indication

For the acute and maintenance treatment of schizophrenia and related psychotic disorders, as well as acute treatment of manic or mixed episodes of bipolar 1 disorder. Intramuscular olanzapine is indicated for the rapid control of agitated patients.

pharmacology

Olanzapine, an atypical antipsychotic agent, is used to treat both negative and positive symptoms of schizophrenia, acute mania with bipolar disorder, agitation, and psychotic symptoms in dementia. Future uses may include the treatment of obsessive-compulsive disorder and severe behavioral disorders in autism. Structurally and pharmacologically similar to clozapine, olanzapine binds to alpha(1), dopamine, histamine H1, muscarinic, and serotonin type 2 (5-HT₂) receptors.

mechanism of action

Olanzapine's antipsychotic activity is likely due to a combination of antagonism at D2 receptors in the mesolimbic pathway and 5HT2A receptors in the frontal cortex. Antagonism at D2 receptors relieves positive symptoms while antagonism at 5HT2A receptors relieves negative symptoms of schizophrenia.

toxicity

Symptoms of an overdose include tachycardia, agitation, dysarthria, decreased consciousness and coma. Death has been reported after an acute overdose of 0.45g, but also survival after an acute overdose of 1500g.

biotransformation

Hepatic

absorption

Well absorbed, with approximately 40% of the dose metabolized before reaching the systemic circulation.

half life

21 to 54 hours

route of elimination

It is eliminated extensively by first pass metabolism, with approximately 40% of the dose metabolized before reaching the systemic circulation. Following a single oral dose of 14C labeled olanzapine, 7% of the dose of olanzapine was recovered in the urine as unchanged drug, indicating that olanzapine is highly metabolized.

drug interactions

Donepezil: Possible antagonism of action

Fluvoxamine: Fluvoxamine increases the effect and toxicity of olanzapine

Galantamine: Possible antagonism of action

Ritonavir: Ritonavir decreases the effect of olanzapine

Rivastigmine: Possible antagonism of action

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Olanzapine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.

Tetrabenazine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Trimethobenzamide: Trimethobenzamide and Olanzapine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Triprolidine: Triprolidine and Olanzapine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.

Trospium: Trospium and Olanzapine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.