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Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories.
In long-term studies (at least 48 weeks), both the magnitude of weight gain and the proportion of olanzapine-treated patients who had clinically significant weight gain were greater than in short-term studies. The percentage of patients who gained ≥25% of their baseline body weight with long-term exposure was very common (≥10%).
Glucose: In clinical trials (up to 52 weeks) olanzapine was associated with a greater mean change in glucose relative to placebo.
The difference in mean changes between olanzapine and placebo was greater in patients with evidence of glucose dysregulation at baseline (including those patients diagnosed with diabetes mellitus or who met criteria suggestive of hyperglycemia), and these patients had a greater increase in HbA1c compared to placebo.
The proportion of patients who had a change in glucose level from normal or borderline at baseline to high increased over time. In an analysis of patients who completed 9-12 months of olanzapine therapy, the rate of increase in mean blood glucose slowed after approximately 6 months.
Lipids: In clinical trials of up to 12 weeks in duration, olanzapine-treated patients had a greater mean increase in fasting total cholesterol, LDL cholesterol, and triglycerides, compared to placebo-treated patients.
Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline. For fasting HDL cholesterol, no statistically significant differences were observed between olanzapine-treated patients and placebo-treated patients.
The proportion of patients who had changes in total cholesterol, LDL cholesterol or triglycerides from normal or borderline to high, or changes in HDL cholesterol from normal or borderline to low, was greater in long-term studies (at least 48 weeks) as compared with short-term studies. In an analysis of patients who completed 12 months of therapy, the mean nonfasting total cholesterol did not increase further after approximately 4-6 months.
Prolactin: In controlled clinical trials (up to 12 weeks), elevations in prolactin were observed in 30% of olanzapine-treated patients as compared to 10.5% of placebo-treated patients. In the majority of these patients, the elevations were mild.
In patients with schizophrenia, menstrual-related adverse events potentially associated with prolactin elevations were common (<10% to =1%), whereas sexual function-related and breast-related adverse events were infrequent (<1% to =0.1%). In patients treated for other mental illnesses, sexual function-related adverse events potentially associated with prolactin elevations were common (<10% to =1%), whereas breast-related and menstrual-related adverse events were infrequent (<1% to =0.1%).
(1) TEAEs analysis up to 52 weeks of treatment.
(2) Bipolar Depression, Psychotic Depression, Borderline Personality Disorder and Bipolar Mania.
Hepatic Aminotransferases: Transient, asymptomatic elevations of hepatic transaminases, ALT/SGPT and AST/SGOT, have been seen occasionally.
Eosinophilia: Asymptomatic eosinophilia was occasionally seen.
Undesirable Effects for Special Population: Very common (≥ 10%) undesirable effects associated with the use of Olanzapine in clinical trials with elderly patients with dementia-related psychosis were abnormal gait and falls.
Common (<10% and ≥1%) undesirable effects associated with the use of olanzapine in elderly patients with dementia-related psychosis were urinary incontinence and pneumonia.
In clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with Parkinson's disease, worsening of Parkinsonian symptomatology was reported very commonly and more frequently than with placebo. Also, hallucinations were reported very commonly and more frequently than with placebo. In these trials, patients were required to be stable on the lowest effective dose of anti-Parkinsonian medications (dopamine agonist) prior to the beginning of the study and to remain on the same anti-Parkinsonian medications and dosages throughout the study. Olanzapine was started at 2.5 mg/day and titrated up to a maximum of 15 mg/day based on the investigator judgement.
The following table summarizes the core adverse drug reaction terms and their frequencies identified during clinical trials and/or during post-marketing experience for olanzapine. (See Tables 2a and 2b.)
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Click on icon to see table/diagram/imageAdolescents (Ages 13-17 Years): The types of undesirable effects observed in adolescent patients treated with olanzapine were similar to those seen in adult patients. Although no clinical trials designed to compare adolescents to adults were conducted, the data from the adolescent trials were compared to those of the adult trials.
Mean increase in weight in adolescents (4.6 kg over 3 weeks median duration of exposure) was greater than in adults (2.6 kg over 7 weeks median duration of exposure).
In long-term studies (at least 24 weeks), both the magnitude of weight gain and the proportion of adolescent olanzapine-treated patients who had clinically significant weight gain were greater than in short-term studies and were greater than in adult patients with comparable exposures. With long-term exposure, approximately half of adolescent patients gained ≥15% and almost a third gained ≥25% of their baseline body weight. Among adolescent patients, mean weight gain was greatest in patients who were overweight or obese at baseline.
Mean increases in fasting glucose were similar in adolescents and adults treated with olanzapine, however, the difference between olanzapine and placebo groups was greater in adolescents compared to adults.
In long-term studies (at least 24 weeks), changes in glucose from normal at baseline to high were uncommon (<1% and ≥0.1%).
Mean increases in fasting total cholesterol, LDL cholesterol, and triglycerides were generally greater in adolescents than in adults treated with olanzapine. However, in short term trials the differences between olanzapine and placebo were similar for adolescents and adults.
Adolescents treated with olanzapine experienced a significantly higher incidence of elevated prolactin levels and significantly higher mean increases in prolactin levels compared with adults.
Hepatic aminotransferase elevations are more common in adolescents as compared to adults. Sedation-related events are more common in adolescents as compared to adults.
The following table summarizes core adverse drug reaction terms and their frequencies identified only during clinical trials in adolescent patients (13 to 17 years):See Table 3.
Click on icon to see table/diagram/imageThe following table summarizes additional core adverse drug reaction terms and their frequencies identified only during clinical trials in patients with dementia of the Alzheimer's type: See Table 4.
Click on icon to see table/diagram/imageThe following table summarizes additional core adverse drug reaction terms and their frequencies identified only during clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with Parkinson's Disease: See Table 5.
Click on icon to see table/diagram/imageThe following table summarizes additional core adverse drug reaction terms and their frequencies identified only during bipolar mania clinical trials in patients receiving olanzapine in combination with lithium or valproate: See Table 6.
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