Oxybutynin hydrochloride 2.5mg /5ml oral solution

Each 5ml of oral solution contains 2.5mg of oxybutynin hydrochloride.

Excipients with known effect:

Sorbitol (E420): This medicine contains 125 mg sorbitol in each ml which is equivalent to 625 mg per dose of 5 ml.

Maltitol (E 965): This medicine contains 125 mg maltitol in each ml, which is equivalent to 625 mg per dose of 5 ml.

Methyl parahydroxybenzoate (E218): This medicine contains 1.2 mg methyl parahydroxybenzoate, which is equivalent to 6 mg per dose of 5 ml.

Propylene glycol (E 1520): This medicine contains approximately 1.47 mg propylene glycol in each ml, which is equivalent to 7.35 mg per dose of 5 ml.

Ethanol (E1510): This medicinal product contains small amounts of ethanol (alcohol), less than 100 mg per 5 ml.

For the full list of excipients, see section 6.1.

Oral solution.

Clear, colourless solution, with strawberry odour.

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.

Dosage and administration:

Adults: The usual dose is 5 mg (10 ml) two or three times a day. This may be increased to a maximum of 5 mg (10 ml) 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 2.5 mg (5 ml) twice a day, particularly if the patient is frail, is likely to be adequate. This dose may be titrated upwards to 5 mg (10 ml) 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 2.5 mg (5 ml) twice a day. This dose may be titrated upwards to 5 mg (10 ml) 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 (5 ml) twice a day. This dose may be titrated upwards to 5mg (10 ml) 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.

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.

• 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 (see also section 4.3).

• 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.

Excipient warnings

Sorbitol: 125 mg sorbitol in each ml, which is equivalent to 625 mg per dose of 5 ml. Sorbitol is a source of fructose. The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account.

The content of sorbitol in medicinal products for oral use may affect the bioavailability of other medicinal products for oral use administered concomitantly.

Patients with hereditary fructose intolerance (HFI) should not take/be given this medicinal product.

Sorbitol may cause gastrointestinal discomfort and mild laxative effect.

Maltitol: 125 mg maltitol in each ml, which is equivalent to 625 mg per dose of 5 ml. Patients with rare hereditary problems of fructose intolerance should not take this medicine

Propylene glycol: approximately 1.47 mg propylene glycol in each ml, which is equivalent to 7.35 mg per dose of 5 ml.

Methyl parahydroxybenzoate (E218): May cause allergic reactions (possibly delayed), and exceptionally, bronchospasm.

Ethanol (E1510): This medicinal product contains small amounts of ethanol (alcohol), less than 100 mg per 5 ml.

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 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).

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.

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.

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

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.

Pharmacotherapeutic group: Urologicals, Drugs for urinary frequency and incontinence, ATC code: G04BD04

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. Oxybutynin increases bladder capacity and reduces the incidence of spontaneous contractions of the detrusor muscle.

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.

No data of therapeutic relevance.

Sorbitol (E 420)

Maltitol (E 965)

Glycerol (E 422)

Xanthan gum

Methyl parahydroxybenzoate (E218)

Citric acid monohydrate

Sodium citrate dihydrate

Strawberry flavour (contains propylene glycol)

Citric acid Solution 30%

Ethanol

Purified water

None known.

36 months

Discard after 30 days of first opening. Store in the original packaging after first opening.

Store below 25°C.

For storage conditions after first opening of the medicinal product, see section 6.3.

150 ml amber type III glass bottles with child resistant tamper-evident screw cap and a polypropylene measuring cup of 15ml with 5 ml and 10 ml graduations.

No special requirements.

ROMA Pharmaceuticals Limited

Gibraltar House

Crown Square

Centrum 100

Burton on Trent

DE14 2WE

PL 49578/0002

30/07/2020

03/11/2021