Fluoxetine oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations containing fluoxetine.
Drugs List
Therapeutic Indications
Uses
Bulimia nervosa
Depressive illness
Obsessive-compulsive disorders
Unlicensed Uses
Irritable bowel syndrome
Menopausal symptoms in women with breast cancer
Dosage
Adults
Depression with or without associated anxiety symptoms
A dose of 20 mg once daily is recommended initially, increased gradually after 3 to 4 weeks if necessary, up to 60 mg once daily.
Patients with depression should be treated for a sufficient period of at least 6 months to ensure that they are free from symptoms.
Bulimia nervosa
A dose of 60 mg once daily is recommended. Long term efficacy (more than 3 months) has not been demonstrated.
Obsessive-compulsive disorders
Initially 20 mg once daily increasing gradually if there is no response after 2 weeks up to a maximum of 60 mg once daily.
If no improvement is seen within 10 weeks, treatment with fluoxetine should be reconsidered.
All indications
Recommended dose may be increased or decreased.
Doses above 80 mg per day have not been systematically evaluated.
Menopausal symptoms in women with breast cancer (except those taking tamoxifen) (unlicensed)
20mg once daily
Elderly
Caution is recommended when increasing the dose, and the daily dose should generally not exceed 40 mg (given as a single dose). Maximum recommended dose is 60 mg per day.
Children
Moderate to severe major depressive episode in children and adolescents aged 8 years and above
To be used if depression is unresponsive to psychological therapy after 4 to 6 sessions.
Antidepressant medication should be offered only in combination with a concurrent psychological therapy.
The starting dose is 10 mg once daily. After one to two weeks the dose may be increased to 20 mg once daily. There is limited experience of doses greater than this and treatment beyond 9 weeks.
Due to higher plasma levels in lower weight children, the therapeutic effect may be achieved with lower doses.
If no clinical benefit is achieved within 9 weeks treatment should be discontinued. Paediatric patients who respond to fluoxetine should have the need for continued treatment reviewed after 6 months.
Patients with Renal Impairment
Fluoxetine is excreted by the kidneys. The Renal Drug Handbook recommends the use of a low dose, or dose on alternate days and increase according to response in patients with a glomerular filtration rate (GFR) of less than 10 ml/minute.
When given fluoxetine 20 mg per day for 2 months, patients with a GFR of less than 10 ml/minute requiring dialysis showed no difference in plasma levels of fluoxetine or norfluoxetine compared to controls with normal renal function.
Some manufacturers contraindicate fluoxetine in patients with severe renal impairment (GFR less than 10 ml/minute).
Some manufacturers recommend a reduction of dose (e.g. give on alternate days) in mild to moderate renal impairment (GFR 10 to 50ml/minute).
Patients with Hepatic Impairment
Fluoxetine is metabolised by the liver. A lower dose or less frequent dosing (e.g. 20 mg every other day) is recommended in patients with significant hepatic impairment.
Additional Dosage Information
The capsule, tablet and liquid dosage forms are bioequivalent.
When dosing is stopped, active drug substance will persist in the body for weeks as fluoxetine has a long half life. This should be borne in mind when starting or stopping treatment.
Contraindications
Children under 8 years
Within 2 weeks of discontinuing MAOIs
Long QT syndrome
Mania
Torsade de pointes
Uncontrolled epileptic disorder
Precautions and Warnings
Children aged 8 to 18 years
Elderly
Electroconvulsive therapy
Family history of long QT syndrome
Predisposition to narrow angle glaucoma
Suicidal ideation
Anorexia nervosa
Breastfeeding
Cardiovascular disorder
Diabetes mellitus
Electrolyte imbalance
Epileptic disorder
Galactosaemia
Glucose-galactose malabsorption syndrome
Hereditary fructose intolerance
History of coagulopathy
History of hypomania
History of mania
History of seizures
History of torsade de pointes
Lactose intolerance
Pregnancy
Raised intra-ocular pressure
Renal impairment
Severe hepatic impairment
Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Correct electrolyte disorders before treatment
Patients at risk of suicide should be closely supervised
Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Children under 18: Treatment to be initiated/supervised by a specialist
May reduce seizure threshold
Not all available brands are licensed for all indications
Not all available brands/formulations are licensed for use in children
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain castor oil polyoxyl which may cause diarrhoea
Some formulations contain lactose
Some formulations contain sucrose
Consider monitoring ECG in patients at risk of QT prolongation
Discontinue treatment if patient develops seizures
If growth in children is slowed, consider referral to a paediatrician
May cause weight loss - monitor anorexic patients
Monitor elderly for hyponatraemia if drowsy, confused, fitting
Monitor growth & pubertal development in children during & after therapy
Monitor patient initially- response may take 2 or more weeks
Monitor patients for adverse reactions including restlessness & agitation
Monitor patients with epilepsy while taking this treatment
Monitor serum electrolytes
Reassess need for continued treatment at regular intervals
When used with SSRIs, risk of Serotonin syndrome
Advise patients/carers to seek medical advice if suicidal intent develops
Consider discontinuation if patient develops psychomotor restlessness
Consider hyponatraemia in all patients with drowsiness/confusion/seizures
Do not increase dosage in patients who develop akathisia
Increased risk of fractures in patients over 50 years
May activate mania or hypomania
Potential for withdrawal symptoms
Avoid abrupt withdrawal
Avoid MAOIs for 5 weeks after discontinuing this drug
Discontinue if allergic reaction occurs
Discontinue if patient develops neuroleptic malignant syndrome
Discontinue if patient enters a manic phase
Discontinue if serotonin syndrome develops
Maintain treatment at the lowest effective dose
Advise patient not to take aspirin unless advised by clinician
Advise patient not to take NSAIDs unless advised by clinician
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
May reduce sperm count, function, motility or seminal fluid volume
Ensure patient is informed of risks of treatment
Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of self harm is highest shortly after presentation and the risk of suicide may increase again in the early stages of recovery. Furthermore, there is evidence that in children and adolescents, antidepressants may increase the risk of suicidal thoughts and self harm.
Other psychiatric conditions for which fluoxetine is prescribed can also be associated with an increased risk of suicide related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.
Patients with a history of suicide related events, those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, and young adults, are at a greater risk of suicidal thought or suicide attempt, and should receive careful monitoring during treatment.
Patients, (and caregivers of patients) should be alerted about the need to monitor for the emergence of suicidal thoughts and behaviour, and to seek medical advice immediately if these symptoms present.
The CSM has advised that the balance of risks and benefits for the treatment of depressive illness in individuals under 18 years is considered unfavourable for citalopram, escitalopram, paroxetine, sertraline, mirtazapine and venlafaxine. Clinical trials have failed to show efficacy and have shown an increase in harmful outcomes. However, it is recognised that specialist may sometimes decide to use these drugs in response to individual clinical need; children and adolescents should be monitored carefully for suicidal behaviour, self-harm or hostility, particularly at the beginning of treatment.
Only fluoxetine has been shown in clinical trials to be effective for treating depressive illness in children and adolescents. However, it is possible that, in common with other SSRIs, it is associated with a small risk of self-harm and suicidal thoughts. Overall, the balance of risks and benefits for fluoxetine in the treatment of depressive illness in individuals under 18 years is considered favourable, but children and adolescents must be carefully monitored.
Only limited evidence is available concerning long-term effect on safety in children and adolescents, including effects on growth, sexual maturation and cognitive, emotional and behavioural development.
Pregnancy and Lactation
Pregnancy
Fluoxetine should not be prescribed during pregnancy unless considered essential by the physician.
Recent epidemiological evidence suggests a possible small increased risk of congenital cardiac defects associated with fluoxetine use in the first trimester. The data suggests that the risk of a cardiovascular defect after fluoxetine exposure is in the region of 2 per 100 pregnancies, compared with an expected incidence of 1 per 100 pregnancies in the general population.
In the later stages of pregnancy, epidemiological data suggest that the use of SSRIs may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). After birth, close observation of neonates exposed to SSRIs or SNRIs for signs of PPHN is recommended. The observed risk was approximately 5 cases per 1000 pregnancies whereas in the in the general population there are 1 to 2 cases per 1000 pregnancies. SSRIs may also increase the risk of postpartum haemorrhage within the month prior to birth.
Following fluoxetine use during late pregnancy or just prior to the onset of labour, the following effects have been reported in neonates: irritability, tremor, hypotonia, persistent crying, difficulty in sucking or in sleeping. These symptoms may indicate either serotonergic effects or a withdrawal syndrome. The time to occur and the duration of these symptoms may be related to the long half-life of fluoxetine (4 to 6 days) and its active metabolite, norfluoxetine (4 to 16 days).
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Use fluoxetine with caution in breastfeeding.
The manufacturers do not recommended the use of fluoxetine during breastfeeding, but note that if it is used, the lowest possible dose should be prescribed. Other sources (LactMed, Hale 2014) suggest that if fluoxetine has been used during pregnancy, then it may be continued postpartum but the infant should be observed for adverse effects and it has been used my many thousands of mothers.
Fluoxetine and its metabolite norfluoxetine are known to be excreted in human breast milk at levels above those in the maternal plasma. If an antidepressant is being initiated during breastfeeding, it may be preferable to prescribe one with lower levels of excretion into breast milk. Adverse effects in breast-feeding infants may include colic, fussiness and drowsiness. Decreased infant growth has also been reported.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Side Effects
Abnormal liver function tests
Abnormal thinking
Agitation
Alopecia
Anaphylactoid-like reaction
Angioedema
Anorexia
Anxiety
Arthralgia
Asthenia
Attention disturbances
Blood disorders
Blood sugar changes
Bruxism
Cerebrovascular accident
Chills
Confusion
Decreased alkaline phosphatase
Depersonalisation
Dizziness
Drowsiness
Dry mouth
Dyspepsia
Dysphagia
Dyspnoea
Ejaculation disorders
Eosinophilic pneumonia
Epistaxis
Erectile dysfunction
Erythema multiforme
Euphoria
Fatigue
Feeling abnormal
Feeling hot
Fever
Galactorrhoea
Gastro-intestinal haemorrhage
Gastrointestinal disorder
Growth retardation (children)
Hallucinations
Headache
Hepatitis
Hyperhidrosis
Hyperprolactinaemia
Hypersensitivity reactions
Hyperthermia
Hypomania
Hyponatraemia
Hypotension
Impaired concentration
Impaired memory
Inappropriate secretion of antidiuretic hormone
Increased risk of fractures
Lethargy
Loss of balance
Malaise
Mania
Micturition disorders
Mood changes
Movement disturbances
Mucosal irritation
Myalgia
Nervousness
Neuroleptic malignant syndrome-like effect
Palpitations
Pancreatitis
Panic attack
Pharyngitis
Photosensitivity
Postural hypotension
Priapism
Prolongation of QT interval
Pulmonary fibrosis
Restlessness
Seizures
Sensation of cold
Serotonin syndrome
Serum sickness-like reactions
Sexual disturbances
Skin disorder
Sleep disturbances
Somnolence
Speech disturbances
Suicidal tendencies
Sweating
Tardive dyskinesia
Taste disturbances
Tinnitus
Torsades de pointes
Toxic epidermal necrolysis
Tremor
Urinary retention
Vasodilatation
Ventricular arrhythmias
Violent behaviour
Visual disturbances
Weight loss
Withdrawal symptoms
Yawning
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Signs and Symptoms
Nausea, vomiting, agitation, tremor, nystagmus and drowsiness may occur. Convulsions have been reported in a small percentage of cases and may not occur until up to ten hours after ingestion. Sinus tachycardia is common. Less frequently bradycardia, hypertension and junctional rhythm may occur.
Rarely features of the "serotonin syndrome" may occur. This includes alteration of mental status, neuromuscular hyperactivity and autonomic instability. There may be hyperpyrexia and elevation of serum creatine kinase. Rhabdomyolysis is rare.
Treatment
Consider oral activated charcoal if more than 500 mg has been ingested by an adult or if more than 5 mg/kg has been ingested by a child within one hour. Management should be symptomatic and supportive and include the maintenance of a clear airway and monitoring of cardiac and vital signs until stable.
Further Information
Last full review date: June 2016
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.
The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.
Summary of Product Characteristics: Fluoxetine Capsules 10 mg. Medreich Plc UK Ltd. Revised November 2015.
Summary of Product Characteristics: Fluoxetine Capsules 20 mg. Actavis UK Ltd. Revised February 2013.
Summary of Product Characteristics: Fluoxetine Capsules 20 mg. Goldshield Ltd. Revised January 2009.
Summary of Product Characteristics: Fluoxetine Capsules 20 mg. Milpharm Ltd. Revised July 2012.
Summary of Product Characteristics: Fluoxetine Capsules 20 mg. Sandoz Ltd. Revised July 2009.
Summary of Product Characteristics: Fluoxetine Capsules 30 mg. Medreich Plc. Revised November 2015.
Summary of Product Characteristics: Fluoxetine Capsules 40 mg. Medreich Plc. Revised November 2015.
Summary of Product Characteristics: Fluoxetine Capsules 60 mg. Generics UK Ltd. Revised January 2009.
Summary of Product Characteristics: Fluoxetine 20 mg/5 ml Oral Solution. Pinewood Laboratories Ltd. Revised May 2008.
Summary of Product Characteristics: Fluoxetine 10mg Film-coated Tablets. Par Laboratories Europe Ltd. Revised July 2017.
Summary of Product Characteristics: Olena Dispersible Tablets 20 mg. Mercury Pharmaceuticals Ltd. Revised July 2011.
Summary of Product Characteristics: Oxactin Capsules 20 mg. Niche Generics Ltd. Revised July 2011.
Summary of Product Characteristics: Prozac 20 mg hard capsules, and 20mg/5ml oral liquid. Eli Lilly and Company Ltd. March 2013.
Summary of Product Characteristics: Prozep 20 mg/5 ml Oral Solution. Chemidex Pharma Ltd. Revised July 2012.
MHRA 19th September 2005
https://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Informationforlicenceapplicants/Guidance/OverdosesectionsofSPCs/Genericoverdosesections/Fluoxetine/index.htm
Last accessed: 07 June 2016
Fluoxetine
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Last accessed: 11 February 2021
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Fluoxetine Last revised: 26 April 2016
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NICE Evidence Services Available at: www.nice.org.uk Last accessed: 06 March, 2018
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