This information is intended for use by health professionals

1. Name of the medicinal product

Ditropan tablets 2.5mg

2. Qualitative and quantitative composition

Each tablet contains 2.5mg oxybutynin hydrochloride as the active ingredient.

3. Pharmaceutical form

Ditropan tablets 2.5mg are pale blue oval bi-convex tablets 8 mm x 5.5 mm, marked OXB2.5 on one side.

4. Clinical particulars
4.1 Therapeutic indications

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 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 (including frail elderly): The elimination half-life is increased in the elderly. Therefore, a dose of 2.5mg 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 well tolerated.

Children (under 5 years of age): Not recommended

Children (over 5 years of age): 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 2.5mg 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 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, patients with Parkinson's disease and children who are at greater risk of occurrence of adverse reactions to the product, and in patients with autonomic neuropathy (such as those with Parkinson's disease), severe gastro-intestinal 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, as an anticholinergic agent, may antagonize the effect of 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 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 tablets contain lactose, cellulose, calcium stearate and indigo carmine (E132).

6.2 Incompatibilities

None known.

6.3 Shelf life

4 years

6.4 Special precautions for storage

Store below 30°C.

6.5 Nature and contents of container

Polypropylene container* of 100 or 500 tablets and cartons containing 6*, 21 or 84 tablets in blister strips.

* Not marketed

6.6 Special precautions for disposal and other handling

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 04425/0289

9. Date of first authorisation/renewal of the authorisation

26 March 2009

10. Date of revision of the text

16 September 2016

Legal status

POM