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olanzapine

olanzapine

introduction

  • olanzapine is an atypical antipsychotic, antimanic and mood stabilising agent.
  • it is available in sublingual wafer form, tablets and as a parenteral injectable for im use, although recent studies suggest it can be used safely for iv dosing with 5mg doses in adults.

pharmacology

  • appears to have receptor affinities for the following receptors:
    • serotonin 5HT2A/2C, 5HT3, 5HT6;
    • dopamine D1, D2, D3, D4, D5;
    • cholinergic muscarinic receptors m1 to m5;
    • alpha1-adrenergic;
    • histamine H1-receptors
  • rapidly absorbed sublingually
  • well aborbed orally with peak plasma concentrations within 5-8 hours
  • metabolised in the liver by conjugative and oxidative pathways
  • in healthy subjects, after oral administration, mean terminal elimination half-life was 33 hours and the mean olanzapine plasma clearance was 26 L/hour
  • pharmacokinetics are affected by smoking (smokers have a higher clearance), age (healthy elderly may have almost double the half-life), gender (marginally longer half life in females)
  • renal or liver impairment will prolong the half life
  • it is not removed through dialysis

adverse effects

  • somnolence - should not operate machinery
  • falls risk in the elderly
  • hallucinations and worsening of parkinsonian symtomatology
  • increased risk of hyperglycaemic events
  • dyslipidaemia and weight gain
  • transient elevated LFT's early in Rx course but jaundice has also been reported although rare
  • rarely, may cause drug-induced bone marrow suppression in those at risk
  • may lowe seizure threshold and cause fits
  • although lower risk than with traditional antipsychotics, long term use does increase risk of tardive dyskinesia
  • postural hypotension may occur in the lederly
  • increased mortality in elderly dementia patients (3.5% vs 1.5% for placebo) - particularly if age > 80yrs, sedation, concomitant use of benzodiazepines, or presence of pulmonary conditions (eg. pneumonia)
  • increased risk of stroke (1.3% vs 0.4%) in those at risk of stroke
  • impaired body temperature regulation
  • oesophageal dysmotility and aspiration risk
  • hyperprolactinaemia in >10%
  • pregnancy category C - ie. no evidence of malformations but may cause reversible effects when given in 3rd trimester
    • appears to cause prolonged gestation and increased stillbirths in rats when given in high dose prior to labour (5mg/kg/d)
  • avoid in lactation as the breastfed infant will receive ~1.8% of the maternal dose in mg/kg.
  • caution should be exercised when used concomitantly with medicines known to cause electrolyte imbalance or to increase QT interval
    • cases of QT prolongation, ventricular arrhythmia, sudden unexplained death, cardiac arrest and torsades de

pointes have been reported very rarely with the use of neuroleptics may be considered as a class effect.

  • other common adverse effects which occur in 1-10% patients:
    • anticholinergic symptoms
    • urinary incontinence
    • peripheral oedema
    • dizziness and akathisia
    • speech disorder
  • other less common reactions:
    • bradycardia in < 1%
    • HS reactions

dose

  • usual adult dose in the agitated adult patient in ED is 10mg s/l or im
  • off-label iv dosing of 5mg doses (with 2nd dose as needed) appears to be safe in the ED setting for Mx of the agitated patient - consider also using bolus doses of iv midazolam 2.5mg (<50kg)-5mg (>50kg) 1)
  • maximum dose is usually 20mg/day
  • use lower doses in the elderly
  • safety not established for children

overdosage

  • commonly causes tachycardia, agitation/aggressiveness, dysarthria, various extrapyramidal symptoms and reduced level of consciousness ranging from sedation to coma.
  • may cause delirium, convulsion, neuroleptic malignant syndrome (NMS), respiratory depression, aspiration, hypertension or hypotension, cardiac arrhythmias (< 2% of overdose cases) and cardiopulmonary arrest.
  • Mx is supportive care with airway management, and, cardiac monitoring at least until QTc returns to normal
  • hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids and/or sympathomimetic agents such as noradrenaline / norepinephrine.
  • adrenaline, dopamine or other sympathomimetic agents should not be used since beta-stimulation may worsen hypotension in the setting of alpha-blockade induced by olanzapine.
olanzapine.txt · Last modified: 2012/09/18 18:20 (external edit)