FLUOXETINE

Posology Adults Major depressive episodes Adults and the elderly:

The recommended dose is 20 mg daily. Dosage should be reviewed and adjusted if necessary within 3 to 4 weeks of initiation of 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 increased potential for undesirable effects at higher doses, in some patients, if after two weeks there is insufficient response to 20 mg, the dose may be increased gradually up to a maximum of 60 mg.

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 3 months) has not been demonstrated in bulimia nervosa. All indications The recommended dose may be increased or decreased. Doses above 80 mg/day have not been systematically evaluated.

Paediatric population - Children and adolescents aged 8 years and above (Moderate to severe major depressive episode) Treatment should be initiated and monitored under specialist supervision. 5 ml of Fluoxetine Capsules oral solution.

Dose adjustments should be made carefully, on an individual basis, to maintain the patient at the lowest effective dose. After one to two weeks, the dose may be increased to 20 mg/day. Clinical trial experience with daily doses greater than 20 mg is minimal.

There is only limited data on treatment beyond 9 weeks. 2). For paediatric patients who respond to treatment, the need for continued treatment after 6 months should be reviewed. If no clinical benefit is achieved within 9 weeks, treatment should be reconsidered.

Elderly patients Caution is recommended when increasing the dose and the daily dose should generally, not exceed 40 mg. Maximum recommended dose is 60 mg/day. g. 5).

Withdrawal symptoms seen on discontinuation of Fluoxetine Capsules:

Abrupt discontinuation should be avoided. 8). If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate.

Method of administration For oral administration. Fluoxetine may be administered as a single or divided dose, during or between meals. The capsules should be swallowed whole with a glass of water. When dosing is stopped, active drug substances will persist in the body for weeks.

This should be borne in mind when starting or stopping treatment.

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

b. 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 to 1/1,000). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Very Common Common Uncommon Rare Unknown Blood and lymphatic system disorders Thrombocytopenia Neutropenia Leucopenia Immune system disorders Anaphylactic reaction Serum sickness Endocrine disorders Inappropriate antidiuretic hormone secretion Metabolism and nutrition disorders Decreased appetite1 Hyponatraemia Psychiatric disorders Insomnia 2 Anxiety Nervousness Restlessness Tension Libido decreased3 Sleep disorder Abnormal dreams4 Depersonalisation Elevated mood Euphoric mood Thinking abnormal Orgasmabnormal5 Bruxism Suicidal thoughts and behaviour 6 Hypomania Mania Hallucinations Agitation Panic attacks Confusion Dysphemia Aggression Nervous system disorders Headache Disturbance in attention Dizziness Dysgeusia Lethargy Somnolence7 Tremor Psychomotor hyperactivity Dyskinesia Ataxia Balance disorder Myoclonus Memory impairment Convulsion Akathisia Buccoglossal syndrome Serotonin syndrome Eye disorders Vision blurred Mydriasis Ear and labyrinth disorders Tinnitus Cardiac disorders Palpitations Electrocardiogram QT prolonged (QTcF ≥450 msec)8 Ventricular arrhythmia including torsades de pointes Vascular disorders Flushing9 Hypotension Vasculitis Vasodilatation Respiratory, thoracic and mediastinal disorders Yawning Dyspnoea Epistaxis Pharyngitis Pulmonary events (inflammatory processes of varying histopathology and/or fibrosis) 10 Gastrointestinal disorders Diarrhoea Nausea Vomiting Dyspepsia Dry mouth Dysphagia Gastrointestinal haemorrhage11 Oesophageal pain Hepato-biliary disorders Idiosyncratic hepatitis Skin and subcutaneous tissue disorders Rash12 Urticaria Pruritus Hyperhidrosis Alopecia Increased tendency to bruise Cold sweat Angioedema Ecchymosis Photosensitivity reaction Purpura Erythema multiforme Stevens-Johnson syndrome Toxic Epidermal Necrolysis (Lyell Syndrome) Musculoskeletal and connective tissue disorders Arthralgia Muscle twitching Myalgia Renal and urinary disorders Frequent urination13 Dysuria Urinary retention Micturition disorder Reproductive system and breast disorders Gynaecological bleeding14 Erectile dysfunction Ejaculation disorder15 Sexual dysfunction Galactorrhoea Hyperprolactinaem ia Priapism General disorders and administration site conditions Fatigue16 Feeling jittery Chills Malaise Feeling abnormal Feeling cold Feeling hot Mucosal haemorrhage Postpartum Haemorrhage17 Investigations Weight decreased 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 Includesanorgasmia 6 Includes completed suicide, depression suicidal, intentional self-injury, self-injurious ideation, suicidal behaviour, suicidal ideation, suicide attempt, morbid thoughts, self- injurious behaviour.

6) c. 4).

Bone fractures:

Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving SSRIs and TCAs. The mechanism leading to the risk is unknown.

Withdrawal symptoms seen on discontinuation of fluoxetine treatments:

Discontinuation of fluoxetine commonly leads to withdrawal symptoms. Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), asthenia, agitation or anxiety, nausea and/or vomiting, tremor and headache are the most commonly reported reactions.

4). 4). d. 1) Adverse […]

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 antidepressants compared to those treated with placebo.

Fluoxetine Capsules should only be used in children and adolescents aged 8 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.

3). 1). 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. 8). 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 prescriber discusses carefully the risks and benefits of treatment with 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). 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 suicide may increase in the early stages of recovery. Other psychiatric conditions for which Fluoxetine Capsules 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 or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts and should receive careful monitoring during treatment.

A meta-analysis of placebo-controlled clinical trials of antidepressants drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

9). 5). If patients with stable cardiac disease are treated, an ECG review should be considered before treatment is started. If signs of cardiac arrhythmia occur during treatment with fluoxetine, the treatment should be withdrawn, and an ECG should be performed.

g. iproniazid) Some cases of serious and sometimes fatal reactions have been reported in patients receiving an SSRI in combination with an irreversible, non-selective monoamine oxidase inhibitor (MAOI). These cases presented with features resembling serotonin syndrome (which may resemble and be diagnosed as neuroleptic malignant syndrome).

Cyproheptadine or dantrolene may benefit patients experiencing such reactions. Symptoms of a drug interaction with a MAOI include hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes that include confusion, irritability and extreme agitation progressing to delirium and coma.

3). Because of the two weeks-lasting effect of the latter, treatment of fluoxetine should only be started 2 weeks after discontinuation of an irreversible, non-selective MAOI. Similarly, at least 5 weeks should elapse after discontinuing fluoxetine treatment before starting an irreversible, non-selective MAOI.

Serotonin syndrome or neuroleptic malignant syndrome-like events On rare occasions development of a serotonin syndrome or neuroleptic malignant syndrome-like events have been reported in association with treatment of […]

1. g. 5). 5).