Zyprexa (Tablet)

dailymed-instance:drugs, http://www4.wiwiss.fu-berlin.de/drugbank/vocab/resource/class/Offer

Schizophrenia: Usual Dose���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 5mg 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. The safety of doses above 20 mg/day has not been evaluated in clinical trials. Dosing in 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���While there is no body of evidence available to answer the question of how long the patient treated with olanzapine should remain on it, 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 a period of up to 8 months has been demonstrated in a placebo���controlled trial . Patients should be periodically reassessed to determine the need for maintenance treatment with appropriate dose.<br/>Bipolar Disorder: Usual Monotherapy Dose���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 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 two weeks, was demonstrated in a controlled trial . The physician who elects to use ZYPREXA for extended periods should periodically re���evaluate the long���term usefulness of the drug for the individual patient. Bipolar Mania Usual Dose in Combination with Lithium or Valproate���When administered in combination with lithium or valproate, oral olanzapine dosing should generally begin with 10 mg once���a���day without regard to meals. Short���term (6 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. Dosing in Special Populations���See Dosing in Special Populations under DOSAGE AND ADMINISTRATION, Schizophrenia.<br/>Administration of ZYPREXA ZYDIS (olanzapine orally disintegrating tablets): After opening sachet, peel back foil on blister. Do not push tablet through foil. Immediately upon opening the blister, using dry hands, remove tablet and place entire ZYPREXA ZYDIS in the mouth. Tablet disintegration occurs rapidly in saliva so it can be easily swallowed with or without liquid.<br/>Agitation Associated with Schizophrenia and Bipolar I Mania: Usual Dose for Agitated Patients with Schizophrenia or Bipolar Mania���The efficacy of intramuscular olanzapine for injection in controlling agitation in these disorders was demonstrated in a dose range of 2.5 mg to 10 mg. The recommended dose in these patients is 10 mg. A lower dose of 5 or 7.5 mg may be considered when clinical factors warrant . If agitation warranting additional intramuscular doses persists following the initial dose, subsequent doses up to 10 mg may be given. However, the efficacy of repeated doses of intramuscular olanzapine for injection in agitated patients has not been systematically evaluated in controlled clinical trials. Also, the safety of total daily doses greater than 30 mg, or 10 mg injections given more frequently than 2 hours after the initial dose, and 4 hours after the second dose have not been evaluated in clinical trials. Maximal dosing of intramuscular olanzapine (e.g., three doses of 10 mg administered 2���4 hours apart) may be associated with a substantial occurrence of significant orthostatic hypotension . Thus, it is recommended that patients requiring subsequent intramuscular injections be assessed for orthostatic hypotension prior to the administration of any subsequent doses of intramuscular olanzapine for injection. The administration of an additional dose to a patient with a clinically significant postural change in systolic blood pressure is not recommended. If ongoing olanzapine therapy is clinically indicated, oral olanzapine may be initiated in a range of 5���20 mg/day as soon as clinically appropriate . Intramuscular Dosing in Special Populations���A dose of 5 mg per injection should be considered for geriatric patients or when other clinical factors warrant. A lower dose of 2.5 mg per injection should be considered for patients who otherwise might be debilitated, be predisposed to hypotensive reactions, or be more pharmacodynamically sensitive to olanzapine .<br/>Administration of ZYPREXA IntraMuscular: ZYPREXA IntraMuscular is intended for intramuscular use only. Do not administer intravenously or subcutaneously. Inject slowly, deep into the muscle mass. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.<br/>Directions for preparation of ZYPREXA IntraMuscular with Sterile Water for Injection: Dissolve the contents of the vial using 2.1 mL of Sterile Water for Injection to provide a solution containing approximately 5 mg/mL of olanzapine. The resulting solution should appear clear and yellow. ZYPREXA IntraMuscular reconstituted with Sterile Water for Injection should be used immediately (within 1 hour) after reconstitution. Discard any unused portion. The following table provides injection volumes for delivering various doses of intramuscular olanzapine for injection reconstituted with Sterile Water for Injection.<br/>Physical Incompatibility Information: ZYPREXA IntraMuscular should be reconstituted only with Sterile Water for Injection. ZYPREXA IntraMuscular should not be combined in a syringe with diazepam injection because precipitation occurs when these products are mixed. Lorazepam injection should not be used to reconstitute ZYPREXA IntraMuscular as this combination results in a delayed reconstitution time. ZYPREXA IntraMuscular should not be combined in a syringe with haloperidol injection because the resulting low pH has been shown to degrade olanzapine over time.

Pharmacodynamics: Olanzapine is a selective monoaminergic antagonist with high affinity binding to the following receptors: serotonin 5HT, 5HT, (K=4, 11, and 5 nM, respectively), dopamine D(K=11���31 nM), histamine H(K=7 nM), and adrenergic��receptors (K=19 nM). Olanzapine is an antagonist with moderate affinity binding for serotonin 5HT(K=57 nM) and muscarinic M(K=73, 96, 132, 32, and 48 nM, respectively). Olanzapine binds weakly to GABA, BZD, and��adrenergic receptors (K>10��M). The mechanism of action of olanzapine, as with other drugs having efficacy in schizophrenia, is unknown. However, it has been proposed that this drug's efficacy in schizophrenia is mediated through a combination of dopamine and serotonin type 2 (5HT) antagonism. The mechanism of action of olanzapine in the treatment of acute manic episodes associated with Bipolar I Disorder is unknown. Antagonism at receptors other than dopamine and 5HTmay explain some of the other therapeutic and side effects of olanzapine. Olanzapine's antagonism of muscarinic Mreceptors may explain its anticholinergic���like effects. Olanzapine's antagonism of histamine Hreceptors may explain the somnolence observed with this drug. Olanzapine's antagonism of adrenergic��receptors may explain the orthostatic hypotension observed with this drug.<br/>Pharmacokinetics:<br/>Oral Administration: Olanzapine is well absorbed and reaches peak concentrations in approximately 6 hours following an oral dose. It is eliminated extensively by first pass metabolism, with approximately 40% of the dose metabolized before reaching the systemic circulation. Food does not affect the rate or extent of olanzapine absorption. Pharmacokinetic studies showed that ZYPREXA tablets and ZYPREXA ZYDIS (olanzapine orally disintegrating tablets) dosage forms of olanzapine are bioequivalent. Olanzapine displays linear kinetics over the clinical dosing range. Its half���life ranges from 21 to 54 hours (5th to 95th percentile; mean of 30 hr), and apparent plasma clearance ranges from 12 to 47 L/hr (5th to 95th percentile; mean of 25 L/hr). Administration of olanzapine once daily leads to steady���state concentrations in about one week that are approximately twice the concentrations after single doses. Plasma concentrations, half���life, and clearance of olanzapine may vary between individuals on the basis of smoking status, gender, and age (see Special Populations). Olanzapine is extensively distributed throughout the body, with a volume of distribution of approximately 1000 L. It is 93% bound to plasma proteins over the concentration range of 7 to 1100 ng/mL, binding primarily to albumin and�����acid glycoprotein. Metabolism and Elimination���Following a single oral dose ofC labeled olanzapine, 7% of the dose of olanzapine was recovered in the urine as unchanged drug, indicating that olanzapine is highly metabolized. Approximately 57% and 30% of the dose was recovered in the urine and feces, respectively. In the plasma, olanzapine accounted for only 12% of the AUC for total radioactivity, indicating significant exposure to metabolites. After multiple dosing, the major circulating metabolites were the 10���N���glucuronide, present at steady state at 44% of the concentration of olanzapine, and 4�����N���desmethyl olanzapine, present at steady state at 31% of the concentration of olanzapine. Both metabolites lack pharmacological activity at the concentrations observed. Direct glucuronidation and cytochrome P450 (CYP) mediated oxidation are the primary metabolic pathways for olanzapine. In vitro studies suggest that CYPs 1A2 and 2D6, and the flavin���containing monooxygenase system are involved in olanzapine oxidation. CYP2D6 mediated oxidation appears to be a minor metabolic pathway in vivo, because the clearance of olanzapine is not reduced in subjects who are deficient in this enzyme.<br/>Intramuscular Administration: ZYPREXA IntraMuscular results in rapid absorption with peak plasma concentrations occurring within 15 to 45 minutes. Based upon a pharmacokinetic study in healthy volunteers, a 5 mg dose of intramuscular olanzapine for injection produces, on average, a maximum plasma concentration approximately 5 times higher than the maximum plasma concentration produced by a 5 mg dose of oral olanzapine. Area under the curve achieved after an intramuscular dose is similar to that achieved after oral administrationof the same dose. The half���life observed after intramuscular administration is similar to that observed after oral dosing. The pharmacokinetics are linear over the clinical dosing range. Metabolic profiles after intramuscular administration are qualitatively similar to metabolic profiles after oral administration.<br/>Special Populations: For specific information about the pharmacology of lithium or valproate, refer to the CLINICAL PHARMACOLOGY section of the package inserts for these other products.

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.

http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00334

dailymed-ingredient:Olanzapine

diseasome-diseases:1025, diseasome-diseases:1032, diseasome-diseases:130, diseasome-diseases:1377, diseasome-diseases:1460, diseasome-diseases:1547, diseasome-diseases:2216, diseasome-diseases:3423, diseasome-diseases:347, diseasome-diseases:3841, diseasome-diseases:3852, diseasome-diseases:54, diseasome-diseases:852, diseasome-diseases:94

Human Experience: In premarketing trials involving more than 3100 patients and/or normal subjects, accidental or intentional acute overdosage 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 events: aspiration, cardiopulmonary arrest, cardiac arrhythmias (such as supraventricular tachycardia and one 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 one 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.<br/>Overdosage Management: The possibility of multiple drug involvement should be considered. In case of acute overdosage, 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 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.

Zyprexa (Tablet)

Increased Mortality in Elderly Patients with Dementia���Related Psychosis���Elderly patients with dementia���related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. ZYPREXA is not approved for the treatment of patients with dementia���related psychosis . In placebo���controlled clinical trials of elderly patients with dementia���related psychosis, the incidence of death in olanzapine���treated patients was significantly greater than placebo���treated patients (3.5% vs 1.5%, respectively). Cerebrovascular Adverse Events, Including Stroke, in Elderly Patients with Dementia���Related Psychosis���Cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, were reported in patients in trials of olanzapine in elderly patients with dementia���related psychosis. In placebo���controlled trials, there was a significantly higher incidence of cerebrovascular adverse events in patients treated with olanzapine compared to patients treated with placebo. Olanzapine is not approved for the treatment of patients with dementia���related psychosis. Hyperglycemia���Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics including olanzapine. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increasedbackground risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia���related adverse events is not completely understood. However, epidemiological studies suggest an increased risk of treatment���emergent hyperglycemia���related adverse events in patients treated with the atypical antipsychotics. While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose levels appears to fall on a continuum and olanzapine appears to have a greater association than some other atypical antipsychotics. Mean increases in blood glucose have been observed in patients treated (median exposure of 9.2 months) with olanzapine in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). The mean increase of serum glucose (fasting and nonfasting samples) from baseline to the average of the two highest serum concentrations was 15.0 mg/dL. Olanzapine Monotherapy in Adults���In an analysis of 5 placebo���controlled adult olanzapine monotherapy studies with treatment duration up to 12 weeks, olanzapine was associated with a greater mean change in fasting glucose levels compared to placebo (2.76 mg/dL versus 0.17 mg/dL). The difference in mean changes between olanzapine and placebo was greater in patients with evidence ofglucose dysregulation at baseline (patients diagnosed with diabetes mellitus or related adverse events, patients treated with anti���diabetic agents, patients with a baseline random glucose level���200 mg/dL, and/or a baseline fasting glucose level���126 mg/dL). These patients had a statistically significantly greater mean increase in HbAcompared to placebo. In patients with baseline normal fasting glucose levels (<100 mg/dL), 2.2% (N=543) of those treated with olanzapine were found to have high glucose levels (���126 mg/dL) during olanzapine treatment versus 3.4% (N=293) of those treated with placebo. In patients with baseline borderline fasting glucose levels (���100 mg/dL and<126 mg/dL), 17.4% (N=178) of those treated with olanzapine were found to have high glucose levels (���126 mg/dL) during olanzapine treatment versus 11.5% (N=96) of those treated with placebo. Olanzapine Monotherapy in Adolescents���The safety and efficacy of olanzapine have not been established in patients under the age of 18 years. In an analysis of 3 placebo���controlled olanzapine monotherapy studies of adolescent patients, including those with schizophrenia (6 weeks) or bipolar disorder (manic or mixed episodes) (3 weeks), olanzapine was associated with a statistically significantly greater mean change in fasting glucose levels compared to placebo (2.68 mg/dL versus���2.59 mg/dL). In patients with baseline normal fasting glucose levels (<100 mg/dL), zero out of 124 (0%) of those treated with olanzapine were found to have high glucose levels (���126 mg/dL) during olanzapine treatment versus 1 out of 53 (1.9%) of those treated with placebo. In patients with baseline borderline fasting glucose levels (���100 mg/dL and<126 mg/dL), 2 out of 14 (14.3%) of those treated with olanzapine were found to have high glucose levels (���126 mg/dL) during olanzapine treatment versus zero out of 13 (0%) of those treated with placebo. Physicians should consider the risks and benefits when prescribing olanzapine to patients with an established diagnosis of diabetes mellitus, or having borderline increased blood glucose level (fasting 100���126 mg/dL, non���fasting 140���200 mg/dL). Patients taking olanzapine should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti���diabetic treatment despite discontinuation of the suspect drug. Hyperlipidemia���Undesirable alterations in lipids have been observed with olanzapine use. Clinical monitoring, including baseline and follow���up lipid evaluations in patients using olanzapine, is advised. Significant, and sometimes very high (>500 mg/dL), elevations in triglyceride levels have been observed with olanzapine use. Modest mean increases in total cholesterol have also been seen with olanzapine use. Olanzapine Monotherapy in Adults���In an analysis of 5 placebo���controlled olanzapine monotherapy studies with treatment duration up to 12 weeks, olanzapine���treated patients had statistically significant increases from baseline in mean fasting total cholesterol, LDL cholesterol, and triglycerides of 5.3 mg/dL, 3.0 mg/dL, and 20.8 mg/dL respectively compared to decreases from baseline in mean fasting total cholesterol, LDL cholesterol, and triglycerides of 6.1 mg/dL, 4.3 mg/dL, and 10.7 mg/dL for placebo���treated patients. For fasting HDL cholesterol, no statistically significant differences were observed between olanzapine���treated patients and placebo���treated patients. Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline, where lipid dysregulation was defined as patients diagnosed with dyslipidemia or related adverse events, patients treated with lipid lowering agents, or patients with high baseline lipid levels. Table 1 shows categorical changes in fasting lipid values. In phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), over a median exposure of 9.2 months, the mean increase in triglycerides in patients taking olanzapine was 40.5 mg/dL. In phase 1 of CATIE, the mean increase in total cholesterol was 9.4 mg/dL. Olanzapine Monotherapy in Adolescents���The safety and efficacy of olanzapine have not been established in patients under the age of 18 years. In an analysis of 3 placebo���controlled olanzapine monotherapy studies of adolescent patients, including those with schizophrenia (6 weeks) or bipolar disorder (manic or mixed episodes) (3 weeks), for fasting HDL cholesterol, no statistically significant differences were observed between olanzapine���treated patients and placebo���treated patients. Table 2 shows categorical changes in fasting lipid values in adolescent patients. Weight Gain���Potential consequences of weight gain should be considered prior to starting olanzapine. Patients receiving olanzapine should receive regular monitoring of weight. Olanzapine Monotherapy in Adults���In an analysis of 13 placebo���controlled olanzapine monotherapy studies, olanzapine���treated patients gained an average of 2.6 kg, which was statistically significantly different compared to an average 0.3 kg weight loss in placebo���treated patients with a median exposure of 6 weeks; 22.2% of olanzapine���treated patients gained at least 7% of their baseline weight, which was statistically significantly different compared to 3% of placebo���treated patients, with a median exposure of 8 weeks; 4.2% of olanzapine���treated patients gained at least 15% of their baseline weight, which was statistically significantly different compared to 0.3% of placebo���treated patients, with a median exposure of 12 weeks. Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories. Discontinuation due to weight gain occurred in 0.2% of olanzapine���treated patients and in zero placebo���treated patients. During long���term continuation therapy with olanzapine (238 median days of exposure), 56% of olanzapine patients met the criterion for having gained greater than 7% of their baseline weight. Average weight gain during long���term therapy was 5.4 kg. Table 3 includes data on weight gain with olanzapine pooled from 68 clinical trials. The data in each column represent data for those patients who completed treatment periods of the durations specified. Olanzapine Monotherapy in Adolescents���The safety and efficacy of olanzapine have not been established in patients under the age of 18 years. In an analysis of 4 placebo���controlled olanzapine monotherapy studies of adolescent patients (ages 13 to 17 years), including those with schizophrenia (6 weeks) or bipolar disorder (manic or mixed episodes) (3 weeks), olanzapine���treated patients gained an average of 4.6 kg, which was statistically significantly different compared to an average of 0.3 kg in placebo���treated patients, with a median exposure of 3 weeks; 40.6% of olanzapine���treated patients gained at least 7% of their baseline body weight, which was statistically significantly different compared to 9.8% of placebo���treated patients, with a median exposure of 4 weeks; 7.1% of olanzapine���treated patients gained at least 15% of their baseline weight, compared to 2.7% of placebo���treated patients, with a median exposure of 19 weeks. Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories, but mean changes in weight were greater in adolescents with BMI categories above normal at baseline. Discontinuation due to weight gain occurred in 1% of olanzapine���treated patients, compared to zero placebo���treated patients. During long���term continuation therapy with olanzapine, 65% of olanzapine���treated patients met the criterion for having gained greater than 7% of their baseline weight. Average weight gain during long���term therapy was 7.4 kg. Neuroleptic Malignant Syndrome (NMS)���A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including olanzapine. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signsmay include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to exclude cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology. The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for NMS. If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported. Tardive Dyskinesia���A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown. The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long���term course of the syndrome is unknown. Given these considerations, olanzapine should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients (1) who suffer from a chronic illness that is known to respond to antipsychotic drugs, and (2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically. If signs and symptoms of tardive dyskinesia appear in a patient on olanzapine, drug discontinuation should be considered. However, some patients may require treatment with olanzapine despite the presence of the syndrome. For specific information about the warnings of lithium or valproate, refer to the WARNINGS section of the package inserts for these other products.

http://www4.wiwiss.fu-berlin.de/dailymed/resource/organization/Eli_Lilly_and_Company

Zyprexa