Torendo Ku-tab, 30 pcs., 1 mg, lozenges
Classification of the incidence of side effects (WHO): very often >1/10 (more than 10%); often >1/100 to <1/10 (more than 1% but less than 10%); infrequently from >1/1000 to <1/100 (more than 0.1%, but less than 1%); rarely from > 1/10000 to <1/1000 (more than 0.01%, but less than 0.1%); very rare from <1/10000, including isolated reports (less than 0.01%).
From the hematopoietic system:
uncommon - neutropenia, thrombocytopenia; very rarely - anemia, eosinophilia, agranulocytosis.
From the endocrine system:
very rarely - weight gain, hyperglycemia and exacerbation of pre-existing diabetes mellitus, water intoxication due to polydipsia or syndrome of inappropriate secretion of antidiuretic hormone (SIADH); often - excitement, anxiety, insomnia, headache, agitation; infrequently - drowsiness, dizziness, increased fatigue, difficulty concentrating; rarely - extrapyramidal symptoms*, mania or hypomania, hypervolemia (due to either polydipsia or SIADH); very rarely - tardive dyskinesia (involuntary rhythmic movements, mainly of the tongue and/or face), neuroleptic malignant syndrome**, convulsions, epileptic seizures, thermoregulation disorders.
From the senses:
uncommon - blurred vision, conjunctivitis, blepharitis, dry cornea, lacrimation, eye pain, ear pain, tinnitus; rarely - glaucoma, blurred vision.
From the SSS side:
often - tachycardia (including reflex tachycardia); uncommon - decreased blood pressure (including orthostatic hypotension), increased blood pressure, stroke (in elderly patients with predisposing factors), AV block, sinus bradycardia, thrombosis.
From the respiratory system:
often - rhinitis, cough; uncommon - nasal congestion, sore throat, aspiration pneumonia; rarely - sleep apnea, pneumonia, influenza, sinusitis, otitis media, tonsillitis.
From the digestive system:
uncommon - dryness of the oral mucosa, hyper- or hyposalivation, constipation, dyspepsia, nausea, vomiting, abdominal pain, anorexia; rarely - intestinal obstruction.
From the skin:
rarely - dry skin, hyperpigmentation, rash, itching, seborrhea, angioedema, photosensitivity.
From the urinary system:
often - urinary incontinence; infrequently - cystitis.
From the reproductive system:
uncommon - galactorrhea, amenorrhea, menstrual irregularities; rarely - gynecomastia, priapism, erectile dysfunction, ejaculation disorders, anorgasmia.
From the musculoskeletal system:
often - back pain, pain in the limbs; uncommon - muscle weakness, myalgia, arthralgia; rarely - rhabdomyolysis.
Laboratory indicators:
uncommon - hyperprolactinemia***; very rarely - hyperglycemia; increased activity of liver transaminases.
Other:
rarely - peripheral edema.
*Extrapyramidal symptoms: Risperidone has less potential to cause extrapyramidal disorders compared to classical antipsychotics. However, in some cases, the following extrapyramidal symptoms may develop: tremor, rigidity, hypersalivation, bradykinesia, akathisia, acute dystonia. These symptoms are usually mild and reversible after dose reduction and/or administration of antiparkinsonian drugs (if necessary).
**Neuroleptic malignant syndrome (NMS): a rare, potentially dangerous condition associated with the use of antidepressants, incl. risperidone. Symptoms of NMS: increased body temperature (hyperpyrexia), muscle rigidity, changes in mental status and instability of the autonomic nervous system (arrhythmia, blood pressure fluctuations, tachycardia, profuse sweating, cardiac arrhythmia, increased CPK activity).
Some cerebrovascular symptoms have been reported during use of risperidone; they developed predominantly among elderly patients with existing risk factors.
***Hyperprolactinemia: Risperidone, depending on the dose, can cause an increase in prolactin levels in the blood with the following possible manifestations: galactorrhea, gynecomastia, menstrual irregularities and amenorrhea.
Torendo® Q-Tab®
Use in elderly patients with dementia
Increased mortality in older patients with dementia
A meta-analysis of clinical trials in elderly patients with dementia using atypical antipsychotic drugs showed an increase in mortality compared with the placebo group. Mortality rates in patients receiving risperidone or placebo were 4.0% and 3.1%, respectively. The mean age of patients who died was 86 years (range, 67–100 years). Elderly patients with dementia treated with typical antipsychotic drugs have a small increased risk of death compared with those not treated, according to two large observational studies. At present, insufficient data have been collected to accurately assess this risk. The reason for the increase in this risk is also unknown. Also unknown is the extent to which the increased mortality may be attributable to antipsychotic drugs rather than to the characteristics of this patient population.
Concomitant use with furosemide
When furosemide and oral risperidone were taken concomitantly in elderly patients with dementia, there was an increased mortality rate (7.3%, mean age 89 years, range 75-97 years) compared with the group taking risperidone alone (3.1%, mean age 84 years, range 70-96 years) and the furosemide-only group (4.1%, mean age 80 years, range 67-90 years). An increase in mortality when furosemide was used concomitantly with risperidone was observed in 2 of 4 clinical studies.
Concomitant use of risperidone with other diuretics (mainly low-dose thiazide diuretics) was not associated with an increase in mortality.
No pathophysiological mechanisms have been established to explain this observation. However, special care should be taken when using the drug in such cases.
Before use, the risk/benefit ratio must be carefully assessed. No increased mortality was found in patients taking other diuretics concomitantly with risperidone. Regardless of therapy, dehydration is a common risk factor for mortality and should be carefully monitored in elderly patients with dementia.
An increase in cerebrovascular adverse events (acute and transient cerebrovascular accidents), including deaths, including deaths (mean age 85 years, range 73-97 years) was observed when risperidone was used compared with placebo in elderly patients with dementia.
Cerebrovascular adverse events
In placebo-controlled clinical trials, an approximately 3-fold increased risk of cerebrovascular side effects was observed in patients with dementia taking certain atypical antipsychotic drugs. Pooled data from 6 placebo-controlled studies, mainly including elderly patients with dementia (age >65 years), show that cerebrovascular adverse events (serious and non-serious) occurred in 3.3% (33/1009) of patients treated with risperidone , and in 1.2% (8/712) of patients receiving placebo. The risk ratio was 2.96 (1.34, 7.50) with a 95% confidence interval. The mechanism by which this risk increases is unknown. An increased risk cannot be excluded with the use of other antipsychotic drugs or in other patient populations. The drug Torendo® Qu-tab® should be used with caution in patients with risk factors for stroke. The risk of developing 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. It is necessary to assess the risk/benefit ratio before using Torendo® Qu-tab® in elderly patients with dementia, taking into account the risk factors for stroke in each individual patient. Patients and their caregivers should be advised to immediately report possible manifestations of cerebrovascular disorders (such as sudden weakness or stiffness/numbness in the face, legs, arms, as well as difficulty speaking and blurred vision) to the physician. Necessary treatment measures should be taken immediately, including discontinuation of risperidone.
Torendo® Qu-tab® can only be used for short-term treatment of persistent aggression in patients with moderate to severe dementia due to Alzheimer's disease, as an adjunct to non-pharmacological methods of correction, in case of their ineffectiveness or limited effectiveness, and when there is a risk of causing harm by the patient to himself or others.
The patient's condition and the need for continued risperidone therapy should be continually assessed.
Orthostatic hypotension
Due to the alpha-blocking effect of risperidone, some patients may develop orthostatic hypotension, especially during the initial dose titration period. Cases of clinically significant arterial hypotension have been described with simultaneous use of risperidone with antihypertensive drugs in the post-marketing period. The drug Torendo® Ku-tab® should be used with caution in patients with cardiovascular diseases (for example, chronic heart failure, myocardial infarction, cardiac muscle conduction disorders, dehydration, hypovolemia or cerebrovascular disease). Appropriate dose adjustment is also necessary. It is recommended to evaluate the possibility of dose reduction in case of arterial hypotension.
Leukopenia, neutropenia and agranulocytosis
Cases of leukopenia, neutropenia and agranulocytosis have been described with the use of antipsychotics, including the use of the drug risperidone. Agranulocytosis was observed very rarely (< 1/10,000 patients) during post-marketing surveillance. Patients with a clinically significant decrease in white blood cell count or a history of drug-induced leukopenia/neutropenia should be monitored in the first few months after initiation of therapy, and discontinuation should be considered at the first sign of a clinically significant decrease in white blood cell count and in the absence of other causative factors. risperidone therapy Patients with clinically significant neutropenia should be closely monitored for fever or other symptoms of infection, and treatment should be initiated immediately if such symptoms occur. Patients with severe neutropenia (absolute neutrophil count < 1x 109/l) should discontinue the drug Torendo® Ku-tab® and monitor the number of leukocytes in the blood until their number returns to normal levels.
Tardive dyskinesia and extrapyramidal symptoms
Therapy with dopamine receptor antagonists can cause tardive dyskinesia, which is characterized by rhythmic involuntary movements, mainly of the tongue and/or facial muscles. The occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. Due to the fact that the potential for stimulation of extrapyramidal disorders is lower with risperidone than with classical antipsychotics, the risk of developing tardive dyskinesia with its use should be lower than with the use of classical antipsychotics. If a patient experiences objective or subjective symptoms indicating tardive dyskinesia, the advisability of discontinuing all antipsychotic drugs, including Torendo® Qu-tab®, should be considered.
Extrapyramidal symptoms and psychostimulants
Caution should be exercised in patients taking psychostimulants (e.g., methylphenidate) and risperidone concomitantly due to the potential for extrapyramidal symptoms when the dosage of one or both drugs is adjusted.
ZNS
When treated with antipsychotic drugs, including risperidone, the development of NMS, characterized by hyperthermia, muscle rigidity, instability of the autonomic nervous system, depression of consciousness and increased serum creatine phosphokinase activity, is possible. Myoglobinuria (rhabdomyolysis) and acute renal failure may also occur in patients with NMS. If a patient experiences objective or subjective symptoms of NMS, all antipsychotic medications, including risperidone, should be immediately discontinued.
Parkinson's disease and dementia with Lewy bodies
The use of antipsychotic drugs, including the drug Torendo® Qu-tab®, in patients with Parkinson's disease or dementia with Lewy bodies should be carried out with caution, since both groups of patients have an increased risk of developing NMS and increased sensitivity to antipsychotic drugs (including dulling of pain sensitivity, confusion, postural instability with frequent falls and extrapyramidal symptoms). Parkinson's disease may worsen when taking risperidone.
Hyperglycemia and diabetes mellitus
Cases of the development of hyperglycemia, diabetes mellitus and exacerbation of existing diabetes mellitus have been described. Assessing the relationship between the use of atypical antipsychotic drugs and abnormal glucose concentrations is difficult due to the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia, as well as due to the increased incidence of diabetes mellitus in the general population. Taking into account additional influencing factors, the relationship between the use of atypical antipsychotic drugs and adverse events related to hyperglycemia is not completely clear. In some cases, there was an increase in body weight preceding 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, patients should be monitored for symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia, and weakness). In patients with diabetes mellitus, blood glucose concentrations should be regularly monitored.
Weight gain
During risperidone therapy, a significant increase in body weight was observed. It is necessary to regularly monitor patients' body weight.
Hyperprolactinemia
in vitro studies
It has been suggested that the growth of mammary tumor cells can be stimulated by prolactin. Despite the fact that clinical and epidemiological studies have not revealed a clear connection between hyperprolactinemia and the use of antipsychotic drugs, caution should be exercised when using risperidone in patients with a family history. Torendo® Ku-tab® should be used with caution in patients with existing hyperprolactinemia and in patients with possible prolactin-dependent tumors.
QT prolongation
In very rare cases, prolongation of the QT interval has been observed in the post-registration period. As with other antipsychotics, caution should be exercised when using Torendo® Qu-tab® in patients with cardiovascular disease, family history of QT interval prolongation, bradycardia, electrolyte imbalance (hypokalemia, hypomagnesemia), as this may increase the risk of arrhythmogenic effects or when used simultaneously with drugs that prolong the QT interval.
Convulsions
The drug Torendo® Qu-tab® should be used with caution in patients with a history of seizures or in conditions accompanied by a decrease in the threshold of seizure activity.
Priapism
Since risperidone has an alpha-adrenergic blocking effect, priapism may develop with its use.
Dysregulation of body temperature
When using antipsychotic drugs, such an undesirable effect as impaired thermoregulation is described. Caution must be exercised when using the drug Torendo® Qu-tab® in patients who may be exposed to factors that cause an increase in body temperature, such as intense physical activity, dehydration, high ambient temperature, and simultaneous use with drugs that have anticholinergic activity.
Venous thromboembolism
Cases of venous thromboembolism have been described with the use of antipsychotic drugs. It is necessary to identify all possible risk factors for the development of thromboembolic complications before and during therapy with Torendo® Qu-tab®, and preventive measures must also be taken.
ISDR
ISDR has been observed during cataract surgery in patients receiving drugs that antagonize alpha-adrenergic receptors, including risperidone. ISDR may increase the risk of ocular complications during and after surgery. It is necessary to inform the ophthalmologist in advance about the use of drugs that antagonize alpha-adrenergic receptors currently or in the past. The potential benefit of discontinuing therapy with alpha1-adrenergic receptor antagonizing drugs before cataract surgery has not been established, and therefore the benefit/risk ratio of discontinuing antipsychotic therapy needs to be assessed.
Children and teenagers
Before using Torendo® Qu-tab® in children or adolescents with mental retardation, it is necessary to carefully assess their condition for the presence of physical or social causes of aggressive behavior, such as pain or inadequate demands of the social environment.
The sedative effect of risperidone should be carefully monitored in this population due to the possible effect on learning ability. Changing the timing of risperidone administration may reduce the effects of sedation on alertness in adolescents and children.
Risperidone use was associated with increases in mean body weight and body mass index. Height changes in longitudinal studies were within expected age-related norms. The effects of long-term use of risperidone on sexual development and growth have not been fully studied.
Due to the possible impact of prolonged hyperprolactinemia on growth and sexual development in children and adolescents, regular clinical assessment of hormonal status should be carried out, including measurement of height, body weight, monitoring of sexual development, menstrual cycle and other possible prolactin-dependent effects.
During risperidone therapy, regular assessment should be carried out to identify extrapyramidal symptoms and other movement disorders.
Special information on excipients
Torendo® Ku-tab® contains aspartame and sorbitol, and therefore its use is contraindicated in patients with phenylketonuria and congenital fructose intolerance.
Torendo ku-tab instructions for use, contraindications, side effects, reviews
Antipsychotic drug (neuroleptic). Drug: TORENDO® KU-TAB Active substance of the drug:
risperidone ATC coding: N05AX08 KFG: Antipsychotic drug (neuroleptic) Registration number: LS-002602 Registration date: 12/29/06 Registration owner. ID: KRKA dd {Slovenia}
Torendo ku-tab release form, drug packaging and composition.
Lozenges are round, biconvex, light pink in color with visible inclusions.
1 tab. risperidone 500 mcg -“- 1 mg -“- 2 mg
Excipients: mannitol, basic butyl methacrylate copolymer, povidone, microcrystalline cellulose, hyprolose (low-substituted hydroxypropylcellulose LH-21), aspartame, crospovidone, red iron oxide (E172), mint and menthol flavoring, calcium silicate, magnesium stearate.
10 pieces. - blisters (3) - cardboard packs.
The description of the drug is based on the officially approved instructions for use.
Pharmacological action of Torendo ku-tab
Antipsychotic drug (neuroleptic).
Risperidone is a selective monoaminergic antagonist with pronounced affinity for serotonergic 5-HT2 receptors and dopaminergic D2 receptors, also binds to 1-adrenergic receptors and, with slightly lower affinity, to H1-histamine and 2-adrenergic receptors. Does not have tropism for cholinergic receptors. It also has a sedative, antiemetic and hypothermic effect.
The antipsychotic effect is due to the blockade of dopamine D2 receptors in the mesolimbic and mesocortical systems.
The sedative effect is due to the blockade of adrenergic receptors in the reticular formation of the brain stem.
The antiemetic effect is due to the blockade of dopamine D2 receptors in the trigger zone of the vomiting center.
The hypothermic effect is due to the blockade of dopamine receptors in the hypothalamus.
Reduces productive symptoms (delusions, hallucinations), automatism. Causes less suppression of motor activity and induces catalepsy to a lesser extent than classical antipsychotics (neuroleptics).
Balanced central antagonism of serotonin and dopamine may reduce the risk of extrapyramidal symptoms.
Risperidone may cause a dose-dependent increase in plasma prolactin concentrations.
Pharmacokinetics of the drug.
Suction
When taken orally, risperidone is completely absorbed (regardless of food intake) and Cmax in blood plasma is observed after 1-2 hours.
Distribution
The concentration of risperidone in plasma is proportional to the dose of the drug (within therapeutic doses).
Risperidone is rapidly distributed in the body. Vd is 1-2 l/kg. In plasma, risperidone binds to albumin and acidic -1-glycoprotein. The fractions of risperidone and 9-hydroxy-risperidone bound by plasma proteins are 88% and 77%, respectively.
Metabolism
Risperidone is metabolized by the cytochrome P450 IID6 isoenzyme to form 9-hydroxy-risperidone, which has a similar pharmacological effect.
Risperidone and 9-hydroxy-risperidone are an effective antipsychotic fraction. Further metabolism of risperidone involves N-dealkylation. When taken orally, risperidone is eliminated with a T1/2 of about 3 hours. T1/2 of 9-hydroxy-risperidone and the active antipsychotic fraction is 24 hours.
In most patients, CSS of risperidone is observed 1 day after the start of treatment. Css of 9-hydroxy-risperidone is in most cases achieved 3-4 days after the start of treatment.
Removal
70% is excreted in urine (of which 35-45% is in the form of a pharmacologically active fraction) and 14% in bile.
Pharmacokinetics of the drug.
in special clinical cases
In elderly patients or patients with insufficient renal function, with a single use of the drug, high levels of concentrations of active substances in plasma and their slow elimination are observed.
