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Active ingredient: Olanzapine - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Antiemetics
  • Antipsychotics

Dosage Forms

  • Tablet (oral)

Brands / Synonyms

Olansek; Olanzapine [Usan:Inn]; Symbyax; Zydis; Zyprexa; Zyprexa Intramuscular; Zyprexa Zydis

Indications

For the treatment of schizophrenia and manic depression (bipolar disorder).

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 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.

Absorption

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

Toxicity

Not Available

Biotrnasformation / Drug Metabolism

Hepatic

Contraindications

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.

Drug Interactions

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 clearance.

Ethanol ó Ethanol (45mg/70kg singledose) did not have an effect on olanzapine pharmacokinetics.

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 pharmacokinetics.

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 lithium.

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.

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