Adult: For the rapid control of agitation and disturbed behaviours in patients with schizophrenia or manic episodes when oral treatment is inappropriate: Initially, 5-10 mg followed by 5-10 mg as needed after 2 hours according to patient's clinical status. No more than 3 inj must be given in any 24-hour period. Max: 20 mg daily (combined oral and IM dose). May give inj for up to Max 3 days but should switch to oral therapy as soon as possible.
Intramuscular Schizophrenia
Adult: Establish tolerability by giving oral olanzapine before switching to extended-release inj. As extended-release inj: In patients taking 10 mg oral olanzapine daily: Initially, 210 mg every 2 weeks or 405 mg every 4 weeks. Maintenance: 150 mg every 2 weeks or 300 mg every 4 weeks. In patients taking 15 mg oral olanzapine daily: Initially, 300 mg every 2 weeks. Maintenance: 210 mg every 2 weeks or 405 mg every 4 weeks. In patients taking 20 mg oral olanzapine daily: Initially, 300 mg every 2 weeks. Maintenance: 300 mg every 2 weeks. Initial doses are to be given during the 1st 8 weeks; maintenance doses are to be started after 2 months of initial treatment. Doses are administered via deep IM gluteal inj. Reassess patient periodically to determine the need for continued treatment.
Oral Schizophrenia
Adult: Initially, 10 mg daily as a single dose; may adjust dose according to response at intervals of not less than 24 hours to a dose of 5-20 mg daily. Dosage recommendations may vary among individual products and between countries (refer to specific product guidelines). Elderly: Initiate with a lower dose (5 mg daily).
Oral Adjunct in treatment-resistant depression
Adult: As adjunct with fluoxetine for depressive episodes: Initially, 5 mg once daily in the evening. May adjust dose within 5-12.5 mg daily based on efficacy and tolerability. Consider using fixed-dose combination products or individual components based on patient's dose requirements. Dosage and treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).
Oral Bipolar I disorder
Adult: As monotherapy for the treatment of acute manic or mixed episodes associated with bipolar I disorder: Initially, 10-15 mg daily. As adjunct to lithium or valproic acid: 10 mg. Dose may be adjusted according to response and tolerability in increments of 5 mg, if needed, at intervals of not less than 24 hours to a dose of 5-20 mg daily. If a response is achieved, may continue therapy at the same dose to prevent recurrence. In patients whose manic episodes have responded previously to olanzapine: Maintenance: Initially, 10 mg. Dosage and treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).
What are the brands available for Olanzapine in Hong Kong?
Patients who are medically ill, predisposed to orthostatic hypotension, and combined factors for reduced metabolism (e.g. females, nonsmokers): Initiate with a lower dose (e.g. 5 mg daily) and gradually increase the dose if necessary. Dosage recommendations may vary among individual products and between countries (refer to specific product guidelines).
Powder for inj: Short-acting inj: Reconstitute vial labelled as 10 mg with 2.1 mL of sterile water for inj to provide a final concentration of 5 mg/mL. Extended-release inj: Dilute vials labelled as 210 mg, 300 mg, and 405 mg with 1.3 mL, 1.8 mL, and 2.3 mL of the provided solvent, respectively. Shake the vial vigorously to mix.
Incompatibility
IM: Incompatible with haloperidol and benzodiazepines (e.g. diazepam, lorazepam) in the same syringe.
Special Precautions
Patient with severe cardiac disease, ischaemic heart disease, CHF, heart hypertrophy, congenital long QT syndrome, haemodynamic instability, prior MI, hypercholesterolaemia, hypokalaemia, hypomagnesaemia; diabetes; conditions predisposing to hypotension; decreased gastrointestinal motility (e.g. paralytic ileus); known risk of narrow-angle glaucoma; Parkinson's disease; predisposition for seizures including history of seizures, head trauma, brain damage, alcoholism, or conditions that may decrease seizure threshold (e.g. Alzheimer's disease); low leucocyte and/or neutrophil counts, hypereosinophilic conditions or myeloproliferative disease, bone marrow depression caused by concomitant illness, radiation therapy or chemotherapy, history of drug-induced bone marrow depression or toxicity, urinary retention (e.g. benign prostatic hyperplasia); conditions that may contribute to an increase in core body temperature (e.g. exposure to extreme heat, strenuous exercise, dehydration); elevated ALT and/or AST, pre-existing conditions associated with limited hepatic functional reserve. IM: Patients with unstable medical conditions (e.g. unstable angina pectoris, severe hypotension, bradycardia, sick sinus syndrome, post-heart surgery). Avoid abrupt withdrawal. Patients who are smokers; with combined factors for reduced metabolism (e.g. females, nonsmokers). Not recommended for use in patients with dementia-related psychosis and/or behavioural disturbances. Hepatic impairment. Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Suicidal ideation, anticholinergic effects (e.g. constipation, urinary retention, xerostomia); metabolic changes including significant weight gain (≥7% from baseline weight) and dyslipidaemia (mainly manifested as hypercholesterolaemia and/or hypertriglyceridaemia, including acute pancreatitis); hyperglycaemia, hyperprolactinaemia; extrapyramidal symptoms (e.g. akathisia, dystonia, tardive dyskinesia, drug-induced parkinsonism); haematologic abnormalities (e.g. leucopenia, neutropenia, thrombocytopenia); hypersensitivity reactions (e.g. drug reaction with eosinophilia and systemic symptoms); orthostatic hypotension; post-injection delirium/sedation syndrome (IM); QT prolongation; sedation, sexual dysfunction (e.g. decreased libido, erectile dysfunction, abnormal orgasm), increased transaminases, ALT, and AST. Rarely, venous thromboembolism. Blood and lymphatic system disorders: Eosinophilia. Cardiac disorders: Bradycardia. Gastrointestinal disorders: Abdominal distention, salivary hypersecretion. General disorders and admin site conditions: Fatigue, asthenia, oedema, pyrexia. Investigations: High creatine phosphokinase, GGT, and uric acid; increased total bilirubin. Metabolism and nutrition disorders: Increased appetite. Musculoskeletal and connective tissue disorders: Restless legs syndrome, arthralgia. Nervous system disorders: Dizziness, somnolence, seizure, dysarthria, stuttering. Psychiatric disorders: Amnesia. Renal and urinary disorders: Glucosuria. Reproductive system and breast disorders: Gynaecomastia, amenorrhoea, galactorrhoea. Respiratory, thoracic and mediastinal disorders: Epistaxis. Skin and subcutaneous tissue disorders: Rash, alopecia, photosensitivity reaction. Potentially Fatal: Cerebrovascular effects (e.g. stroke, CVA, TIA), temperature dysregulation which may lead to heatstroke and hypothermia, neuroleptic malignant syndrome (NMS), hyperglycaemia and exacerbation of diabetes occasionally associated with ketoacidosis or coma.
This drug may cause somnolence, if affected, do not drive or operate machinery.
Monitoring Parameters
Evaluate for history of metabolic syndrome annually. Monitor electrolytes, renal function, LFTs, and TSH annually; CBC as clinically indicated; vital signs (at least weekly during 1st 3-4 weeks of therapy and 4 weeks after dose changes; weight, height, BMI 8-12 weeks after treatment initiation and dose changes, then quarterly thereafter. Obtain prolactin level (if symptoms are reported); fasting plasma glucose, HbA1c and lipid panel 12 weeks after treatment initiation, dose changes, and annually thereafter; check more frequently than annually if abnormal. Assess for fall risk and extrapyramidal symptoms (every visit, 4 weeks after starting treatment, dose changes and annually thereafter). IM: Monitor for sedation or delirium for 3 hours after each dose.
Overdosage
Symptoms: Agitation or aggressiveness, dysarthria, various extrapyramidal symptoms, decreased level of consciousness ranging from sedation to coma, delirium, convulsion, possible NMS, aspiration, respiratory depression, hypotension or hypertension, cardiac arrhythmias, cardiopulmonary arrest. Management: Symptomatic and supportive treatment. May perform gastric lavage or administer activated charcoal. Treat hypotension and circulatory collapse with appropriate measures including IV fluids and/or sympathomimetic agents. Do not give epinephrine, dopamine, or other sympathomimetics with β-agonist activity. Respiratory support including ventilation may be needed. Monitor vital organ function based on clinical presentation; CV status to detect possible arrhythmias.
Drug Interactions
Increased clearance with CYP1A2 inducers (e.g. carbamazepine, rifampicin). Decreased clearance with CYP1A2 inhibitors (e.g. fluvoxamine). May enhance the effects of certain antihypertensives. Decreased bioavailability with activated charcoal; take at least 2 hours before or after olanzapine. May antagonise the effects of levodopa and dopamine agonists. May potentiate orthostatic hypotension with benzodiazepines (e.g. diazepam). Increased risk of QT prolongation with other drugs that may prolong QT intervals. Potentially Fatal: IM: May enhance adverse effects with parenteral benzodiazepines.
Food Interaction
May enhance the CNS depressant effect of alcohol.
Action
Description: Mechanism of Action: Olanzapine is a 2nd generation thiebenzodiazipine antipsychotic agent. Its exact mechanism of action is unknown; however, it may be facilitated by combined antagonism of dopamine and serotonin type 2 receptor sites. It shows a potent antagonistic effect in the serotonin 5-HT2A and 5-HT2C, dopamine D1-4, histamine H1, and α1-adrenergic receptors; moderate antagonistic effect in the serotonin 5-HT3 and muscarinic M1-5; and weakly binds to gamma-aminobutyric acid-A (GABA-A), benzodiazepine, and β-adrenergic receptors. Pharmacokinetics: Absorption: Well absorbed from the gastrointestinal tract (oral); rapidly absorbed (inj). Bioavailability: Time to peak plasma concentration: Approx 6 hours (oral); 15-45 minutes (short-acting IM inj); approx 7 days (extended-release IM inj). Distribution: Crosses the placenta and enters breast milk. Extensively distributed throughout the body. Volume of distribution: 1,000 L. Plasma protein binding: 93%, mainly to albumin and α1-acid glycoprotein. Metabolism: Extensively metabolised in the liver via direct glucuronidation and oxidation by CYP450 isoenzymes (CYP1A2, CYP2D6 [lesser extent]) into 10-N-glucuronide and 4'-N-desmethyl olanzapine (major inactive metabolites). Undergoes extensive first-pass metabolism. Excretion: Via urine (57% as metabolites, 7% as unchanged drug); faeces (30%). Elimination half-life: 30 hours (oral/short-acting IM inj); Approx 30 days (extended-release IM inj).
Chemical Structure
Olanzapine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 135398745, Olanzapine. https://pubchem.ncbi.nlm.nih.gov/compound/Olanzapine. Accessed Jan. 31, 2024.
Storage
Tab/intact vial: Store between 15-30°C. Protect the tab from light and moisture. Protect the intact vial from light. Reconstituted solution for inj (short-acting inj): Use immediately within 1 hour after reconstitution. Reconstituted susp for inj (extended-release inj): May be stored at room temperature for 24 hours. Use immediately once susp is withdrawn into the syringe.
N05AH03 - olanzapine ; Belongs to the class of diazepines, oxazepines and thiazepines antipsychotics
References
Anon. Olanzapine. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 02/05/2024.Buckingham R (ed). Olanzapine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 30/04/2024.Joint Formulary Committee. Olanzapine Embonate. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 13/05/2024.Joint Formulary Committee. Olanzapine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 30/04/2024.Olanzapine. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 30/04/2024.Olenza 10 mg Tablet (Noripharma Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 30/04/2024.Onzapin Orodispersible Tablets (DCH Auriga [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 30/04/2024.Pharmaco (N.Z.) Ltd. Zyprexa IM 10 mg Powder for Injection data sheet 21 August 2023. Medsafe. http://www.medsafe.govt.nz. Accessed 30/04/2024.Viatris Ltd. Zypine, 2.5 mg, 5 mg and 10 mg, Film-coated Tablets data sheet 27 February 2023. Medsafe. http://www.medsafe.govt.nz. Accessed 30/04/2024.Zypadhera 210 mg, 300 mg, and 405 mg Powder and Solvent for Prolonged Release Suspension for Injection (Cheplapharm Registration GmbH). European Medicines Agency [online]. Accessed 30/04/2024.Zyprexa 10 mg Powder for Solution for Injection (Eli Lilly Nederland B.V.). MHRA. https://products.mhra.gov.uk. Accessed 30/04/2024.Zyprexa 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg Coated Tablets (Cheplapharm Registration GmbH). European Medicines Agency [online]. Accessed 30/04/2024.Zyprexa Relprevv (Eli Lilly and Company). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 30/04/2024.Zyprexa Tablet, Zyprexa Zydis Tablet, Orally Disintegrating, Zyprexa Intramuscular Injection, Powder, for Solution (Eli Lilly and Company). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 30/04/2024.Zyprexa Velotab 5 mg Orodispersible Tablets (Neon Healthcare Limited). MHRA. https://products.mhra.gov.uk. Accessed 30/04/2024.
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