hardly found in the urine. The elimination half-life of oxybutynin is rapid, being about 2 - 3 hours
5.3 Preclinical safety data
Preclinical data reveal no special hazard for humans based on conventional studies of general toxicity, genotoxicity and carcinogenicity beyond the information included in other sections of the SmPC. Oxybutynin given to pregnant rats induced cardiac malformations, consisting mainly of interventricular septal defects, an increased incidence of supernumerary thoracolumbar ribs, and increased neonatal mortality in the offspring, at maternally toxic dosages.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Crospovidone, microcrystalline cellulose, lactose monohydrate, magnesium stearate.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years
6.4 Special precautions for storage
Do not store above 25oC.
Store in the original package.
Keep out of the sight and reach of children
6.5
Nature and contents of container
Aluminium / PVC / PVdC strips
Pack with blisters of 7, 28, 56 and 84 tablets
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
Any unused product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Morningside Healthcare Ltd
115 Narborough Road
Leicester
LE30PA
UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 20117/0201
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
14/06/2013
10 DATE OF REVISION OF THE TEXT
20/05/2015