Summary for UKPID
OXYBUTYNIN
Helen Seymour, BPharm (Hons)
National Poisons Information Service (Newcastle Centre)
Regional Drug & Therapeutics Centre
Wolfson Building
Claremont Place
Newcastle upon Tyne
NE1 4LP
UK
This monograph has been produced by staff of a National Poisons
Information Service Centre in the United Kingdom. The work was
commissioned and funded by the UK Departments of Health, and was
designed as a source of detailed information for use by poisons
information centres.
Peer review group: Directors of the UK National Poisons Information
Service.
SUMMARY
Type of product
For treatment of urinary incontinence
Ingredients
Oxybutynin hydrochloride 2.5mg, 5mg
Tablets - 2.5mg, 3mg, 5mg
Elixir - 2.5mg/5ml
Toxicity
Is mainly due to anticholinergic effects at autonomic nerve endings
and in the brain.
Common systemic features
Systemic features of toxicity include flushing, dilated pupils, dry
mouth and tongue, hot dry skin, sinus tachycardia, ataxia, nystagmus,
drowsiness and delirium with confusion, agitation and visual
hallucinations.
Uncommon systemic features
Coma, convulsions, cardiac conduction abnormalities and dysrhythmias,
urinary retention.
Management
1. Give oral activated charcoal if ingestion has occurred within 2
hours.
2. Observation without other specific treatment will be sufficient
for the majority of patients.
In seriously poisoned patients the following measures may be required:
3. Ensure a clear airway.
4. Carry out arterial blood gas analysis in patients who are deeply
unconscious.
5. Assisted ventilation is indicated if hypercapnia is present.
6. Correct hypoxia.
7. Correct hypotension by raising the legs above the level of the
trunk. If this is ineffective, insert a central venous line and
expand the intravascular volume. Dopamine may be necessary in
addition in the most severe cases.
8. Rewarm slowly using conventional methods.
9. Treat skin blisters as burns.
10. Control convulsions with intravenous diazepam, 10mg.
11. Control delirium with oral diazepam (doses upto 20-30 mg every 2h
may be required)/.
12. Resist the temptation to treat dysrhythmias with antiarrhythmic
drugs. Correct hypoxia and acidosis and even in the absence of
acidosis give 50mmol sodium bicarbonate intravenously.
13. Forced diuresis, haemodialysis and haemoperfusion are of no
value.
SUBSTANCE
Oxybutynin Hydrochloride
ORIGIN OF SUBSTANCE
Synthetic
NAME
Brand Name Cystrin
Ditropan
Generic name Oxybutynin
CHEMICAL GROUP
Drugs for urinary frequency, enuresis and incontinence.
BNF 7.4.2
SUBSTANCE IDENTITY
REFERENCE NUMBER
CAS
5633-20-5 (oxybutynin)
1508-65-2 (oxybutynin hydrochloride)
Product licence number
Cystrin 3mg 3433/0145
Cystrin 5mg 3433/0146
Ditropan elixir 13374/0003
Ditropan 2.5mg 13374/0001
Ditropan 5mg 13374/0002
MANUFACTURER
Cystrin (+ generic oxybutynin)
Pharmacia and Upjohn
Davy Avenue
Knowlhill
Milton Keynes
Bucks
MK5 8PH
Tel: 01908 661101
Fax: 01908 603051
Ditropan
Smith and Nephew Healthcare Ltd.
Healthcare House
Goulton Street
Hull
HU3 4DJ
Tel: 01482 222200
Fax: 01482 222211
PRESENTATION
Form
Tablets 2.5mg, 3mg, 5mg
Liquid 2.5mg/5ml
Pack sizes
Cystrin 3mg 100 tablet pack
Cystrin 5mg 100 tablet pack
Ditropan 2.5mg 84 tablet pack
Ditropan 5mg 84 tablet pack
Ditropan elixir 150ml bottle
PHYSIOCHEMICAL PROPERTIES
Chemical structure
C22H31NO3.HCl
4-Diethylaminobut-2-ynylalpha-cyclohexylmandelate hydrochloride
Physical structure at room temperature
Solid
Colour
White
Odour
Practically odourless
Viscosity
NA
pH
NA
Solubility
Freely soluble in water and alcohol
Very soluble in methylalcohol and in chloroform
Soluble in acetone
Very slightly soluble in hexane
USES
Indications
Urinary frequency and incontinence, neurogenic bladder
instability and nocturnal enuresis
Therapeutic dosage
Adults
5mg 2-3 times a day, increased if necessary to a maximum of 5mg
four times a day
Elderly
2.5mg - 3mg twice daily initially, increased to 5mg twice daily
according to response and tolerance
Child (over 5 years):
Neurogenic instability - 2.5mg - 3mg twice daily increased to 5mg
twice daily (maximum 5mg 3 times a day)
Nocturnal enuresis (preferably over 7 years) - 2.5mg - 3mg twice
daily increased to 5mg 2 - 3 times daily
Contraindications
Intestinal obstruction or atony, severe ulcerative colitis or
toxic megacolon; significant bladder outflow obstruction;
glaucoma, myasthenia gravis
Abuses
NIF
HAZARD/RISK CLASSIFICATION
NIF
PHARMACOKINETICS
Absorption
Oral - approx. 100%
Distribution
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
Metabolism
approx. 94% undergoes first pass metabolism
Elimination
Very little unchanged drug is excreted in the urine
Half-life
Range 0.84h - 2.90h
Mean 1.6h
Breast milk
Likely to be excreted
TOXICOKINETICS
NIF
EPIDEMIOLOGY OF POISONING
There is one report in the literature of oxybutynin overdose.
ADVERSE EFFECTS
Commonly reported adverse effects include dry mouth,
constipation, blurred vision, nausea, abdominal discomfort,
facial flushing and difficulty in micturition. Less frequently
reported side effects include headache, urinary retention,
dizziness, dry skin, diarrhoea and cardiac arrythmias.
INTERACTIONS
Other anticholinergic drugs
Phenothiazines, amantadine, butyrophenones, levodopa, digitalis
and tricyclic antidepressants
MECHANISM OF ACTION
Oxybutynin has anticholinergic and direct antispasmodic actions.
The myorelaxant effects may reduce bladder spasm thus decreasing
frequency of micturition.
FEATURES OF POISONING
Acute
Ingestion: Common systemic features
Systemic features of toxicity include flushing, dilated pupils, dry
mouth and tongue, hot dry skin, sinus tachycardia, ataxia, nystagmus,
drowsiness and delirium with confusion, agitation and visual
hallucinations.
Uncommon systemic features
Coma, convulsions, cardiac conduction abnormalities and dysrhythmias,
urinary retention.
MANAGEMENT
Prevention of absorption may be accomplished by giving activated
charcoal/cathartic.
Treatment is primarily supportive and includes monitoring for the
development of seizures, hypertension, rhabdomyolysis, and
arrhythmias. If the patient is deeply unconscious carry out arterial
blood gases.
Assisted ventilation is indicated if hypercapnia is present.
Correct hypoxia.
Correct hypotension by raising the legs above the level of the trunk.
If this is ineffective, insert a central venous line and expand the
intravascular volume. Dopamine may be necessary in addition in the
most severe cases.
Control convulsions with intravenous diazepam.
Control delirium with oral diazepam (doses upto 20-30 mg every 2h may
be required).
Resist the temptation to treat dysrhythmias with antiarrhythmic drugs.
Correct hypoxia and acidosis and even in the absence of acidosis give
50mmol sodium bicarbonate intravenously.
Physostigmine is rarely used except in cases of otherwise refractory
life-threatening emergencies and as a diagnostic challenge. Avoid when
ingestion of tricyclic antidepressants is suspected.
Bethanechol has been used to alleviate peripheral anticholinergic side
effects.
Alkaline diuresis and mannitol may be used to treat rhabdomyolysis.
Peritoneal dialysis and hemodialysis are ineffective.
Investigations
Serum levels of anticholinergic drugs are not clinically useful.
Monitor serum electrolytes, renal function and CPK levels in patients
with prolonged seizures or coma.
CASE DATA
1. Banerjee et al (1991) reported anticholinergic effects following
ingestion of 100mg of oxybutynin in a 34 year old female. She had
a sinus tachycardia which resolved 3 hours after admission, and
in addition ventricular ectopics and bigeminy which continued for
a further 30 hours. She recovered fully on symptomatic treatment
alone.2
ANALYSIS
NIF
PREVENTION OF POISONING
NIF
OTHER TOXICOLOGICAL DATA
Teratogenicity
A small risk cannot be excluded, but a high risk of congenital
anomalies in the children of women treated with oxybutynin during
pregnancy is unlikely.
No epidemiological studies of congenital anomalies among infants born
to women who were treated with oxybutynin during pregnancy have been
reported.
An increased frequency of ventricular septal defects and decreased
postnatal growth were observed among the offspring of pregnant rats
treated with 250 times the usual human dose of oxybutynin in one study
(Edwards et al., 1986). Such doses also produced maternal toxicity. No
teratogenic effects were seen in rats after maternal treatment with
10-50 times the human therapeutic dose or in rabbits after maternal
treatment with 8-120 times the human therapeutic dose of oxybutynin
during pregnancy (Edwards et al., 1986).
Author
Helen Seymour, BPharm (Hons)
National Poisons Information Service (Newcastle Centre)
Regional Drug & Therapeutics Centre
Wolfson Building
Claremont Place
Newcastle upon Tyne
NE1 4LP
UK
This monograph was produced by the staff of the Newcastle Centre of
the National Poisons Information Service in the United Kingdom. The
work was commissioned and funded by the UK Departments of Health, and
was designed as a source of detailed information for use by poisons
information centres.
Peer review was undertaken by the Directors of the UK National Poisons
Information Service.
Last updated November 1996
REFERENCES
1. Edwards JA, Reid YJ, Cozens DD: Reproductive toxicity studies with
oxybutynin hydrochloride. Toxicology 40:31-44, 1986.
2. Banerjee S, Routledge PA, Pugh S and Smith PM. Poisoning with
oxybutynin. Hum Exp Toxicol 1991; 10: 225 - 226.
3. Martindale: The Extra Pharmacopoeia. 31st Edition. Reynolds JEF
(Ed.). Pharmaceutical Press 1996.
4. ABPI Compendium of Data Sheets and Summaries of Product
Characteristics. Datapharm Publications Ltd. 1996-97
5. Therapeutic Drugs. Dollery C. (Ed.). Curchill Livingstone. 1991
6. British National Formulary. Number 32 (September 1996). British
Medical Association and Royal Pharmaceutical Society
7. Poisindex System(R), Micromedex, inc., Denver Colorado, Edition
Expires 31.12.96
8. Teratogen Information System (TERIS)(R), Micromedex, Inc., Denver
Colorado, Edition Expires 31.12.96