Risperdal

/ Janssen

Schizophrenia
Adults: This medicinal product 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. From then on the dosage can be maintained unchanged, or further individualized, 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 been shown to be superior in efficacy to lower doses and may cause extrapyramidal symptoms. Since the safety of doses above 16 mg/day has not been evaluated, doses above this level should not be used.
A benzodiazepine may be added to risperidone when additional sedation is required.
Elderly (65 years and older): A starting dose of 0.5 mg twice daily is recommended. This dosage can be individually adjusted with 0.5 mg twice daily increments to 1 to 2 mg twice daily.
Adolescents (13-17 years): A starting dose of 0.5 mg daily is recommended, administered as a single-daily dose either in the morning or evening. If indicated, this dosage can then be adjusted at intervals not less than 24 hours in increments of 0.5 or 1 mg/day, as tolerated, to a recommended dose of 3 mg/day. Efficacy has been demonstrated at doses between 1 and 6 mg/day. Doses higher than 6 mg/day have not been studied.
Patients experiencing persistent somnolence may benefit from administering half the daily dose twice daily.
Children: Experience in schizophrenia is lacking in children aged less than 13 years of age.
Bipolar mania
Adults: This medicinal product should be administered on a once daily schedule, starting with 2 or 3 mg.
Dosage adjustments, if indicated, should occur at intervals of not less than 24 hours and in dosage increments of 1 mg per day. Efficacy was demonstrated in flexible doses over a range of 1 to 6 mg per day.
As with all symptomatic treatments, the continued use of risperidone must be evaluated and justified on an ongoing basis.
Children and Adolescents (10-17 years of age): A starting dose of 0.5mg once daily is recommended, administered as a single-daily dose in either the morning or evening. If indicated, this dosage can then be adjusted at intervals not less than 24 hours in increments of 0.5 or 1 mg/day, as tolerated, to a recommended dose of 2.5 mg/day. Although efficacy has been demonstrated at doses between 0.5 and 6 mg/day. No additional benefit was seen above 2.5 mg/day, and higher doses were associated with more adverse events. Doses higher than 6 mg/day have not been studied.
Patients experiencing persistent somnolence may benefit from administering half the daily dose twice daily.
As with all symptomatic treatments, the continued use of risperidone must be evaluated and justified on an ongoing basis.
Experience is lacking in bipolar mania in children less than 10 years of age.
Psychotic manifestations of dementia: A starting dose of 0.25 mg twice daily is recommended. This dosage can be individually adjusted by increments of 0.25 mg twice daily not more frequently than every other day, if needed. The optimum dose is 0.5 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.
Conduct and other disruptive behavior disorders (5-18 years of age):
Subjects ≥ 50 kg: A starting dose of 0.5 mg once daily is recommended. This dosage can be individually adjusted by increments of 0.5 mg once daily not more frequently than every other day, if needed. The optimum dose is 1 mg once daily for most patients. Some patients, however, may benefit from 0.5 mg once daily while others may require 1.5 mg once daily.
Subjects < 50 kg: A starting dose of 0.25 mg once daily is recommended. This dosage can be individually adjusted by increments of 0.25 mg once daily not more frequently than every other day, if needed. The optimum dose is 0.5 mg once daily for most patients. Some patients, however, may benefit from 0.25 mg once daily while others may require 0.75 mg once daily.
As with all symptomatic treatments, the continued use of risperidone must be evaluated and justified on an ongoing basis.
Experience is lacking in children aged less than 5 years of age.
Renal and Hepatic Impairment: Patients with renal impairment have less ability to eliminate the active antipsychotic fraction than in adults with normal renal fraction. 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. This medicinal product should be used with caution in these groups of patients.
Method of administration: Risperdal is for oral use. Food does not affect the absorption of this drug. Upon discontinuation, gradual withdrawal is advised. Acute withdrawal symptoms, including nausea, vomiting, sweating, and insomnia have very rarely been described after abrupt cessation of high doses of antipsychotic medicines. 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 medications should be re-evaluated periodically.

This medicinal product is indicated for the management schizophrenia, and the manifestations of psychotic disorders. The antipsychotic efficacy of this medicinal product was established in short-term (6 to 8-weeks) controlled trials of schizophrenic inpatients.
This drug is also effective in maintaining the clinical improvement during continuation therapy in patients who have shown an initial treatment response
This medicinal product 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.
Conduct and other disruptive disorders:
Treatment of behavioral disorders expressed by impulse control disorders or self-alienatedaggressive or treatment-requiring behavioral disorders with reduced or substandard intelligence. Treatment should not be given to children under the age of 5 years.
Risperdal is indicated for the treatment of mania in bipolar disorder. These episodes are characterized by symptoms such as elevated, expansive or irritable mood, inflated self-esteem, decreased need for sleep, pressured speech, racing thoughts, distractibility, or poor judgment, including disruptive or aggressive behaviors.

Hypersensitivity to the active substance or to any of the excipients.

Elderly patients with dementia
Increased mortality in elderly people with dementia: In a meta-analysis of 17 controlled trials of atypical antipsychotics, including RISPERDAL, elderly patients with dementia treated with atypical antipsychotics have an increased mortality compared to placebo.
Concomitant use with furosemide: In the Risperdal® placebo-controlled trials in elderly patients with dementia, a higher incidence of mortality was observed in patients treated with furosemide plus risperidone when compared to patients treated with risperidone alone or furosemide alone.
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 randomized placebo controlled clinical trials in the dementia population with some atypical antipsychotics. RISPERDAL 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 RISPERDAL 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.
RISPERDAL 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.
Leukopenia, neutropenia, and agranulocytosis: Events of leucopenia, neutropenia and agranulocytosis have been reported with antipsychotic agents, including RISPERDAL®. Agranulocytosis has been reported very rarely (< 1/10,000 patients) during post-marketing surveillance.
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. If signs and symptoms of tardive dyskinesia appear, the discontinuation of all antipsychotics should be considered. Caution is warranted in patients receiving both psychostimulants (e.g. methylphenidate) and risperidone concomitantly, as extrapyramidal symptoms could emerge when adjusting one or both medications. Gradual withdrawal of stimulant treatment is recommended.
Neuroleptic malignant syndrome (NMS):  NMS, characterised by hyperthermia, muscle rigidity, autonomic instability, altered consciousness and elevated serum creatine phosphokinase levels has been reported to occur with antipsychotics. Additional signs may include myoglobinuria (rhabdomyolysis) and acute renal failure. In this event, all antipsychotics, including this drug, should be discontinued.
Parkinson’s disease and dementia with Lewy bodies: Physicians should weigh the risks versus the benefits when prescribing antipsychotics, including risperidone, to patients with Parkinson’s Disease or Dementia with Lewy Bodies (DLB). Parkinson’s Disease may worsen with risperidone. Both groups may be at increased risk of NMS as well as having an increased sensitivity to antipsychotic medicinal products; these patients were excluded from clinical trials. Manifestation of this increased sensitivity can include confusion, obtundation, postural instability with frequent falls, in addition to extrapyramidal symptoms.
Hyperglycaemia and diabetes mellitus: Hyperglycaemia, diabetes mellitus, and exacerbation of pre-existing diabetes have been reported during treatment with risperidone. In some cases, a prior increase in body weight has been reported which may be a predisposing factor. Association with ketoacidosis has been reported very rarely and rarely with diabetic coma. Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines. Patients treated with any atypical antipsychotic, including this drug, should be monitored for symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia and weakness) and patients with diabetes mellitus should be monitored regularly for worsening of glucose control.
Weight gain: Significant weight gain has been reported with risperidone use. Weight should be monitored regularly.
Hyperprolactinaemia: Hyperprolactinaemia is a common side effect of treatment with risperidone. Evaluation of the prolactin plasma level is recommended in patients with evidence of possible prolactin-related side effects (e.g., gynaecomastia, menstrual disorders, anovulation, fertility disorder, decreased libido, erectile dysfunction, and galactorrhoea).
Tissue culture studies suggest that cell growth in human breast tumours may be stimulated by prolactin. Although no clear association with the administration of antipsychotics has so far been demonstrated in clinical and epidemiological studies, caution is recommended in patients with relevant medical history.
risperidone should be used with caution in patients with pre-existing hyperprolactinaemia and in patients with possible prolactin-dependent tumours.
QT prolongation: QT prolongation has very rarely been reported post-marketing. As with other antipsychotics, caution should be exercised when risperidone is prescribed in patients with known cardiovascular disease, family history of QT prolongation, bradycardia, or electrolyte disturbances (hypokalaemia, hypomagnesaemia), as it may increase the risk of arrhythmogenic effects, and in concomitant use with medicines known to prolong the QT interval.
Seizures: Risperidone should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold.
Priapism: Priapism may occur with risperidone treatment due to its alpha-adrenergic blocking effects.
Body temperature regulation: Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic medicines. Appropriate care is advised when prescribing risperidone to patients who will be experiencing conditions which may contribute to an elevation in core body temperature, e.g., exercising strenuously, exposure to extreme heat, receiving concomitant treatment with anticholinergic activity, or being subject to dehydration.
Antiemetic effect: An antiemetic effect was observed in preclinical studies with risperidone. This effect, if it occurs in humans, may mask the signs and symptoms of overdosage with certain medicines or of conditions such as intestinal obstruction, Reye’s syndrome, and brain tumour.
Renal and hepatic impairment: Patients with renal impairment have less ability to eliminate the active antipsychotic fraction than adults with normal renal function. Patients with impaired hepatic function have increases in plasma concentration of the free fraction of risperidone.
Venous thromboembolism: Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with risperidone and preventative measures undertaken.
Intraoperative floppy iris syndrome: Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in patients treated with medicines with alpha1a-adrenergic antagonist effect, including this drug.
IFIS may increase the risk of eye complications during and after the operation. Current or past use of medicines with alpha1a-adrenergic antagonist effect should be made known to the ophthalmic surgeon in advance of surgery. The potential benefit of stopping alpha1-blocking therapy prior to cataract surgery has not been established and must be weighed against the risk of stopping the antipsychotic therapy.
Paediatric population: Before risperidone is prescribed to a child or adolescent with conduct disorder they should be fully assessed for physical and social causes of the aggressive behaviour such as pain or inappropriate environmental demands.
The sedative effect of risperidone should be closely monitored in this population because of possible consequences on learning ability. A change in the time of administration of risperidone could improve the impact of the sedation on attention faculties of children and adolescents.
Weight Gain: Risperidone was associated with mean increases in body weight and body mass index (BMI). Baseline weight measurement prior to treatment and regular weight monitoring are recommended. Changes in height in the long-term open-label extension studies were within expected age-appropriate norms. The effect of long-term risperidone treatment on sexual maturation and height has not been adequately studied.
See prescribing information for full details.

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.
See prescribing information for full details.

Pharmacodynamic-related Interactions
Drugs known to prolong the QT interval: As with other antipsychotics, caution is advised when prescribing risperidone with medicinal products known to prolong the QT interval, such as antiarrhythmics (e.g., quinidine, dysopiramide, procainamide, propafenone, amiodarone, sotalol), tricyclic antidepressant (i.e., amitriptyline), tetracyclic antidepressants (i.e., maprotiline), some antihistamines, other antipsychotics, some antimalarials (i.e., quinine and mefloquine), and with medicines causing electrolyte imbalance (hypokalaemia, hypomagnesaemia), bradycardia, or those which inhibit the hepatic metabolism of risperidone. This list is indicative and not exhaustive.
Centrally-acting drugs and alcohol: Risperidone should be used with caution in combination with other centrally-acting substances notably including alcohol, opiates, antihistamines and benzodiazepines due to the increased risk of sedation.
Levodopa and dopamine agonists: RISPERDAL® may antagonize the effect of levodopa and other dopamine agonists. If this combination is deemed necessary, particularly in end-stage Parkinson’s disease, the lowest effective dose of each treatment should be prescribed.
Drugs with hypotensive effect: Clinically significant hypotension has been observed post-marketing with concomitant use of risperidone and antihypertensive treatment.
Paliperidone: Concomitant use of oral RISPERDAL with paliperidone is not recommended as paliperidone is the active metabolite of risperidone and the combination of the two may lead to additive active antipsychotic fraction exposure.
Pharmacokinetic-related interactions
Food does not affect the absorption of RISPERDAL.
Risperidone is mainly metabolized through CYP2D6, and to a lesser extent through CYP3A4. Both risperidone and its active metabolite 9-hydroxy- risperidone are substrates of P-glycoprotein (P-gp). Substances that modify CYP2D6 activity, or substances strongly inhibiting or inducing CYP3A4 and/or P-gp activity, may influence the pharmacokinetics of the risperidone active antipsychotic fraction.
Strong CYP2D6 inhibitors: Co-administration of RISPERDAL with a strong CYP2D6 inhibitor may increase the plasma concentrations of risperidone, but less so of the active antipsychotic fraction.
Higher doses of a strong CYP2D6 inhibitor may elevate concentrations of the risperidone active antipsychotic fraction (e.g., paroxetine, see below). It is expected that other CYP2D6 inhibitors, such as quinidine, may affect the plasma concentrations of risperidone in a similar way. When concomitant paroxetine, quinidine, or another strong CYP2D6 inhibitor, especially at higher doses, is initiated or discontinued, the physician should re-evaluate the dosing of RISPERDAL.
CYP3A4 and/or P-gp inhibitors: Co-administration of RISPERDAL with a strong CYP3A4 and/or P-gp inhibitor may substantially elevate plasma concentrations of the risperidone active antipsychotic fraction. When concomitant itraconazole or another strong CYP3A4 and/or P-gp inhibitor is initiated or discontinued, the physician should re-evaluate the dosing of RISPERDAL.
CYP3A4 and/or P-gp inducers: Co-administration of RISPERDAL with a strong CYP3A4 and/or P-gp inducer may decrease the plasma concentrations of the risperidone active antipsychotic fraction. When concomitant carbamazepine or another strong CYP3A4 and/or P-gp inducer is initiated or discontinued, the physician should re-evaluate the dosing of RISPERDAL. CYP3A4 inducers exert their effect in a time-dependent manner, and may take at least 2 weeks to reach maximal effect after introduction. Conversely, on discontinuation, CYP3A4 induction may take at least 2 weeks to decline.
Highly protein-bound drugs: When RISPERDAL is taken together with highly protein-bound drugs, there is no clinically relevant displacement of either drug from the plasma proteins.
When using concomitant medication, the corresponding label should be consulted for information on the route of metabolism and the possible need to adjust dosage.
See prescribing information for full details.

Pregnancy: The potential risk for humans is unknown. Neonates exposed to antipsychotics (including RISPERDAL) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal
symptoms that may vary in severity and duration following delivery. Consequently, newborns should be monitored carefully.
RISPERDAL should not be used during pregnancy unless clearly necessary. If discontinuation during pregnancy is necessary, it should not be done abruptly.
Breast-feeding: It has been demonstrated that risperidone and 9-hydroxy-risperidone are excreted in human breast milk in small quantities. There are no data available on adverse reactions in breast-feeding infants. Therefore, the advantage of breast-feeding should be weighed against the potential risks for the child.
See prescribing information for full details.

Symptoms: In general, reported signs and symptoms have been those resulting from an exaggeration of the known pharmacological effects of risperidone. These include drowsiness and sedation, tachycardia and hypotension, and extrapyramidal symptoms. In overdose, QT-prolongation and convulsions have been reported. Torsade de pointes has been reported in association with combined overdose of RISPERDAL® and paroxetine.
In case of acute overdose, the possibility of multiple drug involvement should be considered.
Treatment: Establish and maintain a clear airway and ensure adequate oxygenation and ventilation.
Gastric lavage (after intubation, if the patient is unconscious) and administration of activated charcoal together with a laxative should be considered only when drug intake was less than one hour before. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias.
There is no specific antidote to RISPERDAL®. Therefore, appropriate supportive measures should be instituted. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids and/or sympathomimetic agents. In case of severe extrapyramidal symptoms, an anticholinergic medicinal product should be administered. Close medical supervision and monitoring should continue until the patient recovers.

Incompatibilities: RISPERDAL® oral solution: incompatible with most types of tea including black tea.