Torendo Ku-tab, 0.5 mg 30 pcs

Schizophrenia, Alzheimer’s Disease, Manic Depressive Psychosis, Mental Disorders

• The treatment of schizophrenia in adults and children from 13 years old.
• Treatment of manic episodes associated with bipolar disorder of moderate to severe degree in adults and children from 10 years.
• Short-term (up to 6 weeks) treatment of persistent aggression in patients with moderate to severe dementia due to Alzheimer’s disease that does not respond to non-pharmacological methods of correction, and when the patient risks harming himself or others.

• Short-term (up to 6 weeks) symptomatic treatment for persistent aggression as part of a conduct disorder in children 5 years and older with mental retardation, diagnosed according to DSM-IV criteria, in which medication treatment is required because of the severity of aggression or other disruptive behavior. Pharmacotherapy should be part of a comprehensive treatment program, including psychological and educational interventions. Risperidone should be prescribed by a specialist in child neurology and child psychiatry or by a physician familiar with the treatment of conduct disorder in children and adolescents.
  

Active ingredient

Composition

1 oral dispersible 0.5 mg/1 mg/2 mg tablet contains:

Active substance:

Risperidone 0.50 mg/1.00 mg/2.00 mg

Associates: mannitol, butyl methacrylate, dimethylaminoethyl methacrylate and methyl methacrylate copolymer [1:2:1], povidone-K25, microcrystalline cellulose, low-substituted hyprolose, aspartame, crosspovidone, iron oxide dye (E172), mint flavoring1, menthol flavoring2, calcium silicate, magnesium stearate

1Mint flavoring: corn maltodextrin, acacia gum, sorbitol, field mint oil, levomenthol.

2Menthol flavoring: corn maltodextrin, flavoring components.

How to take, the dosage

The drug Torendo® Cu-tab® may be used as an alternative to the drug Torendo® in patients who have difficulty swallowing the tablet.

Due to the fact that tablets are fragile, they should not be squeezed through the foil of the package as they may break. Do not take the tablet with wet hands, because the tablet may melt.

Take out the pill as follows:

1. Take the blister, bend along the tear line and tear it off.

2. Open the blister by gently pulling the edge of the foil.

3. Carefully shake out the tablet onto your palm.

4. It should then be immediately placed on the tongue.

The tablet should be held in the mouth for several seconds until completely dissolved (to make swallowing easier), then can be infused with liquid. The tablet should not be mixed with food in the mouth.

You may also place the tablet in a full glass of water and drink immediately.

Schizophrenia

Adults

The drug Torendo®Cu-tab® may be used 1 or 2 times daily.

The starting dose of Torendo®Cu-tab® is 2 mg daily. On the second day, the dose can be increased to 4 mg per day. From that point on, the dose can either be maintained at the same level or individually adjusted as needed. Usually the optimal dose is 4-6 mg per day. In some cases, a slower dose increase and lower starting and maintenance doses may be warranted.

Doses above 10 mg daily have not been shown to be more effective than lower doses and may cause extrapyramidal symptoms. Because the safety of doses above 16 mg per day has not been studied, doses above this level are not recommended.

Elderly patients

The recommended starting dose is 0.5 mg per dose twice daily. The dose may be increased individually by 0.5 mg 2 times a day to 1-2 mg 2 times a day.

Children over 13 years

The recommended starting dose is 0.5 mg per administration once daily, morning or evening. If necessary, the dosage can be increased at least 24 hours later by 0.5 to 1 mg daily to the recommended dose of 3 mg daily if well tolerated. Although efficacy has been demonstrated in the treatment of schizophrenia in adolescents at doses of 1-6 mg daily, no additional efficacy has been observed at doses above 3 mg daily, and higher doses have caused more side effects. The use of doses above 6 mg daily has not been studied.

Patients who have persistent somnolence are advised to take half the daily dose twice daily.

Manic episodes associated with moderate to severe bipolar disorder

Adults

The recommended starting dose of Torendo® Cu-tab® is 2 mg once daily. If necessary, this dose may be increased after at least 24 hours by 1 mg per day. For most patients, the optimal dose is 1-6 mg daily. The use of doses above 6 mg daily in patients with manic episodes has not been studied. As with any other symptomatic therapy, the appropriateness of continuing treatment with Torendo® Cu-tab® must be regularly evaluated and confirmed.

Elderly patients

The recommended starting dose is 0.5 mg per dose twice daily. The dose can be individually increased by 0.5 mg 2 times a day to 1-2 mg 2 times a day. Experience of use in elderly patients is limited, caution should be exercised.

Children from 10 years

A starting dose of 0.5 mg per administration once daily in the morning or evening is recommended. If necessary, the dosage can be increased at least 24 hours later by 0.5-1mg per day to the recommended dose of 1-2.5mg per day if well tolerated. Although efficacy has been demonstrated in the treatment of manic episodes associated with bipolar disorder in children at doses of 0.5-6 mg daily, no additional efficacy has been observed at doses above 2.5 mg daily, and higher doses have caused more side effects. The use of doses higher than 6 mg daily has not been studied.

Patients who have persistent somnolence are recommended to take half the daily dose twice daily.

Incontinuous aggression in patients with moderate to severe dementia due to Alzheimer’s disease

The recommended starting dose is 0.25 mg per administration 2 times daily. If necessary, it is possible to increase the dose individually by 0.25 mg 2 times a day with an interval of at least 1 day. For most patients, the optimal dose is 0.5 mg twice daily. In some patients, however, the effective dose may be 1 mg twice daily. Torendo® Ku-tab® should not be used for more than 6 weeks for persistent aggression in patients with dementia due to Alzheimer’s disease. During treatment with Torendo® Ku-tab® frequent and regular evaluation of the patient is necessary to decide if continuation of therapy is necessary.

Incontinuous aggression in conduct disorder in children 5 years and older with mental retardation

Children from 5 to 18 years

The initial dose of Torendo® Cu-tab®0.5 mg once daily is recommended for patients with a body weight of 50 kg or more. If necessary, this dose may be increased by 0.5 mg once daily at least 24 hours later. For most patients, the optimal dose is 1 mg once daily. However, for some patients 0.5 mg daily is preferable, while some patients need to increase the dose to 1.5 mg daily.

For patients with a body weight less than 50 kg, a starting dose of 0.25 mg once daily is recommended. If necessary, this dose may be increased by 0.25 mg once daily for at least 24 hours. For most patients, the optimal dose is 0.5 mg once daily. However, for some patients 0.25 mg daily is preferable, while some patients need to increase the dose to 0.75 mg daily.

As with any symptomatic therapy, the appropriateness of continuing treatment with Torendo® Ku-tab® should be regularly evaluated and confirmed.

Use in children younger than 5 years is not recommended due to lack of data.

Special patient groups

Kidney and liver function disorders

In patients with impaired renal function, the ability to excrete the active antipsychotic fraction is reduced compared to other patient groups. In patients with impaired liver function, an increased concentration of the free fraction of risperidone in plasma is observed.

The initial and maintenance dose should be reduced by half as indicated; dose increases should be slower in patients with impaired hepatic and renal function.

The drug Torendo® Ku-tab® should be used with caution in this category of patients.

Method of administration

Orally, regardless of the time of meals.

An adequate dosage form of risperidone with a 0.25-mg dosage option should be used when starting and increasing the dose, as well as when a 0.25-mg dose of risperidone is needed.

The drug Torendo® Ku-tab® should be withdrawn gradually. When antipsychotic drugs including risperidone are stopped abruptly in high doses, the development of “withdrawal” syndrome (nausea, vomiting, increased sweating and insomnia), relapse of psychotic symptoms and appearance of involuntary movements (such as akathisia, dystonia and dyskinesia) has been observed in very rare cases.

Transition from therapy with other antipsychotics

At the beginning of Torendo® Cu-tab®, it is recommended that prior therapy be gradually withdrawn if clinically warranted. In the case of previous therapy with depot forms of antipsychotic drugs, therapy with Torendo® Cu-tab® is recommended to be started instead of the next scheduled injection. The need for continuation of current antiparkinsonian drug therapy should be evaluated periodically.

Interaction

Interactions related to the pharmacodynamics of the drug

Drugs that prolong the interval QT

As with other antypsychotic drugs, caution should be exercised when using Torendo® simultaneously. Ku-tab® with drugs that prolong the QT interval, such as antiarrhythmic agents (quinidine, disopyramide, procainamide, propafenone, amiodarone, sotalol, etc.).), tricyclic antidepressants (amitriptyline, etc.), tetracyclic antidepressants (maprotiline, etc.), some antihistamines, other antipsychotics, some antimalarials (quinine, mefloquine, etc.), drugs that cause electrolytes.), drugs that cause electrolyte imbalance (hypokalemia, hypomagnesemia), bradycardia or inhibit hepatic metabolism of risperidone. This list is not exhaustive.

Central agents and alcohol

The drug Torendo® Cu-tab® should be used with caution in combination with other drugs and centrally acting agents, especially alcohol, opiates, antihistamines and benzodiazepines because of the increased risk of sedation.

Levodopa and dopamine receptor agonists

The drug Torendo® Ku-tab® may decrease the effectiveness of levodopa and other dopamine receptor agonists. If this combination is necessary, especially in terminal Parkinson’s disease, the lowest effective dose of each drug should be administered.

Hypotensive drugs

When risperidone was used concomitantly with hypotensive drugs, clinically significant arterial hypotension was observed during the post-registration period.

Paliperidone

Torendo® Cu-tab® and paliperidone are not recommended for concomitant use because paliperidone is the active metabolite of risperidone. Concomitant use of the combination of risperidone and paliperidone may result in higher concentrations of the active antipsychotic fraction.

Interactions related to the pharmacokinetics of the drug

Food intake has no effect on the absorption of risperidone.

Risperidone is mainly metabolized by CYP2D6 isoenzyme and to a lesser extent by CYP3A4 isoenzyme. Risperidone and its active metabolite 9-hydroxyrisperidone are substrates of P-glycoprotein (P-gp). Drugs affecting the activity of CYP2D6 isoenzyme and drugs significantly inhibiting or inducing the activity of CYP3A4 isoenzyme and/or P-gp may affect the pharmacokinetics of the active antipsychotic fraction of risperidone.

strong CYP2D6 isoenzyme inhibitors

Concomitant use of risperidone and potent CYP2D6 isoenzyme inhibitors may increase the plasma concentration of risperidone and, to a lesser extent, the active antipsychotic fraction. Higher doses of a potent CYP2D6 isoenzyme inhibitor may increase the concentration of the active antipsychotic fraction of risperidone (e.g., paroxetine, see below). It is expected that other CYP2D6 isoenzyme inhibitors, such as quinidine, may have similar effects on the plasma concentration of risperidone. When initiating or withdrawing therapy with a combination of risperidone and paroxetine, quinidine, or another potent CYP2D6 isoenzyme inhibitor, especially at higher doses, the dose of Torendo® Ku-tab® should be adjusted.

CYP3A4 and/or P-gp isoenzyme inhibitors

The concomitant use of Torendo® Cu-tab® and potent CYP3A4 and/or P-gp isoenzyme inhibitors may significantly increase the plasma concentration of the active antipsychotic fraction of risperidone. When initiating or cancelling therapy with a combination of risperidone and itraconazole or another potent CYP3A4 and/or P-gp isoenzyme inhibitor, the dose of Torendo® Ku-tab® should be adjusted.

CYP3A4 and/or P-gp isoenzyme inducers

Concomitant use of Torendo® Cu-tab® with a potent CYP3A4 and/or P-gp isoenzyme inducer may decrease the plasma concentration of the active antipsychotic fraction of risperidone. When initiating or cancelling therapy with a combination of risperidone and carbamazepine or other potent CYP3A4 and/or P-gp isoenzyme inducer, the dose of Torendo® Ku-tab® should be adjusted. The effects of CYP3A4 isoenzyme inducers occur over time, so it may take up to 2 weeks before maximum effect is achieved after initiation. Correspondingly, if CYP3A4 isoenzyme inducers are discontinued, it may take up to 2 weeks until the effect has disappeared.

Drugs firmly bound to plasma proteins

When concomitant use of Torendo® Cu-tab® with drugs with high plasma protein binding, there is no clinically significant displacement of the drug from the complex with blood plasma proteins.

When using concomitant treatment, refer to the instructions for use of the respective medication and adjust the doses of the drugs taken if necessary.

Psychostimulants

If psychostimulants (e.g., methylphenidate) and risperidone are used concomitantly, changing the order of taking one or both drugs may result in extrapyramidal symptoms (see “Special Precautions”).

Children

Drug interaction studies were conducted only in adult patients. The relevance of the results of these studies in children is unknown.

The concomitant use of psychostimulants (e.g., methylphenidate) and the drug Torendo® Ku-tab in children does not alter the pharmacokinetic parameters and effectiveness of risperidone.

Effects of other drugs on the pharmacokinetics of risperidone

Antibacterial drugs

Eritromycin, a moderate inhibitor of the CYP3A4 and P-gp isoenzyme, does not affect the pharmacokinetics of presperidone or the active antipsychotic fraction.

Rifampicin, a potent inducer of CYP3A4 isoenzyme and P-gp, causes a decrease in the plasma concentration of the active antipsychotic fraction.

Anticholinesterase drugs

Donepezil and galantamine, which are substrates of the CYP2D6 and CYP3A4 isoenzymes, have no clinically significant effect on the pharmacokines of neticuriousperidone and the active antipsychotic fraction.

Epileptic drugs

Carbamazepine, a potent inducer of the CYP3A4 isoenzyme and P-gp, reduces the plasma concentration of the active antipsychotic fraction of risperidone. Similar effects have been observed with phenytoin and phenobarbital, which are also inducers of CYP3A4 and P-gp isoenzyme.

Topiramate moderately reduces the bioavailability of risperidone, but not the active antipsychotic fraction. This interaction is not considered clinically significant.

Antifungal drugs

Itraconazole, a potent inhibitor of the CYP3A4 isoenzyme and P-gp, at a dose of 200 mg/day increases the plasma concentration of the active antipsychotic fraction by approximately 70% when using risperidone at a dose of 2 to 8 mg/day.

Ketoconazole, a potent inhibitor of CYP3A4 isoenzyme and P-gp, at a dose of 200 mg/day increases the plasma concentration of risperidone and decreases the plasma concentration of 9-hydroxysperidone.

Neuroleptics

Phenothiazines can increase the plasma concentration of risperidone, but not the active antipsychotic fraction.

Antiviral drugs

Protease inhibitors: no official study data available. Because ritonavir is a potent inhibitor of the CYP3A4 isoenzyme and a weak inhibitor of the CYP2D6 isoenzyme, ritonavir and protease inhibitors enhanced by ritonavir may lead to increased concentrations of the active antipsychotic fraction of risperidone.

Beta-adrenal blockers

Some beta-adrenoblockers may increase the plasma concentration of risperidone, but not the active antipsychotic fraction.

Calcium channel blockers

Verapamil, a moderate inhibitor of the CYP3A4 isoenzyme and P-gp, increases plasma concentrations of risperidone and the active antipsychotic fraction.

Drugs to treat gastrointestinal disorders

Antagonists of H2 receptors: cimetidine and ranitidine, which are weak inhibitors of CYP2D6 and CYP3A4 isoenzymes, increase bioavailability of risperidone, but have minimal effect on the concentration of active antipsychotic fraction in blood plasma.

Serotonin reuptake inhibitors and tricyclic antidepressants

Fluoxetine, a potent inhibitor of the CYP2D6 isoenzyme, increases the plasma concentration of risperidone, but has less effect on the concentration of the active antipsychotic fraction.

Paroxetine, a potent inhibitor of the CYP2D6 isoenzyme, increases the plasma concentration of risperidone, but at doses up to 20 mg/day has less effect on the concentration of the active antipsychotic fraction. However, higher doses of paroxetine may increase 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 is a weak inhibitor of the CYP2D6 isoenzyme and fluvoxamine is a weak inhibitor of the CYP3A4 isoenzyme. At doses up to 100 mg/day, sertraline and fluvoxamine have no clinically significant effect on the concentration of the active antipsychotic fraction of risperidone. However, the use of sertraline or fluvoxamine in doses above 100 mg/day may increase the concentration of the active antipsychotic fraction of risperidone.

The effect of risperidone on the pharmacokinetics of other drugs

Epileptic drugs

Risperidone has no clinically significant effect on the pharmacokinetics of valproic acid or topiramate.

Neuroleptics

Special Instructions

Diseases of the cardiovascular system (chronic heart failure, myocardial infarction, conduction disorders of the heart muscle);

– hypotension (correction of the drug dose is necessary);

dehydration and hypovolemia;

– cerebral circulation disorders;

– Parkinson’s disease;

convulsions (including history);

– painful renal and/or hepatic insufficiency (see “Dosage and administration”);

– medication abuse or addiction;

– conditions predisposing to pirouette tachycardia (bradycardia, electrolyte imbalance, concomitant use of QT interval prolonging drugs);

– metabolic disorders, including hyperglycemia, dyslipidemia (requires patient weight control);

– hyperprolactinemia;

leukopenia, neutropenia, agranulocytosis;

-brain tumor, intestinal obstruction, cases of acute drug overdose, Reye syndrome (the antiemetic effect of risperidone may mask the symptoms of these conditions);

– risk factors for venous thromboembolism;

Diffuse Levy disease;

– use in elderly patients with cerebrovascular dementia;

– pregnancy;

– current use with furosemide.

Schizophrenia

Children from 13 years

The initial dose of 0.5 mg per administration once daily, morning or evening, is recommended. If necessary, the dosage can be increased at least 24 hours later by 0.5 to 1 mg daily to the recommended dose of 3 mg daily if well tolerated. Although efficacy has been demonstrated in the treatment of schizophrenia in adolescents at doses of 1-6 mg daily, no additional efficacy has been observed at doses above 3 mg daily, and higher doses have caused more side effects. The use of doses above 6 mg daily has not been studied.

Patients who have persistent somnolence are advised to take half the daily dose twice daily.

Manic episodes associated with moderate to severe bipolar disorder

Children from 10 years

The initial dose of 0.5 mg per dose once daily in the morning or evening is recommended. If necessary, the dosage can be increased at least 24 hours later by 0.5-1mg per day to the recommended dose of 1-2.5mg per day if well tolerated. Although efficacy has been demonstrated in the treatment of manic episodes associated with bipolar disorder in children at doses of 0.5-6 mg daily, no additional efficacy has been observed at doses above 2.5 mg daily, and higher doses have caused more side effects. The use of doses higher than 6 mg daily has not been studied.

Patients who have persistent somnolence are recommended to take half the daily dose twice daily.

Incontinuous aggression in the pattern of conduct disorder in children 5 years and older with mental retardation

Children from 5 to 18 years

The initial dose of Torendo® Cu-tab®0.5 mg once daily is recommended for patients with a body weight of 50 kg or more. If necessary, this dose may be increased by 0.5 mg once daily at least 24 hours later. For most patients, the optimal dose is 1 mg once daily. However, for some patients 0.5 mg daily is preferable, while some patients need to increase the dose to 1.5 mg daily.

For patients with a body weight less than 50 kg, a starting dose of 0.25 mg once daily is recommended. If necessary, this dose may be increased by 0.25 mg once daily for at least 24 hours. For most patients, the optimal dose is 0.5 mg once daily. However, for some patients 0.25 mg daily is preferable, while some patients need to increase the dose to 0.75 mg daily.

As with any symptomatic therapy, the appropriateness of continuing treatment with Torendo® Ku-tab® should be regularly evaluated and confirmed.

Use in children younger than 5 years is not recommended due to lack of data.

Elderly patients

The recommended starting dose is 0.5 mg per administration twice daily. The dose can be individually increased by 0.5 mg 2 times a day to 1-2 mg 2 times a day. Experience of use in elderly patients is limited, caution should be exercised.

Kidney and liver function disorders

In patients with impaired renal function, the ability to excrete the active antipsychotic fraction is reduced compared to other patient groups. In patients with impaired liver function, an increased concentration of the free fraction of risperidone in plasma is observed.

The initial and maintenance dose should be reduced by half as indicated; dose increases should be slower in patients with hepatic and renal impairment.

The drug Torendo® Ku-tab® should be used with caution in this category of patients.

Application in elderly patients with dementia

An increase in mortality in elderly patients with dementia

A meta-analysis of clinical trials in elderly patients with dementia who used atypical antipsychotics found increased mortality compared to the placebo group. Mortality in patients receiving risperidone or placebo was 4.0% and 3.1%, respectively. The mean age of the patients who died was 86 years (range 67-100 years). Two large observational studies of elderly patients with dementia with treatment with typical antipsychotics have reported a small increase in the risk of death compared with that of untreated patients. Insufficient data have been collected to accurately estimate this risk. The cause of the increased risk is also unknown. Also, the extent to which the increase in mortality can be applied to antipsychotic medications, rather than to the characteristics of this patient group, has not been determined.

Simultaneous use with furosemide

Concomitant use of oral furosemide and risperidone resulted in increased mortality (7.3%, mean age 89 years, range 75-97 years) in elderly patients with dementia compared with the group taking risperidone alone (3.1%, mean age 84 years, range 70-96 years) and the group taking furosemide alone (4.1%, mean age 80 years, range 67-90 years). Increased mortality when furosemide was used concomitantly with risperidone was observed in 2 of the 4 clinical trials. Concomitant use of risperidone with other diuretics (mainly low-dose thiazide diuretics) was not associated with increased mortality.

No pathophysiological mechanisms have been established to explain this observation. Nevertheless, special caution should be exercised when using the drug in such cases. The risk/benefit ratio should be carefully evaluated before use. No increase in mortality has been found in patients taking other diuretics concomitantly with risperidone. Regardless of therapy, dehydration is a common risk factor for mortality and should be closely monitored in elderly patients with dementia.

An increase in cerebrovascular side effects (acute and transient cerebrovascular events), including deaths (mean age 85 years, range 73-97 years), was observed in elderly patients with dementia compared with placebo. Therefore, risperidone should be used with caution in patients at risk of stroke.

Cerebrovascular adverse events

In placebo-controlled clinical trials, patients with dementia taking certain atypical antipsychotics had an approximately 3-fold increased risk of cerebrovascular side effects. Summary data from 6 placebo-controlled studies including mostly elderly patients with dementia (age over 65 years) demonstrate that cerebrovascular side effects (serious and non-serious) occurred in 3.3% (33/1009) of patients taking risperidone and in 1.2% (8/712) of patients taking placebo. The risk ratio was 2.96 (1.34; 7.50) with a 95% confidence interval. The mechanism of increased risk is unknown. An increased risk cannot be ruled out with other antipsychotic drugs or in other patient populations. The drug Torendo® Ku-tab® should be used with caution in patients with risk factors for stroke.

The risk of cerebrovascular adverse events in patients with mixed or vascular dementia was significantly higher than in patients with dementia due to Alzheimer’s disease. Therefore, risperidone should not be used in patients with any type of dementia other than dementia due to Alzheimer’s disease.

The risk/benefit ratio before using Torendo® Ku-tab® in elderly patients with dementia should be evaluated, considering risk factors for stroke in the individual patient. Patients and caregivers should be informed to immediately inform their physician of possible manifestations of cerebrovascular disorders (such as sudden weakness or immobility/sensitivity in the face, legs, arms, and speech and vision impairments). Necessary therapeutic measures should be taken immediately, including discontinuation of risperidone.

The drug Torendo® Ku-tab® may only be used for short-term therapy of persistent aggression in patients with moderate to severe dementia due to Alzheimer’s disease, as an adjunct to non-pharmacological methods of correction, when they are ineffective or of limited effectiveness, and when there is risk of harm to the patient himself or others.

The patient’s condition and the need to continue risperidone therapy should be continuously evaluated.

Ortostatic hypotension

Due to the α-adrenoblocking effect of risperidone, orthostatic hypotension may develop in some patients, especially during initial dose adjustment. Cases of clinically significant arterial hypotension have been described when concomitant use of risperidone with hypotensive drugs in the post-marketing period.The drug Torendo® Ku-tab® should be used with caution in patients with cardiovascular diseases (e.g., chronic heart failure, myocardial infarction, cardiac conduction disorders, dehydration, hypovolemia or cerebrovascular disease). Appropriate dose adjustment is also necessary. It is recommended to evaluate the possibility of reducing the dose in case of arterial hypotension.

Leukopenia, neutropenia, and agranulocytosis

Cases of leukopenia, neutropenia, and agranulocytosis have been described with antipsychotic agents, including risperidone. Agranulocytosis was very rare (<1/10000 patients) during post-registration follow-up. Patients with a clinically significant decrease in leukocyte counts or a history of drug-induced leukopenia/neutropenia should be monitored during the first few months of therapy, and if the first signs of a clinically significant decrease in leukocyte counts occur, in the absence of other causative factors, treatment should be stopped.

Patients with clinically significant neutropenia should be closely monitored for fever or other symptoms of infection, and treatment should be started immediately if such symptoms occur. Patients with severe neutropenia (absolute neutrophil count < 1x 109/L) should discontinue Torendo® Ku-tab until the white blood cell count is restored.

Late dyskinesia/extrapyramidal symptoms

Therapy with dopamine receptor antagonists may cause tardive dyskinesia, which is characterized by rhythmic involuntary movements, primarily of the tongue and/or facial muscles. The occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. If a patient presents with objective or subjective symptoms indicating tardive dyskinesia, it is necessary to consider the advisability of withdrawing all antipsychotic drugs, including the drug Torendo® Ku-tab®.

Caution should be exercised in patients simultaneously taking psychostimulants (such as methylphenidate) and risperidone due to the possibility of extrapyramidal symptoms. In these cases, gradual withdrawal of psychostimulants is recommended.

Malignant Neuroleptic Syndrome (MNS)

Treatment with antipsychotics may lead to MNS characterized by hyperthermia, muscle rigidity, instability of autonomic nervous system function, depressed consciousness and increased plasma creatine phosphokinase activity, as well as myoglobinuria (rhabdomyolysis) and acute renal failure. If the patient has objective or subjective symptoms of MNS, all antipsychotic drugs, including risperidone, should be immediately withdrawn.

Parkinson’s disease and dementia with Lewy bodies

The use of antipsychotic drugs, including the drug Torendo® Ku-tab®should be used with caution in patients with Parkinson’s disease or dementia with Lewy bodies, as both groups of patients have an increased risk of MNS and increased sensitivity to antipsychotics (including blunting of pain sensitivity, confusion, postural instability with frequent falls, and extrapyramidal symptoms). Taking risperidone may worsen the course of Parkinson’s disease.

Hyperglycemia and diabetes

Cases of hyperglycemia, diabetes mellitus, and aggravation of the course of diabetes mellitus have been described. In some cases, there was an increase in body weight prior to therapy, which can be regarded as a predisposing factor. In very rare cases, the development of ketoacidosis and rarely – diabetic coma were observed. As with any antipsychotic medication, patients should be monitored by a physician and the symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia, and weakness) should be controlled. In patients with diabetes mellitus, blood glucose concentration should be monitored regularly.

Body weight gain

A significant increase in body weight is observed. It is necessary to monitor the patients’ body weight regularly.

Hyperprolactinemia

Based on invitro studies, it has been suggested that mammary tumor cell growth can be stimulated by prolactin. Although clinical and epidemiological studies have not shown a clear association of hyperprolactinemia with antipsychotic medication, caution should be exercised when using risperidone in patients with a severe medical history. The drug Torendo® Ku-tab® should be used with caution in patients with existing hyperprolactinemia and in patients with possible prolactin-dependent tumors.

Longer interval QT

In very rare cases, prolongation of the QT interval in the post-marketing period has been noted. As with other antipsychotic agents, caution should be exercised when using Torendo® Ku-tab® in patients with cardiovascular diseases, a family history of QT interval prolongation, bradycardia, electrolyte balance disorders (hypokalemia, hypomagnesemia), as this may increase the risk of arrhythmogenic effects or when concomitant use with QT interval prolonging agents.

Convulsions

The drug Torendo® Ku-tab® should be used with caution in patients with a history of seizures or in conditions accompanied by a decrease in the seizure threshold.

Priapism

Because risperidone has an α-adrenoblocking effect, priapism may develop when used.

Disruption of body temperature regulation

In the use of antipsychotic drugs, an undesirable effect such as impaired thermoregulation has been described. Caution should be exercised when using Torendo® Ku-tab in patients who may be exposed to factors that cause body temperature increase, such as intense physical activity, dehydration, high ambient temperature, concurrent use with drugs that have anticholinergic activity.

An anti-emetic effect

In preclinical studies of risperidone use, an antiemetic effect was observed. This effect, when occurring in humans, can mask the signs and symptoms of overdose of certain drugs or diseases such as intestinal obstruction, Reye’s syndrome and brain tumors.

Kidney and liver function disorders

In patients with impaired renal function, the ability to excrete the active antipsychotic fraction is lower than in adult patients with normal renal function. In patients with impaired hepatic function, the plasma concentration of the free fraction of risperidone is increased.

Venous thromboembolism

Cases of venous thromboembolism have been described with antipsychotic drugs. It is necessary to identify all possible risk factors of thromboembolic complications before and during the therapy with Torendo® Ku-tab and take preventive measures.

Intraoperative syndrome “flabby”iris.(ISDR)

ISDR has been noted during cataract surgery in patients receiving drugs that have antagonism to alpha1 adrenoreceptors, including the drug Torendo® Ku-tab®. ISDR may increase the risk of visual complications during and after surgery. A current or past use of drugs with antagonism to alpha1 adrenoreceptors should be informed in advance to the ophthalmic surgeon. The potential benefit of withdrawal of therapy with alpha1-adrenoceptor antagonists prior to cataract surgery has not been established. The benefit/risk ratio of antipsychotic therapy withdrawal should be evaluated.

children and adolescents

Before using Torendo® Cu-tab® in children or adolescents with mental retardation, a thorough evaluation of their condition for physical or social causes of aggressive behavior, such as pain or inadequate social environment demands, should be performed.

The sedative effects of risperidone should be closely monitored in this population because of the possible effect on learning ability. Changing the timing of risperidone administration may reduce the effects of sedation on attention in adolescents and children.

Risperidone use has been associated with increases in mean body weight and BMI. Growth changes in long-term studies were within expected age-related norms. The effects of long-term risperidone administration on sexual development and growth have not been fully investigated.

Due to the possible effects of prolonged hyperprolactinemia on growth and sexual development in children and adolescents, regular clinical evaluation of hormonal status should be performed, including measurement of growth, body weight, monitoring of sexual development, menstrual cycle and other possible prolactin-dependent effects.

During risperidone therapy, regular evaluation should be performed to detect extrapyramidal symptoms and other movement disorders.

Synopsis

Circular, slightly biconvex, light pink tablets with visible flecks.

Contraindications

– High sensitivity to risperidone or any other component of the drug.

Phenylketonuria.

Fructose intolerance inborn.

Side effects

The most frequently observed adverse reactions (incidence ≥ 5%) were insomnia, anxiety, headache, upper respiratory tract infections, parkinsonism.

Dose-dependent adverse reactions were parkinsonism and akathisia.

The side effects of risperidone reported in clinical trials of risperidone in oral dosage forms and in sustained-release injectable form, and obtained during post-registration surveillance, are listed with a frequency and organ system distribution. The frequency of side effects was classified as follows: very common (≥ 1/10 cases), common (≥ 1/100 to < 1/10 cases), infrequent (≥ 1/1000 to < 1/100 cases), rare (≥ 1/10000 to < 1/1000 cases), very rare (< 1/10000 cases), frequency unknown (incidence cannot be estimated from existing data). In each frequency group, side effects are presented in decreasing order of importance.

Infectious and parasitic diseases:

often: pneumonia, flu, bronchitis, upper respiratory tract infections, urinary tract infections, sinusitis, ear infections;

infrequent: viral infections, tonsillitis, inflammation of subcutaneous fatty tissue, otitis media, eye infections, localized infections, acarodermatitis, respiratory infections, cystitis, onychomycosis;

rarely: lower respiratory tract infections, chronic otitis media, infections, subcutaneous abscess.

Disorders of blood and lymphatic system:

infrequent: neutropenia, decreased leukocyte count, anemia, thrombocytopenia, decreased hematocrit, decreased eosinophil count, decreased hemoglobin;

rare: granulocytopenia, agranulocytosis.

immune system disorders:

infrequent: hypersensitivity reactions to the drug components;

rare: drug hypersensitivity, anaphylactic reaction.

Endocrine system disorders:

often: increased prolactin1 levels;

rarely: disruption of antidiuretic hormone production, glucosuria.

disorders of metabolism and nutrition:

often: weight gain, increased appetite, decreased appetite;

infrequent: weight loss, diabetes3, anorexia, polydipsia, hyperglycemia, increased plasma cholesterol concentration;

rare: hypoglycemia, water intoxication, increased insulin, increased plasma concentration of triglycerides;

very rare: diabetic ketoacidosis.

Mental disorders:

often: restlessness, agitation, sleep disturbance, anxiety, depression;

infrequent: confusion, mania, decreased libido, lethargy, nervousness, nightmares;

rare: anorgasmia, flattening of affect.

Nervous system disorders:

very often: parkinsonism2,headache, drowsiness, sedation;

often: akathisia2 , dizziness2 , tremor2, dystonia2, lethargy, dyskinesia2;

infrequent: lack of response to stimuli, loss of consciousness, decreased level of consciousness, syncope, impaired consciousness, stroke, transient ischemic attack, dysarthria, attention disorder, hypersomnia, postural dizziness, balance disorder, tardive dyskinesia, speech disorder, coordination disorder, hypoesthesia, taste disorder, distorted taste, seizures, cerebral ischemia, movement disorder, psychomotor agitation, paresthesia;

rarely: malignant neuroleptic syndrome (MNS), diabetic coma, cerebrovascular disorders, head tremor;

frequency unknown: stuttering.

Visual disorders:

infrequent: conjunctival hyperemia, visual disturbance, ocular discharge, periorbital edema, dry eyes, increased lacrimation, photophobia;

seldom: decreased visual acuity, impaired eye movement, involuntary rotation of the eyeballs, crusting at the eyelid edge, glaucoma, intraoperative “flabby” iris syndrome (ISDR), retinal artery occlusion.

Hearing organ and labyrinth disorders:

infrequent: vertigo, ear pain, tinnitus.

Cardiac disorders:

infrequent: atrioventricular block, right or left bundle branch block, atrial fibrillation, palpitations, cardiac conduction disturbances, prolongation of QT interval on ECG, bradycardia, abnormal ECG;

rarely: sinus arrhythmia, sinus bradycardia;

frequency unknown: atrioventricular block of degree I.

vascular disorders:

infrequent: hypotension, orthostatic hypotension, hot flashes;

rare: pulmonary embolism, deep vein thrombosis.

Disorders of the respiratory system, thorax and mediastinum:

often:shortness of breath, nasal bleeding, cough, stuffy nose, pain in the larynx and pharynx;

infrequent: wheezing, aspiration pneumonia, lung congestion, respiratory distress, wet rales, airway obstruction, dysphonia;

rare:sleep apnea syndrome, hyperventilation.

digestive system disorders:

often: vomiting, diarrhea, constipation, nausea, abdominal pain, dyspepsia, dry oral mucosa, abdominal discomfort, hyper salivation, toothache;

infrequent: dysphagia, gastritis, fecal incontinence, fecaloma, gastroenteritis, flatulence;

rarely:bowel obstruction, pancreatitis, lip edema, tongue edema, cheilitis;

very rarely:ileus.

Liver and biliary tract disorders:

infrequent: increased activity of transaminases, gamma-glutamyltransferase, “liver” enzymes (in particular, increased level of alanine aminotransferase) in plasma;

rare: jaundice.

Skin and subcutaneous tissue disorders:

infrequent: urticaria, skin lesions, skin integrity disorders, skin itching, acne, acne, skin discoloration, alopecia, seborrheic dermatitis, dry skin, hyperkeratosis, eczema;

rarely: medicated rash, dandruff;

very rarely: Quincke’s edema.

Muscular and connective tissue disorders:

often: muscle spasms, musculoskeletal pain, arthralgia, back pain, pain in the extremities, pain in the buttocks;

infrequent: increased plasma creatine phosphokinase activity, muscle weakness, myalgia, neck pain, joint swelling, bad posture, stiffness in joints, muscle chest pain;

rare: rhabdomyolysis.

Kidney and urinary tract disorders:

often:enuresis, urinary incontinence;

infrequently: urinary retention, dysuria, pollakiuria.

Pregnancy, postpartum and perinatal conditions:

rare: withdrawal syndrome in newborns.

Gender and breast disorders:

infrequent: amenorrhea, sexual dysfunction, erectile dysfunction, ejaculation disorders, galactorrhea, gynecomastia, menstrual disorders, vaginal discharge, breast pain, breast discomfort;

rarely: priapism, delayed menstruation, breast engorgement, breast enlargement, mammary gland discharge.

General disorders and disorders at the site of administration:

often: edema, pyrexia, fatigue, peripheral edema, generalized edema, asthenia, chest pain, pain;

infrequent: facial edema, impaired gait, malaise, slowness, flu-like condition, malaise, thirst, chest discomfort, chills, increased body temperature, discomfort;

rarely:hypothermia, decreased body temperature, “withdrawal” syndrome, coldness of extremities, induration.

Injuries, intoxications and complications of manipulations:

often: fall;

infrequently:pain during procedures.

1-hyperprolactinemia in some cases may lead to gynecomastia, menstrual irregularities, amenorrhea and galactorrhea.

2- Extrapyramidal disorders may manifest as parkinsonism (hypersalivation, musculoskeletal stiffness, parkinsonism, salivation, cogwheel-like rigidity, bradykinesia, hypokinesia, mask-like face, muscle tightness, akinesia, neck muscle rigidity muscle rigidity, parkinsonian gait, glabellar reflex disorders, parkinsonian resting tremor), akathisia (akathisia, restlessness, hyperkinesia and restless legs syndrome), tremor, dyskinesia (dyskinesia, muscle twitching, choreoathetosis, athetosis and myoclonus), dystonia.

The term “dystonia” includes dystonia, muscle spasms, muscle hypertonia, torticollis, involuntary muscle contractions, muscle contractures, blepharospasm, eyeball movements, tongue paralysis, facial spasm, laryngospasm, myotonia, opisthotonus, oropharyngeal spasm, pleurottonus, tongue spasm and trismus. Tremors include tremor and parkinsonian resting tremor. It should also be noted that there is a broader range of symptoms that do not always have an extrapyramidal origin. Insomnia includes a sleep disorder, intrasomnia disorder. Seizures include grand mal seizure. Menstrual disorders include irregular menstruation, oligomenorrhea. Edema includes generalized edema, peripheral edema, mild edema.

3- In placebo-controlled studies, diabetes occurred in 0.18% of patients taking risperidone, compared with 0.11% of patients in the placebo group. In all clinical trials, the overall incidence of diabetes mellitus in patients taking risperidone was 0.43%.

adverse effects of paliperidone

Paliperidone is the active metabolite of risperidone, so the adverse reaction profiles of risperidone and paliperidone are related. In addition to the above, the following adverse reactions have been noted when using paliperidone, which can also occur when using risperidone:

Cardiovascular System: postural orthostatic tachycardia syndrome.

Class effects

As with other antipsychotics, very rare cases of QT interval prolongation in the post-marketing follow-up period have been noted. Other cardiovascular class effects observed with antipsychotic QT interval prolongers: ventricular arrhythmias, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac arrest, and polymorphic pirouette-type ventricular tachycardia.

Venous thromboembolism

Cases of venous thromboembolism, including pulmonary embolism and cases of deep vein thrombosis, have been observed with antipsychotic drugs (incidence unknown).

increased body weight

In placebo-controlled studies in patients with schizophrenia, an increase in body weight of at least 7% after 6-8 weeks was observed in 18% of patients taking risperidone and 9% of patients taking placebo. In placebo-controlled clinical trials in patients with manic episodes, the number of body weight gain of 7% or more after 3 weeks of treatment was comparable in the group taking risperidone (2.5%) and the group taking placebo (2.4%), and slightly higher in the active control group (3.5%).

In children with behavioral disorders in long-term clinical trials, body weight increased by an average of 7.3 kg after 12 months of therapy. The expected increase in body weight in children 5-12 years old with normal development is 3-5 kg per year, from 12-16 years old – 3-5 kg per year for girls and about 5 kg per year for boys.

Special patient groups

Side effects that have been reported with greater frequency in elderly patients with dementia and in children than in adult patients are described below.

Elderly patients with dementia

Transient ischemic attacks and stroke were observed in clinical trials with a frequency of 1.4% and 1.5%, respectively, in elderly patients with dementia. In addition, the following adverse events were observed in elderly patients with dementia with an incidence of ≥5% and at least 2-fold higher than in other patient populations: urinary tract infections, peripheral edema, lethargy, and cough.

Children

The following adverse effects have been reported in children (5 to 17 years of age) with an incidence of ≥5% and with an incidence at least 2 times that of other patient populations in clinical trials Drowsiness/sedation, fatigue, headache, increased appetite, vomiting, upper respiratory tract infections, nasal congestion, abdominal pain, dizziness, cough, pyrexia, tremor, diarrhea, enuresis.

Overdose

Symptoms:drowsiness, sedation, depression of consciousness, tachycardia, arterial hypotension, extrapyramidal disorders, in rare cases, prolongation of the QT interval and seizures. In case of overdose, the development of polymorphic ventricular tachycardia of “pirouette” type has been described in patients simultaneously taking risperidone and paroxetine.

In case of acute overdose, the possibility of overdose from multiple medications should be considered.

treatment:ensure free airway patency for adequate oxygenation and ventilation. Gastric lavage (after intubation if unconscious) and use activated charcoal and laxatives only if risperidone was taken less than 1 hour ago.

EKG monitoring should be started as soon as possible to diagnose a possible heart rhythm disturbance in time. There is no specific antidote, an appropriate symptomatic therapy should be carried out. In case of decreased blood pressure and vascular collapse, intravenous infusion of infusion solutions and/or sympathomimetic drugs is recommended. If acute extrapyramidal symptoms develop, anticholinergic agents should be prescribed. Close medical observation and ECG monitoring shall be performed until the symptoms of intoxication have completely disappeared.

Pregnancy use

Pregnancy

There have been no controlled studies of risperidone in pregnant women. In animal studies, risperidone did not have teratogenic effects, but other reproductive toxicities were observed. The potential risk of risperidone use in humans is unknown.

The use of antipsychotics (including risperidone) during the third trimester of pregnancy in the newborn developed reversible extrapyramidal symptoms and/or withdrawal syndrome that varied in severity and duration. Cases of agitation, hypertension, hypotension, tremor, somnolence, respiratory distress, and eating disorders have been reported. Therefore, newborns should be closely monitored.

The use of Torendo® Cu-tab® during pregnancy is possible only if the expected benefits to the mother exceed the potential risk to the fetus. If it is necessary to stop therapy during pregnancy, the drug should be withdrawn gradually.

Breastfeeding period

In animal studies, risperidone and 9-hydroxysperidone penetrated breast milk. Risperidone and 9-hydroxyrisperidone have also been shown to penetrate human breast milk in small amounts. There are no data on the development of side effects in infants during breastfeeding. Therefore, the question of breastfeeding should be decided taking into account the possible risk to the baby.

Fertility

Like other drugs that are antagonists of dopamine D2 receptors, risperidone increases plasma prolactin concentration. Hyperprolactinemia can inhibit hypothalamic gonadotropin-releasing hormone secretion, resulting in decreased pituitary gonadotropin secretion. This, in turn, may cause suppression of reproductive function due to impaired steroidogenesis in the sex glands in male and female patients. No significant effects have been observed in preclinical studies.

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