Olanzapine + Fluoxetine

Oral
Depressive phase of bipolar disorder

Oral
Adjunct in treatment-resistant depression

No dosage adjustment needed.

Initially, olanzapine 3 mg and fluoxetine 25 mg increased to olanzapine 6 mg and fluoxetine 25 mg.

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.

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.

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.

PO: C

May impair ability to drive or operate machinery.

Monitor worsening of suicidal thoughts and behaviour. Monitor ECG periodically and fasting blood lipid testing prior and during treatment.

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.

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).

Concomitant use w/ alcohol may potentiate sedation and orthostatic hypotension.

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-HT_2A/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.

Store at 25°C.

Antipsychotics

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.