Olanzapine + Fluoxetine


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Depressive phase of bipolar disorder; Adjunct in treatment-resistant depression Each cap contains olanzapine 6 mg and fluoxetine 25 mg: 1 cap once daily at night.
Dosage Details
Oral
Depressive phase of bipolar disorder
Adult: Each cap contains olanzapine 6 mg and fluoxetine 25 mg: 1 cap once daily at night.
Child: 10-17 yr Each cap contains olanzapine 3 mg and fluoxetine 25 mg: 1 cap once daily at night.

Oral
Adjunct in treatment-resistant depression
Adult: Each cap contains olanzapine 6 mg and fluoxetine 25 mg: 1 cap once daily at night.
Renal Impairment
No dosage adjustment needed.
Hepatic Impairment
Initially, olanzapine 3 mg and fluoxetine 25 mg increased to olanzapine 6 mg and fluoxetine 25 mg.
Contraindications
Not to be used w/ or w/in 14 days of discontinuing treatment w/ MAOIs (e.g. linezolid, methylene blue). Concomitant MAOIs or w/in 5 wk of discontinuing treatment w/ olanzapine and fluoxetine. Concomitant use w/ QT prolonging drugs (e.g. pimozide, thioridazine). Childn <10 yr.
Special Precautions
Elderly w/ dementia-related psychosis. Increased risk of suicidal thinking and behaviour in childn, adolescents and young adults. Patients w/ congenital long QT syndrome. Hepatic impairment. Pregnancy and lactation.
Adverse Reactions
Hyperglycaemia, hyperlipidaemia, increased wt, rash and/or urticaria, bronchospasm, angioedema, mania activation/hypomania, tardive dyskinesia, orthostatic hypotension, neutropenia, agranulocytosis, leukopenia, dysphagia, seizures, abnormal bleeding, hyponatremia, body temp dysregulation, hyperprolactinaemia.
Potentially Fatal: Serotonin and neuroleptic malignant syndrome; QT prolongation including torsade de pointes.
Patient Counseling Information
May impair ability to drive or operate machinery.
MonitoringParameters
Monitor worsening of suicidal thoughts and behaviour. Monitor ECG periodically and fasting blood lipid testing prior and during treatment.
Overdosage
Symptoms: Coma, loss of consciousness, convulsions, ataxia, confusion, dysarthria, somnolence, lethargy, agitation, essential tremor, arrhythmias, acute psychosis, aggression, HTN, hypotension. Management: Establish and maintain airway for adequate ventilation (e.g. intubation). Monitor CV function immediately w/ continuous ECG monitoring to detect possible arrhythmias.
Drug Interactions
Increased risk of bleeding w/ NSAIDs, warfarin and aspirin. May potentiate orthostatic hypotension w/ benzodiazepines. May increase serum levels and toxicity of phenytoin and carbamazepine. May enhance the effects of certain antihypertensives. Olanzapine may antagonise the effects of levodopa and dopamine agonists. May increase serum levels of clozapine and haloperidol. Fluvoxamine may increase the serum levels of olanzapine.
Potentially Fatal: Concomitant use w/ MAOI (e.g. methylene blue, linezolid) may cause serotonin syndrome. Increased risk of QT prolongation w/ QT prolonging drugs (e.g. pimozide and thioridazine).
Food Interaction
Concomitant use w/ alcohol may potentiate sedation and orthostatic hypotension.
Action
Description: Fluoxetine is a potent and predominantly selective inhibitor of serotonin (monoamine transmitter) which has no affinity for adrenoceptors or histamine, GABA-B, or muscarinic receptors. It prevents the reuptake of serotonin, which potentiates its action in the brain. Olanzapine is an atypical antipsychotic w/ affinity for serotonin 5-HT2A/2C, dopamine, muscarinic M1-M5, histamine H1 and adrenergic α1 receptors.
Pharmacokinetics:
Absorption: Fluoxetine is readily absorbed from the GI tract. Olanzapine is well absorbed from the GI tract. Bioavailability: Fluoxetine: Approx 60-80%. Time to peak plasma concentration: Fluoxetine: Approx 6-8 hr. Olanzapine: Approx 5-8 hr.
Distribution: Fluoxetine crosses the blood-brain barrier. Olanzapine crosses the placenta and highly lipophilic. Plasma protein binding: Fluoxetine: Approx 95%. Olanzapine: Approx 93%.
Metabolism: Both are extensively metabolised in the liver. Fluoxetine undergoes hepatic demethylation via CYP2D6 isoenzyme to its primary active metabolite norfluoxetine. Olanzapine undergoes direct glucuronidation and oxidation via CYP1A2 isoenzyme and to a lesser extent via CYP2D6 isoenzyme to its metabolites 10-N-glucuronide and 4'-N-desmethyl.
Excretion: Fluoxetine: Mainly via urine. Elimination half-life: Approx 1-3 days (acute use); 4-6 days (long-term use). Olanzapine: Via urine (approx 57%, mainly as metabolites); via faeces (approx 30%). Elimination half-life: Approx 30-38 hr.
Storage
Store at 25°C.
MIMS Class
References
Buckingham R (ed). Fluoxetine Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 16/09/2013.

Buckingham R (ed). Olanzapine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 16/09/2013.

Joint Formulary Committee. Fluoxetine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 16/09/2013.

Joint Formulary Committee. Olanzapine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 16/09/2013.

McEvoy GK, Snow EK, Miller J et al (eds). Fluoxetine Hydrochloride. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 16/09/2013.

McEvoy GK, Snow EK, Miller J et al (eds). Olanzapine, Olanzapine Pamoate. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 16/09/2013.

Symbyax (Eli Lilly and Company). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 16/09/2013.

Symbyax (Olanzapine and Fluoxetine HCL) Capsules. U.S. FDA. https://www.fda.gov/. Accessed 16/09/2013.

Disclaimer: This information is independently developed by MIMS based on Olanzapine + Fluoxetine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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