ZYPREXA^® IntraMuscular (Olanzapine for Injection)

ZYPREXA IntraMuscular is approved for the treatment of agitation associated with schizophrenia and bipolar I mania.

• An injectable formulation that enables you to intervene and calm agitated patients quickly and effectively
• Dose range 2.5, 5, 7.5, and 10 mg:
  • For agitation in schizophrenia and bipolar I mania, recommended dose is 10 mg
  • After short-term treatment with ZYPREXA IntraMuscular, a person may receive a prescription for oral ZYPREXA for schizophrenia or acute bipolar I mania if clinically indicated

Follow the steps below to reconstitute and use ZYPREXA IntraMuscular:

1. Inject 2.1 mL of Sterile Water for Injection into single-packaged vial for up to 10-mg dose.
2. Dissolve contents of vial completely; resulting solution should be clear and yellow.
3. Use solution within 1 hour; discard any unused portion.
4. Refer to table for injection volumes and corresponding doses of ZYPREXA IntraMuscular.
5. Immediately after use, dispose of syringe in approved sharps box.

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.

Important Safety Information about Olanzapine

Warnings and Precautions

• Cerebrovascular adverse events including fatalities were reported significantly more commonly with olanzapine than placebo in trials of elderly patients with dementia-related psychosis. Olanzapine is not approved for the treatment of patients with dementia-related psychosis.
• The possibility of a suicide attempt is inherent in schizophrenia and bipolar I disorder, and close supervision of high-risk patients should accompany drug therapy.
• As with all antipsychotic medications, a rare and potentially fatal condition known as Neuroleptic Malignant Syndrome (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.
• 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 levels. Patients taking olanzapine should be monitored regularly for worsening of glucose control. Patients starting treatment with olanzapine 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 should undergo fasting blood glucose testing.
• Undesirable alterations in lipids have been observed with olanzapine use. Clinical monitoring, including baseline and follow-up lipid evaluations in patients using olanzapine, is recommended. Clinically 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.
• Potential consequences of weight gain should be considered prior to starting olanzapine. Patients receiving olanzapine should receive regular monitoring of weight.
• As with all antipsychotic medications, prescribing should be consistent with the need to minimize the risk of Tardive Dyskinesia (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.
• Olanzapine may induce orthostatic hypotension associated with dizziness, tachycardia, bradycardia, and in some patients, syncope, especially during the initial dose-titration period.
  
  Hypotension, bradycardia with or without hypotension, tachycardia, and syncope were also reported with intramuscular olanzapine. 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.
  
  Olanzapine should be used with particular caution in patients with known cardiovascular disease, cerebrovascular disease, or those predisposed to hypotension.
• Leukopenia, neutropenia, and agranulocytosis have been reported with antipsychotics, including olanzapine. Patients with a history of a clinically significant low white blood cell count (WBC) or drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of olanzapine should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors.
• Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in patients with advanced Alzheimer's disease. Olanzapine is not approved for the treatment of patients with Alzheimer's disease.
• Olanzapine should be used cautiously in patients with a history of seizures or with conditions that lower the seizure threshold.
• As with any CNS-active drug, olanzapine has the potential to impair judgment, thinking or motor skills.
• Body temperature dysregulation may occur with antipsychotic agents. Appropriate care is advised when prescribing olanzapine for patients who will be experiencing conditions which may contribute to elevation in core body temperature.
• Olanzapine should be used with caution in patients with clinically significant prostatic hypertrophy, narrow angle glaucoma, a history of paralytic ileus, or related conditions.
  
  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 is not approved for treatment of patients with dementia-related psychosis.
• As with other drugs that antagonize dopamine receptors, olanzapine elevates prolactin levels, and a modest elevation persists during administration.

Use in Specific Populations

• Pregnancy: Use only if the potential benefit justifies the potential risk to the fetus
• Nursing mothers: Breast feeding is not recommended
• Pediatric: Olanzapine is not approved for use in children and adolescents.

Additional 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

Adverse Events

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

ZYPREXA is a registered trademark of Eli Lilly and Company.
Zyrtec is a registered trademark of UCB, SA.