- 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;
- 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
- 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
- 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.
olanzapine.txt · Last modified: 2012/09/18 08:20 by 127.0.0.1