Rizem 2 ODT

Each Orally Disintegrating Tablet contains: Risperidone USP 2 mg.
Product Name: Risperidone Orally Disintegrating Tablet - 2 mg.

Pharmaco-therapeutic group: Other antipsychotics. ATC code: N05AX08.
Pharmacology: Pharmacodynamics: Schizophrenia: The efficacy of risperidone in the short-term treatment of schizophrenia was established in four studies, 4- to 8-weeks in duration, which enrolled over 2500 patients who met DSM-IV criteria for schizophrenia. In a 6-week, placebo-controlled trial involving titration of risperidone in doses up to 10 mg/day administered twice daily, risperidone was superior to placebo on the Brief Psychiatric Rating Scale (BPRS) total score. In an 8-week, placebo-controlled trial involving four fixed doses of risperidone (2, 6, 10, and 16 mg/day, administered twice daily), all four risperidone groups were superior to placebo on the Positive and Negative Syndrome Scale (PANSS) total score. In an 8-week, dose comparison trial involving five fixed doses of risperidone (1, 4, 8, 12, and 16 mg/day administered twice-daily), the 4, 8, and 16 mg/day risperidone dose groups were superior to the 1 mg risperidone dose group on PANSS total score. In a 4-week, placebo-controlled dose comparison trial involving two fixed doses of risperidone (4 and 8 mg/day administered once daily), both risperidone dose groups were superior to placebo on several PANSS measures, including total PANSS and a response measure (>20% reduction in PANSS total score). In a longer-term trial, adult outpatient's predominantly meeting DSM-IV criteria for schizophrenia and who had been clinically stable for at least 4 weeks on an antipsychotic medicinal product were randomized to risperidone 2 to 8 mg/day or to haloperidol for 1 to 2 years of observation for relapse. Patients receiving risperidone experienced a significantly longer time to relapse over this time period compared to those receiving haloperidol.
Manic episodes in bipolar disorder: The efficacy of risperidone monotherapy in the acute treatment of manic episodes associated with bipolar l disorder was demonstrated in three double-blind, placebo-controlled monotherapy studies in approximately 820 patients who had bipolar I disorder, based on DSM-IV criteria. In the three studies, risperidone 1 to 6 mg/day (starting dose 3 mg in two studies and 2 mg in one study) was shown to be significantly superior to placebo on the pre-specified primary endpoint, i.e., the change from baseline in total Young Mania Rating Scale (YMRS) score at Week 3. Secondary efficacy outcomes were generally consistent with the primary outcome. The percentage of patients with a decrease of 50% in total YMRS score from baseline to the 3-week endpoint was significantly higher for risperidone than for placebo. One of the three studies included a haloperidol arm and a 9-week double-blind maintenance phase. Efficacy was maintained throughout the 9-week maintenance treatment period. Change from baseline in total YMRS showed continued improvement and was comparable between risperidone and haloperidol at Week 12.
The efficacy of risperidone in addition to mood stabilizers in the treatment of acute mania was demonstrated in one of two 3-week double-blind studies in approximately 300 patients who met the DSM-IV criteria for bipolar I disorder. In one 3-week study, risperidone 1 to 6 mg/day starting at 2 mg/day in addition to lithium or valproate was superior to lithium or valproate alone on the pre-specified primary endpoint, i.e., the change from baseline in YMRS total score at Week 3. In a second 3-week study, risperidone 1 to 6 mg/day starring at 2 mg/day, combined with lithium, valproate, or carbamazepine was not superior to lithium, valproate, or carbamazepine alone in the reduction of YMRS total score. A possible explanation for the failure of this study was induction of risperidone and 9-hydroxy-risperidone clearance by carbamazepine, leading to subtherapeutic levels of risperidone and 9-hydroxyrisperidone. When the carbamazepine group was excluded in a post-hoc analysis, risperidone combined with lithium or valproate was superior to lithium or valproate alone in the reduction of YMRS total score.
Persistent aggression in dementia: The efficacy of risperidone in the treatment of behavioral and Psychological Symptoms of Dementia (BPSD), which includes behavioral disturbances, such as aggressiveness, agitation, psychosis, activity, and effective disturbances was demonstrated in three double-blind, placebo-controlled studies in 1550 elderly patients with moderate to severe dementia. One study included fixed risperidone doses of 0.5, 1, and 2 mg/day. Two flexible-dose studies included risperidone dose groups in the range of 0.5 to 4 mg/day and 0.5 to 2 mg/day, respectively. Risperidone showed statistically significant and clinically important effectiveness in treating aggression and less consistently in treating agitation and psychosis in elderly dementia patients (as measured by the Behavioral Pathology in Alzheimer's Disease Rating Scale [BEHAVE-AD] and the Cohen-Mansfield Agitation Inventory [CMAI]). The treatment effect of risperidone was independent of Mini-Mental State Examination (MMSE) score (and consequently of the severity of dementia); of sedative properties of risperidone; of the presence or absence of psychosis; and of the type of dementia, Alzheimer's, vascular, or mixed.
Conduct disorder: The efficacy of risperidone in the short-term treatment of disruptive behaviors was demonstrated in two double-blind placebo-controlled studies in approximately 240 patients 5 to 12 years of age with a DSM-IV diagnosis of disruptive behavior disorders (DBD) and borderline intellectual functioning or mild or moderate mental retardation/learning disorder. In the two studies, risperidone 0.02 to 0.06 mg/kg/day was significantly superior to placebo on the pre-specified primary endpoint, i.e., the change from baseline in the Conduct Problem subscale of the Nisonger-Child Behavior Rating Form (N-CBRF) at week 6.
Pharmacokinetics: Risperidone is metabolized to 9-hydroxy-risperidone, which has a similar pharmacological activity to risperidone.
Absorption: Risperidone is completely absorbed after oral administration, reaching peak plasma concentrations within 1 to 2 hours. The absolute oral bioavailability of risperidone is 70% (CV=25%). The relative oral bioavailability of risperidone from a tablet is 94% (CV=10%) compared with a solution. The absorption is not affected by food and thus, risperidone can be given with or without meals. 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.
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 90% that of 9-hydroxy-risperidone is 77%.
Biotransformation and Elimination: Risperidone is metabolized by CYP 2D6 to 9-hydroxy-risperidone, which has a similar pharmacological activity as risperidone. Risperidone plus 9-hydroxy-risperidone form the active antipsychotic fraction. CYP 2D6 is subject to genetic polymorphism. Extensive CYP 2D6 metabolizers convert risperidone rapidly into 9-hydroxy-risperidone, whereas poor CYP 2D6 metabolizers convert it much more slowly. Although extensive metabolizers have lower risperidone and higher 9-hydroxy-risperidone concentrations than poor metabolizers, the pharmacokinetics of risperidone and 9-hydroxy-risperidone combined (i.e., the active antipsychotic fraction), after single and multiple doses, are similar in extensive and poor metabolizers of CYP 2D6.
Another metabolic pathway of risperidone is N-dealkylation. In vitro studies in human liver microsomes showed that risperidone at clinically relevant concentration does not substantially inhibit the metabolism of medicines metabolized by cytochrome P450 isozymes, including CYP 1A2, CYP 2A6, CYP 2C8/9/10, CYP 2D6, CYP 2E1, CYP 3A4 and CYP 3A5. 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. 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.
Linearity: Risperidone plasma concentrations are dose-proportional within the therapeutic dose-range.
Elderly, hepatic and renal impairment: A single-dose study showed on average a 43% higher active antipsychotic fraction plasma concentrations, a 38% longer half-life and a reduced clearance of the active antipsychotic fraction by 30% in the elderly. Higher active antipsychotic fraction plasma concentrations and a reduced clearance of the active antipsychotic fraction by on average 60% were observed 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%.
Pediatric patients: The pharmacokinetics of risperidone, 9-hydroxy-risperidone and the active antipsychotic fraction in children are similar to those in adults.
Gender, race and smoking habits: A popular pharmacokinetic analysis revealed no apparent effect of gender, race or smoking habits on the pharmacokinetics of risperidone or the active antipsychotic fraction.

Risperidone Orally Disintegrating Tablet is indicated for the treatment of schizophrenia.
Risperidone Orally Disintegrating Tablet is indicated for the treatment of moderate to severe manic episodes associated with bipolar disorders.
Risperidone Orally Disintegrating Tablet 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.
Risperidone Orally Disintegrating Tablet 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 behaviors require pharmacologic treatment. Pharmacological treatment should be an integral part of a more comprehensive treatment program, 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.

Schizophrenia: Adults: Risperidone Orally Disintegrating Tablet 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 individualized, if needed. Most patients will benefit from daily doses between 4 and 6 mg.
In some patients, a slower titration phase and a slower 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.
Elderly: A starting dose of 0.5 mg twice daily is recommended. This dosage can be individually adjusted with 0.5 mg twice increments to 1 to 2 mg twice daily.
Pediatric 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 Orally Disintegrating Tablets 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 Orally Disintegrating Tablet must be evaluated and justified on an ongoing basis.
Elderly: 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. Since clinical experience in elderly is limited, caution should be exercised.
Persistent aggression in patients with moderate to severe Alzheimer's 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 Orally Disintegrating Tablet 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 must be reassessed.
Conduct disorder: Child and adolescents from 5 to 18 years of age: For 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. For 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 Orally Disintegrating Tablet must be evaluated and justified on an ongoing basis.
Risperidone Orally Disintegrating Tablet 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 Orally Disintegrating Tablet should be used with caution in these groups of patients.
Mode of Administration: 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.

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 Risperidone Orally Disintegrating Tablet 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 Risperidone Orally Disintegrating Tablet. 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.

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 antipsychotic drugs, including Risperidone Orally Disintegrating Tablet, elderly patients with dementia treated with atypical antipsychotics have an increased mortality compared to placebo. In placebo-controlled trials with oral Risperidone Orally Disintegrating Tablet in this population, the incidence of mortality was 4.0% for Risperidone Orally Disintegrating Tablet treated patients compared to 3.1% for placebo-treated patients. The odds ratio (95% exact confidence interval) was 1.21 (0.7, 2.1). 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.
Concomitant use with furosemide: In the Risperidone Orally Disintegrating Tablet 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. 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 randomized placebo controlled clinical trials in the dementia population with some atypical antipsychotics. The pooled data from six placebo-controlled studies with Risperidone Orally Disintegrating Tablet in mainly elderly patients (>65 years of age) with dementia showed that CVAEs (serious and non-serious, combined) occurred in 3.3% (33/1009) of patients treated with risperidone and 1.2% (8/712) of patients treated with placebo. The odds ratio (95% exact confidence interval) was 2.96 (1.34, 7.50). The mechanism for this increased risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient populations. Risperidone Orally Disintegrating Tablet 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 Orally Disintegrating Tablet 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 Orally Disintegrating Tablet 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. Risperidone Orally Disintegrating Tablet 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. A dose reduction should be considered if hypotension occurs.
Tardive dyskinesia/extrapyramidal symptoms (TD/EPS): Medicines 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. 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.
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 antipsychotics, including Risperidone Orally Disintegrating Tablet should be discontinued.
Parkinson's disease and dementia with Lewy bodies: Physicians should weigh the risks versus the benefits when prescribing antipsychotics, including Risperidone Orally Disintegrating Tablet, 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 Neuroleptic Malignant Syndrome 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.
Hyperglycemia and diabetes mellitus: Hyperglycemia, diabetes mellitus and exacerbation of pre-existing diabetes have been reported during treatment with Risperidone Orally Disintegrating Tablet. 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 utilized antipsychotic guidelines. Patients treated with any atypical antipsychotic, including Risperidone Orally Disintegrating Tablets should be monitored for symptoms of hyperglycemia (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 Orally Disintegrating Tablet use. Weight should be monitored regularly.
Hyperprolactinemia: Tissue culture studies suggest that cell growth in human breast tumors 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 Orally Disintegrating Tablet should be used with caution in patients with pre-existing hyperprolactinemia and in patients with possible prolactin-dependent tumors.
QT prolongation: QT prolongation has very rarely been reported postmarketing. 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 (hypokalemia, hypomagnesemia), as it may increase the risk of arrhythmogenic effects, and in concomitant use with medicines known to prolong the QT interval.
Seizures: Risperidone Orally Disintegrating Tablet should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold.

Pregnancy: There are no adequate data from the use of risperidone in pregnant women. According to postmarketing data reversible extrapyramidal symptoms in the neonate were observed following the use of risperidone during the last trimester of pregnancy. Consequently newborns should be monitored carefully. Risperidone was not teratogenic in animal studies but other types of reproductive toxicity were seen. The potential risk for humans is unknown. Therefore, Risperidone Orally Disintegrating Tablet should not be used during pregnancy unless clearly necessary. If discontinuation during pregnancy is necessary, it should not be done abruptly.
Lactation: 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 in small quantities. There are no data available on adverse reactions in breastfeeding infants. Therefore, the advantage of breastfeeding should be weighed against the potential risks for the child.

The most frequently reported adverse drug reactions (ADRs) (incidence 10%) are: Parkinsonism, headache and insomnia.
The following are all the ADRs that were reported in clinical trials and postmarketing. 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. (See table.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

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 Risperidone Orally Disintegrating Tablet 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 Risperidone Orally Disintegrating Tablet (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 Risperidone Orally Disintegrating Tablet (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 behavior 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 pediatric patients than in adult populations are described as follows:
Elderly patients with dementia: Transient ischemic 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 edema, lethargy and cough.
Pediatric patients: The following ADRs were reported with a frequency 5% in pediatric 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, diarrhea, and enuresis.

As with other antipsychotics, caution is advised when prescribing risperidone with medicinal products known to prolong the QT interval, e.g., class Ia antiarrhythmics (e.g. quinidine, disopiramide, procainamide), class III antiarrhythmics (e.g. amiodarone, sotalol), tricyclic antidepressant (i.e. amitriptyline), tetracyclic antidepressants (i.e. maprotiline), some antihistaminics, other antipsychotics, some antimalarials (i.e. chinice and mefloquine), and with medicines causing electrolyte imbalance (hypokalemia, hypomagnesemia), bradycardia, or those which inhibit the hepatic metabolism of risperidone. This list is indicative and not exhaustive.
Potential for Risperidone Orally Disintegrating Tablet to affect other medicinal products: 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.
Risperidone Orally Disintegrating Tablet 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. Clinically significant hypotension has been observed postmarketing with concomitant use of risperidone and antihypertensive treatment.
Risperidone Orally Disintegrating Tablet does not show a clinically relevant effect on the pharmacokinetics of lithium, valproate, digoxin or topiramate.
Potential for other medicinal products to affect Risperidone Orally Disintegrating Tablet: Carbamazepine has been shown to decrease the plasma concentrations of the active antipsychotic fraction of risperidone. Similar effects may be observed with e.g. rifampicin, phenytoin and phenobarbital which also induce CYP 3A4 hepatic enzyme as well as P-glycoprotein. When carbamazepine or other CYP 3A4 hepatic enzyme/P-glycoprotein (P-gp) inducers are initiated or discontinued, the physician should re-evaluate the dosing of Risperidone Orally Disintegrating Tablet.
Fluoxetine and paroxetine, CYP 2D6 inhibitors, increase the plasma concentration of risperidone, but less so of the active antipsychotic fraction. It is expected that other CYP 2D6 inhibitors, such as quinidine, may affect the plasma concentrations of risperidone in a similar way. When concomitant fluoxetine or paroxetine is initiated or discontinued, the physician should re-evaluate the dosing of Risperidone Orally Disintegrating Tablet.
Verapamil, an inhibitor of CYP 3A4 and P-gp, increases the plasma concentration of risperidone.
Galantamine and donepezil do not show a clinically relevant effect on the pharmacokinetics of risperidone and on the active antipsychotic fraction.
Phenothiazines, tricyclic antidepressants, and some beta-blockers 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. Cimetidine and ranitidine increase the bioavailability of risperidone, but only marginally that of the active antipsychotic fraction. Erythromycin, a CYP 3A4 inhibitor, does not change the pharmacokinetics of risperidone and the active antipsychotic fraction.
The combined use of psychostimulants (e.g., methylphenidate) with Risperidone Orally Disintegrating Tablet in children and adolescents did not alter the pharmacokinetics and efficacy of Risperidone Orally Disintegrating Tablet.
Concomitant use of oral Risperidone Orally Disintegrating Tablet 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.

Store at temperatures not exceeding 30°C.

Antipsychotics

N05AX08 - risperidone ; Belongs to the class of other antipsychotics.

Rx