RISPERIDONE

Posology Schizophrenia Adults Risperidone may be given once daily or twice daily. Patients should start with 2 mg/day risperidone. The dosage may be increased on the second day to 4 mg. Subsequently, the dosage can be maintained unchanged, or further individualised, if needed.

Most patients will benefit from daily doses between 4 and 6 mg. In some patients, a slower titration phase and a lower starting and maintenance dose may be appropriate. Doses above 10 mg/day have not demonstrated superior efficacy to lower doses and may cause increased incidence of extrapyramidal symptoms.

Safety of doses above 16 mg/day has not been evaluated and are therefore not recommended. 5 mg twice daily is recommended. 5 mg twice daily increments to 1 to 2 mg twice daily. Paediatric population Risperidone is not recommended for use in children and adolescents below age 18 with schizophrenia due to a lack of data on efficacy.

Manic episodes in bipolar disorder Adults Risperidone should be administered on a once daily schedule, starting with 2 mg risperidone. Dosage adjustments, if indicated, should occur at intervals of not less than 24 hours and in dosage increments of 1 mg per day.

Risperidone can be administered in flexible doses over a range of 1 to 6 mg per day to optimize each patient’s level of efficacy and tolerability. Daily doses over 6 mg risperidone have not been investigated in patients with manic episodes.

As with all symptomatic treatments, the continued use of Risperidone must be evaluated and justified on an ongoing basis. 5 mg twice daily is recommended. 5 mg twice daily increments to 1 to 2 mg twice daily. Since clinical experience in elderly is limited, caution should be exercised.

Paediatric population Risperidone is not recommended for use in children and adolescents below age 18 with bipolar mania due to a lack of data on efficacy. 25 mg* twice daily is recommended. 25 mg* twice daily, not more frequently than every other day, if needed.

5 mg twice daily for most patients. Some patients, however, may benefit from doses up to 1 mg twice daily. Risperidone should not be used more than 6 weeks in patients with persistent aggression in Alzheimer’s dementia. During treatment, patients must be evaluated frequently and regularly, and the need for continuing treatment reassessed.

The most frequently reported adverse drug reactions (ADRs) (incidence ≥10%) are: Parkinsonism, sedation/somnolence, headache, and insomnia. The ADRs that appeared to be dose-related included parkinsonism and akathisia. The following are all the ADRs that were reported in clinical trials and post-marketing experience with risperidone by frequency category estimated from clinical trials.

The following terms and frequencies are applied: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), and not known (cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Adverse Drug Reactions (ADRs) by System Organ Class and Frequency MedDRA System Organ Class Frequency ADRs Common Pneumonia, Bronchitis, Upper respiratory tract infection, Sinusitis, Urinary tract infection, Ear infection, Influenza Uncommon Respiratory tract infection, Cystitis, Eye infection, Tonsillitis, Onychomycosis, Cellulitis, Localised infection, Viral infection, Acarodermatitis Infections and infestations Rare Infection Uncommon Neutropenia, White blood cell count decreased, Thrombocytopenia, Anaemia, Haematocrit decreased, Eosinophil count increased Blood and lymphatic system disorders Rare Agranulocytosisc Uncommon HypersensitivityImmune system disorders Rare Anaphylactic reactionc Common Hyperprolactinaemiaa Endocrine disorders Rare Inappropriate antidiuretic hormone secretion, Glucose urine present Common Weight increased, Increased appetite, Decreased appetite Metabolism and nutrition disorders Uncommon Diabetes mellitusb, Hyperglycaemia, Polydipsia, Weight decreased, Anorexia, Blood cholesterol increased Rare Water intoxicationc ,Hypoglycaemia, Hyperinsulinaemiac, Blood triglycerides increased Very rare Diabetic ketoacidosis Very common Insomniad Common Sleep disorder, Agitation, Depression, Anxiety Uncommon Mania, Confusional state, Libido decreased, Nervousness, Nightmare Psychiatric disorders Rare Catatonia, Somnambulism, Sleep-related eating disorder, Blunted affect, Anorgasmia Very common Sedation/Somnolence, Parkinsonismd, Headache Common Akathisiad, Dystoniad, Dizziness, Dyskinesiad, Tremor, Uncommon Tardive dyskinesia, Cerebral ischaemia, Unresponsive to stimuli, Loss of consciousness, Depressed level of consciousness, Convulsiond, Syncope, Psychomotor hyperactivity, Balance disorder, Coordination abnormal, Dizziness postural, Disturbance in attention, Dysarthria, Dysgeusia, Hypoaesthesia, Paraesthesia, Nervous system disorders Rare Neuroleptic malignant syndrome, Cerebrovascular disorder, Diabetic coma, Head titubation Common Vision blurred, Conjunctivitis Uncommon Photophobia, Dry eye, Lacrimation increased, Ocular hyperaemia Eye disorders Rare Glaucoma, Eye Movement disorder, Eye rolling, Eyelid margin crusting, Floppy iris syndrome (intraoperative)c Ear and labyrinth disorders Uncommon Vertigo, Tinnitus, Ear pain Common Tachycardia Uncommon Atrial fibrillation, Atrioventricular block, Conduction disorder, Electrocardiogram QT prolonged, Bradycardia, Electrocardiogram abnormal, Palpitations Cardiac disorders Rare Sinus arrhythmia Common Hypertension Uncommon Hypotension, Orthostatic hypotension, Flushing Vascular disorders Rare Pulmonary embolism, Venous thrombosis Common Dyspnoea, Pharyngolaryngeal pain, Cough, Epistaxis, Nasal congestion Respiratory, thoracic and mediastinal disorders Uncommon Pneumonia aspiration, Pulmonary congestion, Respiratory tract congestion, Rales, Wheezing, Dysphonia, Respiratory disorder Rare Sleep apnea syndrome, Hyperventilation Common Abdominal pain, Abdominal discomfort, Vomiting, Nausea, Constipation, Diarrhoea, Dyspepsia, Dry mouth, Toothache Uncommon Faecal incontinence, Faecaloma, Gastroenteritis, Dysphagia, Flatulence Rare Pancreatitis, Intestinal obstruction, Swollen tongue, Cheilitis Gastrointestinal disorders Very rare Ileus Uncommon Transaminases increased, Gamma- glutamyltransferase increased, Hepatic enzyme increased Hepato-biliary disorders Rare Jaundice Common Rash, Erythema Uncommon Urticaria, Pruritus, Alopecia, Hyperkeratosis, Eczema, Dry skin, Skin discolouration, Acne, Seborrhoeic dermatitis, Skin disorder, Skin lesion, Rare Drug eruption, Dandruff Skin and subcutaneous tissue disorders Very rare Angioedema Not known Stevens-Johnson syndrome/toxic epidermal necrolysisc Common Muscle Spasms, Musculoskeletal pain, Back pain, Arthralgia Uncommon Blood creatine phosphokinase increased, Posture abnormal, Joint stiffness, Joint swelling, Muscular weakness, Neck pain Musculoskeletal and connective tissue disorders Rare Rhabdomyolysis Common Urinary incontinenceRenal and urinary disorders Uncommon Pollakiuria, Urinary retention, Dysuria Pregnancy, puerperium and neonatal conditions Rare Drug withdrawal syndrome neonatalc Uncommon Erectile dysfunction, Ejaculation disorder, Amenorrhoea, Menstrual disorderd, Gynaecomastia, Galactorrhoea, Sexual dysfunction, Breast pain, Breast discomfort, Vaginal discharge Reproductive system and breast disorders Rare Priapismc, Menstruation delayed, Breast engorgement, Breast enlargement, Breast discharge Common Oedemad, Pyrexia, Chest pain, Asthenia, Fatigue, Pain General disorders and administration site conditions Uncommon Face oedema, Chills, Body temperature increased, Gait abnormal, Thirst, Chest discomfort, Malaise, Feeling abnormal, Discomfort Rare Hypothermia, Body temperature decreased, Peripheral coldness, Drug withdrawal syndrome, Indurationc Common FallInjury, poisoning and procedural complications Uncommon Procedural pain a Hyperprolactinaemia can in some cases lead to gynaecomastia, menstrual disturbances, amenorrhoea, anovulation, galactorrhea, fertility disorder, decreased libido, erectile dysfunction.

Elderly patients with dementia Increased mortality in elderly people with dementia In a meta-analysis of 17 controlled trials of atypical antipsychotics, including risperidone, elderly patients with dementia treated with atypical antipsychotics have an increased mortality compared to placebo.

1% for placebo-treated patients. 1). The mean age (range) of patients who died was 86 years (range 67-100). Data from two large observational studies showed that elderly people with dementia who are treated with conventional antipsychotics are also at a small increased risk of death compared with those who are not treated.

There are insufficient data to give a firm estimate of the precise magnitude of the risk and the cause of the increased risk is not known. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.

1%; mean age 80 years, range 67-90). The increase in mortality in patients treated with furosemide plus risperidone was observed in two of the four clinical trials. Concomitant use of risperidone with other diuretics (mainly thiazide diuretics used in low dose) was not associated with similar findings.

No pathophysiological mechanism has been identified to explain this finding, and no consistent pattern for cause of death observed. Nevertheless, caution should be exercised and the risks and benefits of this combination or co-treatment with other potent diuretics should be considered prior to the decision to use.

There was no increased incidence of mortality among patients taking other diuretics as concomitant treatment with risperidone. Irrespective of treatment, dehydration was an overall risk factor for mortality and should therefore be carefully avoided in elderly patients with dementia.

Cerebrovascular Adverse Events (CVAE) An approximately 3-fold increased risk of cerebrovascular adverse events has been seen in randomised placebo controlled clinical trials in the dementia population with some atypical antipsychotics.

1.