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olanzapine

Brand: Zyprexa, Zyprexa Zydis, Symbyax (with fluoxetine), Zyprexa Relprevv

⚠ BBW Beers Criteria Prototype: risperidone
Drug Class: antipsychotic
Drug Family: antipsychotic
Subclass: atypical antipsychotic / thienobenzodiazepine
Organ Systems: cns

Mechanism of Action

Broad receptor antagonism including D2, 5-HT2A, muscarinic, histamine H1, and alpha-1 adrenergic receptors; most metabolically toxic atypical antipsychotic due to profound H1 and muscarinic blockade driving appetite and weight gain.

dopamine D2 receptorsserotonin 5-HT2A receptorsmuscarinic M1-M5 receptorshistamine H1 receptors

Indications

  • schizophrenia
  • bipolar I disorder (mania and maintenance)
  • bipolar I depression (with fluoxetine — Symbyax)
  • treatment-resistant schizophrenia (second-line)
  • agitation in schizophrenia/bipolar (IM)

Contraindications

  • dementia-related psychosis
  • IM olanzapine + IM/IV benzodiazepine (cardiovascular collapse risk)

Adverse Effects

Common

  • significant weight gain (average 4–5 kg at 10 weeks)
  • metabolic syndrome
  • sedation
  • anticholinergic effects (dry mouth, constipation, urinary retention)
  • orthostatic hypotension

Serious

  • new-onset diabetes mellitus
  • severe metabolic syndrome
  • tardive dyskinesia
  • NMS
  • Zyprexa Relprevv PDSS (post-injection delirium/sedation syndrome — requires 3-hour observation)

Pharmacokinetics (ADME)

Absorption Well absorbed (~80%); food does not affect absorption
Distribution Highly protein-bound (93%); Vd ~1000 L
Metabolism CYP1A2 (primary) and CYP2D6 (minor); smoking induces CYP1A2 — smokers need higher doses
Excretion Renal (~57%) and fecal (~30%)
Half-life 21–54 hours
Onset Days to weeks
Peak 5–8 hours
Duration 24 hours
Protein Binding 93%
Vd ~1000 L

Drug Interactions

Drug / Agent Mechanism Severity
fluvoxamine CYP1A2 inhibition increases olanzapine levels significantly major
smoking cessation (or new smoking) CYP1A2 induction/de-induction dramatically alters olanzapine levels major
benzodiazepines (IM combination) cardiovascular depression — avoid combining IM olanzapine with IM/IV benzodiazepines major

Nursing Considerations

  1. Monitor fasting glucose, HbA1c, lipid panel, weight, and waist circumference at baseline, 1 month, then quarterly; olanzapine has the worst metabolic profile of any atypical
  2. Smoking status dramatically affects olanzapine levels due to CYP1A2 induction; if a patient stops smoking during hospitalization, olanzapine levels may increase by 50%
  3. Never administer IM olanzapine with IV/IM benzodiazepines simultaneously; a minimum 1-hour gap is required due to cardiovascular collapse risk
  4. For Zyprexa Zydis (orally disintegrating tablet): place on tongue and allow to dissolve — useful for patients suspected of cheeking medications

Clinical Pearls

  • Olanzapine is the most metabolically harmful atypical antipsychotic — weight gain and diabetes risk exceed all others; ADA/APA consensus recommends highest frequency metabolic monitoring with this agent
  • Olanzapine + lorazepam IM for acute agitation is highly effective but the combination is specifically contraindicated due to risk of respiratory depression and cardiovascular collapse — the sequential administration (separate by ≥1 hour) is permissible

Safety Profile

Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

Agitation In Schizophrenia/bipolar (IM) Antipsychotic Bipolar I Depression (with Fluoxetine — Symbyax) Bipolar I Disorder (mania And Maintenance) Schizophrenia Treatment-resistant Schizophrenia (second-line)
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