Torendo - instructions for use, dose, side effects, contraindications

Excipients: cellulose ** 155.20 mg, microcrystalline cellulose 41.00 mg, croscarmellose sodium 8.40 mg, silicon dioxide colloid 0.70 mg, sodium lauryl sulfate 2.10 mg, magnesium stearate 1.60 mg

Film sheath: Opadrai 03H28758 white *** 7.00 mg

1 tablet, film-coated, 2 mg contains:

Core:

Active substance:

Risperidone 2.00 mg

Excipients: cellulose ** 154.20 mg, microcrystalline cellulose 41.00 mg, croscarmellose sodium 8.40 mg, silicon dioxide colloid 0.70 mg, sodium lauryl sulfate 2.10 mg, magnesium stearate 1.60 mg

Film sheath: Opaprai 03H28758 white *** 6.92 mg, ferric iron oxide yellow (E172) 0.06 mg, ferric iron oxide red (E172) 0.02 mg

1 tablet, film-coated, 3 mg contains:

Core:

Active substance:

Risperidone 3.00 mg

Excipients: cellulose ** 153.20 mg, microcrystalline cellulose 41.00 mg, croscarmellose sodium 8.40 mg, silicon dioxide colloid 0.70 mg, sodium lauryl sulfate 2.10 mg, magnesium stearate 1.60 mg

Film sheath: Opadrai 03H28758 white *** 6.98 mg, dye quinoline yellow (E104) 0.02 mg

1 tablet, film-coated, 4 mg contains:

Core:

Active substance:

Risperidone 4.00 mg

Excipients: cellulose ** 152.20 mg, microcrystalline cellulose 41.00 mg, croscarmellose sodium 8.40 mg, silicon dioxide colloid 0.70 mg, sodium lauryl sulfate 2.10 mg, magnesium stearate 1.60 mg

Film sheath: Opaprai 03H28758 white *** 6.99 mg, dye quinoline yellow (E104) 0.008 mg, indigocarmine (E132) 0.002 mg

** Cellactose is a spray-dried compound consisting of 75% alpha-lactose monohydrate and 25% cellulose powder, dry matter.

*** Opadrai 03H28758 white: hypromellose 72%, titanium dioxide (E171) 16%, talc 7%, propylene glycol 5%.

Description:Tablets 1 mg: oval, biconvex tablets, covered with a film shell of white or almost white, with a risk on one side.
Type of tablet on a cross-section: a white rough mass with a film shell of white or almost white color.
Tablets 2 mg: oval, biconvex tablets, covered with a film coating of light orange color, with a risk on one side.
Type of tablet on a cross-section: white rough mass with a film cover of light orange color.
Tablets 3 mg: oval, biconvex tablets, covered with a film coating of yellow color, with a risk on one side.
Type of tablet on a cross-section: a white rough mass with a film coating of yellow color.
Tablets 4 mg: oval, biconvex tablets, covered with a film shell of light green color, with a risk on one side.
Type of tablet on a cross-section: a white rough mass with a film shell of light green color.

Pharmacotherapeutic group:antipsychotic agent (antipsychotic).

ATX: & nbsp

N.05.A.X Other antipsychotics

N.05.A.X.08 Risperidone

Pharmacodynamics:

Risperidone is a selective monoaminergic antagonist with a high affinity for serotonin 5-HT₂and dopamine D₂receptors. Risperidone is also associated with α₁-adrenoceptors and, to a lesser extent, H₁-histamine and α₂-adrenoceptors. Risperidone has no tropism for cholinergic receptors. Risperidone reduces the productive symptoms of schizophrenia, causes less inhibition of motor activity and to a lesser degree induces catalepsy than classical antipsychotics. Balanced central antagonism to serotonin and dopamine reduces the likelihood of developing extrapyramidal disorders and expands the therapeutic effect of the drug to include negative and affective symptoms of schizophrenia.

Pharmacokinetics:Suction
Risperidone after ingestion is completely absorbed, reaching the maximum concentrations in the blood plasma after 1-2 hours. Absolute bioavailability of risperidone after oral administration is 70%. The relative bioavailability after oral administration of risperidone in the form of tablets is 94% when compared with risperidone in the form of a solution.Eating does not affect the absorption of the drug, so risperidone can be used regardless of the time you take the food. The equilibrium concentration of risperidone in the body in most patients is reached within 1 day. The equilibrium concentration of 9-hydroxyriperidone is reached within 4-5 days.
Distribution
Risperidone is rapidly distributed in the body. The volume of distribution is 1-2 l / kg. In the blood plasma risperidone binds to albumin and alpha-1-acid glycoprotein. Risperidone 90% bound by plasma proteins, 9-hydroxyrisperidone - by 77%.
Metabolism and excretion
Risperidone is metabolized in the liver with the participation of the CYP2D6 isoenzyme. The main metabolite is 9-hydroxyrisperidone, which has a similar pharmacological activity with risperidone. Risperidone and 9-hydroxyrisperidone constitute the active antipsychotic fraction. The CYP2D6 isozyme is susceptible to genetic polymorphism. In patients with intensive metabolism by the isoenzyme CYP2D6 risperidone quickly turns into 9-hydroxyrisperidone, while in patients with a weak metabolism of the isoenzyme CYP2D6 this process is much slower.Although the concentration of risperidone is lower in patients with intensive metabolism and the concentration of 9-hydroxyrisperidone is higher than in patients with weak metabolism, the pharmacokinetics of the active antipsychotic fraction after taking one or more doses is similar in two groups of patients.
Another way of metabolizing risperidone is N-dealkylation. In vitro studies on microsomes of human liver have shown that risperidone at clinically significant concentrations does not significantly inhibit the metabolism of drugs biotransformed under the action of cytochrome P450 isozymes, including CYP1A2, CYP2A6, CYP2C8 / 9/10, CYP2D6, CYP2E1, CYP3A4 and CYP3A5. One week after starting risperidone, 70% of the dose is excreted by the kidneys (the excretion of risperidone and 9-hydroxyrisperidone by kidneys is 35-45% of the dose taken, the rest is inactive metabolites) and 14% through the intestine. After ingestion in patients with psychoses, the half-life (T1 / 2) of risperidone is about 3 hours, T1 / 2 of 9-hydroxyrisperidone and the active antipsychotic fraction - 24 hours.
Linearity
The concentration of risperidone in blood plasma is directly proportional to the dose taken in the therapeutic range of doses.
Pharmacokinetics in selected patient groups
Patients with advanced age, patients with impaired liver and kidney function
After a single dose of risperidone in elderly patients, the concentration of the active antipsychotic fraction in the blood plasma increased, on average, by 43%, T1 / 2 by 38%, and the clearance - by 30%.
In patients with renal insufficiency, an increase in plasma concentration and a decrease in the clearance of the active antipsychotic fraction was observed on average by 60%. In patients with hepatic insufficiency, the concentrations of risperidone in the blood plasma did not change, but the average concentration of the free fraction of risperidone increased by 35%.
Children
The pharmacokinetics of risperidone, 9-hydroxyrisperidone and the active antipsychotic fraction in children are comparable to that of adult patients.
Sex, race, smoking
Population pharmacokinetic analysis did not reveal the obvious effect of sex, race or smoking on the pharmacokinetics of risperidone and the active antipsychotic fraction.

Indications:- Treatment of schizophrenia in adults and children from 13 years.
- Treatment of manic episodes associated with bipolar disorder, moderate and severe in adults and children from 10 years.
- Short-term (up to 6 weeks) treatment of persistent aggression in patients with dementia due to Alzheimer's disease, medium and severe, not amenable to non-pharmacological correction methods, and if there is a risk of harm to the patient or others.
- Short-term (up to 6 weeks) symptomatic treatment of persistent aggression in the structure of behavioral disorder in children from the age of 13 with mental retardation diagnosed according to the DSM-IV criteria, in which medical treatment is required due to the severity of aggression or other destructive behavior. Pharmacotherapy should be part of an integrated treatment program, including psychological and educational activities. Risperidone should be appointed by a specialist in the field of pediatric neurology and child psychiatry or a physician familiar with the treatment of behavioral disorders in children and adolescents.

Contraindications:Hypersensitivity to risperidone or other components of the drug, lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome, children under 13 years of age in the treatment of schizophrenia,children under 13 years of age (or body weight less than 50 kg) in the treatment of persistent aggression in the structure of conduct disorder, children under 10 years of age in the treatment of manic episodes associated with bipolar disorder.

Carefully:- diseases of the cardiovascular system (chronic heart failure, suffered myocardial infarction, conduction disorders of the heart muscle);
- dehydration and hypovolemia;
- disorders of cerebral circulation;
- Parkinson's disease;
- convulsions (including in the anamnesis);
- severe renal or hepatic insufficiency (see section "Method of administration and dose");
- Drug abuse or drug dependence;
- conditions predisposing to the development of tachycardia such as "pirouette" (bradycardia, electrolyte imbalance, simultaneous intake of drugs that extend the QT interval);
- Brain tumor, intestinal obstruction, cases of acute drug overdose, Reye's syndrome (antiemetic effect of risperidone may mask the symptoms of these conditions);
- risk factors for thromboembolism of venous vessels;
- disease of diffuse Levi bodies;
- use in elderly patients with cerebrovascular dementia;
- Pregnancy.

Pregnancy and lactation:Pregnancy
Controlled studies of the use of risperidone in pregnant women have not been conducted. In animal studies risperidone did not have a teratogenic effect, but other types of toxic effects on the reproductive system were observed. The potential risk of using risperidone in humans is not known.
When using antipsychotics (including risperidone) during the third trimester of pregnancy, the neonate had reversible extrapyramidal symptoms and / or withdrawal syndrome, which varied in severity and duration. There have been reports of agitation, hypertension, hypotension, tremor, drowsiness, breathing disorder and eating disorders. Therefore, newborns should be carefully monitored.
The use of the drug Thorendo® during pregnancy is possible only if the expected benefit to the mother exceeds the potential risk to the fetus. If it is necessary to stop therapy during pregnancy, the drug should be discontinued gradually.
Breastfeeding period
In animal studies risperidone and 9-hydroxyrisperidone penetrated into breast milk. It was also demonstrated that risperidone and 9-hydroxyrisperidone penetrate in human breast milk in small amounts. There is no evidence of adverse effects in infants during breastfeeding. Therefore, the question of breastfeeding should be addressed in the light of the possible risk to the child.
Fertility
Like other drugs that are antagonists of dopamine D2 receptors, risperidone increases the level of prolactin. Hyperprolactinemia can inhibit the secretion of the hypothalamic gonadotropin-releasing hormone, which leads to a decrease in the secretion of the pituitary gonadotropin. This, in turn, can cause suppression of reproductive function due to the violation of steroidogenesis in the sex glands in male and female patients. In preclinical studies, no significant effects were observed.

Dosing and Administration:

Schizophrenia

Adults

The drug Torendo® can be used 1 or 2 times a day.

The initial dose is 2 mg per day. On the second day, the dose can be increased to 4 mg per day.From this moment, the dose can either be kept at the same level, or individually correct if necessary. Usually the optimal dose is 4-6 mg per day. In some cases, a slower dose increase and lower initial and maintenance doses may be justified.

Doses higher than 10 mg per day ns showed higher efficacy compared with smaller doses and may cause extrapyramidal symptoms. Due to the fact that safety of doses above 16 mg per day has not been studied, doses above this level should not be used.

Elderly patients

The recommended initial dose is 0.5 mg 2 times a day. The dose can be individually increased by 0.5 mg twice a day to 1-2 mg twice a day.

Children from 13 years old

An initial dose of 0.5 mg is recommended for taking 1 time per day in the morning or evening. If necessary, the dosage can be increased at least after 24 hours by 0.5-1 mg per day to a recommended dose of 3 mg per day with good tolerability. Despite the efficacy shown in the treatment of schizophrenia in adolescents at doses of 1-6 mg per day, no additional efficacy was observed at doses above 3 mg per day, and higher doses caused more side effects. The use of doses above 6 mg per day has not been studied.Patients who have sustained drowsiness, it is recommended to take half the daily dose 2 times a day.

Manic episodes associated with bipolar disorder, moderate to severe

Adults

The recommended initial dose of Thorendo® - 2 mg once a day. If necessary, this dose can be increased at least 24 hours per 1 mg per day. For most patients, the optimal dose is 1-6 mg per day. The use of doses above 6 mg per day in patients with manic episodes has not been studied. As with any other symptomatic therapy, the advisability of continuing treatment with Torendo^®must be regularly evaluated and confirmed.

Elderly patients

The recommended initial dose is 0.5 mg 2 times a day. The dose can be individually increased by 0.5 mg twice a day to 1-2 mg twice a day. Experience with elderly patients is limited, care should be taken.

Children from 10 years

An initial dose of 0.5 mg is recommended for taking 1 time per day in the morning or evening. If necessary, the dosage can be increased at least in 24 hours by 0.5 mg-1 mg per day to a recommended dose of 1-2.5 mg per day with good tolerability.Despite the efficacy shown in the treatment of manic episodes associated with bipolar disorder in children with doses of 0.5-6 mg per day, no additional efficacy was observed at doses above 2.5 mg per day, and higher doses caused more side effects. The use of doses above 6 mg per day has not been studied.

Patients who have sustained drowsiness, it is recommended to take half the daily dose 2 times a day.

Continuous aggression in patients with dementia, caused by Alzheimer's disease, moderate and severe

The recommended initial dose is 0.25 mg twice a day. If necessary, it is possible to increase the dose of 0.25 mg 2 times a day with an interval of at least 1 day. The optimal dose is 0.5 mg 2 times a day. In some patients, however, the effective dose can be 1 mg twice a day. Torendo® should not be used for more than 6 weeks in patients with persistent aggression with Alzheimer's dementia. During treatment with Thorendo®, a frequent and regular assessment of the patient's condition is necessary to decide whether to continue therapy.

At the beginning of dosing, as well as when increasing the dose, appropriate dosage forms of risperidone should be used with a dosage of 0.25 mg.

Continuous aggression in the structure of conduct disorder

Children from 13 years of age (or with a body weight of 50 kg or more)

The recommended initial dose of Thorendo® is 0.5 mg once a day. If necessary, this dose can be increased by 0.5 mg once a day in not less than 24 hours. The optimal dose is 1 mg 1 time per day. However, for some patients it is preferable to take 0.5 mg per day, while some require an increase in the dose to 1.5 mg per day.

Long-term use of Thorendo® in children and adolescents should be carried out under the constant supervision of a physician.

Special patient groups

Impaired renal and hepatic function

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

The initial and maintenance dose in accordance with the indications should be reduced 2 times,an increase in the dose in patients with impaired liver and kidney function should be slower.

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

Mode of application

Inside, regardless of meal time.

The drug Thorendo® should be withdrawn gradually. With the sharp discontinuation of antipsychotic drugs in high doses, including risperidone, in very rare cases, the development of withdrawal syndrome (nausea, vomiting, increased sweating and insomnia), recurrence of psychotic symptoms and the appearance of involuntary movements (such as akathisia, dystonia and dyskinesia).

Transition from therapy with other antipsychotic drugs

After the beginning of the use of the preparation Torendo® a gradual decrease in the dose of another antipsychotic is recommended. In the case of previous therapy with depot forms of antipsychotics, therapy with TORENDO® it is recommended to start instead of the next scheduled injection. Periodically, the need to continue the use of antiparkinsonian drugs should be evaluated.

Side effects:

The most frequently observed undesirable reactions (incidence ≥ 10%) were: parkinsonism, sedation / drowsiness, headache and insomnia.

Parkinsonism and akathisia are dose-dependent undesirable reactions. Undesirable reactions of risperidone in therapeutic doses are given with a frequency distribution and organ systems. The incidence of adverse reactions was classified as follows: very often (≥ 1/10), often (from ≥ 1/100 to <1/10), infrequently (from ≥ 1/1000 to <1/100), rarely (from ≥ 1 / 10,000 to <1/1000 cases), very rarely (<1/10000), the frequency is unknown (nc can be estimated based on available data).

In each group, adverse reactions are presented in order of decreasing severity.

Laboratory and instrumental data:

often: increased prolactin concentration¹ in the blood serum, increase in body weight;

infrequent: interval lengthening QT electrocardiogram (ECG), ECG disorder, weight loss, increased activity of liver enzymes, a decrease in the number of leukocytes in the blood, an increase in body temperature, an increase in the number of eosinophils in the blood, a decrease in hemoglobin, a decrease in hematocrit, an increase in activity of creatine phosphokinase, an increase in the concentration of cholesterol in the blood plasma .

rarely: a decrease in body temperature, an increase in the concentration of triglycerides in the blood plasma.

Heart Disease:

often: tachycardia;

infrequently: atrioventricular block, bundle branch block, Atrial fibrillation, sinus bradycardia, palpitations, conduction disturbance;

rarely: sinus arrhythmia.

Vascular disorders:

often: increased blood pressure;

infrequently: arterial hypotension, orthostatic hypotension, "tides" of blood to the skin of the face;

rarely: pulmonary embolism, venous thrombosis.

Violations from the blood and lymphatic system:

infrequently: neutropenia, anemia, thrombocytopenia;

rarely: granulocytopenia, agranulocytosis⁴.

Impaired nervous system:

very often: sedation / drowsiness, Parkinsonism², headache;

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

infrequently: lack of response to irritants, loss of consciousness, fainting, depressed level of consciousness, stroke, transient ischemic attack, dysarthria, attention disturbance, hypersomnia, postural dizziness, imbalance, tardive dyskinesia, speech impairment, coordination disorder, hypoesthesia. Cerebral ischemia, impaired movement, convulsions², psychomotor hyperactivity, dysgeusia, paresthesia;

rarely: malignant neuroleptic syndrome, diabetic coma, cerebrovascular disorders, tremor of the head.

Disorders from the side of the organ of vision:

often: blurred vision, conjunctivitis;

infrequently: ocular hyperemia, blurred vision, eye discharge, swelling around the eyes, dry eyes, tearing, photophobia;

rarely: decreased visual acuity, involuntary eyeball rotation, glaucoma, intraoperative syndrome of flabby iris⁴, impellent eye disorder.

Hearing impairment and labyrinthine disturbances:

infrequently: pain in the ear, tinnitus.

Disturbances from the respiratory system, chest and mediastinal organs:

often: shortness of breath, nosebleed, cough, nasal congestion, pain in the larynx and pharynx;

infrequently: wheezing, aspiration pneumonia, pulmonary congestion, impaired respiration, moist rales, impaired airway dysphonia;

rarely: sleep apnea syndrome, hyperventilation.

Disorders from the gastrointestinal tract:

frequent vomiting, diarrhea, constipation, nausea, abdominal pain, dyspepsia, dryness of the oral mucosa, stomach discomfort, toothache;

infrequently: dysphagia, gastritis, fecal incontinence, hypersalivation, fecaloma, gastroenteritis, flatulence;

rarely: intestinal obstruction, pancreatitis, edema of the lips, edema of the tongue, cheilitis.

Disorders from the kidneys and urinary tract:

often: enuresis;

infrequently: urinary retention, dysuria, urinary incontinence, pollakiuria.

Disturbances from the skin and subcutaneous tissues:

often: skin rash, erythema;

infrequently: urticaria, eczema, skin lesions, skin disorders, skin itching, acne, skin discoloration, alopecia, seborrheic dermatitis, dry skin, hyperkeratosis; rarely: toxicoderma, dandruff;

very rarely: angioedema.

Disturbances from the musculoskeletal and connective tissue:

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

infrequently: muscle weakness, pain in the neck, swelling of the joints, impaired posture, stiffness in the joints;

rarely: rhabdomyolysis.

Disorders from the endocrine system:

rarely: disruption of the production of antidiuretic hormone, glucosuria.

Disorders from the metabolism and nutrition:

often: increased appetite, decreased appetite;

infrequently: diabetes mellitus³anorexia, polydipsia, hyperglycemia;

rarely: hypoglycemia, water intoxication⁴, hyperinsulinemia⁴; very rarely: diabetic ketoacidosis.

Infectious and parasitic diseases:

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

infrequently: viral infections, tonsillitis, inflammation of subcutaneous fat, otitis media, eye infections, localized infections, acarobacteria, respiratory infections, cystitis, onychomycosis;

rarely: chronic otitis media.

General disorders and disorders at the site of administration:

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

infrequently: swelling of the face, gait disturbance, poor health, sluggishness, flu-like condition, thirst, discomfort in the chest, chills;

rarely: hypothermia, withdrawal syndrome, cold extremities.

Trauma, intoxication and complication of manipulation:

often: falling.

Immune system disorders:

infrequently: hypersensitivity;

rarely: anaphylactic reaction⁴.

Disorders from the liver and bile ducts:

rarely: jaundice.

Violations of the genitals and breast:

infrequently: amenorrhea, sexual dysfunction, erectile dysfunction, ejaculation disorder, galactorrhea, gynecomastia, menstruation disorder², vaginal discharge, discomfort and chest pain;

rarely: priapism⁴, delay in menstruation, engorgement of the mammary glands, enlargement of mammary glands, discharge from the mammary glands.

Pregnancy postpartum and perinatal conditions:

rarely: withdrawal syndrome in newborns⁴.

Disorders of the psyche:

very often: insomnia²;

often: depression, anxiety, agitation, sleep disturbances;

infrequently: confusion, mania, decreased libido, lethargy, nervousness, nightmarish dreams;

rarely: anorgasmia, flattening of affect.

¹Hyperprolactinemia in some cases can lead to gynecomastia, menstrual cycle disorders, amenorrhea and galactorrhea.

²Extrapyramidal disorders can manifest as: Parkinsonism (hypersalivation, musculoskeletal stiffness, parkinsonism, drooling, rigidity as a "cogwheel", bradykinesia, hypokinesia, masculine face, muscle tension, akinesia, stiff neck,muscular rigidity, parkinsonic gait, glabellar reflex disorders), akathisia (akathisia, anxiety, hyperkinesia and restless leg syndrome), tremor, dyskinesia (dyskinesia, muscle twitching, choreoathetosis, athetosis and myoclonus), dystonia.

Dystonia includes dystonia, muscle spasms, muscle hypertension, torticollis, involuntary muscle contractions, muscle contracture, blepharospasm, eyeball movements, paralysis of the tongue, facial spasm, laryngospasm, myotonia, opisthotonus, oropharyngeal spasm, pleurototonus, spasm of the tongue and trismus. Tremor includes tremor and Parkinson's tremor tremor. It should also be noted that there is a wider range of symptoms that do not always have extrapyramidal origin. Insomnia includes a sleep disorder, an intrasomnia disorder. Seizures include a large epileptic fit. Menstrual disorders include irregular menstruation, oligomenorrhoea. Edema includes generalized edema, peripheral edema, mild edema.

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

⁴Not observed in clinical studies of risperidone, but observed with the post-marketing application of risperidone.

Class Effects

As with the use of other antipsychotics, very rare cases of lengthening of the interval QT in the post-marketing period of observation. Other class effects from the cardiovascular system, observed with the use of antipsychotics, extending the interval QT: ventricular arrhythmias, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac arrest and polymorphic ventricular tachycardia of the pirouette type.

Venous thromboembolism

Cases of venous thromboembolism, including pulmonary embolism and cases of deep vein thrombosis, were observed with the use of antipsychotics (the frequency is unknown).

Weight gain

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

In children with behavioral disorders during long-term clinical trials, the 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 - 3-5 kg per year for girls and about 5 kg per year for boys.

Special patient groups

Older 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 side effects were observed in elderly patients with dementia with a frequency of ≥ 5% and at a frequency at least twice that in other patient populations: urinary tract infections, peripheral edema, lethargy and cough.

Children

The following side effects were observed in children (5 to 17 years) with a frequency ≥ 5% and at a frequency at least twice that in other patient populations in clinical trials: drowsiness / sedation, fatigue, headache, appetite, vomiting, upper respiratory tract infection, nasal congestion, abdominal pain, dizziness, cough, pyrexia, tremor, diarrhea, enuresis.

Overdose:Symptoms: drowsiness, sedation, tachycardia, arterial hypotension, extrapyramidal disorders, in rare cases, prolongation of the QT interval and convulsions. In case of an overdose in patients simultaneously taking risperidone Mr. paroxetine, described the development of polymorphic ventricular tachycardia of the type "pirouette". In the case of acute overdose, it is necessary to take into account the possibility of an overdose from taking several medications.
Treatment: ensure airway patency for adequate oxygenation and ventilation. Gastric lavage (after intubation, if the patient is unconscious) and taking activated charcoal and laxatives should be done only if risperidone was adopted no more than 1 hour ago. For timely diagnosis of a possible heart rhythm disturbance, it is necessary to start ECG monitoring as soon as possible. There is no specific antidote, and appropriate symptomatic therapy should be performed. With a reduction in blood pressure and vascular collapse, intravenous infusion solutions and / or sympathomimetic drugs are recommended. In case of development of severe extrapyramidal symptoms - anticholinergics. Careful medical supervision and monitoring of the ECG is performed until the symptoms of intoxication disappear completely.

Interaction:Risperidone, like any other antipsychotic, should be used with caution at the same time as the drugs that extend the QT interval, for example, with antiarrhythmic agents of the IA class (quinidine, disopyramide, procainamide and others), class III (amiodarone, sotalol and others), tricyclic antidepressants (amitriptyline and others), tetracyclic antidepressants (maprotiline , etc.), some antihistamines, other antipsychotic drugs, some antimalarial drugs (quinine, mefloquine et al.), drugs that cause electrolyte disturbances (hypokalemia, hypomagnesemia), bradycardia, as well as inhibiting metabolism of risperidone in the liver. This list is not exhaustive.
Effect of risperidone on other drugs
Given the increased risk of developing sedation, risperidone should be used with caution at the same time as other central-action drugs, including ethanol, opiates, antihistamines and benzodiazepines. Risperidone can reduce the effectiveness of levodopa and other dopamine agonists. If this combination is necessary, especially at the terminal stage of Parkinson's disease, the minimum effective dose of each drug should be used.
When using risperidone simultaneously with antihypertensive drugs in the postmarketing period, clinically significant arterial hypotension was observed. Risperidone does not have a clinically significant effect on the pharmacokinetics of lithium, valproate, digoxin, or topiramate.
Effect of the use of other drugs on risperidone
When carbamazepine was used, a decrease in the concentration of the active antipsychotic fraction of risperidone in blood plasma was noted. Similar effects can be observed with the use of other inducers of the isoenzyme CYP3A4 and P-glycoprotein (for example, rifampicin, phenytoin, phenobarbital). With the simultaneous use and after withdrawal of carbamazepine or other inducers of the isoenzyme CYP3A4 and P-glycoprotein, the dosage of risperidone should be adjusted.
Fluoxetine and paroxetine, inhibiting the isoenzyme CYP2D6, can increase the concentration of risperidone in the blood plasma and, to a lesser extent, the concentration of the active antipsychotic fraction. It is suggested that other inhibitors of the CYP2D6 isoenzyme (eg, quinidine) affect the concentration of risperidone in blood plasma in the same way. At simultaneous application and after the abolition of fluoxetine or paroxetine, the dosage of risperidone should be adjusted.
Verapamil, an inhibitory isoenzyme CYP3A4 and P-glycoprotein, increases the concentration of risperidone in the blood plasma.
Galantamine and donepezil have no clinically significant effect on the pharmacokinetics of risperidone and its active antipsychotic fraction.
Phenothiazines, tricyclic antidepressants and some β-blockers may increase the concentration of risperidone in the blood plasma, but this does not affect the concentration of the active antipsychotic fraction. Amitriptyline does not affect the pharmacokinetics of risperidone and its active antipsychotic fraction. Cimetidine and ranitidine increase the bioavailability of risperidone, but have a minimal effect on the concentration of the active antipsychotic fraction. Erythromycin, an inhibitory isoenzyme CYP3A4, does not affect the pharmacokinetics of risperidone and its active antipsychotic fraction.
The simultaneous use of risperidone with psychostimulants (eg, methylphenidate) in children was not accompanied by a change in the pharmacokinetic parameters and the effectiveness of risperidone.
Simultaneous reception of risperidone with paliperidone is not recommended, since paliperidone is an active metabolite of risperidone, and combination therapy can lead to an increase in the concentration of the active antipsychotic fraction.

Special instructions:Older patients with dementia
Increased mortality in elderly patients with dementia
Based on the results of a meta-analysis of clinical trials in elderly patients with dementia who have used atypical antipsychotics, an increase in mortality was found in comparison with the placebo group. Mortality in patients who received risperidone or placebo, were 4.0% and 3.1%, respectively. The average age of the deceased patients was 86 years (range 67-100 years). According to two extensive observational studies in elderly patients with dementia in the treatment of typical antipsychotics, there is a slight increase in the risk of death compared to that in patients not receiving treatment. At the moment, there is insufficient data to accurately assess this risk. The cause of this risk increase is also unknown. Also, the extent to which an increase in mortality may not be applicable to antipsychotics, nor to the characteristics of this group of patients, has been determined.
Simultaneous application with furosemide
With simultaneous administration of furosemide and risperidone inside, elderly patients with dementia experienced an increased mortality (7.3%, mean age 89 years, range 75-97 years) compared with the group taking only risperidone (3.1%, average age 84 years, range 70-96 years) and a group that only took furosemide (4.1%, average age 80 years, range 67-90 years). An increase in mortality with furosemide combined with risperidone was noted in 2 out of 4 clinical studies. Simultaneous use of risperidone with other diuretics (mainly with thiazide diuretics in small doses) was not accompanied by an increase in mortality.
There are no pathophysiological mechanisms that explain this observation. However, special care should be taken when using the drug in such cases. Before use, the risk / benefit ratio should be carefully assessed. There was no increase in mortality in patients taking other diuretics concurrently with risperidone. Regardless of therapy, dehydration is a common risk factor for mortality and should be carefully monitored in elderly patients with dementia.
Cerebrovascular adverse events
In placebo-controlled clinical trials in patients with dementia, taking some atypical antipsychotics, an increased risk of cerebrovascular side effects was approximately 3-fold.A summary of 6 placebo-controlled trials, mainly of elderly patients with dementia (age over 65 years), showed 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 confidence interval of 95%. The mechanism of increasing the risk is unknown. It can not be ruled out that the risk increases with other antipsychotics or in other patient populations. Torendo® 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. Consequently, risperidone Do not use in patients with dementia of any type other than dementia due to Alzheimer's disease.
It is necessary to assess the risk / benefit ratio before using Torendo® in elderly patients with dementia, taking into account risk factors for stroke in a particular patient.Patients and caregivers should be informed of the immediate communication to the doctor about possible manifestations of cerebrovascular disorders (such as sudden weakness or immobility / numbness in the face, legs, hands, as well as speech difficulties and visual impairment). Immediately take the necessary medical measures, including the abolition of risperidone.
Torendo® can be used only for short-term therapy of persistent aggression in patients with dementia due to Alzheimer's disease, moderate and severe, as an adjunct to non-pharmacological correction methods, if they are ineffective or limited in effectiveness, and when there is a risk of self-harm to the patient or other persons.
It is necessary to constantly assess the patient's condition and the need to continue therapy with risperidone.
Orthostatic hypotension
In connection with the α-adrenoblocking action of risperidone, some patients may develop orthostatic hypotension, especially during the initial dose selection. Cases of clinically significant arterial hypotension with simultaneous application of risperidone with antihypertensive drugs in the postmarketing period are described.Thorendo® should be used with caution in patients with cardiovascular disease (eg, chronic heart failure, myocardial infarction, cardiac muscle conduction disorders, dehydration, hypovolemia or cerebrovascular disease). Corresponding dose adjustment is also necessary. It is recommended to evaluate the possibility of reducing the dose in the case of development of arterial hypotension.
Leukopenia, neutropenia and agranulocytosis
The cases of leukopenia, neutropenia, and agranulocytosis have been described with the use of antipsychotics, including the use of the drug Thorendo®. Agranulocytosis was very rare (<1 / 100,000 patients) during post-registration follow-up. Patients with a clinically significant decrease in the number of leukocytes or drug-induced leukopenia / neutropenia in the anamnesis should be monitored in the first few months after the initiation of therapy, and when the first signs of a clinically significant reduction in the number of white blood cells appear, in the absence of other causative factors, treatment should be discontinued.
Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms of the infection, and immediately begin treatment if such symptoms occur. Patients with severe neutropenia (absolute neutrophil count < 1 x 10⁹/ l) should stop taking the drug Thorendo® before recovering the number of white blood cells.
Late dyskinesia / extrapyramidal symptoms
Therapy with dopamine receptor antagonists can cause tardive dyskinesia, which is characterized by rhythmic involuntary movements, predominantly of the tongue and / or facial musculature. The occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. If the patient has objective or subjective symptoms that indicate tardive dyskinesia, it is necessary to consider the feasibility of the abolition of all antipsychotics, including the drug Thorendo®.
Malignant neuroleptic syndrome (CNS)
When treating with antipsychotic drugs, it is possible to develop a CNS characterized by hyperthermia, rigidity of muscles,instability in the function of the autonomic nervous system, depression of consciousness and increased concentration of creatine phosphokinase in blood plasma, as well as myoglobinuria (rhabdomyolysis) and acute renal insufficiency. If the patient experiences objective or subjective symptoms of the NSA, all antipsychotics, including the Thorendo® preparation, should be immediately discontinued.
Parkinson's disease and dementia with Levi bodies
The use of antipsychotics, including Thorendo®, in patients with Parkinson's disease or dementia with Levy bodies should be carried out with caution, since both groups of patients have increased risk of developing CNS and increased sensitivity to antipsychotic drugs (including blunting of pain sensitivity, confusion, postural instability with frequent falls and extrapyramidal symptoms). When taking risperidone, there may be a worsening of the course of Parkinson's disease.
Hyperglycemia and diabetes mellitus
The cases of development of hyperglycemia, diabetes mellitus and aggravation of the course of diabetes mellitus are described. In some cases, a previous increase in body weight is noted, which can be regarded as a predisposing factor.In very rare cases observed the development of ketoacidosis and rarely - diabetic coma. As with any antipsychotic medication, patients should be under medical supervision, symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia and weakness) should be monitored. Patients with diabetes should regularly monitor the concentration of glucose in the blood serum.
Weight gain
There is a significant increase in body weight. It is necessary to conduct regular monitoring of body weight of patients.
Hyperprolactinemia
Based on the results of in vitro studies, it is suggested that the growth of breast tumor cells can be stimulated by prolactin. Despite the fact that in clinical and epidemiological studies there is no clear connection between hyperprolactinaemia and antipsychotic medications, caution should be exercised when using risperidone in patients with a history of history. Torendo® should be used with caution in patients with existing hyperprolactinemia and in patients with possible prolactin-dependent tumors.
QT interval extension
In very rare cases, the QT interval is extended in the postmarketing period. As with other antipsychotics, caution should be exercised when using the drug Torendo® in patients with cardiovascular diseases, QT interval elongation in the family history, bradycardia, disorders of electrolyte balance (hypokalemia, hypomagnesemia), as this may increase the risk of arrhythmogenic action or with simultaneous use with drugs that extend the QT interval.
Convulsions
Torendo® drug should be used with caution in patients with a history of seizures or in state, accompanied by a decrease in the threshold for seizure activity.
Priapism
As risperidone has an α-adrenergic blocking effect, it is possible to develop priapism when applied.
Violation of body temperature regulation
When using antipsychotic drugs, such an undesirable effect as a violation of thermoregulation is described. Care must be taken when using the drug Torendo® patients who may be exposed to factors that increase the body temperature,such as intensive physical activity, dehydration, high ambient temperature, simultaneous use with drugs with anticholinergic activity.
Antiemetic effect
In preclinical studies of the use of risperidone, an antiemetic effect was observed. This effect in humans can mask the signs and symptoms of an overdose of some drugs or diseases such as intestinal obstruction, Reye's syndrome and brain tumor.
Impaired renal and hepatic function
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 liver function, the concentration of the free fraction of risperidone in the blood plasma increases.
Venous thromboembolism
When using atypoxy drugs, cases of venous thromboembolism are described. It is necessary to identify all possible risk factors for the development of thromboembolic complications before and during therapy with Thorendo® and take preventive measures.
Intraoperative syndrome of sagging iris
Intraoperative flabby iris syndrome (ISDR) was noted during the operation for cataracts in patients receiving drugs with antagonism to alpha1-adrenergic receptors, including the drug Thorendo®. The ISDR can increase the risk of complications from the visual organ during and after the operation. It is necessary to inform the ophthalmologist in advance about the use of drugs that have antagonism to alpha1-adrenergic receptors at the present time or in the past. The potential benefit of discontinuing therapy with drugs that antagonize alpha-1-adrenergic receptors before surgery for cataracts has not been established. It is necessary to assess the relationship between the benefit and the risk of discontinuing therapy with an antipsychotic.
Children and teens
Before using Torendo® in children or adolescents with mental retardation, it is necessary to carefully evaluate their condition for the presence of physical or social causes of aggressive behavior, such as pain or inadequate requirements of the social environment.
The sedative effect of risperidone should be carefully monitored in this population because of the possible effect on learning ability.The change in the time of taking risperidone can reduce the effect of sedation on the attention of adolescents and children.
The use of risperidone was associated with an increase in the average body weight and body mass index. Changes in growth during long-term studies were within the expected age norms. The long-term effect of risperidone on sexual development and growth has not been fully investigated.
Due to the possible impact of prolonged hyperprolactinemia on growth and sexual development in children and adolescents, regular clinical evaluation of hormonal status should be carried out, including measurement of growth, body weight, monitoring of sexual development, menstrual cycle and other possible prolactin-dependent effects.
During treatment with risperidone, regular examination should be performed to identify extrapyramidal symptoms and other motor disorders.
Special information on excipients
The composition of the drug Thorendo® includes lactose, therefore, it should not be used in patients with lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Effect on the ability to drive transp. cf. and fur:The preparation of Torendo® can have a slight or moderate effect on the ability to drive vehicles and mechanisms. Patients should be advised not to drive the car and from working with the mechanisms to determine their individual sensitivity to the drug.

Form release / dosage:Tablets, film-coated, 1 mg, 2 mg, 3 mg, 4 mg.

Packaging:For 10 tablets in a blister (contour acrylic packaging) from the combined material PVC / PE / PVDC - aluminum foil.
For 2, 3 or 6 blisters (contour mesh packages), together with the instruction for use, is placed in a cardboard package.

Storage conditions:At a temperature of no higher than 25 ° C, in the original packaging.
Keep out of the reach of children.

Shelf life:5 years.
Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-002406

Date of registration:22.02.2012

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, dd, Novo mesto, AO Slovenia

KRKA-RUS, LLC Russia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp18.10.2015

Illustrated instructions

Instructions

Torendo® (Torendo®)