OLENA

Posology Adults Major depressive episodes Adults and the elderly Adults and the elderly: The recommended dose is 20mg 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 20mg 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 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 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 60mg/day is recommended. Long-term efficacy (more than 3 months) has not been demonstrated in bulimia nervosa.

All indications:

Adults: The recommended dose may be increased or decreased. Doses above 80mg/day have not been systematically evaluated. Fluoxetine may be administered as a single or divided dose, during or between meals. 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. 5).

Withdrawal symptoms seen on discontinuation of Olena Tablets:

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.

Elderly:

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

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. The starting dose is 10mg/day given as half of a tablet of Olena 20mg dispersible tablet.

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 20mg/day. Clinical trial experience with daily doses greater than 20mg 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.

Method of administration For oral administration. g. half a glass of water). Alternatively, the tablet (or half tablet) can be dispersed in half a glass of water just before taking the dose. Do not crush or chew the tablets.

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), not known (frequency cannot be estimated from the available data). Very Commo n Common Uncommon Rare Not known 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 Insomni a2 Anxiety Nervousness Restlessness Tension Libido decreased3 Sleep disorder Abnormal dreams4 Depersonalisa tion Elevated mood Euphoric mood Thinking abnormal Orgasm abnormal5 Bruxism Suicidal Hypomania Mania Hallucinations Agitation Panic attacks Confusion Dysphemia Aggression thoughts and Behaviour6 Nervous system disorders Headach e 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 Electrocardi ogram 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 Diarrho ea Nausea Vomiting Dyspepsia Dry mouth Dysphagia Gastrointesti nal haemorrhage1 1 Oesophageal pain Hepato-biliary disorders Idiosyncratic hepatitis Skin and subcutaneous tissue disorders Rash12 Urticaria Pruritus Hyperhidros is Alopecia Increased tendency to bruise Cold sweat Angioedema Ecchymosis Photosensitivity reaction Purpura Erythema Multiforme Stevens-Johnson syndrome Toxic Epidermal Necrolysis (Lyell Syndrome) Musculoskeletal, connective tissue and bone disorders Arthralgia Muscle twitching Myalgia Renal and urinary disorders Frequent urination13 Dysuria Urinary retention Micturition disorder Reproductive system and breast disorders Gynaecologi cal bleeding14 Erectile dysfunction Sexual dysfunction16 Galactorrhoea Hyperprolactinaemia Priapism Postpartum haemorrhage* Ejaculation disorder15 General disorders and administration site conditions Fatigue1 7 Feeling jittery Chills Malaise Feeling abnormal Feeling cold Feeling hot Mucosal haemorrhage Investigations Weight decreased Transaminase s increased Gamma- glutamyltrans ferase 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.

6). 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 this 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) Paediatric […]

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.

Olena Tablets 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.

Rash and allergic reactions Rash, anaphylactoid events and progressive systemic events, sometimes serious (involving skin, kidney, liver or lung) have been reported. Upon the appearance of rash or of other allergic phenomena for which an alternative aetiology cannot be identified, fluoxetine should be discontinued.

Seizures Seizures are a potential risk with antidepressant drugs. Therefore, as with other antidepressants, fluoxetine should be introduced cautiously in patients who have a history of seizures. Treatment should be discontinued in any patient who develops seizures or where there is an increase in seizure frequency.

5). Electroconvulsive Therapy (ECT) There have been rare reports of prolonged seizures in patients on fluoxetine receiving ECT treatment, therefore caution is advisable. Mania Antidepressants should be used with caution in patients with a history of mania/hypomania.

As with all antidepressants, fluoxetine should be discontinued in any patient entering a manic phase. Hepatic/Renal function Fluoxetine is extensively metabolised by the liver and excreted by the kidneys. , alternate day dosing, is recommended in patients with significant hepatic dysfunction.

When given fluoxetine 20mg/day for 2 months, patients with severe renal failure (GFR <10ml/min) requiring dialysis showed no difference in plasma levels of fluoxetine or norfluoxetine compared to controls with normal renal function.

Tamoxifen:

Fluoxetine, a potent inhibitor of CYP2D6, may lead to reduced concentrations of endoxifen, one of the most important active metabolites of tamoxifen. 5). 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. Weight loss Weight loss may occur in patients taking fluoxetine, but it is usually proportional to baseline body weight.

Diabetes In patients with diabetes, treatment with an SSRI may alter glycaemic control. Hypoglycaemia has occurred during therapy with fluoxetine and hyperglycaemia has developed following discontinuation. Insulin and/or oral hypoglycaemic dosage may need to be adjusted.

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 Olena Tablets are 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 […]

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