Use in Children and adolescents under 18 years of ageSuicide-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. Oxactin Capsules should only be used in children and adolescents aged 8-18 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. In addition, long term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking. In addition, 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 developments. (see section 5.3)In a 19 week clinical trial, decreased height and weight gain was observed in children and adolescents treated with fluoxetine (see section 4.8). It has not been established whether there is an effect on achieving normal adult height. The possibility of a delay in puberty cannot be ruled out (see section 5.3 and 4.8). 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.In paediatric trials, mania and hypomania were commonly reported (see section 4.8). 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. Fluoxetine should be avoided in patients with unstable seizure disorders/epilepsy, and patients with controlled epilepsy should be carefully monitored. 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. A lower dose, eg, alternate day dosing, is recommended in patients with significant hepatic dysfunction. When given fluoxetine 20 mg/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. Cardiac disease: No conduction abnormalities that resulted in heart block were observed in the ECG of 312 patients who received fluoxetine in double-blind clinical trials. However, clinical experience in acute cardiac disease is limited, therefore caution is advisable. 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 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, 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 antidepressant 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.Akathisia/psychomotor restlessness: The use of fluoxetine has been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.Withdrawal symptoms seen on discontinuation of SSRI treatment: Withdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt (see section 4.8). In clinical trials adverse events seen on treatment discontinuation occurred in approximately 60% of patients in both the fluoxetine and placebo groups. Of these adverse events, 17% in the fluoxetine group and 12% in the placebo group were severe in nature.The risk of withdrawal symptoms may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction. 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. Generally these symptoms are mild to moderate however, in some patients they may be severe in intensity. They usually occur within the first few days of discontinuing treatment. Generally these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or more). It is therefore advised that Fluoxetine should be gradually tapered when discontinuing treatment over a period of at least one to two weeks, according to the patient's needs (see "Withdrawal Symptoms Seen on Discontinuation of Fluoxetine", Section 4.2).Haemorrhage: There have been reports of cutaneous bleeding abnormalities, such as ecchymosis and purpura, with SSRIs. Ecchymosis has been reported as an infrequent event during treatment with fluoxetine. Other haemorrhagic manifestations (e.g., gynaecological haemorrhages, gastro-intestinal bleedings, and other cutaneous or mucous bleedings) have been reported rarely. Caution is advised in patients taking SSRIs, particularly in concomitant use with oral anticoagulants, drugs known to affect platelet function (e.g., atypical antipsychotics, such as clozapine, phenothiazines, most TCAs, aspirin, NSAIDs), or other drugs that may increase risk of bleeding, as well as in patients with a history of bleeding disorders. Electroconvulsive therapy (ECT): There have been rare reports of prolonged seizures in patients on fluoxetine receiving ECT treatment, therefore caution is advisable. St John's Wort: An increase in serotonergic effects, such as serotonin syndrome, may occur when selective serotonin reuptake inhibitors and herbal preparations containing St John's Wort (Hypericum perforatum) are used together. On rare occasions, development of a serotonin syndrome or neuroleptic malignant syndrome-like events have been reported in association with treatment of fluoxetine, particularly when given in combination with other serotonergic (among others, L-tryptophan) and/or neuroleptic drugs. As these syndromes may result in potentially life-threatening conditions, treatment with fluoxetine should be discontinued if such events (characterised by clusters of symptoms, such as hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes, including confusion, irritability, extreme agitation, progressing to delirium and coma) occur, and supportive symptomatic treatment should be initiated. This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.