see also:

• managing violence or the aggressive patient in the ED
• bipolar disorder
• psychosis
• schizophrenia
• anti-psychotic medications

• 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.

• 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

• 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 cause neuroleptic malignant syndrome (NMS)
• 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
  • eosinophilia
• other less common reactions:
  • bradycardia in < 1%
  • HS reactions

• 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

• 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.