Geriatric — Based on the individual pharmacokinetic profiles of olanzapine and fluoxetine, the pharmacokinetics of olanzapine and fluoxetine capsules may be altered in geriatric patients. Caution should be used in dosing the elderly, especially if there are other factors that might additively influence drug metabolism and/or pharmacodynamic sensitivity. 

In a study involving 24 healthy subjects, the mean elimination half-life of olanzapine was about 1.5 times greater in elderly subjects (≥65 years of age) than in non-elderly subjects (<65 years of age). 

The disposition of single doses of fluoxetine in healthy elderly subjects (≥65 years of age) did not differ significantly from that in younger normal subjects. However, given the long half-life and nonlinear disposition of the drug, a single-dose study is not adequate to rule out the possibility of altered pharmacokinetics in the elderly, particularly if they have systemic illness or are receiving multiple drugs for concomitant diseases. The effects of age upon the metabolism of fluoxetine have been investigated in 260 elderly but otherwise healthy depressed patients (≥60 years of age) who received 20 mg fluoxetine for 6 weeks. Combined fluoxetine plus norfluoxetine plasma concentrations were 209.3 ± 85.7 ng/mL at the end of 6 weeks. No unusual age-associated pattern of adverse reactions was observed in those elderly patients. 

Renal Impairment — The pharmacokinetics of olanzapine and fluoxetine capsules has not been studied in patients with renal impairment. However, olanzapine and fluoxetine individual pharmacokinetics do not differ significantly in patients with renal impairment. Olanzapine and fluoxetine capsule dosing adjustment based upon renal impairment is not routinely required. 

Because olanzapine is highly metabolized before excretion and only 7% of the drug is excreted unchanged, renal dysfunction alone is unlikely to have a major impact on the pharmacokinetics of olanzapine. The pharmacokinetic characteristics of olanzapine were similar in patients with severe renal impairment and normal subjects, indicating that dosage adjustment based upon the degree of renal impairment is not required. In addition, olanzapine is not removed by dialysis. The effect of renal impairment on olanzapine metabolite elimination has not been studied. 

In depressed patients on dialysis (N=12), fluoxetine administered as 20 mg once daily for 2 months produced steady-state fluoxetine and norfluoxetine plasma concentrations comparable with those seen in patients with normal renal function. While the possibility exists that renally excreted metabolites of fluoxetine may accumulate to higher levels in patients with severe renal dysfunction, use of a lower or less frequent dose is not routinely necessary in renally impaired patients. 

Hepatic Impairment — Based on the individual pharmacokinetic profiles of olanzapine and fluoxetine, the pharmacokinetics of olanzapine and fluoxetine capsules may be altered in patients with hepatic impairment. The lowest starting dose should be considered for patients with hepatic impairment [see Dosage and Administration (2.3) and Warnings and Precautions (5.20)].

Although the presence of hepatic impairment may be expected to reduce the clearance of olanzapine, a study of the effect of impaired liver function in subjects (N=6) with clinically significant cirrhosis (Child-Pugh Classification A and B) revealed little effect on the pharmacokinetics of olanzapine. 

As might be predicted from its primary site of metabolism, liver impairment can affect the elimination of fluoxetine. The elimination half-life of fluoxetine was prolonged in a study of cirrhotic patients, with a mean of 7.6 days compared with the range of 2 to 3 days seen in subjects without liver disease; norfluoxetine elimination was also delayed, with a mean duration of 12 days for cirrhotic patients compared with the range of 7 to 9 days in normal subjects. 

Gender — Clearance of olanzapine is approximately 30% lower in women than in men. There were, however, no apparent differences between men and women in effectiveness or adverse effects. Dosage modifications based on gender should not be needed. 

Smoking Status — Olanzapine clearance is about 40% higher in smokers than in nonsmokers, although dosage modifications are not routinely required. 

Race — No olanzapine and fluoxetine capsule pharmacokinetic study was conducted to investigate the effects of race. In vivo studies have shown that exposures to olanzapine are similar among Japanese, Chinese and Caucasians, especially after normalization for body weight differences. Dosage modifications for race, therefore, are not routinely required. 

Combined Effects — The combined effects of age, smoking, and gender could lead to substantial pharmacokinetic differences in populations. The clearance of olanzapine in young smoking males, for example, may be 3 times higher than that in elderly nonsmoking females. Olanzapine and fluoxetine capsule dosing modification may be necessary in patients who exhibit a combination of factors that may result in slower metabolism of the olanzapine component [see Dosage and Administration (2.3)].

Children and Adolescents (ages 10 to 17 years) — Based on the pediatric olanzapine and fluoxetine capsule study, steady-state olanzapine, fluoxetine, and norfluoxetine plasma concentrations were about 31%, 76%, and 38% higher, respectively, in pediatric patients with lower body weights (less than 50 kg) than in pediatric patients with high body weight (greater than or equal to 50 kg). Exposures in pediatric patients with high body weight were similar to those previously observed in adults. Dose modifications based on body weight are not required.