Ditropan Elixir 2.5mg/5ml
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ditropan elixir 2.5mg/5ml
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Ditropan elixir contains 2.5mg oxybutynin hydrochloride per 5ml.
Excipient(s) of known effect:
Sodium methyl-p-hydroxybenzoate 5.72mg per 5ml
For the full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Ditropan elixir is a clear and colourless elixir.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For use in urinary incontinence, urgency and frequency in the 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 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 Dosage and administration
Adults: The usual dose is 5mg (10ml) two or three times a day. This may be increased to a maximum of 5 mg four times a day to obtain a clinical response provided that the side effects are tolerated.
Elderly: The elimination half-life is increased in the elderly, therefore, a dose of 2.5mg (5ml) twice a day, particularly if the patient is frail, is likely to be adequate. This dose may be titrated upwards to 5mg two times a day to obtain a clinical response provided the side effects are tolerated.
Children (under 5 years of age): Not recommended
Children (over 5 years of age): Neurogenic bladder: the usual dose is 2.5mg (5ml) twice a day. This dose may be titrated upwards to 5mg (10ml) two or three times a day to obtain a clinical response provided that the side effects are tolerated. Nocturnal enuresis: the usual dose is 2.5mg (5ml) twice a day. This dose may be titrated upwards to 5mg (10ml) two or three times a day to obtain a clinical response provided that the side effects are tolerated. The last dose should be given before bedtime.
4.3 Contraindications
Hypersensitivity to oxybutynin or any component.
Myasthenia gravis.
Narrow-angle glaucoma or shallow anterior chamber.
Gastrointestinal obstructive disorders including paralytic ileus, intestinal atony.
Patients with toxic megacolon.
Patients with severe ulcerative colitis.
Patients with bladder outflow obstruction where urinary retention may be precipitated.
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 be cautious in case of 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.
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 Ditropan as potentiation of anticholinergic effects could 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 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.
* Lactation: 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: diarrhoea, 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 drugs that decrease intestinal motility)
• Psychiatric disorders Common: confusional state
Not known: agitation, anxiety, hallucinations, nightmares, paranoia, cognitive disorders in elderly, symptoms of depression, dependence to oxybutynin (in patients with history of drug or substance abuse)
• Nervous system disorders
Very common: dizziness, headache, somnolence
Not known: cognitive disorders, convulsions, drowsiness, disorientation
• Cardiac disorders
Not known: tachycardia, arrhythmia
• Injury, poisoning and procedural complications Not known: heat stroke
• Eye disorders
Very common: vision blurred Common: dry eyes
Not known: Angle closure glaucoma, mydriasis, ocular hypertension
• Renal and urinary disorders Common: urinary retention
Not known: difficulty in micturition
• Vascular disorders
Common: flushing which may be more marked in children
• Skin and subcutaneous tissue disorders Very common: dry skin
Not known: angioedema, rash, urticaria, hypohidrosis, photosensitivity
• 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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
4.9 Overdose
The symptoms of overdosage with oxybutynin 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.
Measures to be taken are:
1) immediate gastric lavage
2) physostigmine by slow intravenous injection
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 bladder 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 both direct antispasmodic action on the smooth muscle of the bladder detrusor muscle as well as an anticholinergic action in blocking the muscarinic effects of acetylcholine on smooth muscle. These properties cause relaxation of the detrusor muscle of the bladder in patients with an unstable bladder. Ditropan increases bladder capacity and reduces the incidence of spontaneous contractions of the detrusor muscle.
5.2 Pharmacokinetic properties
Oxybutynin is poorly absorbed from the gastrointestinal tract. It is highly bound to plasma proteins, the peak plasma level is reached between 0.5 to 1 hour after administration. The half life is biexponential, the first phase being about 40 minutes and the second about 2-3 hours. The elimination half life may be increased in the elderly, particularly if they are frail.
Oxybutynin and its metabolites are excreted in the faeces and urine. There is no evidence of accumulation.
5.3 Preclinical safety data
No data of therapeutic relevance.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Ditropan elixir contains citric acid, sodium citrate, sucrose (1.3g per 5ml dose), sorbitol, glycerol, sodium methyl-p-hydroxybenzoate (E219), purified water.
6.2 Incompatibilities
None known.
6.3 Shelf life
Ditropan Elixir 2.5mg/5ml has a 12 month shelf life.
6.4 Special precautions for storage
Ditropan Elixir 2.5mg/5ml : Store below 25oC. Protect from light Discard any medicine remaining 28 days after opening the bottle
6.5 Nature and contents of container
Ditropan Elixir 2.5mg/5ml : 30ml (sample size) and 150ml amber glass bottle with a child resistant screw cap.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Aventis Pharma Limited
One Onslow Street
Guildford
Surrey
GU1 4YS
UK
or trading as:-
Sanofi-aventis or Sanofi
One Onslow Street
Guildford
Surrey
GU1 4YS
UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 04425/0286
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
24 January 2001
10
DATE OF REVISION OF THE TEXT
24/07/2015