Instructions for Risperidone-Teva film-coated tablets 4 mg No. 30
Composition
active ingredient: risperidone;
1 film-coated tablet contains 2 mg or 4 mg of risperidone;
excipients: core: lactose monohydrate, sodium lauryl sulfate, colloidal anhydrous silica, microcrystalline cellulose, pregelatinized starch, sodium starch glycolate (type A), magnesium stearate;
film coating: hypromellose, titanium dioxide (E 171), macrogol 6000, macrogol 400, iron oxide yellow (E 172); 2 mg tablets - iron oxide red (E 172); 4 mg tablets - quinoline yellow (E 104), indigo carmine (E 132).
Dosage form
Film-coated tablets.
Main physicochemical properties:
film-coated tablets, 2 mg: brown, round, slightly convex tablets with a diameter of approximately 8 mm and a thickness of approximately 3.5 mm, embossed with RIS 2 and a score line on one side and a score line on the other side;
Film-coated tablets, 4 mg: green, round, slightly convex tablets with a diameter of approximately 10.5 mm and a thickness of approximately 4.5 mm, embossed with RIS 4 and a score line on one side and a score line on the other side.
Pharmacotherapeutic group
Drugs that act on the nervous system. Psycholeptic drugs.
Antipsychotics. Risperidone. ATX code N05A X08.
Pharmacological properties
Pharmacodynamics
Mechanism of action. Risperidone is a selective monoaminergic antagonist with unique properties. It exhibits high affinity for serotonergic 5-HT2 and dopaminergic D2 receptors. Risperidone also binds to α1-adrenergic receptors and, with lower affinity, to H1-histaminergic and α2-adrenergic receptors. Risperidone has no affinity for cholinergic receptors. Although risperidone is a potent D2 antagonist, which is associated with its efficacy in the positive symptoms of schizophrenia, it does not cause significant motor depression and induces catalepsy to a lesser extent than classical antipsychotics. Balanced central antagonism of serotonin and dopamine reduces the tendency for extrapyramidal side effects and extends the therapeutic effect of the drug to cover the negative and affective symptoms of schizophrenia.
Pharmacokinetics
Risperidone is metabolized to 9-hydroxyrisperidone, which has the same pharmacological activity as risperidone.
Absorption. After oral administration, risperidone is completely absorbed and reaches peak plasma concentrations within 1–2 hours, in elderly patients within 2–3 hours. The absolute bioavailability of risperidone when administered orally is 70% (CV = 25%). The relative bioavailability of oral risperidone from tablets is 94% (CV = 10%) compared with that from solution. Food does not affect absorption, so risperidone can be taken without regard to meals. Absolute bioavailability is 66% in extensive metabolizers and 82% in poor metabolizers.
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 plasma protein binding of risperidone is 90%, and that of 9-hydroxyrisperidone is 77%.
In most patients, steady-state concentrations of risperidone are achieved within 1 day, and steady-state concentrations of 9-hydroxyrisperidone are achieved within 4–5 days of treatment.
Biotransformation and elimination. Risperidone is metabolized by cytochrome CYP2D6 to 9-hydroxyrisperidone, which has similar pharmacological effects to risperidone. Risperidone and 9-hydroxyrisperidone form the active antipsychotic fraction. Cytochrome CYP2D6 is subject to genetic polymorphism. In extensive CYP2D6 metabolizers, risperidone is rapidly converted to 9-hydroxyrisperidone, while in poor CYP2D6 metabolizers, this conversion occurs much more slowly. Although extensive metabolizers have lower concentrations of risperidone and higher concentrations of 9-hydroxyrisperidone than poor metabolizers, the pharmacokinetics of the combination of risperidone and 9-hydroxyrisperidone (i.e., the active antipsychotic moiety) after single and multiple doses are similar in extensive and poor CYP2D6 metabolizers. Another metabolic pathway of risperidone is N-dealkylation. In vitro studies in human liver microsomes have shown that risperidone does not significantly inhibit the metabolism of drugs metabolized by cytochrome P450 isoenzymes, including CYP1A2, CYP2A6, CYP2C8/9/10, CYP2D6, CYP2E1, CYP3A4, and CYP3A5, at clinically relevant concentrations. One week after administration, 70% of the dose is excreted in the urine and 14% in the feces. The combined urinary content of risperidone and 9-hydroxyrisperidone is 35–45% of the administered dose. The remainder is made up of inactive metabolites. After oral administration in patients with psychosis, the elimination half-life of risperidone is approximately 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.
Elderly, hepatically and renally impaired. A single oral pharmacokinetic study of risperidone demonstrated an average 43% higher plasma concentration of the active antipsychotic fraction in elderly patients, a 38% longer half-life, and a 30% decrease in clearance of the active antipsychotic fraction. In adult patients with renal impairment, clearance of the active fraction was 48% of that in adults without renal impairment. In adult patients with severe renal impairment, clearance was 31% of that in adults without renal impairment.
The half-life of the active fraction in younger adults was 16.7 h, in adults with moderate renal impairment it was 24.9 h (1.5 times longer than in younger adults), and in adults with severe renal impairment it was 28.8 h (1.7 times longer than in younger adults). Plasma concentrations of risperidone were normal in patients with hepatic impairment, but the mean plasma free fraction of risperidone was increased by 37.1%. The clearance and half-life of risperidone and the active antipsychotic fraction after oral administration in adults with moderate and severe hepatic impairment were not significantly different from those in healthy young adults.
Children: The pharmacokinetics of risperidone, 9-hydroxyrisperidone and the active antipsychotic fraction in children are similar to those in adults.
Gender, race, and smoking: A population pharmacokinetic analysis revealed no apparent effect of gender, race, or smoking on the pharmacokinetics of risperidone or the active antipsychotic fraction.
Indication
- Treatment of schizophrenia;
- treatment of moderate to severe manic episodes associated with bipolar disorder;
- short-term treatment (up to 6 weeks) of severe aggression in patients with moderate to severe Alzheimer's dementia who are at risk of harm to themselves or others and have not responded to non-pharmacological treatments (see sections "Method of administration and dosage" and "Special instructions for use");
- symptomatic short-term treatment (up to 6 weeks) of severe aggression in conduct disorders in children aged 5 years and older and adolescents with below-average mental development or mental retardation diagnosed according to DSM-IV criteria, in whom the severity of aggressive or other disruptive behavior requires pharmacological treatment. Pharmacological treatment should be an integral part of a comprehensive treatment program that includes psychological support and educational measures. It is recommended that risperidone be prescribed by a specialist in the field of child neurology, child and adolescent psychiatry or a physician experienced in the treatment of conduct disorders in children and adolescents.
Contraindication
Hypersensitivity to the active substance or to any of the excipients of the medicinal product. 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 may prolong the QT interval. As with other antipsychotics, caution is advised when risperidone is co-administered with drugs that prolong the QT interval, including antiarrhythmics (quinidine, disopyramide, procainamide, propafenone, amiodarone, sotalol), tricyclic antidepressants (amitriptyline), tetracyclic antidepressants (maprotiline), some antihistamines, other antipsychotics, some antimalarials (quinine and mefloquine), and drugs that cause electrolyte imbalance (hypokalemia, hypomagnesemia), bradycardia, or drugs that inhibit the hepatic metabolism of risperidone. This list is indicative and not exhaustive.
Centrally acting drugs and alcohol: Risperidone should be used with caution in combination with other centrally acting drugs, including alcohol, opiates, antihistamines, and benzodiazepines, due to the increased risk of sedation.
Levodopa and dopamine agonists: Risperidone may antagonize levodopa and other dopamine agonists. If such a combination is considered necessary, particularly in end-stage Parkinson's disease, the lowest effective dose of each drug should be used.
Drugs with hypotensive effects: In the post-marketing period, cases of clinically significant hypotension have been observed with the simultaneous use of risperidone and antihypertensive drugs.
Paliperidone: The use of oral risperidone with paliperidone is not recommended because paliperidone is the active metabolite of risperidone and the combination of these drugs may result in excessive cumulative exposure to the active antipsychotic fraction.
Pharmacokinetic interactions
Food does not affect the absorption of risperidone. Risperidone is primarily metabolized by cytochrome 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 may affect the pharmacokinetics of the active antipsychotic fraction of risperidone.
Potent CYP2D6 inhibitors. Concomitant use of risperidone with potent CYP2D6 inhibitors may increase the plasma concentration of risperidone, but to a lesser extent than the concentration of the active antipsychotic fraction. High doses of a potent CYP2D6 inhibitor may increase the concentration of the active antipsychotic fraction of risperidone (e.g. paroxetine, see below). Other CYP2D6 inhibitors, such as quinidine, are expected to have a similar effect on risperidone plasma concentrations. When initiating or discontinuing concomitant use of paroxetine, quinidine or other potent CYP2D6 inhibitors, especially at high doses, the physician should review the dose of risperidone.
CYP3A4 and/or P-gp inhibitors: Concomitant use of risperidone with potent CYP3A4 and/or P-gp inhibitors may result in a significant increase in plasma concentrations of the active antipsychotic fraction of risperidone. The physician should review the dose of risperidone when initiating or discontinuing concomitant use of itraconazole or another potent CYP3A4 and/or P-gp inhibitor.
CYP3A4 and/or P-gp inducers. 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 concomitant use of carbamazepine or other strong CYP3A4 and/or P-gp inducers, the physician should review the dose of risperidone. The effect of CYP3A4 inducers occurs over time, with maximal effect occurring at least 2 weeks after initiation of treatment. Similarly, CYP3A4 induction may persist for at least 2 weeks after discontinuation of treatment.
Highly protein-bound medicinal products. When risperidone was co-administered with other medicinal products that are highly protein-bound, no clinically significant displacement of either medicinal product from the protein fraction was observed. In the case of concomitant use of medicinal products, the prescribing information should be consulted regarding metabolic pathways and the possible need for dose adjustment.
Children: Interaction studies have only been conducted in adults. The relevance of the results obtained in such studies to pediatric patients is unknown.
When psychostimulants (e.g., methylphenidate) were coadministered with risperidone, the pharmacokinetics and efficacy of risperidone in children and adolescents were not altered.
Examples: The following are examples of drugs that have the potential to interact with risperidone or for which no such interaction has been shown.
Effect of other medicinal products on the pharmacokinetics of risperidone
Antibacterial drugs. Erythromycin, a moderate CYP3A4 inhibitor and P-gp inhibitor, does not alter the pharmacokinetics of risperidone and its active antipsychotic fraction. Rifampicin, a potent CYP3A4 inducer and P-gp inducer, decreases the plasma concentration of the active antipsychotic fraction.
Anticholinesterase drugs: Donepezil and galantamine, 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, a potent inducer of CYP3A4 and P-gp, 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 inducers of the hepatic enzyme CYP3A4 and P-gp. 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 clinically significant.
Antifungal drugs. Itraconazole, a potent CYP3A4 inhibitor and P-gp inhibitor, at a dose of 200 mg/day increases the plasma concentration of the active antipsychotic fraction of risperidone administered at a dose of 2–8 mg/day by approximately 70%. Ketoconazole, a potent CYP3A4 inhibitor and P-gp inhibitor, at a dose of 200 mg/day increases the plasma concentration of risperidone and decreases the plasma concentration of 9-hydroxyrisperidone.
Antipsychotic drugs: Phenothiazines may increase the plasma concentration of risperidone, but do not affect the concentration of the active antipsychotic fraction.
Antiviral drugs. Protease inhibitors: There are no formal study data, however, as ritonavir is a potent inhibitor of CYP3A4 and a weak inhibitor of CYP2D6, ritonavir and ritonavir-boosted protease inhibitors have the potential to increase the concentration of the active antipsychotic fraction of risperidone.
Calcium channel blockers: Verapamil, a moderate CYP3A4 inhibitor and P-gp inhibitor, increases plasma concentrations of risperidone and the active antipsychotic fraction.
Drugs for the treatment of gastrointestinal diseases. H2-receptor antagonists: cimetidine and ranitidine, weak inhibitors of CYP2D6 and CYP3A4, increase the bioavailability of risperidone and, to a lesser extent, the bioavailability of the active antipsychotic fraction.
SSRIs and tricyclic antidepressants. Fluoxetine, a potent CYP2D6 inhibitor, increases risperidone plasma concentrations, but less than the concentration of the active antipsychotic fraction. Paroxetine, a potent CYP2D6 inhibitor, increases risperidone plasma concentrations, but at doses up to 20 mg/day, less than the 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.
Sertraline, a weak inhibitor of CYP2D6, and fluvoxamine, a weak inhibitor of CYP3A4, at doses up to 100 mg/day are not associated with clinically significant changes in the concentration of the active antipsychotic fraction of risperidone. However, doses of sertraline or fluvoxamine above 100 mg/day may cause an increase in the concentration of the active antipsychotic fraction of risperidone.
Effect of risperidone on the pharmacokinetics of other drugs
Antiepileptic drugs: Risperidone has not demonstrated a clinically significant effect on the pharmacokinetics of valproate or topiramate.
Antipsychotic drugs: 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 has not demonstrated a clinically significant effect on the pharmacokinetics of digoxin.
Lithium: Risperidone has not demonstrated a clinically significant effect on the pharmacokinetics of lithium.
Concomitant use of risperidone with furosemide
For increased mortality in elderly patients with dementia who are concomitantly treated with furosemide, see section "Special warnings and precautions for use".
Application features
Elderly patients with dementia
Increased mortality in elderly patients with dementia. A meta-analysis of 17 controlled trials of atypical antipsychotics, including risperidone, demonstrated that elderly patients with dementia treated with atypical antipsychotics had an increased mortality compared with placebo. In placebo-controlled trials of oral risperidone in this category of patients, the mortality rate was 4.0% in patients treated with risperidone and 3.1% in patients treated with placebo. The odds ratio (95% exact confidence interval) was 1.21 (0.7, 2.1). The median age of patients who died was 86 years (range 67–100 years). Two large observational studies have shown that elderly patients with dementia treated with conventional (typical) antipsychotics also have a slightly increased risk of mortality compared with those not treated. The exact level of this risk cannot be determined from the available data, and the reason for the increased risk is unknown.
Concomitant use with furosemide. In placebo-controlled trials of risperidone in elderly patients with dementia, an increased incidence of death was observed in patients treated with furosemide and risperidone (7.3%; mean age 89 years, range 75–97 years) compared with patients treated with risperidone alone (3.1%; mean age 84 years, range 70–96 years) or furosemide alone (4.1%; mean age 80 years, range 67–90 years). An increased mortality in patients treated with furosemide and risperidone was observed in two of the four clinical trials. Concomitant use of risperidone with other diuretics was not associated with similar outcomes.
No pathophysiological mechanisms have been identified to explain this finding. The cause of death was not uniform. Nevertheless, caution should be exercised and the benefit/risk ratio should be assessed before deciding to use this combination or concomitant therapy with other potent diuretics. Mortality was not increased in patients taking other diuretics concomitantly with risperidone. Regardless of treatment, dehydration was a common risk factor for mortality, which should be carefully avoided in elderly patients with dementia.
Pooled data from 6 placebo-controlled trials of risperidone in elderly patients with dementia (aged 65 years and older) showed that cerebrovascular events (serious and non-serious, combined) occurred in 3.3% (33/1009) of risperidone-treated patients compared with 1.2% (8/712) of placebo-treated patients. The risperidone-to-placebo ratio (odds ratio; 95% CI) was 2.96 (1.34, 7.50). The mechanism of this increased risk is unknown. An increased risk with other antipsychotics or in other patient populations cannot be excluded. Risperidone should be used with caution in patients with risk factors for stroke.
The risk of CVD was significantly higher in patients with mixed or vascular dementia than in patients with Alzheimer's dementia. Therefore, patients with other types of dementia than Alzheimer's dementia should not be treated with risperidone. It is recommended to assess the benefit/risk ratio when using risperidone in elderly patients with dementia, especially the risk of stroke. Patients/carers should be warned to report immediately any signs and symptoms of potential cerebrovascular disorders, such as sudden weakness or numbness of the face, arms or legs and speech or vision disorders. All possible treatment options, including discontinuation of risperidone, should be considered immediately.
For the treatment of persistent aggression in patients with moderate to severe Alzheimer's dementia, risperidone should only be used short-term, as an adjunct to non-pharmacological treatments that have been ineffective or have limited efficacy, or if there is a risk of harm to self or others. The patient's condition and the need for continued therapy should be reassessed regularly.
Orthostatic hypotension. Orthostatic hypotension may occur due to the α1-lytic effect of risperidone, especially at the beginning of treatment. In the post-marketing period, cases of clinically significant hypotension have been observed with the simultaneous use of risperidone and antihypertensive agents. Risperidone should be used with caution in patients with cardiovascular diseases (such as heart failure, myocardial infarction, conduction disorders, dehydration, hypovolemia or cerebrovascular disease) and the dose should be titrated gradually, according to the recommendations (see section "Method of administration and dosage"). If hypotension occurs, the possibility of reducing the dose should be considered.
Leukopenia, neutropenia and agranulocytosis: Leukopenia, neutropenia and agranulocytosis have been reported with antipsychotics, including risperidone. Agranulocytosis has been observed very rarely in the post-marketing setting (
Patients with clinically significant neutropenia should be closely monitored for fever or other symptoms or signs of infection and appropriate treatment should be initiated promptly if such symptoms or signs develop. In the event of severe neutropenia (absolute neutrophil count < 9/L), risperidone therapy should be discontinued and the white blood cell count monitored until the values return to normal.
Tardive dyskinesia/extrapyramidal symptoms. Medicinal products with dopamine receptor antagonist properties have been associated with the development of tardive dyskinesia, characterised by involuntary rhythmic movements, predominantly of the tongue and/or face. The development 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 medicinal products should be considered.
Patients receiving psychostimulants (e.g. methylphenidate) and risperidone concomitantly should be cautious about the potential for extrapyramidal symptoms during dose titration of one or both drugs. Gradual withdrawal of the psychostimulant is recommended (see Interactions with other medicinal products and other forms of interaction).
Neuroleptic malignant syndrome. Cases of neuroleptic malignant syndrome, characterized by hyperthermia, muscle rigidity, autonomic instability, impaired consciousness, and elevated serum creatine phosphokinase, have been reported with antipsychotic treatment. Additional features may include myoglobinuria (rhabdomyolysis) and acute renal failure. If neuroleptic malignant syndrome develops, all antipsychotic drugs, including risperidone, should be discontinued.
Hyperglycemia and diabetes mellitus. Cases of hyperglycemia, diabetes mellitus and exacerbation of pre-existing diabetes mellitus have been reported with risperidone. In some cases, a pre-existing overweight status has been reported, which may be a factor in the development of these events. These events have been very rarely associated with ketoacidosis and rarely with diabetic coma. Therefore, appropriate clinical monitoring is recommended in accordance with current guidelines for the use of antipsychotic drugs. Patients treated with any atypical antipsychotic drugs, including risperidone, should be observed for symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia and weakness), and patients with diabetes mellitus should be monitored regularly for possible deterioration of glucose control.
Weight gain: Significant weight gain has been reported with risperidone. Regular monitoring of weight should be performed.
Hyperprolactinemia: Hyperprolactinemia is a common adverse event associated with risperidone treatment. In patients with signs of possible prolactin-related adverse events (e.g., gynecomastia, menstrual disorders, anovulation, fertility disorders, decreased libido, erectile dysfunction, and galactorrhea), it is recommended to monitor plasma prolactin levels.
Tissue culture studies suggest that prolactin may stimulate cell growth in human breast tumors. Although clinical and epidemiological studies have not yet demonstrated a clear association with antipsychotic use, caution is advised when prescribing the drug to patients with a relevant medical history. Risperidone should be used with caution in patients with pre-existing hyperprolactinemia and prolactin-dependent tumors.
QT prolongation: Very rare cases of QT prolongation have been reported in the post-marketing setting. As with other antipsychotics, risperidone should be used with caution in patients with known cardiovascular disease, a family history of QT prolongation, bradycardia, or electrolyte imbalance (hypokalemia, hypomagnesemia) due to the potential for increased risk of arrhythmogenic reactions. Risperidone should also be used with caution in patients with known cardiovascular disease, a family history of QT prolongation, bradycardia, or electrolyte imbalance (hypokalemia, hypomagnesemia). Caution should also be exercised when risperidone is administered concomitantly with drugs known to prolong the QT interval.
Seizures: Risperidone should be used with caution in patients with a history of seizures or other conditions that potentially lower the seizure threshold.
Priapism. Priapism may occur with risperidone, which is due to the α-adrenergic blocking effect of the drug.
Body temperature regulation: Antipsychotic drugs may impair the body's ability to lower core body temperature. It is recommended that patients treated with risperidone who may be exposed to factors that increase core body temperature, such as strenuous exercise, high ambient temperatures, concomitant use of anticholinergic drugs, or dehydration, be monitored closely.
Antiemetic effect: Risperidone has been shown to have an antiemetic effect in preclinical studies. This effect may mask the signs and symptoms of overdose of certain drugs or conditions such as intestinal obstruction, Reye's syndrome, and brain tumors.
Renal and hepatic impairment: Patients with renal impairment have a reduced ability to excrete the active antipsychotic fraction compared to adult patients with normal renal function. In patients with hepatic impairment, the free fraction of risperidone is increased in plasma (see Dosage and Administration).
Venous thromboembolism: Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotic drugs often have acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with risperidone and appropriate preventive measures should be taken.
Intraoperative atonic iris syndrome (IAS). ISA has been reported in patients undergoing cataract surgery treated with α1-adrenergic receptor antagonists, including risperidone. This syndrome may increase the risk of ocular complications during and after surgery. The ophthalmic surgeon should be informed prior to surgery of any current or past antipsychotic medications the patient is taking. The potential benefit of discontinuing α1-adrenergic receptor antagonist therapy prior to cataract surgery has not been established and should be weighed against the risks associated with discontinuing antipsychotic medications.
The sedative effects of risperidone should be carefully monitored in this patient group because of the potential impact on learning. Varying the timing of risperidone administration may reduce the effects of sedation on alertness in children and adolescents. Risperidone has been associated with increases in mean body weight and body mass index (BMI). It is recommended that body weight be determined prior to initiation of treatment and monitored regularly thereafter. Growth changes observed in long-term open-label extension studies were within the normal range for age. The effects of long-term risperidone therapy on sexual development and growth have not been adequately investigated.
Given the potential impact of prolonged hyperprolactinemia on growth and puberty in children and adolescents, regular clinical evaluation of the endocrine status of pediatric patients should be considered, including determination of height, weight, sexual development, monitoring of the menstrual cycle, and other prolactin-related effects.
A small postmarketing observational study showed that patients aged 8 to 16 years treated with risperidone were on average 3.0 to 4.8 cm taller than patients treated with other antipsychotics. The data from this study were 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 an effect on bone growth of the underlying disease or to improved control of the underlying disease that resulted in increased linear height. Risperidone treatment should also be monitored regularly for extrapyramidal symptoms and other movement disorders. For specific dosing recommendations for children and adolescents, see section 4.2.
Excipients
Lactose: Patients with rare hereditary problems of galactose intolerance, the total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Sodium: This medicinal product contains less than 1 mmol sodium (23 mg) per film-coated tablet, i.e. essentially 'sodium-free'.
Use during pregnancy or breastfeeding
Pregnancy: There are insufficient data from the use of risperidone in pregnant women. Animal studies have not demonstrated teratogenic effects of risperidone, but other reproductive toxicity has been observed. The potential risk to humans is unknown.
Neonates whose mothers have taken antipsychotics (including risperidone) during the third trimester of pregnancy are at risk of developing extrapyramidal and/or withdrawal symptoms, which may vary in severity and duration. Agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disturbances have been reported. Accordingly, such neonates should be closely monitored. Risperidone should not be used during pregnancy unless clearly necessary. If treatment with the drug must be discontinued during pregnancy, this should not be done abruptly.
Breastfeeding. In animal studies, risperidone and 9-hydroxyrisperidone were excreted in human milk. Risperidone and 9-hydroxyrisperidone have also been found to be excreted in small amounts in human milk. There are no data on adverse reactions in breastfed infants. Therefore, the benefits of breastfeeding should be weighed against the potential risks to the child.
Fertility: Like other dopamine D2 receptor antagonists, risperidone increases prolactin levels. Hyperprolactinemia may suppress hypothalamic gonadotropin-releasing hormone production and lead to decreased pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both women and men.
No relevant effects were observed in preclinical studies.
