Olanzapine

Administration

• Type: Antipsychotic, second generation
• Dosage Forms: tablets, solution, suspension
• Routes of Administration: oral, intramuscular
• Common Trade Names: Zyprexa, Zydis

Adult Dosing

• Acute agitation (associated with schizophrenia or bipolar disorder): Short-acting IM injection:
  • initial dose: 10 mg IM (consider lowering to 5 or 7.5 mg depending on clinical factors), additional dose of 10 mg IM maybe considered. Allowed 2 hours after the first dose and 4 hours after the second dose to evaluate response (maximum dose: 30 mg/day).
  • Special risk patients: consider lowering dose to 2.5 mg IM in patients who are debilitated, who have risk of hypotension or who maybe more pharmacodynamically sensitive to olanzapine.
• Schizophrenia: Oral
  • Initial dose 5-10 mg once daily, increase to 10 mg daily by the first week, adjust by 5 mg daily at 1-week interval (maximum dose: 20 mg daily), maintenance dose: 10-20 mg daily.
  • Special risk patient: Initial dose: 5 mg once daily in patients who are debilitated, who have risk of hypotension or who maybe more pharmacodynamically sensitive to olanzapine.
• Bipolar I (acute mixed or manic episode): Oral
  • Monotherapy: Initial dose: 10-15 mg once daily, increase by 5 mg daily with interval >24 hours, maintenance dose: 5-20 mg daily (maximum dose: 20 mg daily).
  • Combination therapy with lithium or valproate: Initial dose 10 mg daily (dose range: 5-20 mg daily)
• Depression: Oral
  • Depression associated with bipolar disorder (in combination with fluoxetine): Initial dose: 5 mg once daily, adjust to dose range of 5-12.5 mg daily.

Pediatric Dosing

• Schizophrenia: Adolescent ≥13 years: Oral: Initial dose: 2.5-5 mg once daily, adjust by 2.5-5 mg daily to target dose of 10 mg daily (dose range: 2.5-20 mg daily).
• Bipolar I (acute or mixed manic episode): Adolescent ≥13 years: Oral: Initial dose: 2.5-5 mg once daily, adjust by 2.5-5 mg daily to target dose of 10 mg daily (dose range: 2.5-20 mg daily).
• Depression associated with bipolar I disorder (in combination with fluoxetine: Children and adolescent 10 to 17 years: Oral: Initial dose: 2.5 mg once daily in the evening, adjust if needed, safety for dose >12 mg daily of olanzapine and >50 mg daily of fluoxetine has not been studied.

Special Populations

• Pregnancy Rating: C
• Lactation risk: Olanzapine is excreted into breast milk. Brest-feeding is not recommended by manufacturer.

Renal Dosing

• No dosage adjustment is necessary, not removed by dialysis.

Hepatic Dosing

• Use with caution, in combination with fluoxetine, initial dose of olanzapine should not exceed 2.5-5 mg daily.

Contraindications

• Allergy to class/drug

Adverse Reactions

Serious

• Orthostatic hypotension (3%-20%)
• Extrapyramidal reaction
• Akathisia
• Parkinsonian-like syndrome
• Increase serum prolactin
• Increase serum AST, ALT, GGT and bilirubin
• Accidental injury
• Personality disorder

Common

• Drowsiness
• Dizziness
• Insomnia
• Weight gain
• Increase appetite
• Xerostomia
• Constipation
• Dyspepsia
• Weakness
• Abnormal gait
• Increase uric acid
• Bruise
• Tremor
• Limb pain
• Back pain
• Arthralgia
• Rhinitis

Pharmacology

• Half-life: Oral and short-acting IM: children 10 to 18 years ~37 hours, adult ~30 hours, 1.5 times greater in elderly.
• Metabolism: Liver: CYP1A2, CYP2D6, 40% removed via first pass metabolism
• Excretion: Urine (~70%), feces (30%)

Mechanism of Action

• Potent antagonism of serotonin 5-HT_2A and 5T_2C, Dopamine_1-4, histamine H₁ and alpha₁-adrenergic recepter

References

Authors

Yajai Apibunyopas, Ross Donaldson