Oxybutynin hydrochloride 5mg Tablets

Oxybutynin hydrochloride 5mg Tablets

Each tablet contains 5 mg of oxybutynin hydrochloride.

Excipient with known effect: Each tablet contains 118.9mg of lactose (as lactose monohydrate).

For the full list of excipients, see section 6.1

Tablet

Light blue, circular flat bevelled edged tablet with an approximate diameter of 7.5 mm, marked OXB 5 on one side and a break line on reverse.

The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

Oxybutynin hydrochloride has antispasmodic/anticholinergic actions.

Its uses are:

Adults: Urinary incontinence, frequency and urgency in patients with an unstable bladder (urge syndrome), whether due to neurogenic bladder disorders causing 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.

Posology

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 if required to obtain a clinical response, providing that the side effects are tolerated. It is usually wise to institute treatment slowly to minimise the anticholinergic side effects especially that of a dry mouth.

Older people (including frail elderly)

The elimination half-life is increased in the elderly (over 80 years). A dose of 2.5 mg twice daily, particularly if the patient is frail, is likely to be adequate. This dose may be titrated upwards to 5 mg two times a day to obtain a clinical response provided the side effects are well tolerated. In the elderly peak plasma concentrations have also been shown to be greater than in healthy young volunteers.

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 tolerated. In cases of nocturnal enuresis alone, the usual dose is 2.5 mg twice a day. This dose may be titrated upwards 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

The safety and efficacy of oxybutynin hydrochloride tablets have been demonstrated for children 5 years of age and older. There is insufficient clinical data for children under the age of 5 years so that it is not recommended for this age group.

Following initial control, a reduced maintenance dose may be introduced.

Method of administration

Oxybutynin hydrochloride tablets are for oral administration. The tablet should be swallowed with plenty of water or other fluid, to ensure passage through the oesophagus.

Oxybutynin hydrochloride tablets are contra-indicated in patients:

o who have demonstrated hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

o with narrow angle glaucoma or with shallow anterior chamber angles since anticholinergic drugs may aggravate these conditions;

o with partial or complete obstruction of the gastrointestinal tract, paralytic ileus, intestinal atony of the elderly or debilitated patient, megacolon, toxic megacolon complicating ulcerative colitis, severe ulcerative colitis;

o with myasthenia gravis;

o with bladder outflow obstruction where urinary retention may be precipitated;

o with unstable cardiovascular status in acute haemorrhage;

o who are breast-feeding.

Warnings:

Oxybutynin hydrochloride tablets, when administered in the presence of high environmental temperature, can cause heat prostration (fever and heat stroke due to decreased sweating). Diarrhoea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. In this instance treatment with oxybutynin hydrochloride tablets would be inappropriate and possibly harmful.

Precautions:

Oxybutynin hydrochloride tablets should be used with caution in the frail elderly and children who may be more sensitive to the effects of the product and in patients with autonomic neuropathy (such as those with Parkinson's disease), hepatic or renal disease and severe gastro-intestinal motility disorders (also see 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.

Oxybutynin may aggravate tachycardia (and thus be cautious in case of hyperthyroidism, coronary artery/heart disease, congestive cardiac failure, cardiac arrhythmias, 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.

Special care should be taken in patients with hiatus hernia associated with reflux oesophagitis and/or who are concurrently taking medicinal products (such as bisphosphonates), as anticholinergic drugs may cause or aggravate this condition.

If oxybutynin hydrochloride tablets are administered in such patients then this should be accompanied by some clinical monitoring.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Paediatric population

Oxybutynin hydrochloride is not recommended for use in children below age 5 years due to insufficient data on safety and efficacy.

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.

Care should be taken if other anticholinergic agents are administered together with oxybutynin hydrochloride, as potentiation of anticholinergic effects could occur.

Occasional cases of interaction between anticholinergics and other medicinal products with anticholinergic activity such as amantadine, and other anticholinergic antiparkinsonian medicinal products (e.g. biperiden, levodopa),antihistamines, antipsychotics (e.g. phenothiazines, prochlorperazine chlorpromazine, butyrophenones and clozapine), haloperidol, quinidine, cardiac glycosides e.g. digoxin, tricyclic antidepressants, atropine and related compounds like atropinic antispasmodics and dipyridamole have been reported and care should be taken if oxybutynin hydrochloride tablets are administered concurrently with such drugs.

Oxybutynin hydrochloride tablets may cause drowsiness. Alcohol or other sedative drugs may enhance this effect (see section 4.7).

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 may antagonize prokinetic therapies.

Concomitant use with cholinesterase inhibitors e.g. donepezil, rivastigmine, galantamine or tacrine may result in reduced cholinesterase inhibitor efficacy.

Pregnancy

There are no data relating to the safety of oxybutynin hydrochloride tablets in human pregnancy. 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. In pregnant rats it has been noted that oxybutynin crosses the placenta unchanged. The foetal blood levels reach 50% maternal levels after six hours and decline more slowly than maternal levels. Oxybutynin hydrochloride tablets should therefore not be given to pregnant women unless, in the judgement of the physician, the probable clinical benefits outweigh the potential hazards. No embryotoxicity was observed in animal studies at doses which did not produce maternal toxicity.

Breastfeeding

Oxybutynin hydrochloride has been detected in breast milk in animal studies (approximately 60% of that found in the maternal blood). These concentrations decline more slowly than in maternal blood so that oxybutynin hydrochloride tablets should not be taken by breast-feeding mothers.

As oxybutynin hydrochloride tablets may cause drowsiness or blurred vision, the patient should be cautioned regarding activities requiring mental alertness such as driving a motor vehicle, operating machinery or performing hazardous work whilst 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).

Oxybutynin hydrochloride tablets may produce all the side effects that may be associated with anticholinergic drugs:

Infections and infestations

Not known: urinary tract infection

Gastrointestinal disorders

Very common: constipation, dry mouth, nausea

Common: diarrhoea, vomiting

Uncommon: abdominal discomfort, anorexia, decreased appetite, dysphagia

Not known: gastroesophageal reflux, decreased gastrointestinal motility, 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, insomnia, restlessness, 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: headache, dizziness, somnolence

Not known: cognitive disorders, drowsiness, convulsions, disorientation

Cardiac disorders

Not known: palpitations, tachycardia, cardiac arrhythmia

Injury, poisoning and procedural complications

Not known: heat stroke

Eye disorders

Very common: vision blurred

Common: dry eyes

Not known: mydriasis, intraocular hypertension, angle closure glaucoma

Renal and urinary disorders

Common: Urinary retention

Not known: urinary hesitance, difficulty in micturition

Vascular disorders

Common: facial flushing which may be more marked in children.

Not known: vasodilatation

Skin and subcutaneous tissue disorders

Very common: dry skin

Not known: rash, urticaria, angioedema, hypohidrosis, photosensitivity.

Immune system disorders

Not known: hypersensitivity

General disorders and administration site conditions:

Not known: Asthenia

Reproductive system and breast disorders:

Not known: impotence, suppression of lactation.

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.

The symptoms of overdose with oxybutynin hydrochloride tablets 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 and

2. Slow intravenous injection of 1.0 to 2.0 mg of physostigmine

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 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 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: Urinary Antispasmodics

ATC-Code: G04BD

Oxybutynin hydrochloride has direct antispasmodic action on the smooth muscle of the bladder detrusor as well as anticholinergic action in blocking the muscarinic effects of acetylcholine on smooth muscle.

These properties cause relaxation of the detrusor muscle of the bladder and in patients with an unstable bladder, oxybutynin hydrochloride increases bladder capacity and reduces the incidence of spontaneous contraction of the detrusor muscle.

Metabolism

Following oral administration, oxybutynin hydrochloride undergoes extensive first-pass metabolism in the liver. This shows considerable inter-subject variability, with maximum plasma concentrations differing by as much as four- or five-fold amongst individuals. However, this does not significantly affect the pharmacological actions of oxybutynin hydrochloride as much of the oral dose (approximately 90%) is metabolised to desethyloxybutynin. This is the major metabolite which is pharmacologically active with similar potency and efficacy to the parent compound.

Absorption

Oxybutynin hydrochloride is rapidly and well absorbed from the gastro-intestinal tract. In the bioequivalence study peak plasma concentrations for oxybutynin were reached in 0.5 to 1.25 hours with a mean of 0.7 hours. Peak plasma concentrations for desethyloxybutynin were reached in 0.5 to 1.5 hours with a mean of 0.9 hours. Mean elimination half-life for oxybutynin and desethyloxybutynin were 1.4 hours and 2.1 hours respectively. The elimination half-life may be increased in the elderly, particularly if they are frail.

Distribution

In man oxybutynin hydrochloride is 83 – 85% bound to plasma albumin. It is distributed throughout most of the body, with high concentrations in the stomach, intestines and liver, but only very small amounts are found in the central nervous system. It is estimated that only 0.01% of the dose will enter the cerebrospinal fluid. In rats the concentrations achieved in breast milk and in the foetus are approximately 50 – 60% of those found in the maternal blood. Distribution of the drug in the foetus is similar to that in the mother.

Elimination

The elimination of oxybutynin hydrochloride is rapid with a short plasma elimination half-life so that repeated administration of oxybutynin hydrochloride results in little accumulation. Very little oxybutynin hydrochloride is excreted unchanged in the urine – more is excreted in the faeces (approximately 23% compared with 8%). There is no evidence of accumulation.

There was no evidence of genotoxic or carcinogenic potential. High doses of oxybutynin increased the incidence of extra thoracolumbar ribs in rat foetuses as well as mortality of neonates. However, these effects on the reproductive processes occurred only at doses associated with maternal toxicity (100 mg/kg/day).

Crospovidone, microcrystalline cellulose, lactose monohydrate, magnesium stearate, indigo carmine aluminium lake (E132).

None stated.

3 years.

Store below 25°C in a dry place.

Oxybutynin hydrochloride tablets are available in Aluminium / uPVC / PVdC strips. in boxes of 20, 28, 30, 56, 60, 84 and 120 tablets.

Not all packs sizes may be marketed.

No special requirements for disposal. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Tillomed Laboratories Ltd

220 Butterfield

Great Marlings

Luton

LU2 8DL

United Kingdom

PL 11311/0137

30/03/2009

02/05/2018