Instructions for Risperidone-Teva oral solution 1 mg/ml bottle with dispenser 30 ml
Composition
active ingredient: risperidone;
1 ml of solution contains risperidone 1 mg;
excipients: benzoic acid (E 210), tartaric acid, purified water.
Dosage form
Oral solution.
Main physicochemical properties: clear colorless liquid without visible inclusions.
Pharmacotherapeutic group
Antipsychotics. ATX code N05A X08.
Pharmacological properties
Pharmacodynamics
Risperidone is a selective monoaminergic antagonist. It exhibits high affinity for serotonin 5-HT2 and dopamine D2 receptors. Risperidone also binds to α1-adrenergic receptors and, to a lesser extent, to H1-histamine and α2-adrenergic receptors. Risperidone has no affinity for cholinergic receptors. Although risperidone is a potent D2 antagonist that relieves the symptoms of schizophrenia, it is less likely to cause motor depression and catalepsy than classical antipsychotics. Balanced central serotonin and dopamine antagonism provides a lower tendency to extrapyramidal side effects and a broad therapeutic activity against the negative and affective symptoms of schizophrenia.
Pharmacokinetics
The metabolism of risperidone produces 9-hydroxyrisperidone, which has pharmacological activity similar to the parent compound.
Absorption
After oral administration, risperidone is completely absorbed, peak plasma concentrations are reached within 1-2 hours, in elderly patients within 2-3 hours. The absorption of the drug is not affected by food intake, so risperidone can be used regardless of food intake. The equilibrium concentration of risperidone in most patients is achieved within 1 day. The equilibrium concentration of 9-hydroxyrisperidone is achieved in 4-5 days.
Distribution
Risperidone is rapidly distributed in the body. The volume of distribution is 1-2 l/kg. In plasma, risperidone binds to albumin and α1-acid glycoprotein. The binding of risperidone to plasma proteins is 90%, and that of 9-hydroxyrisperidone is 77%.
Biotransformation and excretion
Risperidone is metabolized by CYP2D6 to 9-hydroxyrisperidone, which has pharmacological activity similar to risperidone. Together, these two compounds form the active antipsychotic moiety. CYP2D6 is genetically polymorphic. Extensive CYP2D6 metabolizers rapidly convert risperidone to 9-hydroxyrisperidone, while poor CYP2D6 metabolizers do this more slowly. Although extensive metabolizers produce lower concentrations of risperidone and higher levels of 9-hydroxyrisperidone than poor metabolizers, the overall pharmacokinetics of risperidone and 9-hydroxyrisperidone (i.e., the active antipsychotic moiety) after single and multiple dosing are similar in extensive and poor CYP2D6 metabolizers.
Another route of metabolism of risperidone is N-dealkylation. Risperidone at clinical concentrations does not cause significant inhibition of the metabolism of drugs metabolized in the body with the participation of cytochrome P450 isoenzymes, including CYP1A2, CYP2A6, CYP2C8/9/10, CYP2D6, CYP2E1, CYP3A4 and CYP3A5. Within a week after administration, 70% of the dose is excreted in the urine, another 14% in the feces. In the urine, the content of risperidone and 9-hydroxyrisperidone corresponds to 35-45% of the dose taken.
The remainder are inactive metabolites. After oral administration to patients with psychosis, the elimination half-life of risperidone is 3 hours. The elimination half-life of 9-hydroxyrisperidone and the active antipsychotic fraction is 24 hours, and in elderly patients it is 34 hours.
Linearity
In the therapeutic dose range, plasma concentrations of risperidone are proportional to the dose.
Elderly, renal or hepatic insufficiency
Single-dose pharmacokinetic studies with oral risperidone showed an average of 43% higher plasma concentrations of the active antipsychotic fraction, a 38% longer half-life, and a 30% reduced clearance of the active antipsychotic fraction in elderly patients.
In adult patients with moderate renal impairment, the clearance of the active antipsychotic fraction was approximately 48% of that in young healthy volunteers. In adult patients with severe renal impairment, the clearance of the active antipsychotic fraction was approximately 31% of that in young healthy volunteers. The elimination half-life of the active metabolites was 16.7 hours in adult patients, 24.9 hours in patients with moderate renal impairment (approximately 1.5 times longer than in adult patients), and 28.8 hours in patients with severe renal impairment (approximately 1.7 times longer than in adult patients). Risperidone plasma concentrations were normal in patients with hepatic impairment, but the mean free fraction of risperidone in plasma was increased by 37.1%.
The oral clearance and half-life of risperidone and its active metabolites in adult patients with moderate or severe hepatic impairment were not significantly different from those in healthy volunteers.
Children
Gender, race, and smoking
Population pharmacokinetic analysis revealed no significant effect of gender, race, or smoking on the pharmacokinetics of risperidone and its active antipsychotic fraction.
Indication
– Treatment of schizophrenia and other psychiatric disorders, including maintenance therapy, in patients who have responded to therapy, in order to prevent relapse of the disease;
– short-term treatment of severe aggression or severe psychiatric symptoms in patients with dementia who are at risk of harm to themselves or others;
– treatment of manic episodes in bipolar disorders (adjunctive therapy in combination with mood stabilizers as initial treatment or as monotherapy for a period of up to 12 weeks);
– symptomatic treatment of social behavior disorders, oppositional defiant disorder or other social behavior disorders in children, adolescents and adults with below average mental development or mental retardation who have manifestations of destructive behavior (impulsivity, autoaggression);
– symptomatic treatment of autistic disorders in children aged 5 years and older, in whom symptoms range from hyperactivity to irritability (including aggression, self-harm, anxiety and pathological cyclic actions).
Contraindication
Hypersensitivity to the active substance or to other components of the drug.
Dementia and symptoms of Parkinson's disease (rigidity, bradykinesia and parkinsonian postural disorders).
Dementia and suspected dementia with Lewy bodies (in addition to symptoms of dementia, at least two of the following symptoms: parkinsonism, visual hallucinations, unsteadiness of gait).
Interaction with other medicinal products and other types of interactions
Pharmacodynamic interactions
Drugs that can prolong the QT interval
As with other antipsychotics, caution is advised when prescribing Risperidone with drugs that prolong the QT interval, including antiarrhythmics (e.g. quinidine, disopyramide, procainamide, propafenone, amiodarone, sotalol), tricyclic antidepressants (e.g. amitriptyline), tetracyclic antidepressants (e.g. maprotiline), certain antihistamines, other antipsychotics, certain antimalarials (e.g. quinine and mefloquine), and drugs that disrupt electrolyte balance (cause hypokalemia, hypomagnesemia), cause bradycardia, and drugs that inhibit the metabolism of Risperidone in the liver. The list is indicative and not exhaustive.
Centrally acting drugs and alcohol
Due to the increased risk of excessive sedation, risperidone should be used with caution when used concomitantly with substances that affect the CNS, such as alcohol, opiates, antihistamines, and benzodiazepines.
Levodopa and dopamine agonists
Risperidone may antagonize the therapeutic effects of levodopa and other dopamine agonists. If such a combination is necessary, especially in the terminal stage of Parkinson's disease, the minimum effective dose of each drug should be prescribed.
Drugs with hypotensive effect
Post-marketing surveillance has identified clinically significant arterial hypotension with the simultaneous use of Risperidone® with antihypertensive drugs.
Paliperidone
Concomitant oral administration of risperidone with paliperidone is not recommended, as paliperidone is the active metabolite of risperidone, and the combination of these two drugs may result in excessive total exposure to the active antipsychotic fraction.
Pharmacokinetic interactions
Food intake does not affect the absorption of risperidone.
Risperidone is primarily metabolized by CYP2D6 and to a lesser extent by CYP3A4. Risperidone and its active metabolite, 9-hydroxyrisperidone, are substrates of P-glycoprotein (P-gp). Substances that alter CYP2D6 activity or are potent inhibitors or inducers of CYP3A4 and/or P-gp activity may affect the pharmacokinetics of the active antipsychotic fraction of risperidone.
Strong CYP2D6 inhibitors
Concomitant use of risperidone with strong CYP2D6 inhibitors may increase the plasma concentration of risperidone, but the concentration of the active antipsychotic fraction is not increased as significantly. When using high doses of a strong CYP2D6 inhibitor, an increase in the concentration of the active antipsychotic fraction of risperidone may be observed (e.g. paroxetine, see below). It is expected that other CYP2D6 inhibitors, such as quinidine, may also have a similar effect on the plasma concentrations of Risperidone. When starting or stopping concomitant use of paroxetine, quinidine or another strong CYP2D6 inhibitor, especially at high doses, the physician should review the dose of risperidone.
CYP3A4 and/or P-gp inhibitors
Concomitant use of risperidone with strong CYP3A4 and/or P-gp inhibitors may result in a significant increase in plasma concentrations of the active antipsychotic fraction of risperidone. When initiating or discontinuing concomitant use of itraconazole or other strong CYP3A4 and/or P-gp inhibitors, the physician should review the dose of risperidone.
Concomitant use of risperidone with strong CYP3A4 and/or P-gp inducers may result in decreased plasma concentrations of the active antipsychotic fraction of risperidone. When initiating or discontinuing carbamazepine or other strong CYP3A4 and/or P-glycoprotein inducers, the physician should review the risperidone dose. The effect of CYP3A4 inducers is time-dependent, with the maximum effect occurring at least 2 weeks after initiation of treatment. Similarly, CYP3A4 induction may persist for at least 2 weeks after discontinuation of treatment.
Drugs that are highly bound to plasma proteins
When risperidone is used together with drugs that are extensively bound to plasma proteins, there is no clinically significant substitution of one drug for another in terms of plasma protein binding.
In case of concomitant use of several medicinal products, it is necessary to consult the instructions for medical use of such products regarding metabolic pathways and the possible need for dose adjustment.
Children
Interaction studies have only been conducted in adult patients. It is not known whether the results can be applied to children.
The combined use of psychostimulants (including methylphenidate) with risperidone in children and adolescents did not alter the pharmacokinetics and efficacy of risperidone.
Examples
Examples of drugs that may potentially interact with risperidone or for which no interaction with risperidone has been demonstrated are listed below.
Effect of other medicinal products on the pharmacokinetics of risperidone
Antibacterial agents
– Erythromycin is a moderate CYP3A4 inhibitor and P-gp inhibitor and does not alter the pharmacokinetics of risperidone and its active antipsychotic fraction.
– Rifampicin is a strong inducer of CYP3A4 and an inducer of P-gp and reduces the plasma concentration of the active antipsychotic fraction.
Anticholinesterase agents
– Donepezil and galantamine, both of which are substrates of CYP2D6 and CYP3A4, do not have a clinically significant effect on the pharmacokinetics of risperidone and the active antipsychotic fraction.
Antiepileptic drugs
– Carbamazepine is a strong CYP3A4 and P-gp inducer and reduces the plasma concentration of the active antipsychotic fraction of risperidone. A similar effect may be observed with, for example, phenytoin and phenobarbital, which are also CYP3A4 and P-gp inducers.
– Topiramate moderately reduces the bioavailability of risperidone, but does not affect the bioavailability of the active antipsychotic fraction. Therefore, this interaction is unlikely to be of clinical significance.
Antifungal agents
– Itraconazole is a strong CYP3A4 inhibitor and P-gp inhibitor, at a dose of 200 mg/day it increases the plasma concentration of the active antipsychotic fraction of risperidone, used at a dose of 2-8 mg/day, by approximately 70%.
– Ketoconazole is a strong CYP3A4 inhibitor and P-gp inhibitor, at a dose of 200 mg/day it increases the plasma concentration of risperidone and reduces the plasma concentration of 9-hydroxyrisperidone.
Antipsychotics
– Phenothiazines may increase the plasma concentration of risperidone, but do not affect the concentration of the active antipsychotic fraction.
Antivirals
– Protease inhibitors: there are no formal study data on this, however, since ritonavir is a strong inhibitor of CYP3A4 and a weak inhibitor of CYP2D6, ritonavir and ritonavir-boosted protease inhibitors may increase the concentration of the active antipsychotic fraction of risperidone.
Beta-blockers
– Some beta-blockers may increase the plasma concentration of risperidone without affecting the concentration of the active antipsychotic fraction.
Calcium channel blockers
– Verapamil is a moderate CYP3A4 inhibitor and P-gp inhibitor that increases the plasma concentrations of risperidone and the active antipsychotic fraction.
Remedies for the treatment of the gastrointestinal tract
– H2-histamine receptor antagonists: cimetidine and ranitidine are weak inhibitors of CYP2D6 and CYP3A4, increasing the bioavailability of risperidone with a slight increase in the bioavailability of the active antipsychotic fraction.
SSRIs and tricyclic antidepressants
– Fluoxetine is a strong CYP2D6 inhibitor that increases the plasma concentration of risperidone and, to a minor extent, the concentration of the active antipsychotic fraction.
– Paroxetine is a potent CYP2D6 inhibitor, which increases the plasma concentration of risperidone, but at doses up to 20 mg/day leads to a slight increase in the plasma concentration of the active antipsychotic fraction. However, higher doses of paroxetine may cause an increase in the concentration of the active antipsychotic fraction of risperidone.
– Tricyclic antidepressants may increase the plasma concentration of risperidone, but do not affect the concentration of the active antipsychotic fraction. Amitriptyline does not affect the pharmacokinetics of risperidone or the active antipsychotic fraction.
Concomitant use of psychostimulants (including methylphenidate) with risperidone may lead to the appearance of extrapyramidal symptoms when changing the dosage of one or both drugs (see section "Special warnings and precautions for use").
Clonazepam, gabapentin, lamotrigine, methylphenidate: given the pharmacokinetics of risperidone and these active substances, interactions between them are not expected, although no relevant studies have been conducted.
Effect of risperidone on the pharmacokinetics of other drugs
Antiepileptic drugs
– Risperidone did not demonstrate a clinically significant effect on the pharmacokinetics of valproate or topiramate.
Antipsychotics
– Aripiprazole, a CYP2D6 and CYP3A4 substrate: Risperidone in tablet or injectable form does not affect the combined pharmacokinetics of aripiprazole and its active metabolite, dehydroaripiprazole.
Digitalis glycosides
– Risperidone did not demonstrate a clinically significant effect on the pharmacokinetics of digoxin.
Lithium
– Risperidone has not demonstrated a clinically significant effect on the pharmacokinetics of lithium.
Cases of encephalopathy, extrapyramidal disorders and neuroleptic malignant syndrome have been reported with concomitant use of neuroleptics and lithium. Cases of extrapyramidal disorders and hyperkinesia have been reported more frequently with lithium and neuroleptics than with lithium alone.
Concomitant use of risperidone with furosemide
See section "Special warnings and precautions for use" for information on increased mortality in elderly patients with dementia who are concomitantly treated with furosemide.
Application features
Elderly patients with dementia
Increased mortality. A meta-analysis of 17 controlled trials of atypical antipsychotics (including risperidone) found an increased mortality rate compared with placebo in elderly patients with dementia treated with atypical antipsychotics. Placebo-controlled trials of risperidone in this group of patients showed a mortality rate of 4.0% in the risperidone group compared with 3.1% in the placebo group. The median age of patients who died was 86 years (range 67-100 years). The specific risk factor profile for mortality in the risperidone group has not been determined. Causes of death were typical for this age group (age 65 years and older): cardiovascular and cerebrovascular diseases, neoplasms, infections (e.g. pneumonia), and diabetes. Data from two large, nonexperimental studies suggest that elderly patients with dementia treated with conventional antipsychotics are also at slightly increased risk of death compared with untreated patients. There are insufficient data to estimate the exact magnitude of the risk, and the reason for the increased risk is unknown. The extent to which increased mortality can be associated with antipsychotic use, unlike patient characteristics, is unclear.
Concomitant use with furosemide. In placebo-controlled trials of risperidone in elderly patients with dementia, increased mortality was observed with concomitant use of furosemide with risperidone (7.3%; mean age 89 years, range 75-97), compared with 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). Increased mortality among patients treated with the combination of furosemide plus risperidone was observed in two of the four trials. Concomitant use of risperidone with other diuretics (mainly low-dose thiazide diuretics) was not associated with similar changes.
The pathophysiological mechanisms of such changes have not been identified, and there were no patterns in the causes of these fatalities. Therefore, treatment should be prescribed only after careful consideration of the potential risks and therapeutic benefits of such combinations or concomitant administration with other potent diuretics. Among patients who took other diuretics with risperidone, the risk of fatal outcome was not increased. Regardless of treatment, dehydration is a common risk factor for fatal outcome, which requires careful prevention among elderly patients with dementia.
Cerebrovascular adverse reactions
Studies have shown an approximately 3-fold increased risk of cerebrovascular adverse reactions in patients with dementia taking some atypical antipsychotics. Pooled data from 6 studies of risperidone in predominantly elderly patients (age > 65 years) with dementia showed that cerebrovascular adverse reactions (serious and non-serious, combined) occurred in 3.3% of patients treated with risperidone and 1.2% of patients treated with placebo. The mechanism of this increased risk is unknown. An increased risk cannot be excluded with other antipsychotics or in other patient populations. Risperidone should be used with caution in patients with risk factors for stroke.
The physician should assess the risks and therapeutic benefits of risperidone in elderly patients with dementia, taking into account the prognostic risk factors for stroke in the individual patient. Risperidone should be prescribed with particular caution to patients with dementia who have hypertension, cardiovascular disease, and vascular dementia. Patients and their caregivers should be warned about the need to urgently report symptoms and signs of potential cerebrovascular adverse reactions, including sudden weakness or numbness of the face, arms or legs, speech or vision disorders. In this case, all therapeutic options, including discontinuation of risperidone, should be urgently considered.
For persistent aggression in patients with Alzheimer's dementia, Risset® is intended for short-term use only to supplement non-pharmacological measures when they are ineffective or limited, and there is a risk of harm to oneself or others.
Regular reassessment of patients' condition and justification of the need for further treatment are necessary.
Orthostatic hypotension
Orthostatic hypotension may occur (especially at the beginning of treatment), which is due to the α-adrenergic blocking effect of risperidone. Clinically significant hypotension has been observed in the post-marketing period with the simultaneous use of risperidone and antihypertensive agents. Risperidone should be used with caution in patients with known cardiovascular disease (e.g. heart failure, myocardial infarction, conduction disorders, dehydration, hypovolemia or cerebrovascular disease). In these cases, the dose should be titrated (see section "Method of administration and dosage"). The possibility of reducing the dose should be considered if arterial hypotension occurs.
Leukopenia, neutropenia and agranulocytosis
Leukopenia, neutropenia and agranulocytosis have been reported with antipsychotics, including risperidone. During the post-marketing period, cases of agranulocytosis have been reported very rarely (
Patients with a history of significant leukocyte depletion or drug-induced leukopenia/neutropenia should be monitored during the first few months of therapy, and at the first sign of a clinically significant leukocyte depletion in the absence of other causes, discontinuation of risperidone should be considered.
Patients with clinically significant neutropenia should be closely monitored for fever or symptoms of infection and appropriate treatment should be provided immediately if such symptoms or signs appear. In patients with severe neutropenia (absolute neutrophil count < 9/L), risperidone therapy should be discontinued and the white blood cell count monitored until recovery to normal.
Tardive dyskinesia/extrapyramidal symptoms
Tardive dyskinesia, characterized by involuntary rhythmic movements (predominantly of the tongue and/or face), has been reported with dopamine receptor antagonists. The occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. If signs or symptoms of tardive dyskinesia develop, discontinuation of all antipsychotic drugs should be considered.
Caution is warranted in patients receiving concomitant psychostimulants (e.g. methylphenidate) and risperidone, as extrapyramidal symptoms may occur when changing the dosage of one or both drugs (see section 4.5). Gradual withdrawal of stimulant therapy is recommended.
Neuroleptic malignant syndrome
Cases of neuroleptic malignant syndrome, characterized by hyperthermia, muscle rigidity, autonomic instability, impaired consciousness, and elevated creatine phosphokinase, have been reported with antipsychotic treatment. Other signs may include myoglobinuria (rhabdomyolysis) and acute renal failure. In this case, all antipsychotic drugs, including risperidone, should be discontinued.
Parkinson's disease and dementia with Lewy bodies
When prescribing antipsychotics, including Risperidone, to patients with Parkinson's disease or dementia with Lewy bodies, the physician should weigh the risks against the expected therapeutic benefits. The drug may exacerbate Parkinson's disease. Patients with any of the above conditions may be at increased risk of developing neuroleptic malignant syndrome and may be hypersensitive to antipsychotic drugs; such patients were excluded from clinical trials. In addition to extrapyramidal symptoms, manifestations of this hypersensitive behavior may include confusion, decreased pain sensitivity, and postural instability with frequent falls.
Hyperglycemia, diabetes mellitus and exacerbation of diabetes mellitus have been reported during treatment with Risperidone. In some cases, a prior increase in body weight has been reported, which may contribute to the development of these events. An association with ketoacidosis has been reported very rarely and, rarely, an association with diabetic coma. Therefore, appropriate clinical monitoring is recommended in accordance with the applicable standards for antipsychotic medicinal products. Patients treated with any atypical antipsychotic medicinal product, including risperidone, should be observed for symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia and weakness), and diabetic patients should be regularly evaluated for possible deterioration in glucose control.
Weight gain
Significant weight gain has been reported with risperidone. Weight should be monitored.
Hyperprolactinemia
Hyperprolactinemia is a common adverse reaction observed with risperidone treatment. In patients with signs of prolactin-related adverse reactions (gynecomastia, menstrual disorders, anovulation, fertility disorders, decreased libido, erectile dysfunction, galactorrhea), it is recommended to assess the level of prolactin in the blood plasma.
Tissue culture studies suggest that cell growth in human breast tumors may be stimulated by prolactin. Although clinical and epidemiological studies have not shown a direct relationship with antipsychotic use, caution is advised when treating patients with a history of this condition. Risperidone should be used with caution in patients with hyperprolactinemia or in patients suspected of having prolactin-dependent tumors.
QT prolongation
Cases of QT prolongation have been reported very rarely in the post-marketing period. As with any other antipsychotic, caution should be exercised when prescribing Risperidone to patients with known cardiovascular disease, a family history of QT prolongation, bradycardia and electrolyte imbalance (hypokalemia, hypomagnesemia), as such treatment may increase the risk of arrhythmogenic effects. Caution should also be exercised when prescribing combinations of drugs that can prolong the QT interval.
Epileptic seizures
Risperidone should be used with caution in patients with a history of epileptic seizures or other disorders that may lower the seizure threshold.
Priapism
Due to the α-adrenergic blocking effects, treatment with Risperidone may be accompanied by the occurrence of priapism.
Body temperature regulation
Antipsychotics have been associated with disturbances in the body's ability to regulate core body temperature. Appropriate caution is recommended when prescribing Risperidone to patients whose lifestyle involves exposure to factors that may increase core body temperature, such as intense exercise, exposure to high temperatures, concomitant treatment with agents with anticholinergic activity, and states of dehydration.
Antiemetic effect
Risperidone has been reported to have an antiemetic effect. This effect, if observed in humans, may mask signs of overdose with certain drugs or conditions such as intestinal obstruction, Reye's syndrome, and brain tumors.
Renal and hepatic failure
In patients with renal insufficiency, in contrast to individuals with normal renal function, the ability to excrete the active antipsychotic fraction from the body is reduced. In patients with hepatic insufficiency, an increase in the concentration of the free fraction of risperidone in plasma is observed. It is recommended to prescribe half the initial and maintenance doses to patients with impaired hepatic and renal function (see section "Method of administration and dosage").
Venous thromboembolism
Cases of venous thromboembolism have been reported with antipsychotic drugs. Since patients requiring treatment with antipsychotic drugs often have acquired risk factors for venous thromboembolism, all risk factors for venous thromboembolism should be identified before prescribing (and during treatment with) Risperidone and possible preventive measures should be taken.
Intraoperative atonic iris syndrome
Intraoperative atonic iris syndrome (IAIS) has been reported in patients undergoing cataract surgery treated with α1-adrenergic blocking agents, including risperidone. ISAIS increases the risk of ocular complications during and after surgery. Prior to surgery, the ophthalmic surgeon should be aware of the patient's current or past use of α1-adrenergic blocking agents. The potential benefit of discontinuing α1-adrenergic blocking agents prior to cataract surgery has not been established and should be weighed against the risk of discontinuing antipsychotic medication.
Before prescribing Risset® to children, the risk-benefit ratio should be carefully weighed. The need for continued treatment should be carefully assessed regularly. The indications “symptomatic treatment of social conduct disorders, oppositional defiant disorder and/or other social conduct disorders” and “autistic disorders” have only been studied in children aged 5 years and older. Therefore, Risset® should not be prescribed to children under 5 years of age for these indications.
There is no experience with the use of Risperidone in children under 15 years of age for the treatment of schizophrenia and in children under 10 years of age for the treatment of manic episodes in bipolar disorder.
Children with conduct disorders should be prescribed Risset® only after careful consideration of possible physical and social causes of aggressive behavior (e.g., pain or inappropriate environmental demands).
Due to the possible impact on learning ability in this population, careful monitoring of the sedative effect of the drug is necessary. The time of administration of Risperidone should be chosen in such a way as to optimize the effect of the sedative effect on the ability to concentrate in children and adolescents.
Risperidone treatment has been associated with a modest increase in body weight and body mass index (BMI). It is recommended that weight be measured before starting treatment and that weight be monitored regularly thereafter.
Growth changes observed in long-term open-label extension studies were within the expected age-related range. The effects of long-term treatment with Risperidone on sexual development and growth have not been adequately studied.
Because of the potential impact of prolonged hyperprolactinemia on physical and sexual development in children and adolescents, regular clinical evaluations of endocrinological status are necessary, including height, weight, assessment of sexual development, monitoring of menstrual cycles, and other potential prolactin effects.
Results from a small postmarketing observational study showed that patients aged 8 to 16 years who took risperidone were on average 3.0 to 4.8 cm taller than patients who took other atypical antipsychotics. The data from this study are insufficient to determine whether risperidone had any effect on final adult height or whether the results were due to a direct effect of risperidone on bone growth or to the effect of the underlying disease or to improved control of the underlying disease that resulted in increased linear height.
During treatment with risperidone, regular examinations are necessary to detect extrapyramidal symptoms and other movement disorders.
Somnolence. Somnolence has been reported frequently in children with autism. Most cases were mild to moderate in severity. Somnolence occurred primarily at the start of treatment, with the highest frequency occurring within the first two weeks of treatment, and resolved spontaneously with a median duration of 16 days. For patients with somnolence, a change in dosage regimen may be appropriate.
Use during pregnancy or breastfeeding
Pregnancy
There is no experience with the use of the drug in pregnant women. In animal studies, risperidone did not show teratogenic effects, but other types of reproductive toxicity were observed, and an indirect effect on prolactin levels was observed. The potential risk for humans is unknown. Risperidone should not be used during pregnancy unless clearly necessary.
Neonates whose mothers have taken antipsychotics (including risperidone) during the third trimester of pregnancy are at risk of developing adverse reactions, including reversible extrapyramidal symptoms and/or withdrawal syndrome, which may vary in severity and duration. Agitation, hypertonia, hypotension, tremor, somnolence, respiratory or feeding disorders have been reported. In some cases, these resolved spontaneously after a period of time.
