Oxybutynin Hydrochloride Tablets 5 MG - Summary of Product Characteristics (SMPC) - Print Friendly - (Emc)

Download as pdf or txt
Download as pdf or txt
You are on page 1of 7

Oxybutynin Hydrochloride Tablets 5 mg

Summary of Product Characteristics Updated 16-Jan-2023 | Strides Pharma UK Ltd

1. Name of the medicinal product


2. Qualitative and quantitative composition
3. Pharmaceutical form
4. Clinical particulars
4.1 Therapeutic indications
4.2 Posology and method of administration
4.3 Contraindications
4.4 Special warnings and precautions for use
4.5 Interaction with other medicinal products and other forms of interaction
4.6 Fertility, pregnancy and lactation
4.7 Effects on ability to drive and use machines
4.8 Undesirable effects
4.9 Overdose
5. Pharmacological properties
5.1 Pharmacodynamic properties
5.2 Pharmacokinetic properties
5.3 Preclinical safety data
6. Pharmaceutical particulars
6.1 List of excipients
6.2 Incompatibilities
6.3 Shelf life
6.4 Special precautions for storage
6.5 Nature and contents of container
6.6 Special precautions for disposal and other handling
7. Marketing authorisation holder
8. Marketing authorisation number(s)
9. Date of first authorisation/renewal of the authorisation
10. Date of revision of the text

1. Name of the medicinal product


Oxybutynin Hydrochloride Tablets 5mg
2. Qualitative and quantitative composition
Oxybutynin hydrochloride 5mg
Excipient(s) with known effect: Contains 153.00 mg Lactose monohydrate per tablet.
Sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, i.e. is essentially 'sodium-free'.
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Tablet
Blue, round, biconvex, uncoated tablets, marked OB score-line 5 on one side and plain on the reverse
4. Clinical particulars
4.1 Therapeutic indications

Adults
Urinary incontinence, urgency and frequency in unstable bladder conditions due to idiopathic detrusor instability (motor
urge incontinence) or neurogenic bladder disorders (detrusor hyperreflexia) in conditions such as multiple sclerosis and
spina bifida.
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 over activity)
• 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

Adults
The usual initial dose is 5mg two or three times a day. This dose may be increased to a maximum dose of 5mg four
times a day to obtain a clinical response provided that the side effects are well-tolerated.
Elderly (including frail elderly)
A lower dose is recommended because the elimination half-life is increased in the elderly. A dose of 2.5mg twice a day is
likely to be adequate, particularly if the patient is frail. This dose may be increased if necessary to 5mg twice a day
provided that 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 2.5mg twice a day. This dose may be increased, if necessary, to
5mg two or three times daily provided that the side effects are well-tolerated.
Nocturnal enuresis: The usual dose is 2.5mg twice a day. This dose may be increased, if necessary, to 5mg two or
three times daily provided that the side effects are well-tolerated. The last dose should be given before bedtime.

4.3 Contraindications

Oxybutynin hydrochloride tablets are contraindicated in patients with:


- hypersensitivity to oxybutynin hydrochloride or any of the excipients listed in section 6.1.
- myasthenia gravis
- narrow-angle glaucoma or shallow anterior chamber.
- gastrointestinal obstruction including pyloric stenosis, paralytic ileus and intestinal atony.
- ileostomy, colostomy, toxic megacolon, severe ulcerative colitis.
- bladder flow obstruction where urinary retention may be precipitated.
- porphyria
- frequent urination at night caused by heart or kidney disease

4.4 Special warnings and precautions for use

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), severe
gastrointestinal motility disorders, hepatic or renal impairment (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, 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 central nervous system (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. Regular
dental check-ups are therefore advisable during long-term treatment.
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.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose
malabsorption should not take this medicine.
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 over activity).
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.

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 may 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 anti-Parkinsonian 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 (e.g. ketoconazole, itraconazole, erythromycin). Oxybutynin may
antagonise prokinetic therapies (e.g. metoclopramide and domperidone).
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. Studies in animals have shown minor
reproductive toxicity (see section 5.3). Animal studies are insufficient with respect to effects on pregnancy, embryonic /
foetal development, parturition or postnatal development (see section 5.3). The potential risk for humans is unknown.
Oxybutynin should not be used in pregnancy unless clearly necessary.
Breast-feeding:
Oxybutynin in small amount is excreted in breast milk during lactation. Oxybutynin should not be used during breast-
feeding.
Fertility:
There are no data regarding effects on human fertility. Studies in animals have shown impaired fertility in females.

4.7 Effects on ability to drive and use machines


Oxybutynin hydrochloride tablets can cause drowsiness or blurred vision and patients should be cautioned regarding
activities requiring mental alertness such as driving, operating machinery or performing hazardous work.

4.8 Undesirable effects

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); not
known (cannot be estimated from the available data).
The following adverse events (marked with an asterisk *), which has not been observed in clinical trials but reported after
the drug has been marketed, has been ranked in the frequency of "rare/unknown".

Very Common Common Uncommon Rare Not Known

Infections and urinary tract infection


infestations

Immune System hypersensitivity


Disorders

Psychiatric confusional restlessness, excitation, anxiety*,


disorders state disorientation, hallucinations,
concentration nightmares*, paranoia,
difficulties agitation, cognitive
disorders in elderly,
symptoms of
depression,
dependence to
oxybutynin (in patients
with history of drug or
substance abuse)

Nervous System somnolence, drowsiness Cognitive disorders*,


Disorders fatigue, convulsions*,
headache, disorientation
dizziness

Eye disorders decreased tear light hypersensitivity Narrow angle closure


production /dry glaucoma*, mydriasis,
eyes, vision ocular hypertension
blurred

Cardiac disorders cardiac arrhythmias,


tachycardia

Vascular disorders flushing which


may be more
marked in
children

Gastrointestinal dry mouth, diarrhoea, anorexia, gastroesophageal


Disorders nausea, vomiting, dysphagia, reflux disease,
constipation dyspepsia abdominal pseudo-obstruction in
discomfort/pain, patients at risk (elderly
decreased appetite or patients with
constipation and
treated with other
drugs that decrease
intestinal motility)

Skin and dry skin/ phototoxicity angioedema, rash,


subcutaneous decreased urticaria, hypohidrosis,
tissue disorders sweating
Renal and urinary urinary difficulty in micturition
disorders retention

Reproductive erectile
system and breast dysfunction
disorders

Injury, poisoning heat stroke


and procedural
complications

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 or search for MHRA Yellow Card
in the Google Play or Apple App Store.

4.9 Overdose

The symptoms of over dosage 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.
5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Urinary antispasmodics, ATC code: G04BD04


Oxybutynin has a direct antispasmodic effect on the smooth muscle of the bladder detrusor. Oxybutynin also inhibits the
effects of acetylcholine on smooth muscle by blocking muscarinic receptors. Pharmacological models have established
differences in affinity for subtypes of muscarinic receptors.
The pharmacodynamic properties of oxybutynin result in relaxation of the bladder detrusor muscle. Patients with
unstable bladder experience increased bladder volume and a decreased incidence of spontaneous contractions of the
detrusor muscle.

5.2 Pharmacokinetic properties

Absorption
Following oral administration, oxybutynin is rapidly absorbed from the gastrointestinal tract (tmax 0.5-1.4hours). Studies
have established a Cmax after a 5-10mg dose in young healthy patients of 8-12ng/ml. Larger inter-individual variations in
plasma concentrations are seen. Oxybutynin is subject to extensive first pass metabolism, resulting in an absolute
systemic availability of 6.2%.
Distribution
Oxybutynin is widely distributed in body tissues following systemic absorption. The volume of distribution was estimated
to be 193 L after intravenous administration of 5 mg oxybutynin hydrochloride.
Biotransformation
Oxybutynin is extensively metabolised by the liver, primarily by the cytochrome P450 enzyme system, particularly CYP
3A4 found mostly in the liver and gut wall. Metabolites include phenylcyclohexylglycolic acid, which is pharmacologically
inactive, and N-desethyloxybutynin, which is pharmacologically active.
Elimination
Oxybutynin undergoes extensive hepatic metabolism, with less than 0.02% of the administered dose excreted
unchanged in the urine. Less than 0.1% of the administered dose is excreted as the metabolite N-desethyloxybutynin.
Oxybutynin is 83-85% plasma albumin bound.
Oxybutynin is eliminated biexponentially. Mean elimination half-life is 2 hours. Repeated administration results in little
accumulation.
Elderly
Bioavailability is higher in elderly patients; AUC is 2-4-fold higher after repeated administration and half-life 3-5 times
longer.

5.3 Preclinical safety data

Oxybutynin hydrochloride has been shown to have low acute toxicity when administered orally to either mice, rats or
dogs. In a repeat dosing experiment of 6 months duration in rats, daily oral doses of 63mg/kg or more were associated
with decreases in food consumption and body weight gain and with minor pathological changes in the liver and kidneys.
At daily oral doses of 6mg/kg administered for 6 months, dogs exhibited transient anorexia, tremors and nervousness but
these effects were not associated with microscopic signs of tissue damage.
There is no evidence from preclinical studies to suggest either mutagenic or carcinogenic activity for oxybutynin.
Reproduction tests indicate no adverse effects on fertility or reproductive performance in rats given daily oral doses of
15mg/kg. Oxybutynin hydrochloride was not teratogenic in rats and rabbits at oral dose levels (20mg/kg/day in rats and
48mg/kg/day in rabbits) which did not cause significant maternal toxicity. At maternally toxic doses of oxybutynin
(100mg/kg/day), increased incidence of extra thoracolumbar ribs in rat foetuses, as well as mortality of neonates, was
observed. At oral daily dose levels up to 20mg/kg in rats, oxybutynin hydrochloride had no adverse effects on gestation
or on the birth and development of offspring up to weaning.
6. Pharmaceutical particulars
6.1 List of excipients

Lactose monohydrate
Microcrystalline cellulose
Calcium stearate
Indigo carmine (aluminium lake) E132

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

Store below 25°C in a dry place. Protect from light.

6.5 Nature and contents of container

Polypropylene tablet container with tamper-evident polyethylene cap


Pack sizes: 20, 30, 50, 60, 84, 90, 100, 250, 500
PVC (250µm ± 5µm)/aluminium foil (25µm) blister packs
Pack sizes: 20, 30, 50, 56, 60, 84, 90, 100
Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No specific instructions for use/handling


7. Marketing authorisation holder
Strides Pharma UK Ltd.
Unit 4, Metro Centre,
Tolpits Lane,
Watford, Hertfordshire
WD18 9SS
8. Marketing authorisation number(s)
PL 13606/0071
9. Date of first authorisation/renewal of the authorisation
3 June 1998 / 21 March 2006
10. Date of revision of the text
08/01/2023
Company Contact Details
Strides Pharma UK Ltd
Address WWW
Unit 4, Metro Centre, Tolpits Lane, Watford, www.stridespharma.co.uk
Hertfordshire, UK
Medical Information Direct Line
Telephone +44 8000 988 048
+44 1923 255580

Medical Information e-mail


[email protected]

You might also like