Brands, Medical Use, Clinical Data
Brands / Synonyms
Olansek; Olanzapine [Usan:Inn]; Symbyax; Zydis; Zyprexa; Zyprexa Intramuscular; Zyprexa Zydis
For the treatment of schizophrenia and manic depression (bipolar disorder).
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 is an antagonist at types 1, 2, and 4 dopamine receptors, 5-HT receptor types 2A and 2C, muscarinic receptors 1 through 5, alpha(1)-receptors, and histamine H1-receptors. Olanzapine's antipsychotic effect is due to antagonism at dopamine and serotonin type 2 receptors, with greater activity at serotonin 5-HT2 receptors than at dopamine type-2 receptors. This may explain the lack of extrapyramidal effects. Olanzapine does not appear to block dopamine within the tubero-infundibular tract, explaining the lower incidence of hyperprolactinemia than with typical antipsychotic agents or risperidone. Antagonism at muscarinic receptors, H1-receptors, and alpha(1)-receptors also occurs with olanzapine.
Well absorbed, with approximately 40% of the dose metabolized before reaching the systemic circulation.
Biotrnasformation / Drug Metabolism
ZYPREXA is contraindicated in patients with a known hypersensitivity to the product.
For specific information about the contraindications of lithium or valproate, refer to the
CONTRAINDICATIONS section of the package inserts for these other products.
The risks of using olanzapine in combination with other drugs have not been extensively evaluated in
systematic studies. Given the primary CNS effects of olanzapine, caution should be used when olanzapine is taken in
combination with other centrally acting drugs and alcohol.
Because of its potential for inducing hypotension, olanzapine may enhance the effects of certain
antihypertensive agents. Olanzapine may antagonize the effects of levodopa and dopamine agonists.
The Effect of Other Drugs on Olanzapine ó Agents that induce CYP1A2 or glucuronyl
transferase enzymes, such as omeprazole and rifampin, may cause an increase in olanzapine clearance. Inhibitors of
CYP1A2 could potentially inhibit olanzapine clearance. Although olanzapine is metabolized by multiple enzyme systems,
induction or inhibition of a single enzyme may appreciably alter olanzapine clearance. Therefore, a dosage increase
(for induction) or a dosage decrease (for inhibition) may need to be considered with specific drugs.
Charcoal ó The administration of activated charcoal (1 g) reduced the Cmax and
AUC of olanzapine by about 60%. As peak olanzapine levels are not typically obtained until about 6hours after dosing,
charcoal may be a useful treatment for olanzapine overdose.
Cimetidine and Antacids ó Single doses of cimetidine (800 mg) or aluminum- and
magnesium-containing antacids did not affect the oral bioavailability of olanzapine.
Carbamazepine ó Carbamazepine therapy (200 mg bid) causes an approximately 50%
increase in the clearance of olanzapine. This increase is likely due to the fact that carbamazepine is a potent
inducer of CYP1A2 activity. Higher daily doses of carbamazepine may cause an even greater increase in olanzapine
Ethanol ó Ethanol (45mg/70kg singledose) did not have an effect on olanzapine
Fluoxetine ó Fluoxetine (60 mg single dose or 60 mg daily for 8 days) causes a
small (mean 16%) increase in the maximum concentration of olanzapine and a small (mean 16%) decrease in olanzapine
clearance. The magnitude of the impact of this factor is small in comparison to the overall variability between
individuals, and therefore dose modification is not routinely recommended.
Fluvoxamine ó Fluvoxamine, a CYP1A2 inhibitor, decreases the clearance of
olanzapine. This results in a mean increase in olanzapine Cmax following fluvoxamine of 54% in female nonsmokers and
77% in male smokers. The mean increase in olanzapine AUC is 52% and 108%, respectively. Lower doses of olanzapine
should be considered in patients receiving concomitant treatment with fluvoxamine.
Warfarin ó Warfarin (20mg singledose) did not affect olanzapine
Effect of Olanzapine on Other Drugs ó In vitro studies utilizing human liver
microsomes suggest that olanzapine has little potential to inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A. Thus,
olanzapine is unlikely to cause clinically important drug interactions mediated by these enzymes.
Lithium ó Multiple doses of olanzapine (10 mg for 8 days) did not influence the
kinetics of lithium. Therefore, concomitant olanzapine administration does not require dosage adjustment of
Valproate ó Studies in vitro using human liver microsomes determined that
olanzapine has little potential to inhibit the major metabolic pathway, glucuronidation, of valproate. Further,
valproate has little effect on the metabolism of olanzapine in vitro. In vivo administration of olanzapine (10 mg
daily for 2 weeks) did not affect the steady state plasma concentrations of valproate. Therefore, concomitant
olanzapine administration does not require dosage adjustment of valproate.
Single doses of olanzapine did not affect the pharmacokinetics of imipramine or its active metabolite
desipramine, and warfarin. Multiple doses of olanzapine did not influence the kinetics of diazepam and its active
metabolite N-desmethyldiazepam, ethanol, or biperiden. However, the co-administration of either diazepam or ethanol
with olanzapine potentiated the orthostatic hypotension observed with olanzapine. Multiple doses of olanzapine did
not affect the pharmacokinetics of theophylline or its metabolites.