RISPERDAL CONSTA

Posology Adults Starting dose For most patients the recommended dose is 25 mg intramuscular every two weeks. For those patients on a fixed dose of oral risperidone for two weeks or more, the following conversion scheme should be considered.

5 mg. M. starting dose. The recommended starting dose is 25 mg RISPERDAL CONSTA every two weeks. 5 mg. 2). RISPERDAL CONSTA should not be used in acute exacerbations of schizophrenia without ensuring sufficient antipsychotic coverage with oral risperidone or the previous antipsychotic during the three-week lag period following the first RISPERDAL CONSTA injection.

Maintenance dose For most patients the recommended dose is 25 mg intramuscular every two weeks. 5 mg or 50 mg. Upward dosage adjustment should not be made more frequently than every 4 weeks. The effect of this dose adjustment should not be anticipated earlier than 3 weeks after the first injection with the higher dose.

No additional benefit was observed with 75 mg in clinical trials. Doses higher than 50 mg every 2 weeks are not recommended. Elderly No dose adjustment is required. The recommended dose is 25 mg intramuscularly every two weeks. Where patients are not currently taking oral risperidone, the recommended dose is 25 mg RISPERDAL CONSTA every two weeks.

For those patients on a fixed dose of oral risperidone for two weeks or more, the following conversion scheme should be considered. 5 mg. 2). RISPERDAL CONSTA clinical data in elderly are limited. RISPERDAL CONSTA should be used with caution in elderly.

Hepatic and renal impairment RISPERDAL CONSTA has not been studied in hepatically and renally impaired patients. 5 mg twice daily oral risperidone is recommended during the first week. The second week 1 mg twice daily or 2 mg once daily can be given.

If an oral total daily dose of at least 2 mg is well tolerated, an injection of 25 mg RISPERDAL CONSTA can be administered every 2 weeks. 2). Paediatric population The safety and efficacy of RISPERDAL CONSTA in children below 18 years of age have not been established.

No data are available. Method of administration RISPERDAL CONSTA should be administered every two weeks by deep intramuscular deltoid or gluteal injection using the appropriate safety needle. For deltoid administration, use the 1-inch needle alternating injections between the two arms.

For gluteal administration, use the 2-inch needle alternating injections between the two buttocks. 6). 6.

The most frequently reported adverse drug reactions (ADRs) (incidence ≥ 1/10) are: insomnia, anxiety, headache, upper respiratory tract infection, parkinsonism, and depression. The ADRs that appeared to be dose-related included parkinsonism and akathisia.

Serious injection site reactions including injection site necrosis, abscess, cellulitis, ulcer, haematoma, cyst, and nodule were reported post-marketing. The frequency is considered not known (cannot be estimated from the available data).

Isolated cases required surgical intervention. The following are all the ADRs that were reported in clinical trials and post-marketing experience with risperidone by frequency category estimated from RISPERDAL CONSTA clinical trials.

The following terms and frequencies are applied: 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), 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 ReactionSystem Organ Class Frequency Very Common Common Uncommon Rare Very Rare Not known Infections and infestatio ns upper respiratory tract infection pneumonia, bronchitis, sinusitis, urinary tract infection, influenza respiratory tract infection, cystitis, ear infection, eye infection, tonsillitis, onychomycos is, cellulitis, infection, localised infection, viral infection, acarodermatit is, subcutaneous abscess Blood and lymphatic system disorders anaemia white blood cell count decreased, thrombocytop enia, haematocrit decreased agranulo cytosisc, neutrope nia, eosinoph il count increase d Immune system disorders hypersensitivi ty anaphyla ctic reactionc Endocrine disorders hyperprolactina emiaa glucose urine present inapprop riate antidiure tic hormone secretion Metabolis m and nutrition disorders hyperglycaemi a, weight increased, increased appetite, weight decreased, decreased appetite diabetes mellitusb, anorexia, blood triglycerides increased, blood cholesterol increased water intoxicat ionc, hypoglyc aemia, hyperins ulinaemi ac, polydipsi a diabetic ketoacidosis Psychiatri c disorders insomniad, depression, anxiety sleep disorder, agitation, libido decreased mania, confusional state, anorgasmia, nervousness, nightmare catatonia , somnam bulism, sleep- related eating disorder, blunted affect Nervous system disorders parkinsonis md, headache sedation/somno lence, akathisiad, dystoniad, dizziness, dyskinesiad, tremor tardive dyskinesia, cerebral ischaemia, loss of consciousness , convulsiond, syncope, psychomotor hyperactivity, balance disorder, coordination abnormal, dizziness postural, disturbance in attention, dysarthria, dysgeusia, hypoaesthesia , paraesthesia neurolep tic malignan t syndrom e, cerebrov ascular disorder, unrespon sive to stimuli, depresse d level of consciou sness, diabetic coma, head titubatio n Eye disorders vision blurred conjunctivitis, dry eye, lacrimation increased, ocular hyperaemia retinal artery occlusio n, glaucom a, eye moveme nt disorder, eye rolling, photoph obia, eyelid margin crusting, floppy iris syndrom e (intraope rative)c Ear and labyrinth disorders vertigo, tinnitus, ear pain Cardiac disorders tachycardia atrial fibrillation, atrioventricul ar block, conduction disorder, electrocardio gram QT prolonged, bradycardia, electrocardio gram abnormal, palpitations sinus arrhythm ia Vascular disorders hypotension, hypertension orthostatic hypotension pulmona ry embolis m, venous thrombo sis, flushing Respirato ry, thoracic and mediastin al disorders dyspnoea, pharyngolaryng eal pain, cough, nasal congestion hyperventilati on, respiratory tract congestion, wheezing, epistaxis sleep apnoea syndrom e, pneumon ia aspiratio n, pulmona ry congesti on, rales, dysphoni a, respirato ry disorder Gastroint estinal disorders abdominal pain, abdominal discomfort, vomiting, nausea, constipation, gastroenteritis, diarrhoea, dyspepsia, dry mouth, toothache faecal incontinence, dysphagia, flatulence pancreati tis, intestinal obstructi on, swollen tongue, faecalom a, cheilitis ileus Skin and subcutane ous tissue disorders rash pruritus, alopecia, eczema, dry skin, erythema, skin discolouratio n, acne, seborrhoeic dermatitis drug eruption, urticaria, hyperker atosis, dandruff, skin disorder, skin lesion angioedema Stevens-Johnson syndrome/toxic epidermal necrolysisc Musculos keletal and connectiv e tissue disorders muscle spasms, musculoskeleta l pain, back pain, arthralgia blood creatine phosphokinas e increased, joint stiffness, joint swelling, muscular weakness, neck pain rhabdom yolysis, posture abnorma l Renal and urinary disorders urinary incontinence pollakiuria, urinary retention, dysuria Pregnanc y, puerperiu m, and neonatal conditions drug withdra wal syndrom e neonatalc Reproduc tive system and breast disorders erectile dysfunction, amenorrhoea, galactorrhoea ejaculation disorder, menstruation delayed, menstrual disorderd, gynaecomasti priapism c, breast engorge ment, breast enlargem ent, a, sexual dysfunction, breast pain, breast discomfort, vaginal discharge breast discharg e General disorders and administr ation site conditions oedemad, pyrexia, chest pain, asthenia, fatigue, pain, injection site reaction face oedema, chills, body temperature increased, gait abnormal, thirst, chest discomfort, malaise, feeling abnormal, indurationc hypother mia, body temperat ure decrease d, peripher al coldness, drug withdra wal syndrom e, discomfo rt Hepatobil iary disorders transaminases increased, gamma- glutamyltransfe ras increased hepatic enzyme increased jaundice Injury, poisoning and procedura l complicati ons fall procedural pain a Hyperprolactinaemia can in some cases lead to gynaecomastia, menstrual disturbances, amenorrhoea, anovulation, galactorrhoea, fertility disorder, decreased libido, erectile dysfunction.

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2). Elderly with dementia RISPERDAL CONSTA has not been studied in elderly patients with dementia, hence it is not indicated for use in this group of patients. RISPERDAL CONSTA is not licensed for the treatment of dementia-related behavioural disturbances.

Increased mortality in elderly with dementia In a meta-analysis of 17 controlled trials of atypical antipsychotics, including oral RISPERDAL, 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 have 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. RISPERDAL CONSTA should be used with caution in patients with risk factors for stroke.

Orthostatic hypotension Due to the alpha-blocking activity of risperidone, (orthostatic) hypotension can occur, especially during initiation of treatment. Clinically significant hypotension has been observed post-marketing with concomitant use of risperidone and antihypertensive treatment.

g. heart failure, myocardial infarction, conduction abnormalities, dehydration, hypovolaemia, or cerebrovascular disease). The risk/benefit of further treatment with RISPERDAL CONSTA should be assessed if clinically relevant orthostatic hypotension persists.

Leukopenia, neutropenia, and agranulocytosis Events of leucopenia, neutropenia and agranulocytosis have been reported with antipsychotic agents, including RISPERDAL CONSTA. 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 RISPERDAL CONSTA 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 × 109/L) should discontinue RISPERDAL CONSTA and have their WBC followed until recovery.

Tardive dyskinesia/extrapyramidal symptoms (TD/EPS) Medicines with dopamine receptor antagonistic properties have been associated with the induction of tardive dyskinesia characterised by rhythmical involuntary movements, predominantly of the tongue and/or face.

The onset of extrapyramidal symptoms is a risk factor for tardive dyskinesia. If signs and symptoms of tardive dyskinesia appear, the discontinuation of all antipsychotics should be considered. g. methylphenidate) and risperidone concomitantly, as extrapyramidal symptoms could emerge when adjusting one or both medications.

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