Dosing Tips – Depot

• Initial dose: 210–300 mg/2 weeks (depends on stabilizing oral dose)

• Maintenance dose: 210–300 mg/2 weeks (depends on stabilizing oral dose)

• Maximum recommended dose 300 mg every 2 weeks or 405 mg every 4 weeks

• Conversion from oral dose: if stable on 10 mg/day, then 210 mg LAI every 2 weeks or 405 mg LAI every 4 weeks for the first 8 weeks, then 150 mg LAI every 2 weeks or 300 mg LAI every 4 weeks

• If stable on oral 15 mg/day, then 300 mg LAI every 2 weeks for the first 8 weeks, then 210 mg LAI every 2 weeks or 405 mg LAI every 4 weeks

• If stable on oral 20 mg/day, then 300 mg LAI every 2 weeks

• Injection site: intramuscular gluteal

• Needle gauge: 19

• Injection volume: 150 mg/mL; range 1.0–2.7 mL

• Dosing schedule: 2 weeks, 4 weeks

• No oral supplementation required

• No leading required

• 3-hour post-injection monitoring required due to risk (0.2%) of post-injection delirium from vascular breach

Overdose

• Rarely lethal in monotherapy overdose; sedation, slurred speech

Long-Term Use

• Approved to maintain response in long-term treatment of schizophrenia

• Approved for long-term maintenance in bipolar disorder

• Often used for long-term maintenance in various behavioral disorders

Habit Forming

• No

How to Stop

• See Switching section of individual agents for how to stop olanzapine

• Rapid oral discontinuation may lead to rebound psychosis and worsening of symptoms

Pharmacokinetics

• Metabolites are inactive

• Parent drug has 21–54 hour half-life

Drug Interactions

• May increase effect of antihypertensive agents

• May antagonize levodopa, dopamine agonists

• Dose may need to be lowered if given with CYP450 1A2 inhibitors (e.g., fluvoxamine); raised if given in conjunction with CYP450 1A2 inducers (e.g., cigarette smoke, carbamazepine)

Other Warnings/Precautions

• Use with caution in patients with conditions that predispose to hypotension (dehydration, overheating)

• Use with caution in patients with prostatic hypertrophy, angle-closure glaucoma, paralytic ileus

• Patients receiving the intramuscular formulation of olanzapine should be observed closely for hypotension

• Intramuscular formulation is not generally recommended to be administered with parenteral benzodiazepines; if patient requires a parenteral benzodiazepine it should be given at least 1 hour after intramuscular olanzapine

• Olanzapine should be used cautiously in patients at risk for aspiration pneumonia, as dysphagia has been reported

Do Not Use

• If there is a known risk of angle-closure glaucoma (intramuscular formulation)

• If patient has unstable medical condition (e.g., acute myocardial infarction, unstable angina pectoris, severe hypotension and/or bradycardia, sick sinus syndrome, recent heart surgery) (intramuscular formulation)

• If there is a proven allergy to olanzapine

OLANZAPINE: SPECIAL POPULATIONS

Renal Impairment

• No dose adjustment required for oral formulation

• Not removed by hemodialysis

• For intramuscular formulation, consider lower starting dose (5 mg)

Hepatic Impairment

• May need to lower dose

• Patients with liver disease should have liver function tests a few times a year

• For moderate to severe hepatic impairment, starting oral dose 5 mg; increase with caution

• For intramuscuar formulation, consider lower starting dose (5 mg)

Cardiac Impairment

• Drug should be used with caution because of risk of orthostatic hypotension

Elderly

• Some patients may tolerate lower doses better

• Increased incidence of stroke

• For intramuscular formulation, recommended starting dose is 2.5–5 mg; a second injection of 2.5–5 mg may be administered 2 hours after first injection; no more than 3 injections should be administered within 24 hours

• Although atypical antipsychotics are commonly used for behavioral disturbances in dementia, no agent has been approved for treatment of elderly patients with dementia-related psychosis

• Elderly patients with dementia-related psychosis treated with atypical antipsychotics are at an increased risk of death compared to placebo, and also have an increased risk of cerebrovascular events