This information is intended for use by health professionals

1. Name of the medicinal product

Oxybutynin Hydrochloride 3mg Tablets

2. Qualitative and quantitative composition

Oxybutynin hydrochloride 3.00mg

For excipients, see 6.1.

3. Pharmaceutical form

Tablet

4. Clinical particulars
4.1 Therapeutic indications

Oxybutynin is 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 non-drug therapy, when other treatment has failed.

4.2 Posology and method of administration

Children under 5 years of age: Not recommended

Children over 5 years of age:

Neurogenic bladder disorders: The usual dose is 5mg twice a day. This may be increased to a maximum of 5mg three times a day to obtain a clinical response provided that the side effects are tolerated.

Nocturnal enuresis: The usual dose is 5mg two or three times a day. 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.

Adults: The usual dose is 5mg two or three times a day. This may be increased to a maximum dosage of 5mg four times a day (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 3mg twice a day. 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.

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, 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 oxybutynin, 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 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 antagonise 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 medicinal products that decrease intestinal motility)

• Psychiatric disorders

Common: confusional state

Not known: agitation, anxiety, hallucinations, nightmares, paranoia, cognitive disorders in elderly, symptoms of depression, dependence (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 2.0mg 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 with intravenous propanolol and urinary retention managed by bladder catheterization.

In the event of progression of the curare-like 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: G04B D04

Oxybutynin hydrochloride is an anticholinergic agent which also exerts a direct antispasmodic effect on smooth muscle. It inhibits bladder contraction and relieves spasm induced by various stimuli; it increases bladder volume, diminishes the frequency of contractions and delays the desire to void in the disturbance of neurogenic bladder. The relaxation of smooth muscle results from the papaverin like effect of the antagonism of the processes distal to the neuromuscular junction in addition to the anticholinergic blocking action of the muscarinic type receptors. In addition oxybutynin hydrochloride has local anaesthetic properties.

5.2 Pharmacokinetic properties

Pharmacodynamic reports show oxybutynin to be rapidly absorbed from the gastrointestinal tract following oral administration with maximum plasma concentrations reached in less than 1 hour subsequently falling bioexponentially with a half-life of between 2 and 3 hours. Maximum effect can be seen within 3-4 hours with some effect still evident after 10 hours.

Repeated oral administration achieved steady state after eight days. Oxybutynin does not appear to accumulate in elderly patients and the pharmacokinetics are similar to those in other adults. Some excretion via the biliary system has been observed in the rabbit and partial first-pass metabolism occurs, the metabolites also appearing to have antimuscarinic properties. The main elimination route is via the kidneys with only 0.3-0.4% of unchanged drug appearing in the urine of the rat after 24 hours and 1% appearing in the urine of the dog after 48 hours. In rats and dogs therefore, oxybutynin appears to be almost completely absorbed.

5.3 Preclinical safety data

No additional data available.

6. Pharmaceutical particulars
6.1 List of excipients

Lactose anhydrous, microcrystalline cellulose, calcium stearate, indigo carmine aluminium lake (E132).

6.2 Incompatibilities

None known

6.3 Shelf life

3 years

6.4 Special precautions for storage

Store below 30°C.

6.5 Nature and contents of container

56 tablets in aluminium/PVC blister strips which are contained within a printed cardboard carton.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

7. Marketing authorisation holder

Zentiva Pharma UK Limited

12 New Fetter Lane

London

EC4A 1JP

United Kingdom

8. Marketing authorisation number(s)

PL 17780/0532

9. Date of first authorisation/renewal of the authorisation

31/08/2010

10. Date of revision of the text

29/06/2020