FLUOXETINE

Posology Adults Major Depressive Episodes Adults and the elderly:

The recommended dose is 20 mg/day. Dosage should be reviewed and adjusted if necessary within 3 to 4 weeks of initiation therapy and thereafter as judged clinically appropriate. 1). Dosage adjustments should be made carefully on an individual patient basis, to maintain the patients at the lowest effective dose.

Patients with depression should be treated for a sufficient period of at least 6 months to ensure that they are free from symptoms. Obsessive-compulsive disorder.

Adults and the elderly:

The recommended dose is 20 mg daily. Although there may be an increase in the potential of side-effects at higher doses, in some patients, if after two weeks there is insufficient response to 20mg, the dose may be increased gradually up to a maximum of 60mg.

If no improvement is observed within 10 weeks, treatment with fluoxetine should be reconsidered. If a good therapeutic response has been obtained, treatment can be continued at a dosage adjusted on an individual basis. While there are no systematic studies to answer the question of how long to continue fluoxetine treatment, OCD is a chronic condition and it is reasonable to consider continuation beyond 10 weeks in responding patients.

Dosage adjustments should be made carefully on an individual patient basis, to maintain the patient at the lowest effective dose. The need for treatment should be reassessed periodically. Some clinicians advocate concomitant behavioural psychotherapy for patients who have done well on pharmacotherapy.

Long-term efficacy (more than 24 weeks) has not been demonstrated in OCD.

Bulimia nervosa – Adults and the elderly:

A dose of 60 mg/day is recommended. Long term efficacy (more than three months) has not been demonstrated in bulimia nervosa.

All indications:

The recommended dose may be increased or decreased. Doses above 80mg/day have not been systematically evaluated.

Paediatric Population:

Summary of the safety profile The most commonly reported adverse reactions in patients treated with fluoxetinewere headache, nausea, insomnia, fatigue and diarrhoea. Undesirable effects may decrease in intensity and frequency with continued treatmentand do not generally lead to cessation of therapy.

Tabulated list of adverse reactions The table below gives the adverse reactions observed with fluoxetine treatment in adult and paediatric populations.

Some of these adverse reactions are in common with other SSRIs:

The following frequencies have been calculated from clinical trials in adults (n =9297) and from spontaneous reporting.

Frequency estimate:

Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000), very rare (<1/10,000) not known (frequency cannot be estimated from the available data). System Organ Class Frequency Adverse reactions Blood and lymphatic system disorders Rare Thrombocytopenia Neutropenia Leucopenia Immune system disorders Rare Anaphylactic reaction Serum sickness Endocrine disorders Rare Inappropriate antidiuretic hormone secretion Common Decreased appetite1 Metabolism and nutrition disorders Rare Hyponatraemia Psychiatric disorders Very common Insomnia2 Common Anxiety Nervousness Restlessness Tension Libido decreased3 Sleep disorder Abnormal dreams4 Uncommon Depersonalisation Elevated mood Euphoric mood Thinking abnormal Orgasm abnormal5 Bruxism Suicidal thoughts and behaviour14 Rare Hypomania Mania Hallucinations Agitation Panic attacks Confusion Dysphemia Aggression Very common Headache Common Disturbance in attention Dizziness Dysgeusia Lethargy Somnolence7 Tremor Uncommon Psychomotor hyperactivity Dyskinesia Ataxia Balance disorder Myoclonus Memory impairment Nervous system disorders Rare Convulsion Akathisia Buccoglossal syndrome Serotonin syndrome Common Vision blurredEye disorders Uncommon Mydriasis Ear and labyrinth disorders Uncommon Tinnitus Common Palpitations Electrocardiogram QT prolonged (QTcF ≥450 msec)8 Cardiac disorders Rare Ventricular arrhythmia including torsade de pointes Vascular disorders Common Flushing9 Uncommon Hypotension Rare Vasculitis Vasodilatation Common Yawning Uncommon Dyspnoea Epistaxis Respiratory, thoracic and mediastinal disorders Rare Pharyngitis Pulmonary events (inflammatory processes of varying histopathology and/or fibrosis)10 Very common Diarrhoea Nausea Common Vomiting Dyspepsia Dry mouth Uncommon Dysphagia Gastrointestinal haemorrhage11 Gastrointestinal disorders Rare Oesophageal pain Hepato-biliary disorders Rare Idiosyncratic hepatitis Common Rash12 Urticaria Pruritus Hyperhidrosis Uncommon Alopecia Increased tendency to bruise Cold sweat Skin and subcutaneous tissue disorders Rare Angioedema Ecchymosis Photosensitivity reaction Purpura Erythema multiforme Stevens-Johnson syndrome Toxic Epidermal Necrolysis (Lyell Syndrome) Common Arthralgia Uncommon Muscle twitching Musculoskeletal, connective tissue and bone disorders Rare Myalgia Common Frequent urination13 Uncommon Dysuria Renal and urinary disorders Rare Urinary retention Micturition disorder Common Gynaecological bleeding14 Erectile dysfunction Ejaculation disorder15 Reproductive system and breast disorders Uncommon Sexual dysfunction Rare Galactorrhoea Hyperprolactinaemia Priapism Not known Postpartum haemorrhage17 Very common Fatigue16 Common Feeling jittery Chills Uncommon Malaise Feeling abnormal Feeling cold Feeling hot General disorders and administration site conditions Rare Mucosal haemorrhage Common Weight decreasedInvestigations Uncommon Transaminases increased Gamma-glutamyltransferase increased 1 Includes anorexia 2 Includes early morning awakening, initial insomnia, middle insomnia 3 Includes loss of libido 4 Includes nightmares 5 Includes anorgasmia 6 Includes completed suicide, depression suicidal, intentional self-injury, self- injurious ideation, suicidal behavior, suicidal ideation, suicide attempt, morbid thoughts, self injurious behaviour.

Paediatric population - Children and adolescents under 18 years of age:

Suicide-related behaviours (suicide attempt and suicidal thoughts), and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressantscompared to those treated with placebo.

Fluoxetine should only be used in children and adolescents aged eight to 18 years for the treatment of moderate to severe major depressive episodes and it should not be used in other indications. If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms.

8). It has not been established whether there is an effect on achieving normal adult height. 8). Growth and pubertal development (height, weight and TANNER staging) should therefore be monitored during and after treatment with fluoxetine.

If either is slowed, referral to a paediatrician should be considered. Therefore, regular monitoring for the occurrence of mania/hypomania is recommended. Fluoxetine should be discontinued in any patient entering a manic phase. It is important that the prescribers discuss carefully the risks and benefits of treatmentwith the child/young person and/or their parents.

Suicide/suicidal thoughts or clinical worsening:

Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). 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 suicide may increase in the early stages of recovery. Other psychiatric conditions for which fluoxetine is prescribed can also be associated with an increased risk of suicide-related events.

1. g. 5). 5)