Zyprexa Zydis

Zyprexa Zydis - General Information

Zyprexa Zydis is an atypical antipsychotic, approved by the FDA in 1996. Zyprexa Zydis is manufactured and marketed by the pharmaceutical company Eli Lilly and Company, whose patent for olanzapine proper ends in 2011.

Pharmacology of Zyprexa Zydis

Zyprexa Zydis, 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.

Zyprexa Zydis for patients

PATIENT INFORMATION

Physicians are advised to discuss the following issues with patients for whom they prescribe
olanzapine:

Orthostatic Hypotension: Patients should be advised of the risk of orthostatic hypotension,
especially during the period of initial dose titration and in association with the use of
concomitant drugs that may potentiate the orthostatic effect of olanzapine, e.g., diazepam
or alcohol.

Interference with Cognitive and Motor Performance: Because olanzapine has the potential to
impair judgment, thinking, or motor skills, patients should be cautioned about operating
hazardous machinery, including automobiles, until they are reasonably certain that olanzapine
therapy does not affect them adversely.

Pregnancy: Patients should be advised to notify their physician if they become pregnant or
intend to become pregnant during therapy with olanzapine.

Nursing: Patients should be advised not to breast-feed an infant if they are taking olanzapine.

Concomitant Medication: Patients should be advised to inform their physicians if they are taking,
or plan to take, any prescription or over-the-counter drugs, since there is a potential for
interactions.

Alcohol: Patients should be advised to avoid alcohol while taking olanzapine.

Heat Exposure and Dehydration: Patients should be advised regarding appropriate care in avoiding
overheating and dehydration.

Phenylketonurics: ZYPREXA ZYDIS (olanzapine orally disintegrating tablets) contains phenylalanine
(0.34, 0.45, 0.67, or 0.90 mg per 5, 10, 15, or 20mg tablet, respectively).

Laboratory Tests

Periodic assessment of transaminases is recommended in patients with significant hepatic disease.

Zyprexa Zydis 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 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 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 Warfarin (20mg singledose) did not affect olanzapine pharmacokinetics.

Effect of Olanzapine on Other Drugs 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.

Zyprexa Zydis 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.

Additional information about Zyprexa Zydis

Zyprexa Zydis Indication: For the treatment of schizophrenia and manic depression (bipolar disorder).
Mechanism Of Action: Zyprexa Zydis 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. Zyprexa Zydis'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. Zyprexa Zydis 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.
Drug Interactions: Donepezil Possible antagonism of action
Galantamine Possible antagonism of action
Rivastigmine Possible antagonism of action
Fluvoxamine Fluvoxamine increases the effect and toxicity of olanzapine
Ritonavir Ritonavir decreases the effect of olanzapine
Food Interactions: Avoid alcohol.
Generic Name: Olanzapine
Synonyms: Not Available
Drug Category: Antiemetics; Antipsychotics
Drug Type: Small Molecule; Approved; Investigational

Other Brand Names containing Olanzapine: Olansek; Symbyax; Zydis; Zyprexa; Zyprexa Intramuscular; Zyprexa Zydis;
Absorption: Well absorbed, with approximately 40% of the dose metabolized before reaching the systemic circulation.
Toxicity (Overdose): 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.
Protein Binding: 93%
Biotransformation: Hepatic
Half Life: 21 to 54 hours
Dosage Forms of Zyprexa Zydis: Powder, for solution Intramuscular
Tablet Oral
Tablet, orally disintegrating Oral
Chemical IUPAC Name: 2-methyl-4-(4-methylpiperazin-1-yl)-5H-thieno[3,2-c][1,5]benzodiazepine
Chemical Formula: C17H20N4S
Olanzapine on Wikipedia: https://en.wikipedia.org/wiki/Olanzapine
Organisms Affected: Humans and other mammals