Olanzapine (Zyprexa)

Pharmacokinetics of Olanzapine

Olanzapine: Cytochrome P450 Metabolism

Substrate of (Metabolized by)
  • Olanzapine does not have fast on-off D2 receptor activity, but has potent anticholinergic action at the muscarinic receptor, similar to that of benztropine, which helps reduce incidence of EPS.

Dosing for Olanzapine

  • Olanzapine comes in several formulations, including oral, sublingual (Trade name: Zydis), and intramuscular (IM).
  • The sublingual disintegrating formulation has benefits such as increased adherence, higher patient preference, and reduction in nursing burden over the standard oral tablet formulation[1]
    • Because it is designed to be dissolved rapidly in the mouth (under 10 seconds), it also prevents the “cheeking” of medications.

Smoking induces CYP1A2, which increases the metabolism of olanzapine. When the smoking stops or if a patient quits, this can lead to supratherapeutic levels of olanzapine! Conversely, if patients are discharged from an inpatient setting and start smoking again, this can lead to rapid decreases in plasma olanzapine levels, resulting in relapse of psychotic symptoms.[2] There is a very high prevalence of smokers in the schizophrenia population, making this a very clinically important issue to be aware of.