Antipsychotic

Olanzapine (Zyprexa)

Also called Zyprexa

Reviewed by Alex G, BSN, RN, CEN, CCRN, CMC, NREMT-P · From the Reference tab of the app

Indications

Acute agitation with schizophrenia or bipolar I mania, IM (labeled)
Undifferentiated severe agitation in the ED, IM or IV (off-label)
Schizophrenia and bipolar disorder, oral or orally disintegrating (labeled)
Agitated ICU delirium, short term (off-label; PADIS 2018 advises against routine use)
Refractory nausea and vomiting (off-label)

Dosing

Where	Dose
Seizures and neuro	Olanzapine: 5–10 mg IM
Antiemetics	Olanzapine: Atypical antipsychotic. 5–10 mg PO, often at bedtime, days 1–4 with chemo (ASCO 2020) or for breakthrough; sedation, orthostasis

On the quick cards

Antipsychotics: first generation (haloperidol) and second generation (-apine, -idone)NCLEX Drug Classes: Psychosis, schizophrenia, bipolar mania

Mechanism of action

Olanzapine is an atypical antipsychotic that blocks serotonin 5-HT₂A receptors more strongly than dopamine D₂ receptors. Mesolimbic D₂ blockade treats psychosis and agitation, while 5-HT₂A blockade frees dopamine release in the striatum, so EPS are less common than with haloperidol. It also blocks histamine H₁ (sedation, weight gain), muscarinic M₁–M₅ (anticholinergic effects), α₁ (orthostasis) and 5-HT₂C receptors (appetite, glucose).

Pharmacology

CNS: sedation and calming; dose-related EPS, less than haloperidol; anticholinergic delirium in older adults
Cardiovascular: orthostatic hypotension, bradycardia and syncope, mostly after IM doses; little QTc effect
Respiratory: little depression alone, additive with parenteral benzodiazepines, alcohol or opioids
Metabolic: weight gain, hyperglycemia (rarely DKA), high lipids
Other: antiemetic; dry mouth, constipation, urinary retention

Pharmacokinetics

Onset	IM within about 15–30 min
Peak	IM plasma peak 15–45 min, about 5 times that of the same oral dose; oral about 6 h (label)
Half-life	21–54 h (mean 30 h); longer in older adults
Distribution	Vd about 1000 L (about 14 L/kg)
Protein binding	93%, to albumin and α₁-acid glycoprotein
Metabolism	Direct glucuronidation (UGT1A4) and CYP1A2 oxidation; main metabolites inactive
Clearance	About 40% higher in smokers (CYP1A2 induction), 30% lower in women; fluvoxamine raises levels
Elimination	About 55% in urine (7% unchanged), 30% in feces
Bioavailability	Oral about 60% (40% first pass)

Chemistry

Thienobenzodiazepine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine), a close relative of clozapine; despite the name it has no action at the benzodiazepine site
Achiral yellow solid, practically insoluble in water; weak base (piperazine pKa about 7.8), lipophilic (log P about 3)
IM vial: 10 mg freeze-dried powder with lactose and tartaric acid; add 2.1 mL sterile water for 5 mg/mL and use within 1 h; never mix in a syringe with diazepam or haloperidol (label)

Adverse effects and cautions

In the one-pagers

Mental Health: Meds and CommunicationAntipsychotics and Benzodiazepines: Atypical antipsychotics: Weight, glucose, lipids (worst: clozapine, olanzapine): Metabolic checks, baseline and ongoing

Practice Mental Health: Meds and Communication questions free35 exam-style questions with rationales on the topic where Olanzapine comes up most. No account or download needed.

Haloperidol

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Sources

FDA label: Olanzapine for Injection, Hikma (2026)
PubChem: olanzapine
Wilson 2012 (olanzapine with benzodiazepines)

For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.