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.

5 mg once daily is recommended. 5 mg once daily not more frequently than every other day, if needed. The optimum dose is 1 mg once daily for most patients. 5 mg once daily. 25 mg once daily is recommended. 25 mg once daily not more frequently than every other day, if needed.

5 mg once daily for most patients. 75 mg once daily. As with all symptomatic treatments, the continued use of risperidone must be evaluated and justified on an ongoing basis. Risperidone is not recommended in children less than 5 years of age, as there is no experience in children less than 5 years of age with this disorder.

Renal and hepatic impairment Patients with renal impairment have less ability to eliminate the active antipsychotic fraction than in adults with normal renal function. Patients with impaired hepatic function have increases in plasma concentration of the free fraction of risperidone.

Irrespective of the indication, starting and consecutive dosing should be halved, and dose titration should be slower for patients with renal or hepatic impairment. Risperidone should be used with caution in these groups of patients.

Method of administration Risperidone is for oral use. Food does not affect the absorption of risperidone. Do not open the blister until ready to administer. Peel open the blister to expose the tablet. Do not push the tablet through the foil because it may break.

Remove the tablet from the blister with dry hands. Immediately place the tablet on the tongue. The tablet will begin disintegrating within seconds. Water may be used if desired. No attempt should be made to divide the tablet. Upon discontinuation, gradual withdrawal is advised.

8). Recurrence of psychotic symptoms may also occur, and the emergence of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) has been reported. Switching from other antipsychotics When medically appropriate, gradual discontinuation of the previous treatment while risperidone therapy is initiated is recommended.

Also, if medically appropriate, when switching patients from depot antipsychotics, initiate risperidone therapy in place of the next scheduled injection. The need for continuing existing anti-Parkinson medicines should be re-evaluated periodically.

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

11% in placebo group. Overall […]

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 (CVAEs) 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.

2% (8/712) of patients treated with placebo. 50). The mechanism for this increased risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient populations. Risperidone should be used with caution in patients with risk factors for stroke.

The risk of CVAEs was significantly higher in patients with mixed or vascular type of dementia when compared to Alzheimer’s dementia. Therefore, patients with other types of dementias than Alzheimer’s should not be treated with risperidone.

Physicians are advised to assess the risks and benefits of the use of risperidone in elderly patients with dementia, taking into account risk predictors for stroke in the individual patient. 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.

All treatment options should be considered without delay, including discontinuation of risperidone. Risperidone should only be used short term for persistent aggression in patients with moderate to severe Alzheimer’s dementia to supplement non- pharmacological approaches which have had limited or no efficacy and when there is potential risk of harm to self or others.

Patients should be reassessed regularly, and the need for continuing treatment reassessed. Orthostatic hypotension Due to the alpha-blocking activity of risperidone, (orthostatic) hypotension can occur, especially during the initial dose-titration period.

Clinically significant hypotension has been observed postmarketing with concomitant use of risperidone and antihypertensive treatment. 2). A dose reduction should be considered if hypotension occurs. Leukopenia, neutropenia, and agranulocytosis Events of leucopenia, neutropenia and agranulocytosis have been reported with antipsychotic agents, including risperidone.

Agranulocytosis has been reported very rarely (< 1/10,000 patients) during post-marketing surveillance. Patients with a history of a clinically significant low white blood cell count (WBC) or a drug-induced leukopenia/neutropenia should be monitored during the first few months of therapy and discontinuation of risperidone should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors.

Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count < 1 x 109/L) should discontinue risperidone and have their WBC followed until recovery.

Tardive dyskinesia/ Extrapyramidal […]

1.