Instructions for Eridon tablets 2 mg No. 30
Composition
active ingredient: risperidone;
1 tablet contains 2 mg or 4 mg of risperidone;
excipients: lactose monohydrate, microcrystalline cellulose, corn starch, povidone, magnesium stearate, colloidal anhydrous silicon dioxide, sodium lauryl sulfate;
shell: Opadry Y-1-7000 White (hypromellose, titanium dioxide (E 171), macrogol), carnauba wax.
Dosage form
Film-coated tablets.
Main physicochemical properties: white, capsule-shaped tablets, film-coated.
Pharmacotherapeutic group
Antipsychotics. 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 does not exhibit affinity for cholinergic receptors. Although risperidone is a potent D2 antagonist, which is associated with its efficacy in the productive symptoms of schizophrenia, it does not cause significant motor depression and induces catalepsy to a lesser extent compared to classical neuroleptics. Balanced central antagonism towards serotonin and dopamine reduces the tendency to 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 similar pharmacological effects to risperidone (see section “Biotransformation and elimination”).
Absorption
After oral administration, risperidone is completely absorbed and reaches peak plasma concentrations within 1-2 hours, in elderly patients within 2-3 hours. Absolute bioavailability after oral administration of risperidone is 70% (CV=25%). Relative bioavailability after oral administration of risperidone in tablets is 94% (CV=10%) compared to the solution. Food does not affect the absorption of the drug, so risperidone can be prescribed regardless of food intake. 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 blood plasma, risperidone binds to albumin and acid α1-glycoprotein. Risperidone is 90% bound to plasma proteins, 9-hydroxyrisperidone is 77%. The equilibrium concentration of risperidone in the body is achieved in most patients within 1 day. The equilibrium concentration of 9-hydroxyrisperidone is achieved within 4-5 days.
Biotransformation and excretion
Risperidone is metabolized by CYP2D6 to 9-hydroxyrisperidone, which has similar pharmacological effects to risperidone. Risperidone and 9-hydroxyrisperidone form the active antipsychotic fraction. CYP2D6 is subject to genetic polymorphism. In extensive CYP2D6 metabolizers, risperidone is rapidly converted to 9-hydroxyrisperidone, whereas in poor metabolizers, risperidone is converted much more slowly. Although extensive metabolizers have lower concentrations of risperidone and 9-hydroxyrisperidone than poor metabolizers, the pharmacokinetics of risperidone and 9-hydroxyrisperidone in combination (i.e., the active antipsychotic fraction) after single and multiple doses are similar in extensive and poor metabolizers of CYP2D6.
Another route of metabolism of risperidone is N-dealkylation. In vitro studies in human liver microsomes have shown that risperidone at clinically relevant concentrations does not significantly inhibit the metabolism of drugs metabolized by cytochrome P450 isoenzymes, including CYP1A2, CYP2A6, CYP2C8/9/10, CYP2D6, CYP2E1, CYP3A4, and CYP3A5. One week after administration, 70% of the dose is excreted in the urine and 14% in the feces. The concentration of risperidone and 9-hydroxyrisperidone in the urine is 35-45% of the dose taken. The rest is made up of inactive metabolites. After oral administration in psychotic patients, the half-life is approximately 3 hours. The half-life of 9-hydroxyrisperidone and the active antipsychotic fraction reaches 24 hours, and in elderly patients - 34 hours.
Linearity
The concentration of risperidone in blood plasma is proportional to the dose of the drug (within the therapeutic dose range).
Elderly patients and patients with impaired renal or hepatic function
In adult patients with renal impairment, the clearance of the active fraction was 48% of that in adults without renal impairment. In adult patients with severe renal impairment, the clearance was 31% of that in adults without renal impairment. The elimination half-life of the active fraction was 16.7 hours in young adult patients, 24.9 hours in adults with moderate renal impairment (or 1.5 times longer than that in young adult patients), and 28.8 hours in patients with severe renal impairment (or 1.7 times longer than that in young adult patients). In patients with hepatic impairment, normal plasma concentrations of risperidone were observed, but the mean free fraction of risperidone in plasma was increased by 37.1%.
After oral administration, the clearance and half-life values of risperidone and the active antipsychotic fraction in patients with moderate and severe hepatic impairment were not significantly different from those in young healthy volunteers.
Children
The pharmacokinetics of risperidone, 9-hydroxyrisperidone and the active antipsychotic fraction in children are similar to those in adults.
Gender, race, and smoking
Population pharmacokinetic analysis revealed no apparent effect of gender, race, or smoking status on the pharmacokinetics of risperidone or the active antipsychotic fraction.
Indication
Treatment of schizophrenia;
treatment of moderate to severe manic episodes in 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 "Special instructions" and "Method of administration and dosage");
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 ingredient or to any of the excipients 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 2 of the following symptoms: parkinsonism, visual hallucinations, unsteady gait).
Interaction with other medicinal products and other types of interactions
Pharmacodynamic interaction
QT-prolonging drugs
As with other antipsychotics, caution should be exercised when prescribing risperidone with drugs that prolong the QT interval, such as antiarrhythmics (quinidine, disopyramide, procainamide, propafenone, amiodarone, sotalol), tricyclic antidepressants (amitriptyline), tetracyclic antidepressants (maprolitine), some antihistamines, other antipsychotics, some antimalarials (quinine, 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 substances, including alcohol, opiates, antihistamines and benzodiazepines, due to an increased risk of sedation.
Levodopa and dopamine agonists
Risperidone may have antagonistic effects on levodopa and other dopamine antagonists. If such a combination is considered necessary, especially in end-stage Parkinson's disease, the lowest effective doses of each drug should be used.
Drugs with hypotensive effect
In the post-marketing period, cases of clinically significant arterial hypotension have been observed with the simultaneous use of risperidone and antihypertensive drugs.
Psychostimulants
The use of risperidone in combination with psychostimulants (e.g. methylphenidate) may cause extrapyramidal symptoms after dose adjustment of one or both drugs (see section "Special warnings and precautions for use").
Paliperidone
Concomitant use of oral risperidone with paliperidone is not recommended because paliperidone is the active metabolite of risperidone and their combination may lead to additive effects of the active antipsychotic fraction.
Pharmacokinetic interactions
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 modify 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.
Potent CYP2D6 inhibitors
Concomitant use of risperidone with a potent CYP2D6 inhibitor may increase the plasma concentration of risperidone, but to a lesser extent than the concentration of the active antipsychotic fraction. Higher doses of a potent CYP2D6 inhibitor may increase the concentration of the active antipsychotic fraction of risperidone (e.g. paroxetine, see below). It is expected that other CYP2D6 inhibitors, such as quinidine, may affect the plasma concentration of risperidone in a similar manner. At the beginning of concomitant use, as well as in the event of discontinuation of paroxetine, quinidine or another potent CYP2D6 inhibitor, especially at high doses, the physician should review the dose of risperidone.
CYP3A4 and P-glycoprotein inhibitors
Concomitant use of risperidone with potent CYP3A4 and/or P-glycoprotein inhibitors may significantly increase the plasma concentration of the active antipsychotic fraction of risperidone. At the beginning of concomitant use, as well as in the event of discontinuation of itraconazole or other potent CYP3A4 and/or P-glycoprotein inhibitors, the physician should review the dose of risperidone.
CYP3A4 and P-glycoprotein inducers
Concomitant use of risperidone with strong CYP3A4 and/or P-glycoprotein inducers may reduce the plasma concentration of the active antipsychotic fraction of risperidone. At the beginning of therapy, as well as in the event of discontinuation of carbamazepine or other strong CYP3A4/P-glycoprotein inducers, the physician should review the dose of risperidone. The effect of CYP3A4 inducers is time-dependent, with the maximum effect occurring at least 2 weeks after initiation of treatment. Accordingly, CYP3A4 induction may persist for at least 2 weeks after discontinuation.
Drugs with high protein binding
When risperidone was used with other drugs that are extensively bound to plasma proteins, no clinically significant displacement of either drug from the protein fraction was observed. When used simultaneously with such a drug, the prescribing information for the drug should be consulted regarding metabolic pathways and the 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.
Concomitant use of psychostimulants (e.g. methylphenidate) with risperidone in children and adolescents did not affect the pharmacokinetics and efficacy of risperidone.
Effect of other medicinal products on the pharmacokinetics of risperidone
Antibacterial drugs
Erythromycin, a moderate CYP3A4 inhibitor and P-glycoprotein inhibitor, does not alter the pharmacokinetics of risperidone and the active antipsychotic fraction.
Rifampicin, a potent CYP3A4 inducer and P-glycoprotein inducer, reduces the plasma concentration of the active antipsychotic fraction.
Cholinesterase inhibitors
Donepezil and galantamine, substrates of CYP2D6 and CYP3A4, do not demonstrate a clinically significant effect on the pharmacokinetics of risperidone and the active antipsychotic fraction.
Antiepileptic drugs
Carbamazepine, a potent CYP3A4 and P-glycoprotein inducer, has been shown to decrease the plasma concentration of the active antipsychotic fraction of risperidone. A similar effect may be observed with phenytoin and phenobarbital, which are also inducers of the hepatic enzymes CYP3A4 and P-glycoprotein.
Topiramate modestly reduces the bioavailability of risperidone and does not affect the bioavailability of the active antipsychotic fraction. This interaction is unlikely to have a clinically significant effect.
Antifungal medications
Itraconazole, a potent CYP3A4 inhibitor and P-glycoprotein inhibitor, at a dose of 200 mg per day increases the concentration of the active antipsychotic fraction in blood plasma by approximately 70% when co-administered with risperidone at doses of 2 to 8 mg per day.
Ketoconazole, a potent CYP3A4 inhibitor and P-glycoprotein inhibitor, at a dose of 200 mg per day increases the concentration of risperidone and reduces the concentration of 9-hydroxyrisperidone in blood plasma.
Antipsychotic medications
Phenothiazines may increase the plasma concentration of risperidone, but not the active antipsychotic fraction.
Antiviral drugs
Protease inhibitors: no data available; since ritonavir is a potent CYP3A4 inhibitor and a weak CYP2D6 inhibitor, 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 concentration of risperidone, but do not affect the concentration of the active antipsychotic fraction in the blood plasma.
Calcium channel blockers
Verapamil, a moderate CYP3A4 inhibitor and P-glycoprotein inhibitor, increases the plasma concentrations of risperidone and the active antipsychotic fraction.
H2-receptor antagonists: cimetidine and ranitidine, weak inhibitors of CYP2D6 and CYP3A4, increase the bioavailability of risperidone and minimally affect the bioavailability of the active antipsychotic fraction.
SSRIs and tricyclic antidepressants
Fluoxetine, a potent CYP2D6 inhibitor, increases the plasma concentration of risperidone, but less than the concentration of the active antipsychotic fraction.
Paroxetine, a potent CYP2D6 inhibitor, increases risperidone plasma concentrations, but (up to 20 mg/day) to a lesser extent than the concentration of the active antipsychotic fraction. However, higher doses of paroxetine may increase the concentration of the active antipsychotic fraction.
Tricyclic antidepressants may increase the plasma concentration of risperidone, but not the active antipsychotic fraction. Amitriptyline does not affect the pharmacokinetics of risperidone and the active antipsychotic fraction.
Sertraline, a weak CYP2D6 inhibitor, and fluvoxamine, a weak CYP3A4 inhibitor, at doses up to 100 mg/day do not cause clinically important changes in the concentration of the active antipsychotic fraction of risperidone. However, doses of sertraline or fluvoxamine exceeding 100 mg/day may increase the concentration of the active antipsychotic fraction of risperidone.
Effect of risperidone on the pharmacokinetics of other drugs
Antiepileptic drugs
Risperidone has no clinically important effect on the pharmacokinetics of valproate or topiramate.
Antipsychotic medications
Aripiprazole, a CYP2D6 and CYP3A4 substrate: oral or injectable risperidone formulations do not affect the pharmacokinetics of aripiprazole and its active metabolite dehydroaripiprazole.
Digitalis glycosides
Risperidone has no clinically significant effect on the pharmacokinetics of digoxin.
Lithium
Risperidone has no clinically important effect on the pharmacokinetics of lithium.
Concomitant use of risperidone with furosemide
See section "Special warnings and precautions for use" regarding increased mortality in elderly patients with dementia when used concomitantly with furosemide.
Application features
Elderly patients with dementia
Increased mortality rate
Elderly patients with dementia treated with atypical antipsychotics have been reported to have an increased mortality rate compared with placebo in a meta-analysis of 17 controlled trials of atypical antipsychotics, including risperidone. In a placebo-controlled trial of risperidone, the mortality rate in this group was 4.0% compared with 3.1% in the placebo group. The diagnostic odds ratio (95% confidence interval) was 1.21 (0.7, 2.1). The median age of patients who died was 86 years (range, 67–100 years).
Evidence from two large observational studies suggests that older people with dementia treated with conventional (typical) antipsychotics have a slightly increased risk of death compared with patients not receiving antipsychotics. The precise magnitude of this risk cannot be determined from the available data, and the reason for the increased risk is unknown. The extent to which these observations of an increased risk of death can be attributed to the use of antipsychotic medication, as opposed to individual patient characteristics, is unknown.
Concomitant use with furosemide
In a placebo-controlled study in elderly patients with dementia, an increased mortality rate was observed when risperidone was co-administered with furosemide (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 rate was observed in patients treated with risperidone and furosemide in two of the four clinical trials. There was no increased mortality rate in patients treated with risperidone in combination with other diuretics (mostly thiazide diuretics used in low doses).
No pathophysiological mechanisms have been identified to explain this finding. The cause of death was not uniform. However, caution should be exercised when prescribing the drug in such cases, and the risks and benefits of this combination or of other potential diuretics should be assessed before prescribing the drug. No increased mortality was observed in patients taking other diuretics with risperidone. Regardless of treatment, dehydration was a common risk factor for mortality and should be carefully monitored in patients with dementia.
Cerebrovascular adverse reactions
Pooled data from 6 placebo-controlled trials 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 of CVD cannot be excluded for other antipsychotics or other patient populations. Risperidone should be used with caution in patients with risk factors for stroke.
The risk of cerebrovascular adverse reactions is significantly higher in patients with mixed or vascular dementia compared to Alzheimer's dementia. Therefore, patients with other types of dementia than Alzheimer's dementia should not be treated with risperidone.
The risks and benefits of prescribing risperidone to elderly patients with dementia should be carefully weighed, especially the risk of stroke. Patients and caregivers should be instructed to report immediately any signs of possible cerebrovascular disorders, such as sudden weakness, numbness of the face, arms or legs, and speech and vision disorders. All possible treatment options, including discontinuation of risperidone therapy, should be considered immediately.
For persistent aggression in patients with moderate to severe Alzheimer's disease, risperidone is prescribed only for short-term use as an adjunct to non-pharmacological interventions that have shown limited or no efficacy, provided there is no potential risk of harm to self or others.
During treatment, it is necessary to regularly assess the condition of patients and review the need for further therapy.
Orthostatic hypotension
Due to the α1-lytic activity of risperidone, orthostatic hypotension may occur, especially at the beginning of treatment. In the post-marketing period, clinically significant arterial hypotension has been observed with the simultaneous use of risperidone and antihypertensive agents. Risperidone should be used with caution in patients with cardiovascular diseases (heart failure, myocardial infarction, conduction disorders, dehydration, hypovolemia or cerebrovascular disease). In these cases, the dose should be adjusted gradually (see section "Method of administration and dosage"). If arterial hypotension occurs, the possibility of reducing the dose should be considered.
Leukopenia, neutropenia, agranulocytosis
Leukopenia, neutropenia and agranulocytosis have been reported with antipsychotics, including risperidone. Agranulocytosis has been reported very rarely (< 1/10,000 patients) in the post-marketing setting.
Patients with a history of significant leukopenia or drug-induced leukopenia/neutropenia should be closely monitored during the first few months of treatment and risperidone should be discontinued if signs of significant leukopenia develop and no other cause for the decrease is found.
Patients with clinically significant neutropenia should be monitored for fever and other signs of infection and treated appropriately if symptoms develop. In case of severe neutropenia (< 1×109/L), risperidone treatment should be discontinued and the white blood cell count monitored until recovery.
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 and symptoms of tardive dyskinesia develop, discontinuation of all antipsychotic medications should be considered. Caution should be exercised when psychostimulants (e.g. methylphenidate) and risperidone are used concomitantly, as extrapyramidal symptoms may occur when adjusting the dose of either or both medications. Gradual withdrawal of stimulants is recommended (see Interactions with other medicinal products and other forms of interaction).
Neuroleptic malignant syndrome
Rare cases of neuroleptic malignant syndrome, characterized by hyperthermia, muscle rigidity, autonomic instability, impaired consciousness, and elevated creatine phosphokinase levels, have been reported with classical neuroleptic drugs. Additional features include myoglobinuria (rhabdomyolysis) and acute renal failure. If neuroleptic malignant syndrome develops, all antipsychotic drugs, including risperidone, should be discontinued.
Physicians should weigh the risks and benefits when prescribing antipsychotics, including risperidone, to patients with Parkinson's disease or dementia with Lewy bodies. Risperidone may worsen Parkinson's disease. Patients with any of the above conditions may be at increased risk of neuroleptic malignant syndrome and may be more sensitive to antipsychotic drugs (e.g., confusion, pain sensitivity, and postural instability with frequent falls in addition to extrapyramidal symptoms).
Hyperglycemia and diabetes mellitus
Hyperglycemia, diabetes mellitus, or exacerbation of pre-existing diabetes mellitus have been reported during treatment with risperidone. In some cases, a pre-existing overweight condition has been reported, which may have been a precipitating factor. In this regard, very rare cases of ketoacidosis and rarely, the development of diabetic coma have been reported. Appropriate clinical monitoring is recommended in accordance with the standards for the use of antipsychotics. Patients taking any atypical antipsychotic drugs, including risperidone, should be observed for symptoms of hyperglycemia (such as, for example, polydipsia, polyuria, polyphagia, and weakness), and patients with diabetes mellitus should be regularly examined for worsening of glucose control.
Weight gain
Cases of significant weight gain have been reported with risperidone. Weight monitoring is recommended.
Hyperprolactinemia
Hyperprolactinemia is a common adverse event during treatment with risperidone. Monitoring of prolactin levels is recommended in patients with adverse events that may be related to plasma prolactin levels (e.g. gynecomastia, menstrual disorders, anovulation, impaired fertility, decreased libido, erectile dysfunction and galactorrhea).
Tissue culture studies suggest that cell growth in human breast tumors may be stimulated by prolactin. Although a clear association with antipsychotic use has not yet been established by clinical or epidemiological studies, caution is advised when prescribing risperidone to patients with a history of such conditions. Risperidone should be used with caution in patients with hyperprolactinemia and prolactin-dependent tumors.
QT prolongation
In the post-marketing period, cases of QT prolongation have been reported very rarely. Risperidone, as with other antipsychotics, should be used with caution in patients with known cardiovascular disease, bradycardia, electrolyte disturbances (hypokalemia, hypomagnesemia), or a family history of QT prolongation, as this may increase the risk of arrhythmogenic effects. Precautions should also be taken when risperidone is used concomitantly with other drugs that prolong the QT interval.
Convulsions
Risperidone should be used with caution in patients with a history of seizures or other conditions that potentially lower the seizure threshold.
Priapism
There is a possibility of priapism during treatment with risperidone due to its alpha-adrenergic blocking effect.
Body temperature regulation
Antipsychotic drugs may impair the body's ability to lower core body temperature. Appropriate care is recommended for patients prescribed risperidone if they are exposed to conditions that may cause an increase in core body temperature: intense physical exercise, exposure to high ambient temperatures, concomitant therapy with drugs with anticholinergic activity, or exposure to dehydration.
Antiemetic effect
In preclinical studies, risperidone has been shown to have an antiemetic effect. This property may mask the symptoms of overdose of certain drugs or conditions such as intestinal obstruction, Reye's syndrome, and brain tumors.
Liver and kidney dysfunction
Patients with renal impairment have a reduced ability to excrete the active antipsychotic fraction of the drug compared to adult patients with normal renal function. In patients with hepatic impairment, an increase in the free fraction of risperidone in plasma has been observed (see section 4.2).
Venous thromboembolism
Cases of venous thromboembolism have been reported with antipsychotic drugs. Since patients treated with antipsychotic drugs often have acquired risk factors for venous thromboembolism, all possible risk factors for thromboembolism should be identified before and during treatment with risperidone and appropriate preventive measures should be taken.
Intraoperative atonic iris syndrome (ISAR)
ISAR may increase the risk of complications during and after eye surgery. The ophthalmologist should be informed of any previous or current use of antipsychotic medications. The potential benefits of discontinuing alpha-blocking medications prior to surgery have not been established, and the risks of discontinuing antipsychotic medications should be weighed against the risks of discontinuing antipsychotic medications.
Children
Before prescribing risperidone to children or adolescents with conduct disorder, the risk-benefit ratio should be carefully weighed, and physical and social causes of aggressive behavior, such as painful stimuli or inappropriate responses to the environment, should be assessed. The sedative effect of risperidone should be carefully monitored in pediatric patients because of possible effects on learning ability. Altering the time of administration of risperidone may improve the effect of sedation on the ability of children and adolescents to concentrate.
Risperidone is associated with small increases in body weight and body mass index (BMI). Baseline weight measurement is recommended before starting treatment and regular monitoring of body weight during treatment. Growth changes in long-term open-label extension studies were within the expected range for age. The effects of long-term risperidone treatment on puberty and growth have not been adequately studied.
Due to the potential impact of prolonged hyperprolactinemia on growth and puberty in children and adolescents, the need for regular clinical monitoring of the patient's endocrine status should be considered, including measurement of height, body weight, monitoring of puberty, menstrual cycle and other prolactin-dependent phenomena.
Results from a small postmarketing observational study showed that patients aged 8–16 years treated with risperidone were, on average, 3.0–4.8 cm taller than those treated with other antipsychotic medications. The data from this study are insufficient to determine whether risperidone affects final adult height or whether the measurements are directly related to the effects of risperidone on bone growth, whether the disease itself affects bone growth, or whether this is a result of better disease control and, as a result, greater height retention.
During treatment with risperidone, the presence of extrapyramidal symptoms and other movement disorders should be monitored regularly.
For dosage recommendations for children, see the section “Method of administration and dosage”.
Excipients
This medicinal product contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
This medicinal product contains less than 1 mmol (23 mg) sodium/dose, i.e. essentially 'sodium-free'.
Use during pregnancy or breastfeeding
Pregnancy
It is known that no controlled studies have been conducted in pregnant women. Although no teratogenic effects were observed in animal studies, other types of reproductive toxicity were observed. The potential risk for humans is unknown.
Newborns whose mothers have used antipsychotics (including risperidone) during the third trimester of pregnancy are at risk of developing reversible extrapyramidal symptoms and/or drug withdrawal syndrome. These symptoms include agitation, unusually high or low muscle tone, tremor, drowsiness, respiratory distress, or feeding difficulties. These complications may vary in severity, so the newborn should be closely monitored.
Risperidone should not be used during pregnancy unless clearly necessary. If treatment needs to be stopped during pregnancy, it should not be done abruptly.
Breastfeeding period
In animal studies, risperidone and 9-hydroxyrisperidone were excreted in human milk. There are indications that risperidone and 9-hydroxyrisperidone may also be excreted in human milk. There are no data on adverse reactions in breast-fed infants. Therefore, the benefits of breastfeeding should be weighed against the potential risk to the infant.
Fertility
Like other drugs that are dopamine D2 receptor antagonists, risperidone increases prolactin levels.
Hyperprolactinemia can suppress the production of gonadotropin-releasing hormone in the hypothalamus, leading to a decrease in the secretion of pituitary gonadotropins. This can have a negative impact on reproductive function in both women and men.
