Zyprexa Velotab

/ Eli Lilly

Schizophrenia
Dose Selection: Oral olanzapine should be administered on a once-a-day schedule without regard to meals, generally beginning with 5 to 10 mg initially, with a target dose of 10 mg/day within several days. Further dosage adjustments, if indicated, should generally occur at intervals of not less than 1 week, since steady state for olanzapine would not be achieved for approximately 1 week in the typical patient. When dosage adjustments are necessary, dose increments/decrements of 5 mg QD are recommended. Efficacy in schizophrenia was demonstrated in a dose range of 10 to 15 mg/day in clinical trials. However, doses above 10 mg/day were not demonstrated to be more efficacious than the 10 mg/day dose. An increase to a dose greater than the target dose of 10 mg/day (i.e., to a dose of 15 mg/day or greater) is recommended only after clinical assessment. Olanzapine is not indicated for use in doses above 20 mg/day.
Special Populations: The recommended starting dose is 5 mg in patients who are debilitated, who have a predisposition to hypotensive reactions, who otherwise exhibit a combination of factors that may result in slower metabolism of olanzapine (e.g., nonsmoking female patients 65 years of age), or who may be more pharmacodynamically sensitive to olanzapine. When indicated, dose escalation should be performed with caution in these patients.
Maintenance Treatment: The effectiveness of oral olanzapine, 10 mg/day to 20 mg/day, in maintaining treatment response in schizophrenic patients who had been stable on ZYPREXA for approximately 8 weeks and were then followed for relapse has been demonstrated in a placebo-controlled trial. The physician who elects to use ZYPREXA for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
Bipolar I Disorder (Manic or Mixed Episodes)
Dose Selection for Monotherapy: Oral olanzapine should be administered on a once-a-day schedule without regard to meals, generally beginning with 10 or 15 mg. Dosage adjustments, if indicated, should generally occur at intervals of not less than 24 hours, reflecting the procedures in the placebo-controlled trials. When dosage adjustments are necessary, dose increments/decrements of 5 mg QD are recommended. Short-term (3-4 weeks) antimanic efficacy was demonstrated in a dose range of 5 mg to 20 mg/day in clinical trials. The safety of doses above 20 mg/day has not been evaluated in clinical trials.
Maintenance Monotherapy: The benefit of maintaining bipolar I patients on monotherapy with oral ZYPREXA at a dose of 5 to 20 mg/day, after achieving a responder status for an average duration of 2 weeks, was demonstrated in a controlled trial. The physician who elects to use ZYPREXA for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
Dose Selection for Adjunctive Treatment: When administered as adjunctive treatment to lithium or valproate, oral olanzapine dosing should generally begin with 10 mg once-a-day without regard to meals. Antimanic efficacy was demonstrated in a dose range of 5 mg to 20 mg/day in clinical trials. The safety of doses above 20 mg/day has not been evaluated in clinical trials.
For full details see prescribing information.

Acute and maintenance treatment of schizophrenia: Zyprexa is indicated for the management of the manifestations of psychotic disorders. Zyprexa is indicated for the short-term treatment of acute manic episodes associated with Bipolar I Disorder.
Prevention of recurrence in Bipolar Disorder: In patients whose manic
episode has responded to olanzapine treatment Zyprexa is indicated for the prevention of recurrence in patients with Bipolar Disorder.
Combination therapy in Bipolar I Disorder: The combination of Zyprexa with lithium or valproate is indicated for the short-term treatment of acute manic episodes associated with Bipolar I Disorder.

Known hypersensitivity to the product.

Neuroleptic malignant syndrome has been reported in association with administration of antipsychotic drugs, including olanzapine. Tardive dyskinesia, potentially irreversible, may develop in patients treated with antipsychotic drugs. Should be prescribed in a manner that is most likely to minimize the occurence of tardive dyskinesia. May induce orthostatic hypotension. Patients with known cardiovascular disease (history of myocardial infarction or ischemia, heart failure, or conduction abnormalities), cerebrovascular disease, and conditions which would predispose patients to hypotension. Should be used cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold. As with other drugs that antagonize dopamine D2 receptors, olanzapine elevates prolactin levels, and a modest elevation persists during chronic administration. The possibility of suicide attempt is inherent in schizophrenia and in bipolar disorder, and close supervision of high-risk patients should accompany drug therapy.
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Schizophrenia: Postular hypotension, constipation, weight gain, dizziness, personality disorder, akathisia.
Bipolar mania: Asthenia, dry mouth, constipation, dyspepsia, increased appetite, somnolence, dizziness, tremor.
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Alcohol, CNS depressants, cimetidine, disulfiram, carbamazepine, levodopa.

Pregnancy Teratogenic Effects, Pregnancy Category:  In oral reproduction studies in rats at doses up to 18 mg/kg/day and in rabbits at doses up to 30 mg/kg/day (9 and 30 times the maximum recommended human daily oral dose on a mg/m2 basis, respectively) no evidence of teratogenicity was observed. In an oral rat teratology study, early resorptions and increased numbers of nonviable fetuses were observed at a dose of 18 mg/kg/day (9 times the maximum recommended human daily oral dose on a mg/m2 basis). Gestation was prolonged at 10 mg/kg/day (5 times the maximum recommended human daily oral dose on a mg/m2 basis). In an oral rabbit teratology study, fetal toxicity (manifested as increased resorptions and decreased fetal weight) occurred at a maternally toxic dose of 30 mg/kg/day (30 times the maximum recommended human daily oral dose on a mg/m2 basis). Because animal reproduction studies are not always predictive 22 of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Placental transfer of olanzapine occurs in rat pups. There are no adequate and well-controlled trials with olanzapine in pregnant females. Seven pregnancies were observed during clinical trials with olanzapine, including 2 resulting in normal births, 1 resulting in neonatal death due to a cardiovascular defect, 3 therapeutic abortions, and 1 spontaneous abortion. Nonteratogenic Effects — Neonates exposed to antipsychotic drugs (including ZYPREXA), during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. ZYPREXA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Labor and Delivery: The effect of olanzapine on labor and delivery in humans is unknown. Parturition in rats was not affected by olanzapine.
Nursing Mothers: In a study in lactating, healthy women, olanzapine was excreted in breast milk. Mean infant dose at steady state was estimated to be 1.8% of the maternal olanzapine dose. It is recommended that women receiving olanzapine should not breast-feed.

Human Experience: In premarketing trials involving more than 3100 patients and/or normal subjects, accidental or intentional acute overdose of olanzapine was identified in 67 patients. In the patient taking the largest identified amount, 300 mg, the only symptoms reported were drowsiness and slurred speech. In the limited number of patients who were evaluated in hospitals, including the patient taking 300 mg, there were no observations indicating an adverse change in laboratory analytes or ECG. Vital signs were usually within normal limits following overdoses. In postmarketing reports of overdose with olanzapine alone, symptoms have been reported in the majority of cases. In symptomatic patients, symptoms with 10% incidence included agitation/aggressiveness, dysarthria, tachycardia, various extrapyramidal symptoms, and reduced level of consciousness ranging from sedation to coma. Among less commonly reported symptoms were the following potentially medically serious reactions: aspiration, cardiopulmonary arrest, cardiac arrhythmias (such as supraventricular tachycardia and 1 patient experiencing sinus pause with spontaneous resumption of normal rhythm), delirium, possible neuroleptic malignant syndrome, respiratory depression/arrest, convulsion, hypertension, and hypotension. Eli Lilly and Company has received reports of fatality in association with overdose of olanzapine alone. In 1 case of death, the amount of acutely ingested olanzapine was reported to be possibly as low as 450 mg of oral olanzapine; however, in another case, a patient was reported to survive an acute olanzapine ingestion of approximately 2 g of oral olanzapine.
Management of Overdose: The possibility of multiple drug involvement should be considered. In case of acute overdose, establish and maintain an airway and ensure adequate oxygenation and ventilation, which may include intubation. Gastric lavage (after intubation, if patient is unconscious) and administration of activated charcoal together with a laxative should be considered. The administration of activated charcoal (1 g) reduced the Cmax and AUC of oral olanzapine by about 60%. As peak olanzapine levels are not typically obtained until about 6 hours after dosing, charcoal may be a useful treatment for olanzapine overdose. The possibility of obtundation, seizures, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias. There is no specific antidote to olanzapine. Therefore, appropriate supportive measures should be initiated. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids and/or sympathomimetic agents. (Do not use epinephrine, dopamine, or other sympathomimetics with beta-agonist activity, since beta stimulation may worsen hypotension in the setting of olanzapine-induced alpha blockade.) Close medical supervision and monitoring should continue until the patient recovers. For specific information about overdose with lithium or valproate, refer to the Overdose section of the package inserts for these products.
For full details see prescribing information.