Olanzapine (Zyprexa)

Primer

Olanzapine (Trade name: Zyprexa) is an antipsychotic in the atypical antipsychotic class commonly used in the treatment of schizophrenia and bipolar disorder.

Pharmacokinetics

Pharmacokinetics of Olanzapine

Absorption
Distribution
Metabolism
Elimination
Half-life

Olanzapine: Cytochrome P450 Metabolism

Substrate of (Metabolized by)
Induces
Inhibits

Pharmacodynamics

Mechanism of Action

  • 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.

Toxicity

Indications

Dosing

Dosing for Olanzapine

Starting
Titration
Maximum
Taper

Acute Agitation

Formulations

  • 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.

Monitoring

Contraindications

Absolute

Relative

Drug-Drug Interactions

Smoking

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.

Side Effects

Adverse Events

Clinical Pearls

Special Populations

Geriatric

Pediatric

Obstetric and Fetal

Medically Ill

Resources

References

1) Montgomery, W., Treuer, T., Karagianis, J., Ascher-Svanum, H., & Harrison, G. (2012). Orally disintegrating olanzapine review: effectiveness, patient preference, adherence, and other properties. Patient preference and adherence, 6, 109.
2) Chiu, C. C., Lu, M. L., Huang, M. C., & Chen, K. P. (2004). Heavy smoking, reduced olanzapine levels, and treatment effects: a case report. Therapeutic drug monitoring, 26(5), 579-581.