Quetiapine

Additional information

Pharmacokinetics and dosing

In a pooled analysis of single-dose quetiapine in healthy volunteers (48 men, 31 women) the mean AUC was slightly higher in women than in men. Other pharmacokinetic variables did not differ between men and women in multivariate analysis [4]. In an observational study of quetiapine at steady state in patients (28 men, 31 women) clearance was shown to be similar in men and women [5].In four therapeutic drug monitoring studies (864 men, 1037 women) no sex difference in concentration/dose ratio for quetiapine at steady state conditions was found [5-8]. In one of the larger studies, (574 men, 605 women) men had a higher mean serum concentration although the concentration/dose ratio was similar in men and women [9].Based on the pharmacokinetics of quetiapine, no initial dosage adjustment should be necessary according to sex [4, 5]. In a dose-finding study of quetiapine in patients with psychosis (28 men, 14 women) no difference in effect was observed between men and women at the same doses [9].

Effects

In a dose-finding study of qutiapine in patients with psychosis (28 men, 14 women) similar effect was observed in men and women [9]. In a randomized double-blind, placebo controlled phase III study of quetiapine 150 mg or 300 mg daily in patients with major depressive disorder (263 men, 375 women) no sex difference in effect was found either [10].

Adverse effects

In a pooled analysis of two randomized cross-over clinical trials of single dose quetiapine in healthy volunteers (total 48 men, 31 women) no sex differences in adverse events were found [4].In a pharmacovigilance survey of spontaneously reported adverse events in quetiapine treated patients, 46 reports of quetiapine-associated hyperglycemia or diabetes were found during five years. The male:female ratio was 1.9 [11]. There was no information on sex ratio in the use of the medication during this time in the publication. Studies of spontaneous reported adverse events have to be interpreted with great care as many factors can affect the findings. Thus, the clinical relevance of this finding is unclear.Two studies in healthy volunteers (19 men, 34 women) showed no significant difference in the rise of prolactin between men and women [4,12].A retrospective observational cohort study of 51,878 elderly patients with dementia treated with risperidone, quetiapine, or olanzapine found men to have an overall 2.3 times higher risk than women for developing Parkinsonism in all treatment groups. The most pronounced sex difference in hazard ratio for developing Parkinsonism was found in the high dose quetiapine group [1].In a clinical trial patients with early psychosis were randomized to treatment with olanzapine (101 men, 32 women), quetiapine (92 men, 42 women), or risperidone (99 men, 34 women) during 52 weeks. Men in all treatment groups were more likely than women to increase in BMI and weight after 12 and 52 weeks of treatment [2]. This is in contrast to the findings from a prospective analysis of a randomized, double-blind, placebo-controlled trial in elderly patients with Alzheimer’s disease (186 men, 235 women). In this study, women treated with olanzapine, quetiapine, risperidone, or placebo during 36 weeks showed an increase in BMI while men did not [3].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).