Risperidone - instructions for use, doses, side effects, contraindications

Composition:One tablet, film-coated, contains:
Dosage of 0.25 mg
active substance: risperidone - 0.250 mg;
Excipients: lactose monohydrate - 58.550 mg; cellulose microcrystalline - 16,000 mg; corn starch - 4,000 mg; silicon dioxide colloidal - 0,400 mg; magnesium stearate - 0,800 mg;
film sheath: [hypromellose 1.440 mg, talc 0.480 mg, titanium dioxide 0.264 mg, macrogol 4000 (polyethylene glycol 4000) 0.216 mg] or [dry film coating mixture containing hypromellose (60%), talc (20%), titanium dioxide (11%), macrogol 4000 (polyethylene glycol 4000) (9%)] - 2,400 mg.
Dosage 1 mg
active substance: risperidone - 1,000 mg;
Excipients: lactose monohydrate - 72,500 mg; cellulose microcrystalline - 20,000 mg; corn starch - 5,000 mg; silicon dioxide colloidal - 0,500 mg; magnesium stearate - 1,000 mg;
film sheath: [hypromellose 1,800 mg, talc 0,600 mg, titanium dioxide 0.330 mg, macrogol 4000 (polyethylene glycol 4000) 0.270 mg] or [dry film coating mixture containing hypromellose (60%), talc (20%), titanium dioxide (11%), macrogol 4000 (polyethylene glycol 4000) (9%)] - 3,000 mg.
Dosage 2 mg
active substance: risperidone - 2,000 mg;
Excipients: lactose monohydrate 145,000 mg; microcrystalline cellulose - 40,000 mg; corn starch - 10,000 mg; silicon dioxide colloid - 1,000 mg; magnesium stearate - 2,000 mg;
film sheath: [hypromellose - 3,600 mg, talc - 1,200 mg, titanium dioxide - 0,660 mg, macrogol 4000 (polyethylene glycol 4000) - 0,540 mg] or [dry mixture for film coating containing hypromellose (60%), talc (20%), titanium dioxide (1 1%), macrogol 4000 (polyethylene glycol 4000) (9%)] - 6,000 mg.
Dosage 3 mg
active substance: risperidone - 3,000 mg;
Excipients: lactose monohydrate - 217.500 mg; cellulose microcrystalline - 60,000 mg; corn starch - 15,000 mg; silicon dioxide colloidal - 1,500 mg; magnesium stearate - 3,000 mg;
film sheath: [hypromellose 5,400 mg, talc 1,800 mg, titanium dioxide 0.990 mg, macrogol 4000 (polyethylene glycol 4000) 0.810 mg] or [dry film coating mixture containing hypromellose (60%), talc (20%), titanium dioxide (11%), macrogol 4000 (polyethylene glycol 4000) (9%)] - 9,000 mg.
Dosage 4 mg
active substance: risperidone - 4,000 mg;
Excipients: lactose monohydrate - 290,000 mg; cellulose microcrystalline - 80,000 mg; corn starch - 20,000 mg; silicon dioxide colloid - 2,000 mg; magnesium stearate - 4,000 mg;
film sheath: [hypromellose - 7,200 mg, talc - 2,400 mg, titanium dioxide - 1,320 mg, macrogol 4000 (polyethylene glycol 4000) - 1,080 mg] or [dry mixture for film coating containing hypromellose (60%), talc (20%), titanium dioxide (11%), macrogol 4000 (polyethylene glycol 4000) (9%)] - 12,000 mg.

Description:Round biconvex tablets covered with a film coat of white or almost white color. On the cross section, the nucleus is white or almost white in color.

Pharmacotherapeutic group:Other antipsychotics.

ATX: & nbsp

N.05.A.X Other antipsychotics

N.05.A.X.08 Risperidone

Pharmacodynamics:

Risperidone, an antipsychotic, benzisoxazole derivative, also has a sedative, antiemetic, and hypothermic effect.

Risperidone is a selective monoaminergic antagonist with a high affinity for 5HT₂serotonin and D₂dopamine receptors. Risperidone is also associated with α1-adrenoceptors and, somewhat weaker, with H₁-histamine receptors and α2-adrenoceptors. Risperidone does not have tropism for cholinergic receptors. Antipsychotic action is due to the blockade D₂dopamine receptors of the mesolimbic and mesocortical system. Sedative action is caused by blockade of adrenoreceptors of the reticular formation of the brainstem; antiemetic action - blockade D₂-dophamine receptors of the trigger zone of the vomiting center; hypothermic action - blockade of dopamine receptors of the hypothalamus.

Risperidone reduces the productive symptoms of schizophrenia (delirium, hallucinations), aggressiveness, automatism, it causes less inhibition of motor activity and to a lesser degree induces catalepsy than typical antipsychotics. A balanced central antagonism to serotonin and dopamine may reduce the tendency to

extrapyramidal side effects and expand therapeuticthe effect of the drug on the negative and affective symptoms of schizophrenia.

Pharmacokinetics:Suction
Risperidone after oral administration is completely absorbed, reaching a maximum concentration in the blood plasma after 1-2 hours. Food does not affect the absorption of risperidone, so it can be administered regardless of food intake.
Distribution
Risperidone is rapidly distributed in the body, penetrates the central nervous system and breast milk. The volume of distribution is 1-2 l / kg. In the blood plasma risperidone binds to albumin and α1-acid glycoprotein.
Risperidone is 88% bound by plasma proteins, 9-hydroxyrisperidone - by 77%.
The equilibrium concentration of risperidone in the body in most patients is achieved within one day. The equilibrium concentration of 9-hydroxyrisperidone is reached after 4-5 days. The concentration of risperidone in the blood plasma is proportional to the dose of the drug (within therapeutic doses).
Metabolism
Risperidone is metabolized by the isoenzyme CYP2D6 to 9-hydroxyrisperidone, which has a pharmacological action similar to 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 weak metabolism this transformation occurs much more slowly. Although patients with intensive metabolism have a lower concentration of risperidone and a higher concentration of 9-hydroxyrisperidone than patients with poor metabolism, the total pharmacokinetics of risperidone and 9-hydroxyrisperidone (active antipsychotic fraction) after taking one or more doses is similar in patients with intense and weak metabolism by the isoenzyme CYP2D6.
Another way of metabolizing risperidone is N-dealkylation.
Excretion
The half-life (T1 / 2) of risperidone after oral administration in patients with psychosis is about 3 hours. T1 / 2 9-hydroxyrisperidone and the active antipsychotic fraction are 24 hours.
After a week of taking the drug, 70% of the dose is taken out by the kidneys, 14% - through the intestine. In the urine risperidone and 9-hydroxyrisperidone constitute 35-45% of the dose. The rest is made up of inactive metabolites.
The study of a single dose of risperidone revealed a higher concentration in the blood plasma and a slower elimination in elderly patients and in patients with renal insufficiency. The concentration of risperidone in blood plasma in patients with chronic hepatic insufficiency did not change, however, the average concentration of the free fraction of risperidone increased by 35%.

Indications:- Treatment of schizophrenia in adults and children aged 13 to 17 years;
- treatment of manic episodes associated with bipolar disorder, of moderate to severe severity in adults and children aged 10 years;
- short-term (up to 6 weeks) treatment of persistent aggression in patients with dementia due to Alzheimer's disease, moderate to severe, not amenable to non-pharmacological correction methods, and if there is a risk of harm to the patient and / or others;
- Short-term (up to 6 weeks) symptomatic treatment of persistent aggression in the structure of behavioral disorders in children aged 5 years and those with mental retardation diagnosed according to DSM-IV, in which,due to the severity of aggression or other destructive behavior, drug treatment is required. Pharmacotherapy should be part of a wider 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 any other components of the drug;
- rare hereditary forms of intolerance to galactose;
- deficiency of lactase or impaired absorption of glucose / galactose (because the formulation includes lactose);
- the period of breastfeeding;
- Children under 5 years of age with behavioral disorders in children;
- Children under 13 years of age in the treatment of schizophrenia;
- Children under 10 years of age in the treatment of manic episodes associated with bipolar disorder, moderate and severe severity;
- age up to 18 years for the rest of the indications.

Carefully:Use with caution under the following conditions:
- severe renal or hepatic insufficiency;
- cardiovascular diseases (chronic heart failure, suffered myocardial infarction, intracardiac conduction disturbances, including atrioventricular blockade);
- dehydration and hypovolemia;
- conditions predisposing to the development of tachycardia such as "pirouette" (bradycardia, electrolyte imbalance, concomitant medication prolonging the QT interval);
- disorders of cerebral circulation;
- Parkinson's disease;
- convulsions and epilepsy (including in the anamnesis);
- Drug abuse or drug dependence (see section "Method of administration and dose");
- Brain tumor, intestinal obstruction, cases of acute drug overdose, Reye's syndrome (antiemetic effect of risperidone may mask the symptoms of these conditions);
- elderly age in patients with dementia;
- use in combination with furosemide;
- hyperglycemia;
- risk factors for thromboembolism of venous vessels;
- joint application with drugs of central action;
- disease of diffuse Levi bodies;
- Pregnancy.

Pregnancy and lactation:Controlled studies of the use of risperidone during pregnancy have not been conducted. In animal experiments risperidone did not have a direct toxic effect on the reproductive system, but caused some indirect effects, mediated by the influence on the central nervous system (CNS) and the concentration of prolactin. None of the studies risperidone did not possess a teratogenic effect. There were reversible extrapyramidal symptoms in newborns whose mothers took risperidone during the third trimester of pregnancy. The potential risk to humans is unknown. Use of risperidone during pregnancy is only possible if the intended benefit to the mother exceeds the potential risk to the fetus. Terminate the use of risperidone during pregnancy should be gradual.
Because the risperidone and 9-hydroxyrisperidone penetrate into breast milk, if necessary, taking the drug by nursing mothers should decide whether to stop breastfeeding.
Due to the fact that risperidone can increase the concentration of prolactin in the blood plasma, hyperprolactinemia can inhibit the production of gonadotropin-releasing hormone by the hypothalamus, which leads to a decrease in the secretion of gonadotrophin by the pituitary gland.This, in turn, can reduce the reproductive function due to a violation of steroidogenesis in the sex glands in patients both female and male.

Dosing and Administration:Inside, regardless of food intake.
Schizophrenia
Adults
The initial dose of risperidone for all patients (for acute manifestations of the disease and chronic course) is 2 mg per day (in one or two doses). On the second day, the dose may be increased to 4 mg per day; further, if necessary, the dose may be increased or decreased by 1-2 mg at weekly intervals. 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 above 10 mg per day did not show a 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 can not be used.
For the treatment with risperidone, benzodiazepines can be added if an additional sedative effect is required.
Elderly patients
The recommended starting dose is 0.5 mg twice daily.Dosage can be gradually increased to 1-2 mg per reception twice a day.
Application in children from 13 years old
The recommended initial dose is 0.5 mg once a day in the morning or evening. If necessary, the dose 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.
Mania in bipolar disorders
Adults
The initial dose of risperidone for all patients (for acute manifestations of the disease and chronic course) is 2-3 mg per day (in one or two doses). Correction of the dose should be carried out no earlier than 24 hours per 1 mg per day. Usually the optimal dose varies from 1 mg to 6 mg per day. The use of risperidone in a daily dose of more than 6 mg in the treatment of mania in bipolar disorders has not been studied. Prolonged symptomatic treatment with risperidone should be justified.
Elderly patients
The recommended starting dose is 0.5 mg twice daily. Dosage can be gradually increased to 1-2 mg per reception twice a day.
Use in children from 10 years
The recommended initial dose is 0.5 mg once a day in the morning or evening. If necessary, the dose can be increased not less than 24 hours by 0.5-1 mg per day to the 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.
Behavioral disorders in patients with Alzheimer's dementia
The recommended starting dose is 0.25 mg twice daily. If necessary, it is possible to increase the dose by 0.25 mg twice a day no more often than every other 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.
A drug Risperidone should not be used for more than 6 weeks in patients with persistent aggression in Alzheimer's dementia. During treatment with risperidone, frequent and regular assessment of the patient's condition is necessary to decide whether to continue treatment.
Behavioral disorders
Children and adolescents aged 5 to 18 years
Patients with a body weight of 50 kg or more - The recommended initial dose of the drug is 0.5 mg once a day. If necessary, this dose can be increased by 0.5 mg per day no more often than every other day. For most patients, the optimal dose is 1 mg once a day. However, for some patients it is preferable to take 0.5 mg per day, while other patients require a dose increase of up to 1.5 mg per day.
Patients weighing less than 50 kg - The recommended initial dose of the drug is 0.25 mg once a day. If necessary, this dose may be increased by 0.25 mg per day not more often than every other day. For most patients, the optimal dose is 0.5 mg once daily. However, for some patients it is preferable to take 0.25 mg once a day, while others require an increase in the dose to 0.75 mg once a day.
During treatment with risperidone, frequent and regular assessment of the patient's condition is necessary to decide whether to continue treatment.
Long-term use of risperidone in adolescents should be carried out under the constant supervision of a physician.
Use in children under 5 years of age has not been studied.
Use in patients with renal and / or liver failure.
In patients with renal insufficiency, the excretion of the active antipsychotic fraction is slowed down. With hepatic insufficiency, the concentration of risperidone metabolites in the blood plasma increases. Therefore, in patients with renal and / or liver failure, the initial and effective dose should be reduced by 50%, increasing the dose should be slower. Risperidone should be administered with caution in this category of patients.
In renal failure (creatinine clearance less than 30 ml / min) or liver failure (10-15 points on the Child-Pugh scale), the initial dose of risperidone should not exceed 0.5 mg twice daily. If necessary, the dose may be increased by 0.5 mg when applied 2 times a day. For doses of 1.5 mg or more, twice a day, it is necessary to increase the interval to 1 week or more.
Transition to risperidone treatment
It is recommended that the previously taken antipsychotic is phased out. If a neuroleptic-depot for parenteral administration has previously been used, the first dose of the drug risperidone should be taken instead of injection in accordance with the regimen of administration of neuroleptic-depot.
With a sharp withdrawal of risperidone, there may be a "cancellation" syndrome (including nausea, insomnia, excessive sweating), so it is recommended to stop the use of the drug gradually.

Side effects:The most frequently observed adverse reactions (incidence rate ≥ 5%) were:
insomnia, anxiety, headache, upper respiratory tract infections, parkinsonism.
Parkinsonism and akathisia are dose-dependent and undesirable reactions.
Classification of the incidence of adverse events according to the recommendations of the World Health Organization (WHO):
very often -> 1/10;
often from> 1/100 to <1/10;
infrequently - from> 1/1000 to <1/100;
rarely - from> 1/10000 to <1/1000;
very rarely - <1/10000, including individual messages;
the frequency is unknown - it is not possible to establish the frequency of occurrence from the available data.
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, infection.
Violations from the blood and lymphatic system:
infrequently - anemia, thrombocytopenia, decreased hematocrit, eosinophilia, leukopenia, neutropenia;
rarely - granulocytopenia, agranulocytosis.
Immune system disorders:
infrequently - hypersensitivity;
rarely - drug hypersensitivity, anaphylactic reaction.
Disorders from the endocrine system:
rarely - a violation of the production of antidiuretic hormone, glucosuria.
Disorders from the metabolism and nutrition:
often - increased appetite, decreased appetite, weight gain;
infrequently - diabetes mellitus, anorexia, polydipsia, hyperglycemia, weight loss;
rarely - hypoglycemia, water intoxication, hyperinsulinemia;
very rarely diabetic ketoacidosis.
Disorders of the psyche:
very often insomnia;
often - anxiety, agitation, sleep disturbances, anxiety;
infrequently - confusion, mania, decreased libido, lethargy, nervousness, nightmares;
rarely - anorgasmia, flattening of affect.
Impaired nervous system:
very often - parkinsonism, headache, drowsiness, sedation;
often - akathisia, dizziness, tremor, dystonia, lethargy, dyskinesia;
infrequent - lack of response to irritants, loss of consciousness, fainting, impaired consciousness, stroke, transient ischemic attack, dysarthria, attention disturbance, hypersomnia, postural dizziness, imbalance, tardive dyskinesia, speech impairment, coordination disorder, hypoesthesia, taste disorder, perversion taste, convulsions, cerebral ischemia, impaired movement, paresthesia, psychomotor hyperactivity; 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;
infrequent - redness of the eyes, visual impairment, discharge from the eyes, edema around the eyes, dry eyes, increased lacrimation, photophobia;
rarely - reduced visual acuity, involuntary sprains of eyeballs, glaucoma, intraoperative syndrome of flabby iris.
Hearing disorders and labyrinthine disturbances:
infrequently - pain in the ear, tinnitus, vertigo.
Heart Disease:
often - tachycardia, arterial, hypertension;
infrequently - atrioventricular blockade, bundle bundle blockage, atrial fibrillation, palpitations, conduction disturbance of the heart, bradycardia;
rarely - sinus bradycardia, sinus arrhythmia.
Vascular disorders:
infrequently - hypotension, orthostatic hypotension, "tides" of blood to the face;
rarely - pulmonary embolism, deep vein thrombosis.
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, congestion in the lungs, impaired breathing, wet wheezing, impaired airway, dysphonia;
rarely - sleep apnea syndrome, hyperventilation.
Disorders from the gastrointestinal tract:
often - vomiting, diarrhea, constipation, nausea, abdominal pain, indigestion, dryness of the oral mucosa, discomfort in the stomach, hypersalivation, toothache;
infrequently - dysphagia, gastritis, fecal incontinence, fecaloma, gastroenteritis, flatulence;
rarely - intestinal obstruction, pancreatitis, edema of the lips, edema of the tongue, cheilitis; very rarely - ileus.
Disorders from the liver and bile ducts:
rarely - jaundice.
Disturbances from the skin and subcutaneous tissues:
often - a rash, erythema;
infrequently - skin lesions, skin disorders, itching, acne, acne, skin discoloration, alopecia, seborrheic dermatitis, dry skin, hyperkeratosis, eczema;
rarely - dandruff, toxicoderma;
very rarely - Quincke's edema.
Disturbances from the musculoskeletal and connective tissue:
often - arthralgia, pain in spney, pain in the limbs, muscle spasms;
infrequently - muscle weakness, myalgia, pain in the neck, swelling of the joints, violation of posture, stiffness in the joints, muscle pain in the chest;
rarely rhabdomyolysis.
Disorders from the kidneys and urinary tract:
often - enuresis;
infrequent - urinary retention, dysuria, urinary incontinence, pollakiuria.
Violations of the genitals and breast:
often - absence of ejaculation;
infrequently - amenorrhea, sexual dysfunction, erectile dysfunction, ejaculation disorder, galactorrhea,
gynecomastia, menstrual cycle disorder, vaginal discharge, mammary discomfort;
rarely - priapism, an increase in mammary glands, a delay in menstruation, roughness, tenderness of the mammary glands.
Pregnancy, postpartum and perinatal conditions:
rarely - the syndrome of "cancellation" in newborns.
General disorders and disorders at the site of administration:
often - pyrexia, fatigue, peripheral edema, generalized edema, asthenia, pain in the chest area, falls;
infrequent - swelling of the face, gait disturbance, poor health, sluggishness, flu-like condition, thirst, discomfort in the chest, chills, general malaise and discomfort;
rarely - hypothermia, withdrawal syndrome, cold extremities.
Laboratory and instrumental data:
often - an increase in the concentration of prolactin, an increase in body weight;
infrequent - prolongation of QT interval on electrocardiogram, ECG deviation, increase in transaminase activity,reducing the number of leukocytes in peripheral blood, elevated body temperature, increase in the number of eosinophils in the peripheral blood, a decrease in hemoglobin concentration, increase of CPK activity, increasing concentrations of cholesterol, increased gamma glutamyl transferase, reduced hematocrit, eosinophilia, leukopenia, neutropenia;
rarely - lowering body temperature, increasing the concentration of triglycerides.
Undesirable reactions due to paliperidone
Paliperidone is an active metabolite of risperidone, therefore it is necessary to take into account the profile of undesirable reactions of these active substances (including forms of preparations for ingestion and injection). In addition to the above reactions, the following undesirable reactions were observed when using preparations containing paliperidone, but they can also develop with risperidone.
Heart Disease:
syndrome of postural orthostatic tachycardia.
Class Effects
Heart Disease
As with the use of other antipsychotics, very rare cases of prolongation of the QT interval were noted in the post-registration period of observation.Other class-effects from the cardiovascular system observed with the use of antipsychotics that extend the QT interval include: ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac arrest, and ventricular tachycardia of the "fever" 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 a placebo-controlled study in patients with schizophrenia, a statistically significant increase in body weight of at least 7% at 6-8 weeks was observed in 18% of patients taking piccpidon 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 it was slightly higher (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 to 16 years, the increase in body weight should be 3-5 kg per year for girls and about 5 kg per year for boys.
Special patient groups
Elderly patients with dementia
Transient ischemic attack 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 unwanted reactions were observed in elderly patients with dementia with a frequency of ≥ 5% and 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 of ≥ 5% and at a frequency at least twice that in other patient populations: drowsiness / sedation, fatigue, headache, increased appetite, vomiting, infection upper respiratory tract, nasal congestion, abdominal pain, dizziness, cough, pyrexia, tremor, diarrhea, enuresis.

Overdose:Symptoms
Drowsiness, sedation, tachycardia, lowering of arterial pressure, extrapyramidal symptoms, depression of consciousness. Rarely, QT interval elongation, convulsions.Bi-directional ventricular tachycardia was noted with the simultaneous administration of an increased dose of risperidone and paroxetine.
In case of an overdose, the possibility of an overdose from taking several drugs should be considered.
Treatment
In case of acute overdose, free airway patency should be ensured to ensure adequate oxygen supply and ventilation, ECG monitoring, symptomatic therapy aimed at maintaining vital body functions, gastric lavage. The appointment of activated charcoal and laxatives should be carried out only if no more than one hour has elapsed since the time of taking the drug.
If there is a marked decrease in blood pressure or a vascular collapse, intravenous infusion solutions and / or sympathomimetic drugs should be administered. When developing extrapyramidal symptoms, anticholinergic drugs are prescribed (for example, trihexyphenidyl). Continuous medical supervision should continue until the symptoms of intoxication disappear completely. There is no specific antidote.

Interaction:Care should be taken when using the drug together Risperidone with drugs that increase the QT interval, such as antiarrhythmic drugs of Class Ia (for example, quinidine, procainamide, disopyramide), class III (for example, amiodarone, sotalol), tricyclic antidepressants (for example, maprotiline), some antihistamine drugs, other antipsychotics, some antimalarial drugs (for example, mefloquine).
Cimetidine and ranitidine increase the bioavailability of risperidone, but have a minimal effect on the concentration of the active antipsychotic fraction.
Risperidone reduces the effectiveness of levodopa and other dopamine agonists. If it is necessary to simultaneously use it, it is recommended to use minimally effective doses of drugs.
Hypotensive drugs increase the severity of lowering blood pressure on the background of risperidone.
Carbamazepine and other inducers of "liver" enzymes (for example, rifampicin, phenytoin, phenobarbital) reduce the concentration of the active fraction of risperidone in plasma.With the appointment and after the withdrawal of carbamazepine, the dose of the drug Risperidone should be adjusted.
With the simultaneous administration of fluoxetine / paroxetine, the concentration of risperidone in the blood plasma decreases, but the level of the antipsychotic fraction increases slightly. It is expected that other CYP2D6 inhibitors, such as quinidine, can reduce the plasma concentration of risperidone.
Verapamil (inhibitor of CYP3A4 and P-glycoprotein) increases the concentration of risperidone in plasma.
Given that risperidone has an effect primarily on the central nervous system, it should be used with caution in combination with other drugs of central action and with alcohol.
With the simultaneous use of risperidone with furosemide in elderly patients with dementia, the risk of death increases.
Simultaneous use of risperidone and paliperidone is not recommended, since the latter is an active metabolite of risperidone, and possibly an increase in the antipsychotic effect.
Phenothiazine antipsychotics, tricyclic antidepressants and some β-blockers, when used with risperidone, may increaseits concentration 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 the active antipsychotic fraction.
There was no clinically significant interaction with simultaneous use of risperidone with lithium preparations, sodium valproate, digoxin, topiramate, selective anticholinesterase inhibitors (for example, galantamine, donepezil), amitriptyline, erythromycin, psychostimulating drugs (eg, methylphenidate).

Special instructions:Transition from therapy with other antipsychotic drugs
At the beginning of treatment with the drug Risperidone it is recommended to gradually abolish previous therapy if it is clinically justified. In this case, if patients are transferred from therapy to depot forms of antipsychotics, then drug therapy Risperidone it is recommended to start instead of the next scheduled injection. Periodically, the need to continue the current therapy with antiparkinsonian drugs should be evaluated.
Use in elderly patients with dementia
In elderly patients with dementia in the treatment of atypical antipsychotics, there is an increased mortality compared with placebo in studies of atypical antipsychotics, including risperidone. When using risperidone for a given population, the incidence of fatalities was 4.0% for patients taking risperidone, compared with 3.1% for placebo. At present, the cause of this risk increase is unknown. The causes of death were different, the main causes were cardiovascular (rhythm disturbances, sudden cardiac death, increased risk of strokes, thromboembolism) and infectious diseases (pneumonia). The average age of the deceased patients is 86 years (range 67-100 years).
For elderly patients with dementia, there was an increased mortality with simultaneous application of furosemide and risperidone (7.3%, mean age 89 years, range 75-97 years) compared with the group taking only risperidone (4.1%, average age 84 years, range 75-96 years) and a group that only took furosemide (3.1%, the average age is 80 years, the range is 67-90 years). There are no pathophysiological mechanisms that explain this observation.Nevertheless, special care should be taken when prescribing the drug in such cases. There was no increase in mortality in patients taking other diuretics simultaneously with risperidone. Regardless of treatment, dehydration is a common risk factor for mortality and should be carefully monitored in elderly patients with dementia.
Cerebrovascular disorders
In elderly patients with dementia in the treatment of atypical antipsychotics, there is an increased risk of cerebrovascular unwanted reactions in randomized placebo-controlled clinical trials. A generalized analysis of the results of six placebo-controlled studies of risperidone, mainly in elderly patients (over 65 years) with dementia, showed that cerebrovascular unwanted reactions (serious and non-serious, combined) occurred in 3.3% (33/1009) of patients who received risperidone and in 1.2% (8/712) of the patients receiving the placebo. The odds ratio is 2.96 (95% confidence interval). The mechanism of this risk has not been studied. Increased risk can not be ruled out for other antipsychotics and other groups of patients. Risperidone should be used with caution in patients with risk factors for stroke.
The risk of developing unwanted cerebrovascular reactions is significantly higher in patients with mixed or vascular dementia than with Alzheimer's dementia. Therefore, patients with mixed or vascular dementia should not be prescribed risperidone. It is necessary to assess the risks and therapeutic benefits of using risperidone in elderly patients with dementia, taking into account the prognostic risk factors for stroke in a particular patient. The patient and his environment should be warned about the urgent need to see a doctor if there are signs of cerebral circulation, such as sudden weakness or numbness in the face, hands or feet, speech or vision impairment. In this case, all therapeutic options are urgently considered, including the discontinuation of risperidone.
A drug Risperidone It should be used only for short-term treatment of persistent aggression in patients with dementia due to Alzheimer's disease, moderate and severe, as an additional method of treatment if the non-pharmacological treatment is ineffective or if there is a potential danger of harming yourself and / or people around you.
During treatment with risperidone, frequent and regular assessment of the patient's condition is necessary to decide whether to continue treatment.
Orthostatic hypotension
In connection with the α-adrenoblocking action of risperidone, there may be a marked decrease in blood pressure (hypotension, including orthostatic), especially during the initial dose selection. Clinically significant reduction in blood pressure is observed with the joint appointment of risperidone with antihypertensive drugs. If there is a decrease in blood pressure, consider lowering the dose. In patients with diseases of the cardiovascular system, as well as during dehydration, hypovolemia or cerebrovascular disorders, the dose should be increased gradually, according to the recommendations.
Elongation of the QT interval
As with other antipsychotics, caution should be exercised in prescribing Risperidone to patients with a history of an arrhythmia, with a congenital QT interval prolongation and when combined with drugs that increase the QT interval. And also with bradycardia or electrolyte disorders (hypokalemia, hypomagnesemia),as this may increase the risk of arrhythmia.
Late dyskinesia and extrapyramidal disorders
The use of drugs that can block dopamine receptors may be accompanied by induction of tardive dyskinesia (involuntary rhythmic movements, mostly of the tongue and / or face). There are reports that the occurrence of extrapyramidal symptoms is a risk factor for tardive dyskinesia. If signs and symptoms of tardive dyskinesia occur, you should consider withdrawing all antipsychotics.
Malignant neuroleptic syndrome
When a malignant neuroleptic syndrome characterized by hyperthermia, muscle rigidity, autonomic instability, altered consciousness and increased activity of creatine phosphokinase (also can be observed myoglobinuria (due to rhabdomyolysis) and acute renal failure), it is necessary to cancel all antipsychotics, including risperidone.
Parkinson's disease and dementia with Levi bodies
When using neuroleptics, including risperidone,in patients with Parkinson's disease or dementia with Levy bodies, the physician should evaluate the benefit / risk ratio. The course of Parkinson's disease with risperidone may worsen. Both groups of patients have a risk of malignant neuroleptic syndrome, as well as increased sensitivity to neuroleptic drugs. Manifestations of hypersensitivity, in addition to extrapyramidal symptoms, may include confusion, dull sensitivity, postural instability with frequent falls.
Threshold of convulsive activity
In patients with low seizure threshold, the drug Risperidone Use with caution, as the risk of seizures increases.
Hyperglycemia and diabetes mellitus
When treating the drug Risperidone possibly the emergence of hyperglycemia, diabetes mellitus or exacerbation of an already existing diabetes mellitus. In rare cases, the development of ketoacidosis and diabetic coma is possible. Family history of diabetes and obesity are predisposing factors to the emergence of hyperglycemia and diabetes.All patients need during the treatment with the drug Risperidone conduct clinical monitoring for the presence of symptoms of hyperglycemia and diabetes, and body weight control.
Regulation of body temperature
With the use of neuroleptic drugs, a violation of the central regulation of body temperature is possible. It is recommended that patients be observed when using risperidone, especially if there are conditions that increase body temperature (for example, physical activity, bath / sauna visits), while using drugs with anticholinergic action or in patients with dehydration.
Antiemetic effect
In preclinical studies, the antiemetic effect of risperidone was identified. This effect, if it occurs in humans, can mask the objective and subjective symptoms of an overdose of some antipsychotics, as well as diseases such as intestinal obstruction, Reye's syndrome and a brain tumor.
Venous thromboembolism
When using antipsychotic drugs, cases of venous thromboembolism have been described.Since patients taking antipsychotics often have a risk of developing venous thromboembolism, all possible risk factors should be identified before and during treatment with the drug Risperidone and preventive measures should be taken.
Hyperprolactinemia
Studies on tissue cultures have shown that the growth of cells in breast tumors can be stimulated by prolactin. Risperidone should be used with caution in patients with hyperprolactinemia and in patients with potentially prolactin-dependent tumors.
Intraoperative syndrome of sagging iris
Intraoperative syndrome of flabby iris (ISDR) was observed during the operative intervention for the presence of cataract in patients receiving therapy with the group of α 1 -adrenoreceptor antagonists.
ISDR increases the risk of complications associated with the organ of vision, during and after an operation. The physician conducting such an operation should be informed in advance that the patient has or is currently taking medications that have α1-adrenoreceptor agonist activity.The potential benefit of the abolition of α1-adrenergic antagonists before surgery is not established, and should be evaluated taking into account the risks associated with the abolition of antipsychotic medications.
During treatment with the drug Risperidone a regular examination of the central nervous system function on extrapyramidal and other movement disorders is recommended.
Priapism
In connection with the blocking effect of risperidone on α-adrenoreceptors, priapism may occur during treatment with the drug.
Leukopenia, neuroepenia, agranulocytosis
When using antipsychotic drugs, incl. Risperidone, there may be leukopenia / neutropenia, as well as agranulocytosis. Therefore, before using the drug Risperidone, especially in patients with risk factors for developing leukopenia / neutropenia, it is necessary to perform a clinical blood test with counting the leukocyte formula. Patients with a clinically significant decrease in the number of leukocytes in the blood or with drug-induced leukopenia / neutropenia should be observed during the first few months of treatment.If a patient exhibits severe neutropenia, a rise in body temperature or other symptoms of infection should be carefully monitored. Patients with severe neutropenia (absolute number of neutrophils less than 1000 /mm³) in the absence of other causes of drug treatment Risperidone it is recommended to stop before the complete recovery of the number of white blood cells.
Drowsiness
Drowsiness is the most common side effect when using risperidone and its expression is dose dependent.
Aspiration pneumonia
When using antipsychotic drugs, incl. risperidone, there was reported a violation of esophageal motility and aspiration.
Aspiration pneumonia is the most common cause of morbidity and mortality in patients with dementia due to Alzheimer's disease. Risperidone should be used with caution in patients at risk of developing aspiration pneumonia.
Weight gain
Due to the fact that the use of the drug Risperidone can lead to a significant increase in body weight, it is necessary to monitor the body weight of patients with drug therapy Risperidone and give recommendations to the patient on the diet during the treatment period. When orthostatic hypotension occurs, especially at the beginning of treatment, the question of reducing the dose of the drug should be considered. In patients with diseases of the cardiovascular system, as well as during dehydration, hypovolemia or cerebrovascular disorders, the dose of the drug should be increased gradually.
With the withdrawal of carbamazepine and other inducers of "liver" enzymes, the dose of risperidone should be reduced.
The withdrawal syndrome
It is recommended to gradually phase out risperidone; After a sharp cessation of treatment with high doses of neuroleptics, the development of the "withdrawal" syndrome is possible.
Symptoms of the "cancellation" syndrome: nausea, vomiting, sweating, insomnia are very rarely described.
Children and teens
Before risperidone will be assigned to a child or adolescent with behavioral disorder, it is necessary to fully assess the causes of aggressive behavior, eliminate pain, social problems. The sedative effect of risperidone should be closely monitored in children and adolescents because of a possible decrease in learning ability.The change in the time of application of risperidone can increase sedation and reduce attention in children and adolescents.
Because of the possible effects of long-term hyperprolactinemia on the growth and sexual maturation of children and adolescents, a regular clinical and laboratory evaluation of the endocrinological status is necessary: height, weight, puberty, menstrual cycle control, and other potential effects of prolactin.

Effect on the ability to drive transp. cf. and fur:During the treatment with risperidone, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:Film-coated tablets, 0.25 mg, 1 mg, 2 mg, 3 mg and 4 mg.

Packaging:5, 10, 15, 20 or 30 tablets in a contour cell box made of a polyvinylchloride film and aluminum foil.
20, 30, 60 or 90 tablets in a can of high-density polyethylene.
4 contour cell packs of 5 tablets, 2, 3, 6 or 9 contiguous cell packs of 10 tablets, 2, 4 or 6 contiguous cell packs of 15 tablets,1 or 3 contourcell packs of 20 tablets, 1, 2 or 3 contourcell packs of 30 tablets or one bank together with instructions for medical use in a pack of cardboard.

Storage conditions:Store in a dark place at a temperature of no higher than 25 ° C.
Keep out of the reach of children.

Shelf life:3 years.
Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002706

Date of registration:13.11.2014

The owner of the registration certificate:VERTEKS, AO VERTEKS, AO Russia

Manufacturer: & nbsp

VERTEKS, AO Russia

Information update date: & nbsp12.10.2015

Illustrated instructions

Instructions

Risperidone (Risperidone)