4.1. Therapeutic indications

Oxybutynin hydrochloride has antispasmodic/anticholinergic actions.

It is indicated for:

Adults:

The symptomatic treatment of urinary incontinence, frequency and urgency in patients with an unstable bladder (urge syndrome), 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 over activity, in conjunction with non-drug therapy, when other treatment has failed.

4.2. Posology and method of administration

Posology

The dosage should be determined individually.

Adults

The usual dose is 5 mg two or three times a day. This may be increased up to a maximum of 5 mg four times daily (maximum dose 20 mg Oxybutynin per 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 2.5 mg twice daily, particularly if the patient is frail, is likely to be adequate. This dose may be increased to 5 mg two times a day to obtain a clinical response provided the side effects are well tolerated.

Paediatric population

Children 5 years of age and over

Neurogenic bladder instability: the usual dose is 2.5 mg twice a day. This dose can be increased up to 5 mg two or three times daily 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 increased to 5 mg two or three times daily to obtain a clinical response provided the side effects are tolerated. The last dose should be given before bedtime.

Children under 5 years of age

Oxybutynin is not recommended in children under 5 years of age due to insufficient clinical data.

Method of administration

For oral use.

The tablet should be swallowed with a glass of water.

4.3. Contraindications

o Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

o Myasthenia Gravis;

o Narrow angle glaucoma or shallow anterior chamber;

o Gastrointestinal obstructive disorders including paralytic ileus, intestinal atony.

o Toxic megacolon;

o Severe ulcerative colitis;

o Bladder outflow obstruction where urinary retention may be precipitated.

4.4. Special warnings and precautions for use

Oxybutynin should be used with caution in patients with Parkinson's disease 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.

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 cognitive disorders, symptoms of prostatic hypertrophy and tachycardia (thus be cautious in case of hyperthyroidism, congestive heart failure, cardiac arrhythmia, coronary heart disease, hypertension).

Anticholinergic CNS effects (such as hallucinations, agitation, confusion, somnolence) have been reported. Monitoring is recommended, especially in the first few months after initiating therapy or increasing the dose. If anticholinergic CNS effects develop, termination of treatment or dose reduction may be considered.

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.

Elderly

Anticholinergic medicinal products should be used with caution in elderly patients due to the risk of cognitive impairment. They also have a higher risk of occurrence of adverse reactions to the product.

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.

Excipients

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

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.

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. Fertility, 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.

Breastfeeding

When oxybutynin is used during lactation, a small amount is excreted in breast 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 whilst taking this medicine.

4.8. Undesirable effects

Like all medicines, oxybutynin can cause undesirable effects, although not everybody gets them. The frequency of possible undesirable effects listed below are currently defined as:

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).

ADVERSE REACTIONS REPORTED

System Organ Class

Frequency

Adverse Reaction (MedDRA Terms)

Infections and Infestations

Not known

urinary tract infection

Immune System Disorders

Not known

hypersensitivity

Psychiatric Disorders

Common

confusional state

Not known

agitation, anxiety, cognitive disorders in elderly, hallucinations, nightmares, paranoia, 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

Eye Disorders

Very common

vision blurred

Common

dry eyes

Not known

angle closure glaucoma, increased intraocular pressure, mydriasis

Cardiac Disorders

Common

palpitation

Not known

arrhythmia, tachycardia

Vascular Disorders

Common

flushing (which may be more marked in children)

Respiratory, thoracic, and mediastinal disorders

Not known

epistaxis

Gastrointestinal Disorders

Very common

constipation, dry mouth, nausea

Common

diarrhoea, vomiting

Uncommon

abdominal discomfort, anorexia, decreased appetite, dysphagia

Not known

gastroesophageal reflux, pseudo-obstruction in patients at risk (elderly or patients with constipation and treated with other drugs that decrease intestinal motility)

Skin and Subcutaneous Tissue Disorders

Very common

dry skin

Not known

angioedema, hypohidrosis, rash, urticaria, photosensitivity

Musculoskeletal and connective tissue disorders

Not known

muscle disorders manifested as muscle weakness, myalgia and/ or muscle spasms

Renal and Urinary Disorders

Common

urinary retention

Not known

difficulty in micturition

Injury, Poisoning and Procedural Complications

Not known

heat stroke

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Symptoms of intoxication

The symptoms of overdose 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.

Management

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.

Paediatric population: 30 micrograms/kg of physostigmine by slow intravenous administration. Repeat after 5 minutes, if necessary up to a maximum total dose of 2 mg.

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 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.