Oxybutynin hydrochloride 5 mg tablets

Tablet. White circular, flat, beveled edged tablet marked “5” on one side scored on reverse, diameter 7.0 mm, thickness 3.3 -3.7 mm The scoreline is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

4.1 Therapeutic indications Oxybutynin hydrochloride is indicated for urinary incontinence, urgency and frequency in 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).4.2 Posology and method of administration Posology Adults: The dosage should be determined individually, with an initial dose of 2.5 mg three times daily. Thereafter, the lowest effective dose should be selected. The daily dose may vary between 10 and 15 mg per day (maximum dose is 20 mg per day) divided into 2-3 (max. 4) doses. 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): The safety and efficacy of oxybutynin hydrochloride in children below 5 years of age has not been established. No data are available. Children (over 5 years of age): The dosage should be determined individually, with an initial dose of 2.5 mg twice daily. Thereafter, the lowest effective dose should be selected. The maximum dose, which is related to body weight (0,3 - 0,4 mg / kg / day), is expressed in the following table: | | | | --- | --- | | Age | Dosage | | 5-9 years | 2.5 mg three times daily | | 9-12 years | 5 mg 2 times daily | | Over 12 years | 5 mg three times daily | 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 2.5 mg 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. The tablets can be taken on an empty stomach. The tablet should be swallowed whole, with appropriate amount of water. Method of administration The tablets have to be swallowed with plenty of fluid and may be taken on an empty stomach. If gastric irritation occurs the tablets may also be taken during meals or with some milk.4.3 Contraindications Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1. Narrow-angle glaucoma or shallow anterior chamber. Myasthenia gravis. Gastrointestinal obstructive disorders including paralytic ileus, intestinal atony. Patients with severe ulcerative colitis. Patients with toxic megacolon. 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 (such as 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. 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 P450 isoenzyme CYP 3A4. Concomitant administration with a CYP 3A4 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 hydrochloride 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. Breast feeding while using Oxybutynin 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). | | | | | --- | --- | --- | | **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* | Not known | arrhythmia, tachycardia | | Common | palpitation | | *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, pseudoobstruction 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 national reporting system using 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 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. *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 µg/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 effects to 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: G04BD04 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 Crospovidone, microcrystalline cellulose, lactose monohydrate, magnesium stearate.6.2 Incompatibilities Not applicable.6.3 Shelf life 3 years6.4 Special precautions for storage Do not store above 25ºC. Store in the original package. Keep out of the sight and reach of children6.5 Nature and contents of container Aluminium / PVC / PVdC strips Pack with blisters of 7, 28, 56 and 84 tablets Not all pack sizes may be marketed.6.6 Special precautions for disposal and other handling No special requirements. Any unused product or waste material should be disposed of in accordance with local requirements.