Zyprexa (Page 5 of 14)

5.5 Hyperlipidemia

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 [see Patient Counseling Information (17.5)].

Clinically significant, and sometimes very high (>500 mg/dL), elevations in triglyceride levels have been observed with olanzapine use. Modest mean increases in total cholesterol have also been seen with olanzapine use.

Olanzapine Monotherapy in Adults — In an analysis of 5 placebo-controlled olanzapine monotherapy studies with treatment duration up to 12 weeks, olanzapine-treated patients had increases from baseline in mean fasting total cholesterol, LDL cholesterol, and triglycerides of 5.3 mg/dL, 3.0 mg/dL, and 20.8 mg/dL respectively compared to decreases from baseline in mean fasting total cholesterol, LDL cholesterol, and triglycerides of 6.1 mg/dL, 4.3 mg/dL, and 10.7 mg/dL for placebo-treated patients. For fasting HDL cholesterol, no clinically meaningful differences were observed between olanzapine-treated patients and 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, where lipid dysregulation was defined as patients diagnosed with dyslipidemia or related adverse reactions, patients treated with lipid lowering agents, or patients with high baseline lipid levels.

In long-term studies (at least 48 weeks), patients had increases from baseline in mean fasting total cholesterol, LDL cholesterol, and triglycerides of 5.6 mg/dL, 2.5 mg/dL, and 18.7 mg/dL, respectively, and a mean decrease in fasting HDL cholesterol of 0.16 mg/dL. 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.

The proportion of patients who had changes (at least once) 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. Table 4 shows categorical changes in fasting lipids values.

Table 4: Changes in Fasting Lipids Values from Adult Olanzapine Monotherapy Studies

a Not Applicable.

Up to 12 weeks exposure At least 48 weeks exposure
Laboratory Analyte Category Change (at least once)from Baseline Treatment Arm N Patients N Patients
FastingTriglycerides Increase by ≥50 mg/dL Olanzapine 745 39.6% 487 61.4%
Placebo 402 26.1% NAa NAa
Normal to High(<150 mg/dL to ≥200 mg/dL) Olanzapine 457 9.2% 293 32.4%
Placebo 251 4.4% NAa NAa
Borderline to High(≥150 mg/dL and <200 mg/dL to ≥200 mg/dL) Olanzapine 135 39.3% 75 70.7%
Placebo 65 20.0% NAa NAa
Fasting TotalCholesterol Increase by ≥40 mg/dL Olanzapine 745 21.6% 489 32.9%
Placebo 402 9.5% NAa NAa
Normal to High(<200 mg/dL to ≥240 mg/dL) Olanzapine 392 2.8% 283 14.8%
Placebo 207 2.4% NAa NAa
Borderline to High(≥200 mg/dL and <240 mg/dL to ≥240 mg/dL) Olanzapine 222 23.0% 125 55.2%
Placebo 112 12.5% NAa NAa
Fasting LDLCholesterol Increase by ≥30 mg/dL Olanzapine 536 23.7% 483 39.8%
Placebo 304 14.1% NAa NAa
Normal to High(<100 mg/dL to ≥160 mg/dL) Olanzapine 154 0% 123 7.3%
Placebo 82 1.2% NAa NAa
Borderline to High(≥100 mg/dL and <160 mg/dL to ≥160 mg/dL) Olanzapine 302 10.6% 284 31.0%
Placebo 173 8.1% NAa NAa

In phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), over a median exposure of 9.2 months, the mean increase in triglycerides in patients taking olanzapine was 40.5 mg/dL. In phase 1 of CATIE, the mean increase in total cholesterol was 9.4 mg/dL.

Olanzapine Monotherapy in Adolescents — The safety and efficacy of olanzapine have not been established in patients under the age of 13 years. In an analysis of 3 placebo-controlled olanzapine monotherapy studies of adolescents, including those with schizophrenia (6 weeks) or bipolar I disorder (manic or mixed episodes) (3 weeks), olanzapine-treated adolescents had increases from baseline in mean fasting total cholesterol, LDL cholesterol, and triglycerides of 12.9 mg/dL, 6.5 mg/dL, and 28.4 mg/dL, respectively, compared to increases from baseline in mean fasting total cholesterol and LDL cholesterol of 1.3 mg/dL and 1.0 mg/dL, and a decrease in triglycerides of 1.1 mg/dL for placebo-treated adolescents. For fasting HDL cholesterol, no clinically meaningful differences were observed between olanzapine-treated adolescents and placebo-treated adolescents.

In long-term studies (at least 24 weeks), adolescents had increases from baseline in mean fasting total cholesterol, LDL cholesterol, and triglycerides of 5.5 mg/dL, 5.4 mg/dL, and 20.5 mg/dL, respectively, and a mean decrease in fasting HDL cholesterol of 4.5 mg/dL. Table 5 shows categorical changes in fasting lipids values in adolescents.

Table 5: Changes in Fasting Lipids Values from Adolescent Olanzapine Monotherapy Studies

a Not Applicable.

Up to 6 weeks exposure At least 24 weeks exposure
Laboratory Analyte Category Change (at least once)from Baseline Treatment Arm N Patients N Patients
FastingTriglycerides Increase by ≥50 mg/dL Olanzapine 138 37.0% 122 45.9%
Placebo 66 15.2% NAa NAa
Normal to High(<90 mg/dL to >130 mg/dL) Olanzapine 67 26.9% 66 36.4%
Placebo 28 10.7% NAa NAa
Borderline to High(≥90 mg/dL and ≤130 mg/dL to >130 mg/dL) Olanzapine 37 59.5% 31 64.5%
Placebo 17 35.3% NAa NAa
Fasting TotalCholesterol Increase by ≥40 mg/dL Olanzapine 138 14.5% 122 14.8%
Placebo 66 4.5% NAa NAa
Normal to High(<170 mg/dL to ≥200 mg/dL) Olanzapine 87 6.9% 78 7.7%
Placebo 43 2.3% NAa NAa
Borderline to High(≥170 mg/dL and <200 mg/dL to ≥200 mg/dL) Olanzapine 36 38.9% 33 57.6%
Placebo 13 7.7% NAa NAa
Fasting LDLCholesterol Increase by ≥30 mg/dL Olanzapine 137 17.5% 121 22.3%
Placebo 63 11.1% NAa NAa
Normal to High(<110 mg/dL to ≥130 mg/dL) Olanzapine 98 5.1% 92 10.9%
Placebo 44 4.5% NAa NAa
Borderline to High(≥110 mg/dL and <130 mg/dL to ≥130 mg/dL) Olanzapine 29 48.3% 21 47.6%
Placebo 9 0% NAa NAa

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