Oxybutynin Hydrochloride 2.5 mg/5 ml Oral solution

Oral Solution Clear colourless to slightly straw coloured liquid

4.1 Therapeutic indications Oxybutynin hydrochloride is indicated for the symptomatic treatment of 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 of 5 years of age or older 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** *Adults:* The usual dose is 5mg two or three times a day. This may be increased to a maximum of 5mg four times a day (maximum dose 20 mg Oxybutynin hydrochloride 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 2.5mg twice a day, particularly if the patient is frail, is likely to be adequate. This dose may be increased 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 (5 years of age or older):* Neurogenic bladder instability: the usual dose is 2.5mg twice a day. This dose may be increased 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 increased 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 Method of administration For oral administration. Take Oxybutynin oral solution with a glass of water. An oral dosing device is provided with the pack. For instructions on how to use the device, refer to section 6.6.4.3 Contraindications Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 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 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 (e.g. hallucinations, agitation, confusion, somnolence) have been reported; monitoring recommended, particularly in 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. **Excipient Warnings** • This medicine contains less than 1 mmol sodium (23mg) per 5ml, that is to say essentially 'sodium-free'. • This medicine contains 5.90mg sodium benzoate (E211) in each 5ml. • This medicine contains 1.30g sorbitol solution (E420) in each 5ml. 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.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 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. Breast-feeding 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 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). **Table 1:** Adverse effects and their frequencies: | | | | | | | --- | --- | --- | --- | --- | | **Body systems** | **Very common** (≥1/10) | **Common** (≥1/100 to <1/10) | **Uncommon** (≥ 1 /1000 to <1 / 100) | **Not known** | | **Infections and infestations** | - | - | - | urinary tract infection | | **Gastrointestinal disorders** | constipation, nausea, dry mouth | diarrhoea, vomiting | abdominal discomfort, anorexia, decreased appetite, dysphagia | 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** | - | confusional state | - | 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** | dizziness, headache, somnolence | - | - | cognitive disorders, convulsions, drowsiness, disorientation | | **Cardiac disorders** | - | Palpitation | - | tachycardia, arrhythmia | | **Injury, poisoning and procedural complications** | - | - | - | heat stroke | | **Eye disorders** | vision blurred | dry eyes | - | Angle closure glaucoma, mydriasis, ocular hypertension | | **Renal and urinary disorders** | - | urinary retention | - | difficulty in micturition | | **Vascular disorders** | - | flushing which may be more marked in children | - | - | | **Skin and subcutaneous tissue disorders** | dry skin | - | - | angioedema, rash, urticaria, hypohidrosis, photosensitivity | | **Immune system disorders** | - | - | - | Hypersensitivity | | **Respiratory, thoracic, and mediastinal disorders** | - | - | - | Epistaxis | | **Musculoskeletal and connective tissue disorders** | - | - | - | Muscle disorders manifested as muscle weakness, myalgia and/ or muscle spasms | 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. Website: 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 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. Paediatric population: 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.

5.1 Pharmacodynamic properties Pharmacotherapeutic group: genito urinary system and sex hormones - urologicals –drugs for urinary frequency and incontinence, ATC Code: G04B D04 Mechanism of action 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.5.2 Pharmacokinetic properties Absorption Oxybutynin is rapidly absorbed from the gastrointestinal tract, the peak plasma level is reached between 0.5 to 1 hour after administration. Distribution It is highly bound to plasma proteins. Biotransformation Oxybutynin undergoes extensive first-pass metabolism, particularly by the cytochrome P450 isoenzyme CYP3A4, and systemic oral bioavailability has been reported to be only 6%. N-desethyloxybutynin is an active metabolite. Elimination The half-life is biexponential, the first phase being about 40 minutes and the second about 2 – 3 hours. Oxybutynin and its metabolites are excreted in the faeces and urine. There is no evidence of accumulation. The elimination half-life may be increased in the elderly, particularly if they are frail.5.3 Preclinical safety data No data of therapeutic relevance

6.1 List of excipients Citric acid monohydrate (E330) Sodium citrate (E331) Sodium benzoate (E211) Non-crystallising liquid sorbitol (70%) (E420) Glycerol (E422) Strawberry flavour Purified water6.2 Incompatibilities Not applicable6.3 Shelf life 3 years After first opening: 30 days6.4 Special precautions for storage Do not store above 30°C. Store in the original bottle in order to protect from light6.5 Nature and contents of container Bottle: Amber (Type III glass) Closure: HDPE, EPE wadded, child resistant closure Syringe: Polypropylene body, purple HDPE plunger with a capacity of 5ml and dosage graduation at every 0.25ml Bottle adaptor: Low Density Polyethylene Pack size: 150ml6.6 Special precautions for disposal and other handling No special requirements for disposal. Any unused product or waste material should be disposed of in accordance with local requirements. **Instructions for use of the syringe:**

1. To open the bottle, press the cap down and turn it anti-clockwise (figure 1).
2. Put the syringe adaptor into the bottle neck (figure 2).
3. Take the syringe and put it into the adaptor opening (figure 3).
4. Turn the bottle upside down (figure 4).
5. Fill the syringe with a small amount of solution by pulling the plunger down (figure 4A). Then push the plunger upward in order to remove any possible bubbles (figure 4B). Finally, pull the plunger down to the graduation mark corresponding to the quantity in millilitres (ml) prescribed by your doctor. The top flat edge of the piston should be in line with the graduation mark you are measuring to (Figure 4C).
6. Turn the bottle the right way up (Figure 5A).
7. Remove the syringe from the adaptor (Figure 5B).
8. Put the end of the syringe into your mouth and push the plunger slowly back in to take the medicine (Figure 6).
9. Wash the syringe with water and let it dry before you use it again.
10. Close the bottle with the plastic screw cap - leave the syringe adaptor in the bottle.