Zyprexa, Zyprexa Zydis, Zyprexa Relprevv, and generics
Antipsychotic, atypical second generation

C	2	No	Yes	No
Key

• Tabs: 2.5, 5, 7.5, 10, 15, 20 mg
• Orally disintegrating tabs (Zyprexa Zydis and generics): 5, 10, 15, 20 mg; contain phenylalanine and parabens
• IM injection:
  • Short-acting: 10 mg; contains tartaric acid
  • Long-acting pamoate salt (Zyprexa Relprevv):
    • Every 2 wk dosing: 210, 300 mg; contains mannitol, polysorbate 80
    • Every 4 wk dosing: 405 mg; contains mannitol, polysorbate 80

Dosing

• PO DOSING
• Severe or refractory agitation for psychiatric emergencies in developmental delay, autism, or oppositional defiant/conduct disorder (very limited data; oral disintegrating tab is preferred):
  • Child <12 yr: 2.5 mg PO
  • Child ≥12 yr and adolescent: 5–10 mg PO
• Bipolar I disorder (manic or mixed episodes; not first-line therapy):
  • Child 4–6 yr of age (limited data, based on an open-label trial in 15 subjects): Start at 1.25 mg PO once daily × 7 days, then increase dose Q7 days PRN as tolerated to a target dose of 10 mg once daily.
  • Child 6–12 yr of age (limited data): Start at 2.5 mg PO once daily × 7 days, then increase dose in 2.5 or 5 mg increments Q7 days to a target dose of 10 mg once daily. Suggested max. dose: 20 mg/24 hr
  • Adolescent (see remarks): Start at 2.5 or 5 mg PO once daily × 7 days, then increase dose in 2.5 or 5 mg increments Q7 days to a target dose of 10 mg once daily. Suggested max. dose: 20 mg/24 hr (doses >20 mg/24 hr have not been evaluated)
  • Adult: Start at 10 or 15 mg PO once daily (use 10 mg if used with lithium or valproate). If needed, increase or decrease dose by 5 mg daily at intervals not <24 hr. Maintenance dosage range: 5–20 mg/24 hr. Suggested max. dose: 20 mg/24 hr (doses >20 mg/24 hr have not been evaluated)
• Schizophrenia:
  • Child ≥8 yr of age and adolescent (see remarks): Start with 2.5 or 5 mg PO once daily, then increase dose in 2.5 or 5 mg increments Q7 days to the target dose of 10 mg once daily (doses >20 mg/24 hr have not been evaluated).
  • Adult: Start with 5 or 10 mg PO once daily (use 5 mg for individuals who are debilitated, predisposed to hypotension, pharmacodynamically sensitive to olanzapine, or nonsmoking females ≥65 yr old) with a target dose of 10 mg once daily within 5–7 days. If needed, increase or decrease dose by 5 mg daily at weekly intervals. Usual dosage range: 10–15 mg once daily. Additional clinical assessment is recommended for doses >10 mg/24 hr (doses >20 mg/24 hr have not been evaluated).
• Chemotherapy-induced nausea and vomiting (refractory breakthrough; limited data):
  • Child ≥3 yr and adolescent: 0.1–0.14 mg/kg/dose (rounded to the nearest 1.25 mg dosage increment) PO once daily–BID. Many report use in combination with other antiemetics such as aprepitant, dexamethasone, ondansetron, or granisetron.
• IM DOSING
• Short-acting IM injection:
  • Severe or refractory agitation for psychiatric emergencies in developmental delay, autism, or oppositional defiant/conduct disorder (PO administration is preferred; limited data):
    • Child <12 yr: 1.25–5 mg IM
    • Child ≥12 yr and adolescent: 5–10 mg IM; dose may be repeated after 2 hr if needed
  • Acute agitation associated with bipolar I or schizophrenia:
    • Child and adolescent (limited retrospective data in 15 children and 35 adolescents): ≤12 yr: 5 mg and adolescent (13–17 yr): 10 mg. Dosing frequencies and max. doses were not reported.
    • Adult: 10 mg (5 mg for geriatric patients and 2.5 mg for individuals who are debilitated, predisposed to hypotension, or pharmacodynamically sensitive to olanzapine). If needed, additional doses × 2 may be given; second dose 2 hr after the first dose and third dose 4 hr after the second dose. Recommended max. dose is 30 mg/24 hr (10 mg × 3 given 2–4 hr apart); safety of doses >30 mg/24 hr has not been evaluated.
• Long-acting pamoate salt (Zyprexa Relprevv):
  • Schizophrenia (adult): See remarks and package insert for specific dosage based on established oral dosage.

Notes

• Use with caution in cardiovascular or cerebrovascular disease, hypotensive conditions, diabetes/hyperglycemia, elevated serum lipids and cholesterol, paralytic ileus, hepatic impairment, seizure disorders, narrow angle glaucoma, and prostatic hypertrophy. Medication exhibits anticholinergic effects.
• Common side effects include orthostatic hypotension, peripheral edema, hypercholesterolemia, hyperprolactinemia, appetite simulation, weight gain (greater in adolescents than adults; monitoring is recommended), hypertriglyceridemia, constipation, xerostomia, akathisia, asthenia, dizziness, somnolence, tremor, and personality disorder. Neuroleptic malignant syndrome, dystonia, cognitive and motor impairment, tardive dyskinesia (irreversible with cumulative high doses), neutropenia, leukopenia, agranulocytosis, suicidal intent, acute pancreatitis, pulmonary embolism, increases in liver function tests (ALT, AST, GGT), DRESS, salivary hypersecretion, and hyperthermia have been reported.
• Olanzapine is a major substrate for CYP 450 1A2 and minor substrate for 2D6. It also is a weak inhibitor to CYP 450 1A2, 2C9/19. Do not use in combination with alcohol, benzodiazepines, or opiates due to increased risk for sedation and cardiopulmonary depression. Caution is also indicated with anticholinergic agents (e.g., azelastine, glycopyrrolate), as olanzapine may enhance the anticholinergic effects. Use with QTc-prolonging medications may further increase the risk for QTc prolongation. Metoclopramide may enhance neurologic side effects of olanzapine. Do not use oral disintegrating tablets in phenylketonuria.
• T_1/2: 37 hr for children and 21–54 hr for adults via PO route. Short-acting IM T_1/2 in adults is similar to PO route, but long-acting IM T_1/2 is ∼30 days in adults.
• Maintenance treatment for bipolar I disorder and schizophrenia has not been systematically evaluated in adolescents. Therefore it is recommended to utilize the lowest dose to maintain efficacy and to reassess the need for maintenance treatment periodically for this age group.
• All oral dosages may be taken either with or without food. For orally disintegrating tabs, tablet must be placed in patient's mouth immediately after removing it from the foil pack (by peeling off the foil, not by pushing the tablet through the foil) and allowed to dissolve in saliva; then swallowed with or without liquids.
• Zyprexa Relprevv (long-acting IM injection): Postinjection delirium and sedation syndrome have been reported with this dosage form. Patients must be observed by a healthcare provider at a healthcare facility for at least 3 hr after administration. The FDA REMS program requires prescribers, healthcare facilities, and pharmacies to register with the Zyprexa Relprevv Patient Care Program at 1-877-772-9390 for use of this product.