Risperidone is indicated for the treatment of moderate to severe manic episodes associated with bipolar disorders. Risperidone is metabolised by CYP 2D6 to 9-hydroxy-risperidone, which has a similar pharmacological activity as risperidone. The above effects showed little or no reversibility in females after a 12 week drug-free recovery period.In a study in which juvenile rats were treated with oral Risperidone from days 12 to 50 of age, a reversible impairment of performance in a test of learning and memory was seen, in females only, with a no-effect dose of 0.63 mg/kg/day. The increase in mortality in patients treated with furosemide plus risperidone was observed in two of the four clinical trials. Risperidone should be used with caution in patients with known cardiovascular disease (e.g., heart failure, myocardial infarction, conduction abnormalities, dehydration, hypovolemia, or cerebrovascular disease), and the dosage should be gradually titrated as recommended (see section 4.2). If discontinuation during pregnancy is necessary, it should not be done abruptly. Patients/caregivers should be cautioned to immediately report signs and symptoms of potential CVAEs such as sudden weakness or numbness in the face, arms or legs, and speech or vision problems. The mean age (range) of patients who died was 86 years (range 67-100). This dose produced plasma AUC levels of Risperidone plus paliperidone about half those observed in humans at the MRHD. Doses higher than 2.5 mg/day did not reveal any trend towards greater efficacy.The efficacy of Risperidone in the treatment of irritability associated with autistic disorder was established in two 8-week, placebo-controlled trials in children and adolescents (aged 5 to 16 years) who met the DSM-IV criteria for autistic disorder. (See also section 4.4)The efficacy of risperidone in the short-term treatment of disruptive behaviours was demonstrated in two double-blind placebo-controlled studies in approximately 240 patients 5 to 12 years of age with a DSM-IV diagnosis of disruptive behaviour disorders (DBD) and borderline intellectual functioning or mild or moderate mental retardation/learning disorder. In a 6-week, placebo-controlled trial involving titration of risperidone in doses up to 10 mg/day administered twice daily, risperidone was superior to placebo on the Brief Psychiatric Rating Scale (BPRS) total score. Other class-related cardiac effects reported with antipsychotics which prolong QT interval include ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac arrest and Torsades de Pointes. Risperidone tablets are indicated for the treatment of acute manic or mixed episodes associated with Bipolar I Disorder. QT prolongation has very rarely been reported postmarketing. If this combination is deemed necessary, particularly in end-stage Parkinson's disease, the lowest effective dose of each treatment should be prescribed. A similar trend was observed in the mean change from baseline in body mass index.When treating pediatric patients with Risperidone for any indication, weight gain should be assessed against that expected with normal growth.Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This dosage can be individually adjusted by increments of 0.25 mg twice daily, not more frequently than every other day, if needed. Inactive ingredients are colloidal silicon dioxide, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, propylene glycol, sodium lauryl sulfate, sodium starch glycolate. The following ADRs were reported with a frequency ≥5% in paediatric patients (5 to 17 years) and with at least twice the frequency seen in clinical trials in adults: somnolence/sedation, fatigue, headache, increased appetite, vomiting, upper respiratory tract infection, nasal congestion, abdominal pain, dizziness, cough, pyrexia, tremor, diarrhoea, and enuresis. These include drowsiness and sedation, tachycardia and hypotension, and extrapyramidal symptoms. In short-term schizophrenia trials, higher doses of Risperidone (8 to 16 mg/day) were associated with a higher mean increase in heart rate compared to placebo (4 to 6 beats per minute). The adverse reactions associated with discontinuation for at least one Risperidone-treated patient were dizziness (2%), somnolence (1%), sedation (1%), lethargy (1%), anxiety (1%), balance disorder (1%), hypotension (1%), and palpitation (1%).In double-blind, placebo-controlled trials with Risperidone as monotherapy, approximately 6% (25/448) of Risperidone-treated patients discontinued treatment due to an adverse event, compared with approximately 5% (19/424) of placebo-treated patients. Risperidone is indicated for the short-term treatment (up to 6 weeks) of persistent aggression in patients with moderate to severe Alzheimer's dementia unresponsive to non-pharmacological approaches and when there is a risk of harm to self or others.Risperidone is indicated for the short-term symptomatic treatment (up to 6 weeks) of persistent aggression in conduct disorder in children from the age of five years and adolescents with subaverage intellectual functioning or mental retardation diagnosed according to DSM-IV criteria, in whom the severity of aggressive or other disruptive behaviours require pharmacologic treatment.