Neuroleptic Malignant Syndrome: In premarketing clinical trials there were no reported cases of NMS in patients receiving olanzapine. However, NMS is a potentially fatal symptom complex, that has been reported in association with antipsychotic drugs.
Tardive Dyskinesia: Tardive dyskinesia (TD) a syndrome consisting of potentially irreversible involuntary dyskinetic movements, is associated with the use of antipsychotic drugs. Tardive dyskinesia occurs more frequently in elderly patients, however, patients of any age can be affected. It is unknown whether antipsychotic drugs may differ in their potential to cause TD. However, during long-term, double-blind extension maintenance trials (R94 olanzapine-treated patients; median olanzapine treatment 237 days), olanzapine was associated with a statistically significantly lower incidence of treatment emergent dyskinesia compared to haloperidol.
Potential Effect on Cognitive and Motor Performance: Because olanzapine may cause somnolence patients should be cautioned about operating hazardous machinery, including motor vehicles, until they are reasonably certain that olanzapine therapy does not affect them adversely.
Hypotension and Syncope: As with other drugs that have high alpha-1 adrenergic receptor blocking activity, olanzapine may induce orthostatic hypotension, tachycardia, dizziness, and sometimes syncope especially at the initiation of treatment. In a clinical trial database of 2500 patients treated with olanzapine, syncope was reported in 0.6% (15/2500). The risk of orthostatic hypotension and syncope may be minimized by initiating therapy with 5 mg OD. A more gradual titration to the target dose should be considered if hypotension occurs. Olanzapine should be used with particular caution in patients with known cardiovascular disease (history of myocardial infarction or ischemia heart failure or conduction abnormalities), cerebrovascular disease, and conditions which would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications).
Seizures: Conventional neuroleptics are known to lower seizure threshold. In clinical trials, seizures have occurred in only a small number (0.9%- 22 / 2500) of olanzapine-treated patients. There were confounding factors that may have contributed to the occurrence of seizures in many of these cases. Olanzapine should be used cautiously in patients who have a history of seizures or have conditions associated with seizure or have a lowered seizure threshold.
Transaminase Elevations: During premarketing clinical trials, therapy with olanzapine was associated with elevation of hepatic transaminases, primarily ALT (SGPT). Precautions should be exercised when using olanzapine in patients with pre-existing hepatic disorders, in patients who are being treated with potentially hepatotoxic drugs, or if treatment-emergent signs or symptoms of hepatic impairment appear.
For patients who have known or suspected abnormal hepatic function prior to starting olanzapine, standard clinical assessment, including measurement of transaminase levels is recommended. Periodic clinical reassessment with tnansaminase levels is recommended for such patients, as well as for patients who develop any signs and symptoms suggestive of a new onset liver disorder during olanzapine therapy.
Hematologic Indices: In clinical trials, there were no data to suggest olanzapine adversely affected bone marrow function, even in patients with a history of clozapine-associated neutropenia or leukopenia.
Hyperprolactinemia: As with other drugs that block dopamine D2, and/or serotonin 5-HT2 receptors, olanzapine may elevate prolactin levels Elevations associated with olanzapine treatment are generally mild and may decline during continued administration.
Since tissue culture experiments indicate that approximately one third of human breast cancers are prolactin dependent in vitro, olanzapine should only be administered to patients with previously detected breast cancer if the benefits outweigh the potential risks. Caution should also be exercised when considering olanzapine treatment in patients with pituitary tumors. Possible manifestations associated with elevated prolactin levels are amenorrhea, galactorrhea and menorrhagia.
Uric Acid: In the premarketing clinical trial database. Olanzapine was associated with mild elevations of uric acid in some patients.
Weight Gain: Olanzapine was associated with weight gain during clinical trials. Patients treated at higher doses (15 ± 2.5 mg/day) had the greatest mean weight gain. However, a categorization of patients at baseline on the basis of body mass index (BMI) revealed a significantly greater effect in patents with low BMI compared to normal or overweight patients. Using pooled data from patients treated with olanzapine over the dosage range of 5 mg to 20 mg per day, weight gain tended to level of at 6 to 8 months of treatment with a mean gain of 5.4 kg.
Antiemetic Effect: Consistent with its dopamine antagonist effects olanzapine may have an antiemetic effect. Such an effect may mask signs of toxicity due to overdosage of other drugs, or may mask symptoms of disease such as brain tumor or intestinal obstruction.
Body Temperature Regulation: Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. Appropriate care is advised when prescribing olanzapine for patients who will be experiencing conditions which may contribute to an elevation of core temperature, eg exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration.
possibility of suicide or attempted suicide is inherent in psychosis, and thus
close supervision and appropriate clinical management of high-risk patients
should accompany drug therapy.