What are the contraindications for Olanzapine (olanzapine)?

Contraindications for Olanzapine

Olanzapine is contraindicated in patients with dementia-related psychosis due to increased risk of death, and should not be used concurrently with other dopamine antagonists due to risk of excessive dopamine blockade. 1

Absolute Contraindications

• Dementia-related psychosis in elderly patients

  • Boxed warning indicates increased mortality risk in elderly patients with dementia-related psychosis 2, 1
  • Higher incidence of cerebrovascular adverse events (stroke, TIA) in elderly patients with dementia 1

• Known hypersensitivity to olanzapine

  • Includes rare but serious skin reactions such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) 2
  • Symptoms include fever with rash, swollen lymph glands, or facial swelling

Relative Contraindications/Use with Caution

Concurrent Medications

• Concurrent use with other dopamine antagonists

  • Avoid combining with metoclopramide, phenothiazines, or haloperidol due to risk of excessive dopamine blockade 2

• Benzodiazepine co-administration

  • Fatalities reported with concurrent use of benzodiazepines with high-dose olanzapine 1
  • Parenteral co-administration particularly risky due to potential for excessive sedation and cardiorespiratory depression 1

Medical Conditions

• Cardiovascular disease

  • Use with caution in patients with known cardiovascular disease (history of MI, ischemia, heart failure, conduction abnormalities) 1
  • Risk of orthostatic hypotension, syncope, bradycardia, or tachycardia 1

• Cerebrovascular disease

  • Higher risk of adverse cerebrovascular events 1

• Conditions predisposing to hypotension

  • Dehydration, hypovolemia, and treatment with antihypertensive medications 1

• History of seizures or conditions lowering seizure threshold

  • Olanzapine may lower seizure threshold 1

• Hepatic impairment

  • Dose reduction recommended 2, 1

• Renal impairment (severe)

  • Dose reduction recommended 2

• History of leukopenia/neutropenia

  • Cases of olanzapine-induced neutropenia and leukopenia have been reported 3, 4, 5, 6
  • Monitor CBC frequently in patients with history of drug-induced leukopenia/neutropenia 1

• Poor metabolizers of CYP2D6

  • Dose reduction recommended 7

Special Populations

• Elderly patients

  • Higher risk of adverse effects including falls, somnolence, peripheral edema, abnormal gait, urinary incontinence, lethargy, increased weight, asthenia, pyrexia, pneumonia, dry mouth, and visual hallucinations 1
  • Consider lower starting dose (2.5-5 mg) 2

• Pregnancy and lactation

  • Risk-benefit assessment required

Monitoring Requirements

When prescribing olanzapine, the following monitoring is essential:

• Complete blood count (CBC)

  • Monitor frequently in first few months of therapy in patients with history of low WBC or drug-induced leukopenia/neutropenia 1
  • Discontinue at first sign of clinically significant decline in WBC 1

• Metabolic parameters

  • Regular monitoring for weight gain, hyperglycemia, and dyslipidemia 1
  • Higher risk of type II diabetes and metabolic syndrome 2, 7

• Orthostatic vital signs

  • Monitor for orthostatic hypotension, especially during initial dose titration 1

• Fall risk assessment

  • Complete at initiation and recurrently for long-term therapy 1

Clinical Pearls

• Consider a lower dose (5 mg) in elderly or oversedated patients 2
• Initiate therapy with 5 mg daily to minimize risk of orthostatic hypotension and syncope 1
• Olanzapine is not FDA-approved for chemotherapy-induced nausea and vomiting, though it is used off-label for this purpose 2
• Patients should be monitored for signs of tardive dyskinesia, which may require discontinuation 1

By carefully screening for these contraindications and using appropriate caution in at-risk populations, the morbidity and mortality associated with olanzapine use can be minimized while maintaining its therapeutic benefits.