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    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