Olanzapine — Drug Monograph

Brand names: Zyprexa, Zydis

Drug class: Supportive Care Agent

Mechanism of Action

Atypical antipsychotic with broad receptor antagonism: dopamine D1/D2/D3/D4, serotonin 5-HT2A/2C/3/6, histamine H1, muscarinic M1–5, and α1-adrenergic receptors. The multi-receptor blockade — especially D2 + 5-HT3 + H1 — makes olanzapine uniquely effective for CINV, addressing multiple emetic pathways simultaneously. ASCO (2017) and NCCN upgraded olanzapine to a first-line component of HEC prophylaxis regimens.

FDA Indications

• Schizophrenia (primary psychiatric indication)
• Acute mania and maintenance of bipolar disorder
• Combination with fluoxetine for treatment-resistant depression
• Agitation associated with schizophrenia/bipolar mania (IM formulation)

Common Side Effects

• Sedation/somnolence (very common, often beneficial during chemo days)
• Dizziness/orthostatic hypotension
• Weight gain (with chronic psychiatric dosing — less relevant for 3–5 day CINV courses)
• Hyperglycemia
• Dry mouth
• Constipation

Clinical Pearl

Olanzapine transformed HEC management when the NCCN/ASCO guidelines added it to create the 4-drug regimen (5-HT3 + NK1 + dexamethasone + olanzapine). The CONTROL trial demonstrated that adding olanzapine 10 mg/day ×4 days to standard HEC prophylaxis significantly improved complete response rates in both acute and delayed phases. For breakthrough CINV, a single olanzapine dose often works when all other agents have failed. The sedation — frequently cited as an adverse effect in psychiatric…

Related Therapies & Mechanisms

• Aprepitant (Emend) — Supportive Care Agent
• Avatrombopag (Doptelet) — Supportive Care Agent
• Darbepoetin Alfa (Aranesp) — Supportive Care Agent
• Defibrotide (Defitelio) — Supportive Care Agent