Risperdal

Risperdal

risperidone

Nhà sản xuất:

Janssen-Cilag

Nhà phân phối:

DKSH
Thông tin kê toa chi tiết tiếng Anh
Contents
Risperidone.
Description
The film-coated tablets contain 1 mg, or 2 mg risperidone.
Excipients/Inactive Ingredients: Tablet core: Lactose monohydrate, maize starch, microcrystalline cellulose, hypromellose 2910 15 mPa.s, magnesium stearate, colloidal anhydrous silica, sodium lauryl sulphate.
Film-coating: 1 mg risperidone tablets: Hypromellose 2910 5 mPa.s, propylene glycol.
2 mg risperidone tablets: Hypromellose 2910 5 mPa.s, propylene glycol, talc, titanium dioxide, orange yellow S aluminum lake.
Action
Pharmacotherapeutic group: Other antipsychotics. ATC code: N05AX08.
Pharmacology: Pharmacodynamics: Mechanism of action: Risperidone is a selective monoaminergic antagonist with unique properties. It has a high affinity for serotoninergic 5-HT2 and dopaminergic D2 receptors. Risperidone binds also to alpha1-adrenergic receptors, and, with lower affinity, to H1-histaminergic and alpha2-adrenergic receptors. Risperidone has no affinity for cholinergic receptors. Although risperidone is a potent D2 antagonist, which is considered to improve the positive symptoms of schizophrenia, it causes less depression of motor activity and induction of catalepsy than classical neuroleptics. Balanced central serotonin and dopamine antagonism may reduce extrapyramidal side effect liability and extend the therapeutic activity to the negative and affective symptoms of schizophrenia.
Pharmacokinetics: Absorption: Risperidone is completely absorbed after oral administration, reaching peak plasma concentrations within 1 to 2 hours. The absorption is not affected by food and thus risperidone can be given with or without meals.
Distribution: Risperidone is rapidly distributed. The volume of distribution is 1-2 L/kg. In plasma, risperidone is bound to albumin and alpha1-acid glycoprotein. The plasma protein binding of risperidone is 88%, that of 9-hydroxy-risperidone is 77%.
One week after administration, 70% of the dose is excreted in the urine and 14% in the feces. In urine, risperidone plus 9-hydroxy-risperidone represent 35-45% of the dose. The remainder is inactive metabolites.
Metabolism: Risperidone is metabolized by CYP2D6 to 9-hydroxy-risperidone, which has a similar pharmacological activity as risperidone. Risperidone plus 9-hydroxy-risperidone form the active antipsychotic fraction. Another metabolic pathway of risperidone is N-dealkylation.
Elimination: After oral administration to psychotic patients, risperidone is eliminated with a half-life of about 3 hours. The elimination half-life of 9-hydroxy-risperidone and of the active antipsychotic fraction is 24 hours.
Dose proportionality: Steady-state of risperidone is reached within 1 day in most patients. Steady state of 9-hydroxy-risperidone is reached within 4-5 days of dosing. Risperidone plasma concentrations are dose-proportional within the therapeutic dose-range.
Special populations: Pediatrics: The pharmacokinetics of risperidone, 9-hydroxy-risperidone and the active antipsychotic fraction in children are similar to those in adults.
Renal and hepatic impairment: A single-dose study showed higher active plasma concentrations and a reduced clearance of the active antipsychotic fraction by 30% in the elderly and 60% in patients with renal insufficiency. Risperidone plasma concentrations were normal in patients with liver insufficiency, but the mean free fraction of risperidone in plasma was increased by about 35%.
Toxicology: Non-Clinical Information: In (sub)chronic toxicity studies, in which dosing was started in sexually immature rats and dogs, dose-dependent effects were present in male and female genital tract and mammary gland. These effects were related to the increased serum prolactin levels, resulting from the dopamine D2-receptor blocking activity of risperidone. In a toxicity study with juvenile rats, increased pup mortality and a delay in physical development was observed. In a 40-week study with juvenile dogs, sexual maturation was delayed. Long bone growth was not affected at a dose similar to the maximum human dose in adolescents (6 mg/day); effects were observed at a dose 4-fold (on an AUC basis) or 7-fold (on a mg/m2 basis) the maximum human dose in adolescents.
All other safety data relevant to the prescriber have been included in the appropriate section.
Indications/Uses
RISPERDAL is indicated for the treatment of schizophrenia.
RISPERDAL is indicated for the treatment of acute manic or mixed episodes associated with Bipolar I Disorder (according to DSM-IV diagnosed criteria).
RISPERDAL is indicated for the short-term symptomatic treatment (up to 6 weeks) of persistent aggression in conduct disorder in children from the age of 5 years and adolescents* with subaverage intellectual functioning or mental retardation diagnosed according to DSM-IV criteria, in whom the severity of aggressive or other disruptive behaviours require pharmacologic treatment. Pharmacological treatment should be an integral part of a more comprehensive treatment programme, including psychosocial and educational intervention. It is recommended that risperidone be prescribed by a specialist in child neurology and child and adolescent psychiatry or physicians well familiar with the treatment of conduct disorder of children and adolescents.
RISPERDAL is indicated for the treatment of irritability associated with autistic disorder, including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods.
* For children and adolescents below 50 kg the marketed film-coated tablet of 1 mg and 2 mg are not suitable for initial treatment and dose titration.
Dosage/Direction for Use
Dosage: Schizophrenia: Switching from other antipsychotics: When medically appropriate, gradual discontinuation of the previous treatment while RISPERDAL therapy is initiated is recommended. Also, if medically appropriate, when switching patients from depot antipsychotics, initiate RISPERDAL therapy in place of the next scheduled injection. The need for continuing existing anti-Parkinson medications should be re-evaluated periodically.
Adults: RISPERDAL may be given once daily or twice daily.
Patients should start with 2 mg/day RISPERDAL. 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 RISPERDAL when additional sedation is required.
Special populations: Pediatrics (13-17 years of age): 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.
Experience in schizophrenia is lacking in children less than 13 years of age.
Elderly (65 years of age 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.
Bipolar mania: Adults: RISPERDAL 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 RISPERDAL must be evaluated and justified on an ongoing basis.
Special populations: Pediatrics (10-17 years of age): A starting dose of 0.5 mg 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. Efficacy has been demonstrated at doses between 0.5 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.
As with all symptomatic treatments, the continued use of RISPERDAL must be evaluated and justified on an ongoing basis.
Experience is lacking in bipolar mania in children less than 10 years of age.
Conduct disorder in children from the age of 5 years and adolescents: For patients ≥ 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.
For subjects < 50 kg, the marketed film-coated tablet of 1 mg and 2 mg are not suitable for initial treatment and dose titration.
As with all symptomatic treatments, the continued use of RISPERDAL must be evaluated and justified on an ongoing basis.
Experience is lacking in children less than 5 years of age.
Irritability associated with autistic disorder: Children and Adolescents: The marketed film-coated tablet of 1 mg and 2 mg are not suitable for initial treatment and dose titration in patients < 20 kg.
The dosage of RISPERDAL should be individualized according to the needs and response of the patient.
Dosing should be initiated at 0.5 mg per day for patients ≥ 20 kg.
On Day 4, the dose may be increased by 0.5 mg for patients ≥ 20 kg. This dose should be maintained and response should be assessed at approximately Day 14. Only in patients not achieving sufficient clinical response should additional dose increases be considered. Dose increases may proceed at ≥ 2-week intervals in increments of 0.5 mg for patients ≥ 20 kg.
In clinical studies, the maximum dose studied did not exceed a total daily dose of 1.5 mg in patients < 20 kg, 2.5 mg in patients ≥ 20 kg, or 3.5 mg in patients > 45 kg. Doses below 0.25 mg/day were not effective in clinical studies. (See Table 1.)


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RISPERDAL can be administered once daily or twice daily.
Patients experiencing somnolence may benefit from a switch in dosing from once daily to either once daily at bedtime or twice daily.
Once sufficient clinical response has been achieved and maintained, consideration may be given to gradually lowering the dose to achieve the optimal balance of efficacy and safety.
Experience is lacking in children less than 5 years of age.
Renal and hepatic impairment: Patients with renal impairment have less ability to eliminate the active antipsychotic fraction than normal adults. 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.
RISPERDAL should be used with caution in these groups of patients.
Overdosage
Symptoms and signs: In general, reported signs and symptoms have been those resulting from an exaggeration of the drug's known pharmacological effects. 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 oral RISPERDAL and paroxetine.
In case of acute overdosage, the possibility of multiple drug involvement should be considered.
Treatment: Establish and maintain a clear airway and ensure adequate oxygenation and ventilation. Administration of activated charcoal together with a laxative should be considered. 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, anticholinergic medication should be administered. Close medical supervision and monitoring should continue until the patient recovers.
Contraindications
RISPERDAL is contraindicated in patients with a known hypersensitivity to the active substance or to any of the excipients listed in Description.
Special Precautions
Elderly patients with dementia: Overall mortality: Elderly patients with dementia treated with atypical antipsychotic drugs have an increased mortality compared to placebo in a meta-analysis of 17 controlled trials of atypical antipsychotic drugs, including RISPERDAL. In placebo-controlled trials with RISPERDAL in this population, the incidence of mortality was 4.0% for RISPERDAL-treated patients compared to 3.1% for placebo treated patients. The mean age (range) of patients who died was 86 years (range 67-100).
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 (7.3%; mean age 89 years, range 75-97) when compared to patients treated with risperidone alone (3.1%; mean age 84 years, range 70-96) or furosemide alone (4.1%; 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.
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 should be considered prior to the decision to use. There was no increased incidence of mortality among patients taking other diuretics as concomitant medication 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 (CAE): In placebo-controlled trials in elderly patients with dementia, there was a higher incidence of cerebrovascular adverse events, (cerebrovascular accidents and transient ischemic attacks), including fatalities, in patients treated with RISPERDAL compared to patients receiving placebo (mean age 85 years; range 73-97).
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. RISPERDAL should be used with caution in patients with known cardiovascular disease (e.g. heart failure, myocardial infarction, conduction abnormalities, dehydration, hypovolemia, or cerebrovascular disease), and the dosage should be gradually titrated as recommended (see Dosage & Administration). A dose reduction should be considered if hypotension occurs.
Leucopenia, 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.
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 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 RISPERDAL and have their WBC followed until recovery.
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 RISPERDAL and preventive measures undertaken.
Tardive dyskinesia/extrapyramidal symptoms (TD/EPS): Drugs with dopamine receptor antagonistic properties have been associated with the induction of tardive dyskinesia characterized by rhythmical involuntary movements, predominantly of the tongue and/or face. It has been reported that the occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. If signs and symptoms of tardive dyskinesia appear, the discontinuation of all antipsychotic drugs should be considered.
Extrapyramidal symptoms and psychostimulants: 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 one or both treatments should be considered (see Interactions).
Neuroleptic Malignant Syndrome (NMS): Neuroleptic Malignant Syndrome, characterized 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 antipsychotic drugs, including RISPERDAL, should be discontinued.
Parkinson's Disease and Dementia with Lewy Bodies: Physicians should weigh the risks versus the benefits when prescribing antipsychotics, including RISPERDAL, to patients with Parkinson's Disease or Dementia with Lewy Bodies (DLB) since both groups may be at increased risk of Neuroleptic Malignant Syndrome as well as having an increased sensitivity to antipsychotic medications. Manifestation of this increased sensitivity can include confusion, obtundation, postural instability with frequent falls, in addition to extrapyramidal symptoms.
Hyperglycemia and diabetes mellitus: Hyperglycaemia, diabetes mellitus, and exacerbation of pre-existing diabetes have been reported during treatment with RISPERDAL. 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 RISPERDAL, 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. Monitoring weight gain is advisable when RISPERDAL is being used.
QT interval: As with other antipsychotics, caution should be exercised when RISPERDAL is prescribed in patients with a history of cardiac arrhythmias, in patients with congenital long QT syndrome, and in concomitant use with drugs known to prolong the QT interval.
Priapism: Drugs with alpha-adrenergic blocking effects have been reported to induce priapism. Priapism has been reported with RISPERDAL during postmarketing surveillance (see Adverse Reactions).
Body temperature regulation: Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. Appropriate care is advised when prescribing RISPERDAL 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 medication 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 drugs or of conditions such as intestinal obstruction, Reye's syndrome, and brain tumor.
Seizures: As with other antipsychotic drugs, RISPERDAL should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold.
Intraoperative Floppy Iris Syndrome: Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in patients.
treated with medicines with alpha 1a-adrenergic antagonist effect, including RISPERDAL (see Adverse Reactions).
IFIS may increase the risk of eye complications during and after the operation. Current or past use of medicines with alpha 1a-adrenergic antagonist effect should be made known to the ophthalmic surgeon in advance of surgery. The potential benefit of stopping alpha 1 blocking therapy prior to cataract surgery has not been established and must be weighed against the risk of stopping the antipsychotic therapy.
Other: See Schizophrenia: Special populations: Elderly (65 years of age and older) under Dosage & Administration for specific posology recommendations for elderly patients, Bipolar mania under Dosage & Administration for patients with bipolar mania, Conduct disorder in children from the age of 5 years and adolescents under Dosage & Administration for pediatric patients with conduct and other disruptive behavior disorders, Irritability associated with autistic disorder under Dosage & Administration for pediatric patients with autism, and Renal and hepatic impairment under Dosage & Administration for patients with renal or hepatic impairment.
Excipients: The film-coated tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on Ability to Drive and Use Machines: RISPERDAL may interfere with activities requiring mental alertness. Therefore, patients should be advised not to drive or operate machinery until their individual susceptibility is known.
Use In Pregnancy & Lactation
Pregnancy: The safety of risperidone for use during human pregnancy has not been established.
A retrospective observational cohort study based on a US claims database compared the risk of congenital malformations for live births among women with and without antipsychotic use during the first trimester of pregnancy. The risk of congenital malformations with risperidone, after adjusting for confounder variables available in the database, was elevated compared to no antipsychotic exposure (relative risk=1.26, 95% CI: 1.02-1.56). No biological mechanism has been identified to explain these findings and teratogenic effects have not been observed in non clinical studies. Based on the findings of this single observational study, a causal relationship between in utero exposure to risperidone and congenital malformations has not been established.
Although, in experimental animals, risperidone did not show direct reproductive toxicity, some indirect, prolactin- and CNS-mediated effects were observed.
Neonates exposed to antipsychotic drugs (including RISPERDAL) during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms that may vary in severity following delivery. These symptoms in the neonates may include agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder.
RISPERDAL should only be used during pregnancy if the benefits outweigh the risks. If discontinuation during pregnancy is necessary, it should not be done abruptly.
Breast-feeding: In animal studies, risperidone and 9-hydroxy-risperidone are excreted in the milk. It has been demonstrated that risperidone and 9-hydroxy-risperidone are also excreted in human breast milk. Therefore, women receiving RISPERDAL should not breast-feed.
Adverse Reactions
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 RISPERDAL 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) and very rare (< 1/10,000).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. (See Tables 2a and 2b.)


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Undesirable effects noted with paliperidone formulations: Paliperidone is the active metabolite of risperidone, therefore, the adverse reaction profiles of these compounds (including both the oral and injectable formulations) are relevant to one another. In addition to the previously mentioned adverse reactions, the following adverse reaction has been noted with the use of paliperidone products and can be expected to occur with RISPERDAL.
Cardiac disorders: Postural orthostatic tachycardia syndrome.
Class effects: As with other antipsychotics, very rare cases of QT prolongation have been reported post-marketing with risperidone. Other class-related cardiac effects reported with antipsychotics which prolong QT interval include ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac arrest and Torsades de Pointes.
Venous thromboembolism: Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis, have been reported with antipsychotic drugs (frequency unknown).
Weight gain: The proportions of RISPERDAL and placebo-treated adult patients with schizophrenia meeting a weight gain criterion of ≥ 7% of body weight were compared in a pool of 6- to 8-week, placebo-controlled trials, revealing a statistically significantly greater incidence of weight gain for RISPERDAL (18%) compared to placebo (9%). In a pool of placebo-controlled 3-week studies in adult patients with acute mania, the incidence of weight increase of ≥ 7% at endpoint was comparable in the RISPERDAL (2.5%) and placebo (2.4%) groups, and was slightly higher in the active-control group (3.5%).
In a population of children and adolescents with conduct and other disruptive behaviour disorders, in long-term studies, weight increased by a mean of 7.3 kg after 12 months of treatment. The expected weight gain for normal children between 5-12 years of age is 3 to 5 kg per year. From 12-16 years of age, this magnitude of gaining 3 to 5 kg per year is maintained for girls, while boys gain approximately 5 kg per year.
Additional information on special populations: Adverse drug reactions that were reported with higher incidence in elderly patients with dementia or paediatric patients than in adult populations are described as follows: Elderly patients with dementia: Transient ischaemic attack and cerebrovascular accident were ADRs reported in clinical trials with a frequency of 1.4% and 1.5%, respectively, in elderly patients with dementia. In addition, the following ADRs were reported with a frequency ≥ 5% in elderly patients with dementia and with at least twice the frequency seen in other adult populations: urinary tract infection, peripheral oedema, lethargy, and cough.
Paediatric population: In general, type of adverse reactions in children is expected to be similar to those observed in adults. The following ADRs were reported with a frequency ≥ 5% in paediatric patients (5 to 17 years) and with at least twice the frequency seen in clinical trials in adults: somnolence/sedation, fatigue, headache, increased appetite, vomiting, upper respiratory tract infection, nasal congestion, abdominal pain, dizziness, cough, pyrexia, tremor, diarrhoea, and enuresis. The effect of long-term risperidone treatment on sexual maturation and height has not been adequately studied.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.
Please inform the doctor or pharmacist immediately of all adverse reactions upon drug administration
Drug Interactions
Pharmacodynamic-related interactions: Centrally-acting drugs and alcohol: Given the primary CNS effects of RISPERDAL, it should be used with caution in combination with other centrally acting drugs or alcohol.
Levodopa and dopamine agonists: RISPERDAL may antagonize the effect of levodopa and other dopamine agonists.
Psychostimulants: The combined use of psychostimulants (e.g. methylphenidate) with risperidone can lead to the emergence of extrapyramidal symptoms upon change of either or both treatments (see Precautions).
Drugs with hypotensive effects: Clinically significant hypotension has been observed post-marketing with concomitant use of risperidone and antihypertensive treatment.
Drugs known to prolong the QT interval: Caution is advised when prescribing RISPERDAL with drugs known to prolong the QT interval.
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 as follows). When concomitant paroxetine 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: Coadministration 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.
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 dosages.
Pediatric population: Interaction studies have only been performed in adults. The relevance of the results from these studies in pediatric patients is unknown.
Examples: Examples of drugs that may potentially interact or that were shown not to interact with risperidone are listed as follows: Antibacterials: Erythromycin, a moderate CYP3A4 inhibitor, does not change the pharmacokinetics of risperidone and the active antipsychotic fraction.
Rifampicin, a strong CYP3A4 inducer and a P-gp inducer, decreased the plasma concentrations of the active antipsychotic fraction.
Anticholinesterases: Donepezil and galantamine, both CYP2D6 and CYP3A4 substrates, do not show a clinically relevant effect on the pharmacokinetics of risperidone and the active antipsychotic fraction.
Antiepileptics: Carbamazepine, a strong CYP3A4 inducer and a P-gp inducer, has been shown to decrease the plasma levels of the active antipsychotic fraction of risperidone.
Topiramate modestly reduced the bioavailability of risperidone, but not that of the active antipsychotic fraction. Therefore, this interaction is unlikely to be of clinical significance.
Risperidone does not show a clinically relevant effect on the pharmacokinetics of valproate or topiramate.
Antifungals: Itraconazole, a strong CYP3A4 inhibitor and a P-gp inhibitor, at a dosage of 200 mg/day increased the plasma concentrations of the active antipsychotic fraction by about 70%, at risperidone doses of 2 to 8 mg/day.
Ketoconazole, a strong CYP3A4 inhibitor and a P-gp inhibitor, at a dosage of 200 mg/day increased the plasma concentrations of risperidone and decreased the plasma concentrations of 9-hydroxy-risperidone.
Antipsychotics: Phenothiazines, may increase the plasma concentrations of risperidone but not those of the active antipsychotic fraction.
Aripiprazole, a CYP2D6 and CYP3A4 substrate: Risperidone tablets or injections did not affect the pharmacokinetics of the sum of aripiprazole and its active metabolite, dehydroaripiprazole.
Antivirals: Protease inhibitors: No formal study data are available; however, since ritonavir is a strong CYP3A4 inhibitor and a weak CYP2D6 inhibitor, ritonavir and ritonavir-boosted protease inhibitors potentially raise concentrations of the risperidone active antipsychotic fraction.
Beta-Blockers: Some beta-blockers may increase the plasma concentrations of risperidone but not those of the active antipsychotic fraction.
Calcium Channel Blockers: Verapamil, a moderate inhibitor of CYP3A4 and an inhibitor of P-gp, increases the plasma concentration of risperidone and the active antipsychotic fraction.
Digitalis Glycosides: Risperidone does not show a clinically relevant effect on the pharmacokinetics of digoxin.
Diuretics: Furosemide: See Precautions regarding increased mortality in elderly patients with dementia concomitantly receiving furosemide.
Gastrointestinal Drugs: H2-receptor antagonists: Cimetidine and ranitidine, both weak inhibitors of CYP2D6 and CYP3A4, increased the bioavailability of risperidone, but only marginally that of the active antipsychotic fraction.
Lithium: Risperidone does not show a clinically relevant effect on the pharmacokinetics of lithium.
SSRIs and Tricyclic Antidepressants: Fluoxetine, a strong CYP2D6 inhibitor, increases the plasma concentration of risperidone, but less so of the active antipsychotic fraction.
Paroxetine, a strong CYP2D6 inhibitor, increases the plasma concentrations of risperidone, but, at dosages up to 20 mg/day, less so of the active antipsychotic fraction. However, higher doses of paroxetine may elevate concentrations of the risperidone active antipsychotic fraction.
Tricyclic antidepressants may increase the plasma concentrations of risperidone but not those of the active antipsychotic fraction. Amitriptyline does not affect the pharmacokinetics of risperidone or the active antipsychotic fraction.
Sertraline, a weak inhibitor of CYP2D6, and fluvoxamine, a weak inhibitor of CYP3A4, at dosages up to 100 mg/day are not associated with clinically significant changes in concentrations of the risperidone active antipsychotic fraction. However, doses higher than 100 mg/day of sertraline or fluvoxamine may elevate concentrations of the risperidone active antipsychotic fraction.
Caution For Usage
Incompatibilities: None.
Storage
Do not store above 30°C.
Shelf-Life: 3 years since manufacturing date.
MIMS Class
ATC Classification
N05AX08 - risperidone ; Belongs to the class of other antipsychotics.
Presentation/Packing
FC tab 1 mg (white, half-scored, oblong, biconvex) x 6 x 10's. 2 mg (orange, half-scored, oblong, biconvex) x 6 x 10's.
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