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 is 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 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 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. 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 post- marketing experience with risperidone by frequency category estimated from risperidone 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 clinical trial data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 11% in placebo group. 43% in all risperidone-treated subjects. c Not observed in risperidone clinical studies but observed in post-marketing environment with risperidone.

d Extrapyramidal disorder may occur: Parkinsonism (salivary hypersecretion, musculoskeletal stiffness, parkinsonism, […]

Elderly patients with dementia Increased mortality in elderly people with dementia In a meta-analysis of 17 controlled trials of atypical antipsychotic drugs, 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 cotreatment 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. 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 post-marketing 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 […]

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