WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. OLANZAPINE is not approved for the treatment of patients with dementia-related psychosis.
- Cerebrovascular Adverse Reactions: In trials of elderly patients with dementia-related psychosis, there was a significantly higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, in patients treated with olanzapine compared to placebo. OLANZAPINE is not approved for the treatment of dementia-related psychosis.
- Suicide: The possibility of a suicide attempt is inherent in schizophrenia, and close supervision of high-risk patients should accompany drug therapy.
- Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status including delirium, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If NMS is suspected, immediately discontinue OLANZAPINE and provide symptomatic treatment and monitoring.
- Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): DRESS has been reported with exposure to olanzapine. DRESS may present with a cutaneous reaction, eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. DRESS is sometimes fatal. Discontinue if DRESS is suspected.
- Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes including hyperglycemia, dyslipidemia, and weight gain. Metabolic changes may be associated with increased cardiovascular/cerebrovascular risk. Olanzapine’s specific metabolic profile is presented below.
- Hyperglycemia and Diabetes Mellitus (DM), in some cases extreme and associated with ketoacidosis, hyperosmolar coma, or death, have been reported in patients treated with atypical antipsychotics, including olanzapine. While relative risk estimates are inconsistent, the association between atypical antipsychotics and increase in glucose levels appears to fall on a continuum, and olanzapine appears to have a greater association compared with some other atypical antipsychotics. Physicians should consider the risks and benefits when prescribing OLANZAPINE to patients with an established diagnosis of DM or with a borderline increase in 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. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of OLANZAPINE.
- Dyslipidemia: Undesirable alterations in lipids have been observed with olanzapine use. Clinical monitoring, including baseline and periodic follow-up lipid evaluations in patients using OLANZAPINE, is recommended. Clinically significant, and sometimes very high (≥500 mg/dL), elevations in triglyceride levels have been observed 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.
- 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. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses or may even arise after discontinuation of treatment. The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.
- Orthostatic Hypotension and Syncope: OLANZAPINE may induce orthostatic hypotension associated with dizziness, tachycardia, bradycardia, and in some patients, syncope, especially during the initial dose-titration period with oral OLANZAPINE. OLANZAPINE should be used with particular caution in patients with known cardiovascular disease, with cerebrovascular disease, or who are predisposed to hypotension.
- Falls: OLANZAPINE may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.
- Leukopenia, Neutropenia, and Agranulocytosis have been reported with antipsychotics, including olanzapine. Patients with a history of a clinically significant low white blood cell (WBC) count 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 WBCs in the absence of other causative factors. Patients with severe neutropenia (absolute neutrophil count <1000 mm3) should discontinue OLANZAPINE and have their WBC counts checked until recovery.
- Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Antipsychotic drugs, including OLANZAPINE, should be used cautiously in patients at risk for aspiration.
- Seizures: OLANZAPINE should be used cautiously in patients with a history of seizures or with conditions that lower the seizure threshold, e.g., Alzheimer’s dementia. OLANZAPINE is not approved for the treatment of patients with Alzheimer disease.
- Potential for Cognitive and Motor Impairment: OLANZAPINE has the potential to impair judgment, thinking, and motor skills. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that OLANZAPINE therapy does not affect them adversely.
- Body Temperature Dysregulation may occur with antipsychotic agents. Appropriate care is advised when prescribing OLANZAPINE for patients who will be experiencing conditions that may contribute to elevation in core body temperature (e.g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, being subject to dehydration).
- Anticholinergic Effects: Olanzapine exhibits in vitro muscarinic receptor affinity. In premarketing clinical trials, olanzapine was associated with constipation, dry mouth, and tachycardia, all adverse reactions possibly related to cholinergic antagonism. OLANZAPINE should be used with caution in patients with a current diagnosis or prior history of urinary retention, clinically significant prostatic hypertrophy, constipation, or a history of paralytic ileus or related conditions. In postmarketing experience, the risk for severe adverse reactions (including fatalities) was increased with concomitant use of anticholinergic medications.
- Hyperprolactinemia: As with other drugs that antagonize dopamine receptors, OLANZAPINE elevates prolactin levels, and the elevation persists during administration. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds.
The most common treatment-emergent adverse events (incidence of ≥5% and greater than placebo) associated with oral olanzapine (vs placebo) in 6-week schizophrenia trials in adults were somnolence (26% vs 15%), dizziness (11% vs 4%), weight gain (6% vs 1%), personality disorder (COSTART term for nonaggressive objectional 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 (incidence of ≥5% and greater than placebo) associated with oral olanzapine (vs placebo) in 3- and 4-week bipolar I disorder (manic or mixed episodes) trials in adults 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 (incidence of ≥5% and greater than placebo) associated with oral olanzapine (vs placebo) in clinical trials of adolescents (aged 13-17 years) were sedation (44% vs 9%), weight increased (30% vs 6%), increased appetite (24% vs 6%), headache (17% vs 12%), fatigue (9% vs 4%), liver enzymes increased (8% vs 1%), dizziness (7% vs 2%), dry mouth (6% vs 0%), and pain in extremity (5% vs 1%).
- Diazepam: may potentiate orthostatic hypotension
- Alcohol: may potentiate orthostatic hypotension
- Carbamazepine: increased clearance of olanzapine
- Fluvoxamine: may increase olanzapine levels
- Olanzapine and fluoxetine in combination: also refer to the Drug Interactions section of the package insert for Symbyax
- CNS acting drugs: caution should be used when used in combination with other centrally acting drugs and alcohol
- Antihypertensive agents: enhanced antihypertensive effect
- Levodopa and dopamine agonists: may antagonize levodopa/dopamine agonists
- Other concomitant drug therapy: when using olanzapine in combination with lithium or valproate, refer to the Drug Interactions sections of the package insert for those products
- Pregnancy: Use only if potential benefit justifies the potential risk to the fetus. May cause extrapyramidal symptoms (EPS) and/or withdrawal symptoms in neonates with third-trimester exposure. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including OLANZAPINE, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/
- Lactation: OLANZAPINE is present in human milk. Infants should be monitored for excess sedation, irritability, poor feeding, and extrapyramidal symptoms (tremors and abnormal muscle movements).
- Fertility: OLANZAPINE may cause a reversible reduction in fertility in females.
- Pediatric Use: Oral olanzapine is indicated for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adolescents aged 13 to 17 years. The recommended starting dose for adolescents is lower than that for adults. Compared with patients from adult clinical trials, adolescents were likely to gain more weight, experience increased sedation, and have greater increases in total cholesterol, triglycerides, LDL cholesterol, prolactin, and hepatic transaminase levels. When deciding among the alternative treatments available for adolescents, clinicians should consider the increased potential for weight gain and hyperlipidemia compared with adults. Clinicians should consider the long-term risks when prescribing to adolescents, and in many cases, this may lead them to consider prescribing other drugs first in adolescents. Medication treatment for adolescent schizophrenia and bipolar I disorder should be initiated only after a thorough diagnostic evaluation and careful consideration of the risks associated with medication treatment. Medication treatment for both adolescent schizophrenia and bipolar I disorder is indicated as part of a total treatment program that often includes psychological, educational, and social interventions. Safety and effectiveness of olanzapine in patients younger than 13 years have not been established.
OLANZAPINE Orally Disintegrating Tablets are indicated for the treatment of schizophrenia, for acute manic and mixed episodes of bipolar I disorder, and for maintenance treatment in bipolar I disorder.
Please see the full Prescribing Information for OLANZAPINE, including Boxed WARNING.
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