• Prescribing Information
• Safety Information

Cerebrovascular adverse events (CVAE), including stroke, in elderly patients with dementia—Cerebrovascular adverse events (eg, stroke, transient ischemic attack), including fatalities, were reported in trials of olanzapine in elderly patients with dementia-related psychosis. In placebo-controlled trials, there was a significantly higher incidence of CVAE in patients treated with olanzapine compared to patients treated with placebo. Olanzapine is not approved for the treatment of elderly patients with dementia-related psychosis.

Hyperglycemia—Hyperglycemia, in some cases associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics including olanzapine. 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. 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. Patients taking olanzapine should be monitored regularly for worsening of glucose control. Persons with risk factors for diabetes who are starting on atypical antipsychotics should undergo baseline and periodic fasting blood glucose testing. Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood glucose testing.

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, elevations in triglyceride levels have been observed with olanzapine use. Modest mean increases in total cholesterol have also been seen with olanzapine use.

Weight Gain—Potential consequences of weight gain should be considered prior to starting olanzapine. Patients receiving olanzapine should receive regular monitoring of weight.

Neuroleptic malignant syndrome (NMS)—As with all antipsychotic medications, a rare and potentially fatal condition known as NMS has been reported with olanzapine. If signs and symptoms appear, immediate discontinuation is recommended. 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 signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.

Tardive dyskinesia (TD)—As with all antipsychotic medications, prescribing should be consistent with the need to minimize the risk of TD. The risk of developing TD and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic increase. The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.

Hemodynamic effects—In premarketing trials, some patients taking oral olanzapine experienced orthostatic hypotension associated with dizziness, tachycardia, and, in some cases, syncope (15/2500, 0.6%). Hypotension, bradycardia with or without hypotension, tachycardia, and, in some cases, syncope (2/722, 0.3%) were reported during the clinical trials of intramuscular olanzapine. In a clinical pharmacology study in non-agitated patients with schizophrenia, a regimen of three 10-mg doses administered 4 hours apart was associated with a significant orthostatic decrease in systolic blood pressure in approximately one-third of patients. Additional injections of intramuscular olanzapine are not recommended for patients with a clinically significant postural change in systolic blood pressure after the first dose.

Use caution in patients receiving other drugs that can induce hypotension, bradycardia, respiratory or central nervous system depression. Concomitant administration of intramuscular olanzapine and parenteral benzodiazepines has not been studied and is therefore not recommended. If this combination is considered, careful evaluation of clinical status for excessive sedation and cardiorespiratory depression is recommended.

Seizures—Occurred infrequently in premarketing clinical trials of oral olanzapine (22/2500, 0.9%). Oral olanzapine should be used cautiously in patients with a history of seizures or with conditions that lower the seizure threshold.

Effect on prolactin—Modest elevations of prolactin were seen with oral olanzapine in acute-phase schizophrenia trials (incidence 34% vs 13% with placebo), although mean changes from baseline to endpoint were not statistically significantly different between olanzapine and placebo. Some patients may have persisting modest prolactin elevations.

Transient, asymptomatic elevations of hepatic transaminase—In placebo-controlled schizophrenia studies, clinically significant ALT (SGPT) elevations (≥3 times the upper limit of the normal range) were observed in 2% (6/243) of patients exposed to oral olanzapine compared to none (0/115) of the placebo patients. None of these patients experienced jaundice. Rare postmarketing reports of hepatitis have been received. Very rare cases of cholestatic or mixed liver injury have also been reported in the postmarketing period. Periodic assessment of transaminases is recommended in patients with significant hepatic disease.

Special populations, elderly—Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Olanzapine should be used with caution in patients at risk for aspiration pneumonia. In 5 studies in elderly patients with dementia-related psychosis, adverse events reported more commonly with olanzapine than with placebo were falls, somnolence, peripheral edema, abnormal gait, urinary incontinence, lethargy, increased weight, asthenia, pyrexia, pneumonia, dry mouth, and visual hallucinations. Olanzapine should be used with caution in elderly patients with dementia. Olanzapine is not approved for treatment of patients with dementia-related psychosis.

Special populations, adolescents—The safety and efficacy of olanzapine have not been established in patients under the age of 18 years.

Drug interactions—Coadministration of lorazepam IM and intramuscular olanzapine added to the somnolence observed with either drug alone. Coadministration of diazepam or ethanol with olanzapine may potentiate orthostatic hypotension. Lower doses of olanzapine should be considered in patients receiving concomitant therapy with fluvoxamine.

Physical incompatibility information—Intramuscular olanzapine should be reconstituted only with Sterile Water for Injection. It should not be combined in a syringe with diazepam injection, with lorazepam injection, or with haloperidol injection. See the full Prescribing Information for more information.

Medication dispensing and prescribing errors have occurred between ZYPREXA^® (olanzapine) and Zyrtec^® (cetirizine HCl). These errors could result in unnecessary adverse events or potential relapse in patients suffering from schizophrenia or bipolar disorder. To reduce the potential for dispensing errors, please write ZYPREXA clearly.

The most common treatment-emergent adverse events associated with intramuscular olanzapine vs placebo IM in 24-hour trials involving agitated patients with schizophrenia or bipolar mania were somnolence (6% vs 3%), dizziness (4% vs 2%), hypotension (2% vs 0%), asthenia (2% vs 1%), tremor (1% vs 0%), and postural hypotension (1% vs 0%).

The most common treatment-emergent adverse events associated with oral olanzapine (vs placebo) in 6-week schizophrenia trials were somnolence (26% vs 15%), dizziness (11% vs 4%), weight gain (6% vs 1%), personality disorder (COSTART term for nonaggressive objectionable behavior; 8% vs 4%), constipation (9% vs 3%), akathisia (5% vs 1%), and postural hypotension (5% vs 2%).

The most common treatment-emergent adverse events associated with oral olanzapine (vs placebo) in 3- and 4-week bipolar mania trials were somnolence (35% vs 13%), dry mouth (22% vs 7%), dizziness (18% vs 6%), asthenia (15% vs 6%), constipation (11% vs 5%), dyspepsia (11% vs 5%), increased appetite (6% vs 3%), and tremor (6% vs 3%).

For complete safety profile, see the full Prescribing Information