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Important Safety Information about Olanzapine and Olanzapine + Fluoxetine HCl Combination

Contraindications

• Fluoxetine should not be used with an MAOI or within at least 14 days of discontinuing an MAOI. At least 5 weeks should be allowed after stopping fluoxetine before starting an MAOI.
• Thioridazine should not be given with fluoxetine or within at least 5 weeks after stopping fluoxetine.
• Concomitant use of fluoxetine in patients taking pimozide is contraindicated.

Warnings and Precautions

• Clinical Worsening and Suicide Risk--All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially within the first few months of treatment and when changing the dose. Consider changing the therapeutic regimen, including possibly discontinuing the medication in patients whose depression is persistently worse or includes symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, or suicidality that are severe, abrupt in onset, or were not part of the patient's presenting symptoms. If discontinuing treatment, the medication should be tapered. Families and caregivers or patients being treated with antidepressants for any indication should be alerted about the need to monitor patients. Prescriptions for olanzapine + fluoxetine combination should be written for the smallest quantity consistent with good patient management. It should be noted that the olanzapine + fluoxetine combination is not approved for use in treating any indications in patients under 18 years of age.
• The possibility of a suicide attempt is inherent in the conditions olanzapine is indicated to treat, and close supervision of high risk patients should accompany drug therapy
• 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.
• 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 been seen with olanzapine use. Clinically meaningful increases in total cholesterol have been seen with olanzapine + fluoxetine combination use.
• Potential consequences of weight gain should be considered prior to starting olanzapine. Patients receiving olanzapine should receive regular monitoring of weight.
• Development of a potentially life-threatening serotonin syndrome or NMS-like reactions have been reported with SNRIs and SSRIs alone, including fluoxetine treatment, but particularly with concomitant use of serotonergic drugs, including triptans, with drugs which impair serotonin metabolism, including MAOIs, or with antipsychotics or other dopamine antagonists. If these events occur, treatment with fluoxetine and any concomitant serotonergic or antidopaminergic agents should be discontinued immediately and supportive symptomatic treatment should be initiated.
• If rash or other possibly allergic phenomena appear during fluoxetine treatment for which an alternative etiology cannot be determined, immediate discontinuation is recommended.
• Patients being treated with the olanzapine + fluoxetine combination should be screened for bipolar disorder and monitored for mania/hypomania
• 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.
• Patients should be cautioned regarding the risk of bleeding associated with the concomitant use of fluoxetine with NSAIDs, aspirin, warfarin or other drugs that affect coagulation.
• As with other antidepressants, fluoxetine has been associated with cases of clinically significant hyponatremia that appeared to be reversible when fluoxetine was discontinued.
• As with any CNS-active drug, olanzapine and fluoxetine have 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.
• Caution should be used when prescribing other medications that contain olanzapine or fluoxetine.
• Because of the long elimination half-lives of fluoxetine and its major metabolite, changes in dose will not be fully reflected in plasma for several weeks.
• Symptoms associated with discontinuation of fluoxetine have been reported (e.g., dysphoric mood, irritability, agitation, dizziness, sensory disturbances). While these events are generally self-limiting, some have been serious. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible.

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 and olanzapine + fluoxetine combination are not approved for use in children and adolescents
• Hepatic impairment: Use a lower or less frequent dose of fluoxetine in patients with cirrhosis.

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%).
• The most common treatment-emergent adverse events associated with olanzapine + fluoxetine combination (vs placebo) in clinical trials were weight gain (25% vs 3%), increased appetite (20% vs 4%), dry mouth (15% vs 6%), somnolence (14% vs 6%), fatigue (12% vs 2%), peripheral edema (9% vs 0%), tremor (9% vs 3%), sedation (8% vs 4%), hypersomnia (5% vs 1%), disturbance in attention (5% vs 1%) and blurred vision (5% vs 2%).

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

For complete safety profile, see the full Prescribing Information provided.