Fluoxetine


Generic Medicine Info
Indications and Dosage
Oral
Bulimia nervosa
Adult: 60 mg daily given as a single or in divided doses.

Oral
Major depressive disorder
Adult: Initially, 20 mg once daily given as a single or in divided doses. Dose may be adjusted if necessary, within 3-4 weeks of initiation according to response. Max: 60 mg daily. Individualise dosage adjustments and maintain at the lowest effective dose. Dose >20 mg may be given as single or in 2 divided doses. Treatment duration: At least 6 months. As delayed-release cap for long-term treatment: 90 mg once weekly, initiated 7 days after the last daily dose. If satisfactory response is not maintained, re-establish daily dosing regimen.
Child: ≥8 years As oral solution/dispersible tab: Initially, 10 mg daily, may be increased to 20 mg daily after 1-2 weeks. Individualise dosage adjustments and maintain at the lowest effective dose. Lower weight children: Initially, 10 mg daily, may be increased to 20 mg daily after several weeks. Max: 20 mg daily.
Elderly: Initially, 20 mg once daily given as a single or in divided doses, may be increased gradually within 3-4 weeks of therapy according to response. Usual Max dose: 40 mg daily. Individualise dosage adjustments and maintain at the lowest effective dose.

Oral
Panic disorder with or without agoraphobia
Adult: Initially, 10 mg once daily, increased to 20 mg daily after 1 week. Dose may be further increased after several weeks if no improvement. Max: 60 mg daily.
Elderly: Lower or less frequent dose may be necessary.

Oral
Premenstrual dysphoric disorder
Adult: 20 mg daily given continuously (every day of the menstrual cycle) or intermittently (started 14 days prior to onset of menstruation and continued until the 1st full day of menstruation for each new cycle). Continue treatment for 6 months, then re-assess therapy benefit.

Oral
Obsessive compulsive disorder
Adult: Initially, 20 mg once daily given as a single or in divided doses, may be increased gradually after 2 weeks if no or insufficient response. Max: 60 mg daily. Adjust dose according to patient response and maintain at the lowest effective dose. Re-evaluate therapy if no improvement within 10 weeks.
Child: ≥7 years Higher weight children: Initially, 10 mg daily, may be increased to 20 mg daily after 2 weeks. Dose may be increased further after several more weeks if insufficient response. Usual dose range: 20-60 mg daily. Lower weight children: Initially, 10 mg daily, may be increased after several more weeks if insufficient response. Usual dose range: 20-30 mg daily.
Elderly: Initially, 20 mg once daily given as a single or in divided doses, may be increased gradually according to response. Usual Max dose: 40 mg daily. Re-evaluate therapy if no improvement within 10 weeks.
Special Patient Group
Pharmacogenomics:

Fluoxetine is mainly metabolised by CYP2D6 into norfluoxetine (active metabolite). It is also a racemic mixture of R-fluoxetine and S-fluoxetine enantiomers. S-fluoxetine elimination is slower, and it is predominantly present in the plasma at steady state.

CYP2D6 poor metabolisers have been shown to have increased concentrations of S-fluoxetine and decreased concentration of S-norfluoxetine as well as unchanged metabolism of R-fluoxetine. Approx 7% of the population is considered CYP2D6 poor metabolisers.

According to Royal Dutch Pharmacists Association - Pharmacogenetics Working Group (DPWG) guideline, this ratio does not affect the plasma levels of active substances (fluoxetine and norfluoxetine), and there is no effect on response or on adverse events. Thus, there is no current dosing recommendation for this genotype.
Renal Impairment
Major depressive disorder; Bulimia nervosa; Obsessive compulsive disorder; Premenstrual dysphoric disorder:
Mild to moderate (GFR 10-50 mL/min): Lower or less frequent dose (e.g. alternate-day dosing) may be necessary. Severe (GFR <10 mL/min): Contraindicated.
Hepatic Impairment
Lower dose or less frequent dosing interval may be necessary.
Administration
May be taken with or without food.
Reconstitution
Dispersible tab: Disperse in a half glass of water prior to administration. Alternatively, may be swallowed whole with sufficient amount of water.
Contraindications
Unstable seizure disorders/epilepsy. Severe renal (GFR <10 mL/min) impairment. Concomitant use or within 2 weeks of discontinuing MAOIs (e.g. iproniazid) or within 5 weeks of discontinuing fluoxetine. Concurrent use with metoprolol, linezolid, IV methylene blue, pimozide, and thioridazine.
Special Precautions
Patient with history of suicide-related events or pre-existing suicidal ideation; bipolar disorder, history of mania or hypomania; history of seizure disorder or conditions predisposing to seizures (e.g. brain damage, alcoholism), diabetes mellitus, history of bleeding disorders, CV disease (e.g. history of MI, unstable heart disease), risk factors for QT prolongation (e.g. congenital long QT syndrome, history of prolonged QT) or conditions predisposing to arrhythmias (e.g. hypokalaemia, hypomagnesaemia, bradycardia, acute MI, uncompensated heart failure); volume depletion, raised intraocular pressure or at risk of acute narrow-angle glaucoma. Patient where weight loss is undesirable. CYP2D6 poor metabolisers. Concomitant electroconvulsive therapy. Delayed-release cap: Bariatric surgery (refer to specific institutional protocols). Avoid abrupt withdrawal. Hepatic and mild to moderate renal impairment. Children and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Suicidal thoughts and behaviour in children, adolescents and young adults; activation of mania or hypomania, seizures, CNS depression, CNS effects (e.g. anxiety, insomnia, nervousness), QT prolongation and ventricular arrhythmias, including torsade de pointes; cutaneous bleeding events (e.g. ecchymosis, purpura), bone fractures, akathisia, mild pupillary dilation, sexual dysfunction, anorexia and/or weight loss, altered glycaemic control (e.g. hyper- or hypoglycaemia), syndrome of inappropriate antidiuretic hormone secretion (SIADH), hyponatraemia, withdrawal symptoms.
Cardiac disorders: Palpitation, dyspnoea.
Eye disorders: Blurred vision, abnormal vision.
Gastrointestinal disorders: Nausea, diarrhoea, vomiting, dyspepsia, dry mouth, dysgeusia.
General disorders and administration site conditions: Lethargy, fatigue, chills, feeling jittery, asthenia, flu-like symptoms.
Musculoskeletal and connective tissue disorders: Arthralgia.
Nervous system disorders: Headache, dizziness, drowsiness, tremor, abnormal thinking.
Psychiatric disorders: Psychomotor restlessness, sleep abnormality, tension, abnormal dreams, attention disturbance.
Renal and urinary disorders: Frequent urination, dysuria, urinary retention.
Reproductive system and breast disorders: Decreased libido, erectile dysfunction, ejaculation disorder.
Respiratory, thoracic and mediastinal disorders: Yawning, pharyngitis, sinusitis.
Skin and subcutaneous tissue disorders: Pruritus, hyperhidrosis.
Vascular disorders: Flushing.
Potentially Fatal: Serotonin syndrome or neuroleptic malignant syndrome (NMS)-like events, haemorrhages, severe hyponatraemia. Rarely, significant allergic events and rash (e.g. vasculitis, lupus-like syndrome, pulmonary inflammatory disease; anaphylactoid reactions including bronchospasm, laryngospasm, angioedema, urticaria).
Patient Counseling Information
This drug may cause dizziness or drowsiness, if affected, do not drive or operate machinery. Do not switch between brands or dosage forms unless instructed by your doctor.
MonitoringParameters
Monitor hepatic and renal function at baseline and as clinically indicated; serum Na in at-risk patients; blood glucose in diabetics. Assess ECG periodically in patients at-risk for QT prolongation. Closely monitor mental status for depression; signs and symptoms of clinical worsening, suicidality, or unusual behavioural changes (especially at the start of therapy and during dose adjustments); anxiety, mania, panic attacks, social functioning, serotonin syndrome and akathisia.
Overdosage
Symptoms: Nausea, vomiting, seizure, CV dysfunction ranging from asymptomatic arrhythmias to cardiac arrest (including ventricular arrhythmias and nodal rhythm) or ECG changes indicating QTc prolongation to cardiac arrest, pulmonary dysfunction, altered CNS status ranging from excitation to coma. Management: Symptomatic and supportive treatment. Ensure adequate airway, ventilation and oxygenation; monitor cardiac rhythm and vital signs. May administer activated charcoal with sorbitol.
Drug Interactions
Increased risk of bleeding with warfarin, other oral anticoagulants, aspirin, NSAIDs and atypical antipsychotics (e.g. clozapine, phenothiazines); hyponatraemia with diuretics. May reduce plasma levels and efficacy of tamoxifen. Reduced antidepressant effect with cyproheptadine. Increased risk of QT prolongation with mequitazine and other drugs known to prolong QT interval (e.g. Class IA and III antiarrhythmics, erythromycin, moxifloxacin, pentamidine, halofantrine, mizolastine, astemizole). May increase serum concentration of benzodiazepines (e.g. diazepam, alprazolam). May increase the plasma levels of phenytoin, haloperidol, and carbamazepine.
Potentially Fatal: Increased risk of serotonin syndrome with other serotonergic agents (e.g. triptans, TCAs, fentanyl, lithium, tramadol, buspirone, tryptophan) and agents which impair metabolism of serotonin (e.g. MAOIs including iproniazid, linezolid, IV methylene blue). Increased plasma levels and risk of QT prolongation of pimozide and thioridazine. Increased risk of excessive bradycardia with metoprolol (when used for cardiac failure).
Food Interaction
Increased risk of serotonin syndrome with St. John’s wort.
Action
Description: Fluoxetine selectively inhibits serotonin re-uptake in the CNS neuron with minimal or no effect on norepinephrine or dopamine re-uptake. It also does not significantly bind to α-adrenergic, cholinergic, or histamine receptors.
Onset: Depression: Within 1-2 weeks. Anxiety disorders: Within 2 weeks. Premenstrual dysphoric disorder: Within the 1st few days of treatment.
Pharmacokinetics:
Absorption: Well absorbed from the gastrointestinal tract. Time to peak plasma concentration: 6-8 hours.
Distribution: Widely distributed in the body. Crosses the placenta and enters breast milk. Volume of distribution: 12-43 L/kg. Plasma protein binding: Approx 95% mainly to albumin and α1-glycoprotein.
Metabolism: Extensively metabolised in the liver via demethylation by CYP2D6 and CYP2C19 isoenzymes into its primary active metabolite, norfluoxetine.
Excretion: Mainly via urine (10% as norfluoxetine; 2.5-5% as fluoxetine). Elimination half-life: Fluoxetine: 1-3 days (acute use); 4-6 days (chronic use); Norfluoxetine: 9.3 (range: 4-16) days.
Chemical Structure

Chemical Structure Image
Fluoxetine

Source: National Center for Biotechnology Information. PubChem Database. Fluoxetine, CID=3386, https://pubchem.ncbi.nlm.nih.gov/compound/Fluoxetine (accessed on Jan. 21, 2020)

Storage
Store between 15-30°C. Protect from light, heat and moisture.
MIMS Class
ATC Classification
N06AB03 - fluoxetine ; Belongs to the class of selective serotonin reuptake inhibitors. Used in the management of depression.
References
Annotation of DPWG Guideline for Fluoxetine and CYP2D6. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org/. Accessed 08/06/2020.

Annotation of FDA Label for Fluoxetine and CYP2D6. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org/. Accessed 08/06/2020.

Anon. CYP2D6 - Fluoxetine (Pharmacogenomics). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/06/2020.

Anon. Fluoxetine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/06/2020.

Anzack Tablets (Malaysian Pharmaceutical Industries Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my/. Accessed 08/06/2020.

Buckingham R (ed). Fluoxetine Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/06/2020.

Fluoxetine 20 mg Hard Capsules (Tillomed Laboratories Limited). MHRA. https://products.mhra.gov.uk/. Accessed 08/06/2020.

Fluoxetine 20 mg/5 mL Oral Solution (Kent Pharma UK Limited). MHRA. https://products.mhra.gov.uk/. Accessed 08/06/2020.

Fluoxetine Hydrochloride Capsule, Delayed Release Pellets (Dr. Reddy's Laboratories Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/06/2020.

Fluoxetine Solution (Aurobindo Pharma Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/06/2020.

Joint Formulary Committee. Fluoxetine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/06/2020.

Olena 20 mg Dispersible Tablets (Mercury Pharmaceuticals Limited). MHRA. https://products.mhra.gov.uk/. Accessed 08/06/2020.

Prozac Capsule (Dista Products Company). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/06/2020.

Sarafem Tablet (Allergan, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/06/2020.

Disclaimer: This information is independently developed by MIMS based on 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 © 2021 MIMS. All rights reserved. Powered by MIMS.com
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