When using ZYPREXA and fluoxetine in combination, also refer to the Use in Specific Populations section of the package insert for Symbyax. 

8.1 Pregnancy 

Teratogenic Effects, Pregnancy Category C — In oral reproduction studies in rats at doses up to 18 mg/kg/day and in rabbits at doses up to 30 mg/kg/day (9 and 30 times the maximum recommended human daily oral dose on a mg/m2 basis, respectively) no evidence of teratogenicity was observed. In an oral rat teratology study, early resorptions and increased numbers of nonviable fetuses were observed at a dose of 18 mg/kg/day (9 times the maximum recommended human daily oral dose on a mg/m2 basis). Gestation was prolonged at 10 mg/kg/day (5 times the maximum recommended human daily oral dose on a mg/m2 basis). In an oral rabbit teratology study, fetal toxicity (manifested as increased resorptions and decreased fetal weight) occurred at a maternally toxic dose of 30 mg/kg/day (30 times the maximum recommended human daily oral dose on a mg/m2 basis). Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 

Placental transfer of olanzapine occurs in rat pups. 

There are no adequate and well-controlled trials with olanzapine in pregnant females. Seven pregnancies were observed during clinical trials with olanzapine, including 2 resulting in normal births, 1 resulting in neonatal death due to a cardiovascular defect, 3 therapeutic abortions, and 1 spontaneous abortion. 

8.2 Labor and Delivery 

The effect of olanzapine on labor and delivery in humans is unknown. Parturition in rats was not affected by olanzapine. 

8.3 Nursing Mothers 

In a study in lactating, healthy women, olanzapine was excreted in breast milk. Mean infant dose at steady state was estimated to be 1.8% of the maternal olanzapine dose. It is recommended that women receiving olanzapine should not breast-feed. 

8.4 Pediatric Use 

The safety and effectiveness of oral ZYPREXA in the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder were established in short-term studies in adolescents (ages 13 to 17 years). Use of ZYPREXA in adolescents is supported by evidence from adequate and well-controlled studies of ZYPREXA in which 268 adolescents received ZYPREXA in a range of 2.5 to 20 mg/day [see Clinical Studies (14.1, 14.2)]. Recommended starting dose for adolescents is lower than that for adults [see Dosage and Administration (2.1, 2.2)]. Compared to 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 [see Warnings and Precautions (5.5, 5.6, 5.15, 5.17) and Adverse Reactions (6.2)]. When deciding among the alternative treatments available for adolescents, clinicians should consider the increased potential (in adolescents as compared with adults) for weight gain and hyperlipidemia. Clinicians should consider the potential long-term risks when prescribing to adolescents, and in many cases this may lead them to consider prescribing other drugs first in adolescents [see Indications and Usage (1.1, 1.2)]. 

Safety and effectiveness of olanzapine in children less than 13 years of age have not been established [see Patient Counseling Information (17.13)]. 

Safety and effectiveness of ZYPREXA and fluoxetine in combination in children and adolescents less than 18 years of age have not been established. 

8.5 Geriatric Use 

Of the 2500 patients in premarketing clinical studies with oral olanzapine, 11% (263) were 65 years of age or over. In patients with schizophrenia, there was no indication of any different tolerability of olanzapine in the elderly compared to younger patients. Studies in elderly patients with dementia-related psychosis have suggested that there may be a different tolerability profile in this population compared to younger patients with schizophrenia. Elderly patients with dementia-related psychosis treated with olanzapine are at an increased risk of death compared to placebo. In placebo-controlled studies of olanzapine in elderly patients with dementia-related psychosis, there was a higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack) in patients treated with olanzapine compared to patients treated with placebo. Olanzapine is not approved for the treatment of patients with dementia-related psychosis. Also, the presence of factors that might decrease pharmacokinetic clearance or increase the pharmacodynamic response to olanzapine should lead to consideration of a lower starting dose for any geriatric patient [see Boxed Warning, Dosage and Administration (2.1), and Warnings and Precautions (5.1)]. 

Clinical studies of ZYPREXA and fluoxetine in combination did not include sufficient numbers of patients greater than or equal to 65 years of age to determine whether they respond differently from younger patients.