| 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. |
| Pharmacodynamics |
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. |
| Absorption |
Well absorbed, with approximately 40% of the dose metabolized before reaching the systemic circulation. |
| Volume of distribution |
|
| Protein binding |
93% |
| Metabolism |
Hepatic |
| 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. |
| Half life |
21 to 54 hours |
| Clearance |
|
| 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. |
