May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); therefore, they should be used with caution in patients with decreased gastrointestinal motility, urinary retention, BPH, xerostomia, or visual problems. Conditions which also may be exacerbated by cholinergic blockade include narrow-angle glaucoma (screening is recommended) and worsening of myasthenia gravis. Relative to other neuroleptics, olanzapine has a moderate potency of cholinergic blockade.

May cause extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is very low relative to other neuroleptics). May be associated with neuroleptic malignant syndrome (NMS). May cause hyperglycemia; in some cases may be extreme and associated with ketoacidosis, hyperosmolar coma, or death. Use with caution in patients with diabetes or other disorders of glucose regulation; monitor for worsening of glucose control.

>10%:

Central nervous system: Headache, somnolence, insomnia, agitation, nervousness, hostility, dizziness

Gastrointestinal: Dyspepsia, constipation, weight gain (clinically and long term)

Neuromuscular & skeletal: Weakness

1% to 10%:

Cardiovascular: Postural hypotension, tachycardia, peripheral edema, chest pain, hyper-/hypotension

Central nervous system: Dystonic reactions, parkinsonian events, amnesia, euphoria, stuttering, akathisia, anxiety, personality changes, fever, abnormal dreams, speech disorder

Dermatologic: Rash, bruising

Endocrine & metabolic: Prolactin increased, amenorrhea

Gastrointestinal: Xerostomia, abdominal pain, appetite increased, vomiting, salivation increased

Genitourinary: Premenstrual syndrome, incontinence

Hematologic: Leukopenia

Neuromuscular & skeletal: Arthralgia, neck rigidity, twitching, hypertonia, tremor, back pain, abnormal gait, akathisia, falling (particularly in older patients)

Ocular: Amblyopia

Respiratory: Rhinitis, cough, pharyngitis, dyspnea

Miscellaneous: Diaphoresis

<1% (Limited to important or life-threatening): Agranulocytosis, diabetes mellitus, hyperglycemia, neuroleptic malignant syndrome, neutropenia, photosensitivity reaction, seizure, tardive dyskinesia

Postmarketing and/or case reports: Anaphylactoid reactions, angioedema, diabetic coma, pancreatitis, priapism, pruritus, urticaria

Additional significant effects reported with I.M. administration: Articulation impairment, AV block, injection site pain, syncope

Activated charcoal: Decreases the Cmax and AUC of olanzapine by 60%

Antihypertensives: Increased risk of hypotension and orthostatic hypotension with antihypertensives

Carbamazepine: Decreases olanzapine levels

Clomipramine: When used in combination, clomipramine and olanzapine have been reported to be associated with the development of seizures; limited documentation (case report)

CNS depressants: Sedative effects and may be additive with CNS depressants; includes ethanol, barbiturates, narcotic analgesics, and other sedative agents; monitor for increased effect

Fluvoxamine: Increases olanzapine levels; consider using a lower dose of olanzapine in patients receiving concomitant treatment with fluvoxamine.

Haloperidol: A case of severe Parkinsonism following the addition of olanzapine to haloperidol therapy has been reported

Levodopa: Antipsychotics may inhibit the antiparkinsonian effect of levodopa; avoid this combination

Metoclopramide: May increase extrapyramidal symptoms (EPS) or risk.

Ethanol: Avoid ethanol (may increase CNS depression).

Herb/Nutraceutical: Avoid dong quai, St John's wort (may also cause photosensitization). Avoid kava kava, gotu kola, valerian, St John's wort (may increase CNS depression).

Tablet and orally-disintegrating tablet: Store at room temperature of 20°C to 25°C (68°F to 77°F); protect from light and moisture

Injection, powder for reconstitution: Store at room temperature 20°C to 25°C (68°F to 77°F); protect from light; do not freeze. Reconstitute 10 mg vial with 2.1 mL SWFI; resulting solution is ~5 mg/mL. Use immediately (within 1 hour) following reconstitution. Discard any unused portion.

Absorption:

I.M.: Rapidly absorbed

Oral: Well absorbed; not affected by food; tablets and orally-disintegrating tablets are bioequivalent

Distribution: Vd: Extensive, 1000 L

Protein binding, plasma: 93% bound to albumin and alpha1-glycoprotein

Metabolism: Highly metabolized via direct glucuronidation and cytochrome P450 mediated oxidation (CYP1A2, CYP2D6)

Bioavailability: >57%

Half-life elimination: 21-54 hours; ~1.5 times greater in elderly

Time to peak, plasma: Maximum plasma concentrations after I.M. administration are 5 times higher than maximum plasma concentrations produced by an oral dose.

I.M.: 15-45 minutes

Oral: ~6 hours

Excretion: 40% removed via first pass metabolism; urine (57%, 7% as unchanged drug); feces (30%)

Clearance: 40% increase in olanzapine clearance in smokers

Children: Schizophrenia/bipolar disorder: Oral: Initial: 2.5 mg/day; titrate as necessary to 20 mg/day (0.12-0.29 mg/kg/day)

Adults:

Schizophrenia: Oral: Usual starting dose: 5-10 mg once daily; increase to 10 mg once daily within 5-7 days, thereafter adjust by 5-10 mg/day at 1-week intervals, up to a maximum of 20 mg/day; doses of 30-50 mg/day have been used; typical dosage range: 10-30 mg/day

Bipolar mania: Oral:

Monotherapy: Usual starting dose: 10-15 mg once daily; increase by 5 mg/day at intervals of not less than 24 hours; maintenance: 5-20 mg/day; maximum dose: 20 mg/day

Combination therapy (olanzapine in combination with lithium or valproate): Initial: 10 mg once daily; dosing range: 5-20 mg/day

Agitation (acute, associated with bipolar disorder or schizophrenia): I.M.: Initial dose: 5-10 mg (a lower dose of 2.5 mg may be considered when clinical factors warrant); additional doses (2.5-10 mg) may be considered; however, 2-4 hours should be allowed between doses to evaluate response (maximum total daily dose: 30 mg, per manufacturer's recommendation)

Elderly: Schizophrenia: Oral: Usual starting dose: 2.5 mg/day, increase as clinically indicated and monitor blood pressure; typical dosage range: 2.5-10 mg/day

Dosage comment in renal impairment: Not removed by dialysis

Injection: For I.M. administration only; do not administer injection intravenously; inject slowly, deep into muscle. If dizziness and/or drowsiness are noted, patient should remain recumbent until examination indicates postural hypotension and/or bradycardia are not a problem.

Tablet: May be administered with or without food/meals.

Orally-disintegrating: Remove from foil blister by peeling back (do not push tablet through the foil); place tablet in mouth immediately upon removal; tablet dissolves rapidly in saliva and may be swallowed with or without liquid. May be administered with or without food/meals.

Krishnamoorthy J and King BH, "Open-Label Olanzapine Treatment in Five Preadolescent Children,"J Child Adolesc Psychopharmacol, 1998, 8(2):107-13.

Soutullo CA, Sorter MT, Foster KD, et al, "Olanzapine in the Treatment of Adolescent Acute Mania: A Report of Seven Cases,"J Affect Disord, 1999, 53(3):279-83.

Injection, powder for reconstitution (Zyprexa® IntraMuscular): 10 mg [contains lactose 50 mg]

Tablet (Zyprexa®): 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg

Tablet, orally-disintegrating (Zyprexa® Zydis®): 5 mg [contains phenylalanine 0.34 mg/tablet], 10 mg [contains phenylalanine 0.45 mg/tablet], 15 mg [contains phenylalanine 0.67 mg/tablet], 20 mg [contains phenylalanine 0.9 mg/tablet]

American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity, "Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes,"Diabetes Care, 2004, 27(2):596-601.

Baldwin DS and Montgomery SA, "First Clinical Experience With Olanzapine (LY 170053): Results of an Open-Label Safety and Dose-Ranging Study in Patients With Schizophrenia,"Int Clin Psychopharmacol, 1995, 10(4):239-44.

Davis JM, Chen N, and Glick ID, "A Meta-Analysis of the Efficacy of Second-Generation Antipsychotics,"Arch Gen Psychiatry, 2003, 60(6):553-64.

Goldberg RJ, "Managing Psychosis-Related Behavioral Problems in the Elderly,"Consult Pharm, 1997, 12(Suppl C):4-10.

Gorski ED and Willis KC, "Report of Three Cases Studied With Olanzapine for Chronic Pain,"J Pain, 2003, 4:166-8.

Khojainova N, Santiago-Palma J, Kornick C, et al, "Olanzapine in the Management of Cancer Pain,"J Pain Symptom Manage, 2002, 23(4):346-50.

Kiser RS, Cohen HM, Freedenfeld RN, et al, "Olanzapine for the Treatment of Fibromyalgia Symptoms,"J Pain Symptom Manage, 2001, 22(2):704-8.

Krishnamoorthy J and King BH, "Open-Label Olanzapine Treatment in Five Preadolescent Children,"J Child Adolesc Psychopharmacol, 1998, 8(2):107-13.

Littrell K, Peabody CD, and Littrell SH, "Olanzapine: A New Atypical Antipsychotic,"J Psychosoc Nurs Ment Health Serv, 1996, 34(8):41-6.

"Olanzapine for Schizophrenia,"Med Lett Drugs Ther, 1997, 39(992):5-6.

Rozen TD, "New Treatments in Cluster Headache,"Curr Neurol Neurosci Rep, 2002, 2(2):114-21.

Soutullo CA, Sorter MT, Foster KD, et al, "Olanzapine in the Treatment of Adolescent Acute Mania: A Report of Seven Cases,"J Affect Disord, 1999, 53(3):279-83.

Tollefson GD, Beasley CM Jr, Tran PV, et al, "Olanzapine Versus Haloperidol in the Treatment of Schizophrenia and Schizoaffective and Schizophreniform Disorders: Results of an International Collaborative Trial,"Am J Psychiatry, 1997, 154(4):457-65.