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

Composition:1 tablet, film-coated, contains:
For a dosage of 1 mg
active substance risperidone - 1 mg
Excipients (core): lactose monohydrate (milk sugar) - 83.0 mg; cellulose microcrystalline - 12.0 mg; starch corn pregelatinized (Starch 1500) - 2.0 mg; magnesium stearate 1.0 mg; potato starch - 7.0 mg; povidone (medium-molecular weight polyvinylpyrrolidone) 4.0 mg.
Shell composition:
Opadrai II 3.0 mg (polyvinyl alcohol,partially hydrolyzed - 1,2000 mg; talcum - 0.4440 mg; macrogol (polyethylene glycol 3350) - 0.6060 mg; titanium dioxide E 171 - 0.7500 mg).
For a dosage of 2 mg
active substance risperidone - 2 mg
Excipients (core): lactose monohydrate (sugar milk) - 82.0 mg; cellulose microcrystalline - 12.0 mg; starch corn pregelatinized (Starch 1500) - 2.0 mg; magnesium stearate 1.0 mg; potato starch - 7.0 mg; povidone (medium-molecular weight polyvinylpyrrolidone) 4.0 mg.
Shell composition:
Opadrai II - 3 mg (polyvinyl alcohol, partially hydrolyzed - 1,2000 mg, talc 0,440 mg, macrogol (polyethylene glycol 3350) - 0.6060 mg, titanium dioxide E 171 - 0.6651 mg, aluminum varnish based on yellow quinoline - 0.0903 mg, aluminum varnish based on yellow sunset sunset - 0.0021 mg, iron oxide oxide (II) yellow E 172 - 0.0009 mg, aluminum lignol based on indigocarmine - 0.0006 mg).
For a dosage of 4 mg
active substance risperidone - 4 mg
Excipients (core): lactose monohydrate (milk sugar) - 114.0 mg; cellulose microcrystalline - 19.7 mg; starch corn pregelatinized (Starch 1500) - 3.0 mg; magnesium stearate 1.0 mg; potato starch - 11.0 mg; povidone (medium molecular weight polyvinylpyrrolidone) 7.3 mg.
Shell composition:
Opadrai II 5 mg (polyvinyl alcohol, partially hydrolyzed 2.2000 mg, talc - 1.0000 mg, macrogol (polyethylene glycol 3350) 0.6175 mg, titanium dioxide E 171 0.6545 mg, soy lecithin E 322 - 0.1750 mg, aluminum lacquer based on yellow quinoline - 0.1010 mg, aluminum varnish based on indigo carmine - 0.2520 mg).

Description:The tablets covered with a film cover of white color, round, biconcave with a risk (a dosage of 1 mg). Tablets on a break of white or almost white color.
The tablets covered with a film cover of yellow color, round, biconcave (a dosage of 2 mg). Tablets on a break of white or almost white color.
The tablets covered with a film cover from light green to green color, round, biconcave (a dosage of 4 mg). Tablets on a break of white or almost white color.

Pharmacotherapeutic group:antipsychotic agent (antipsychotic)

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, has a high affinity for serotonergic 5-HT₂ and dopaminergic D₂-peopters. Risperidone is also associated with α1-adrenergic receptors and, somewhat weaker, with H₁-histaminergic and α₂-adrenergic receptors. Risperidone does not have tropism for cholinergic receptors. Antipsychotic action is due to the blockade D₂dopaminergic receptors of the mesolimbic and mesocortical systems.

Risperidone reduces the productive symptoms of schizophrenia (delirium, hallucinations), aggressiveness, automatism, to a lesser degree induces catalepsy than typical antipsychotics. Balanced central antagonism to serotonin and dopamine may reduce the propensity to extrapyramidal side effects and extend the therapeutic effect of the drug to include negative and affective symptoms of schizophrenia.

Clinical data
Schizophrenia
The efficacy of risperidone in the short-term treatment of schizophrenia was demonstrated in four studies lasting 4 to 8 weeks, in which 2,500 patients meeting the criteria for schizophrenia in the DSM-IV system were included. In a 6-week placebo-controlled study with titration up to a dose of 10 mg / day 2 times a day, risperidone was superior to placebo on a brief psychiatric evaluation scale (BPRS). In a 6-week placebo-controlled study using risperidone in four fixed doses (2, 6, 10 and 16 mg / day, 2 times a day), in the 4th group risperidone was more effective than placebo in the scale of assessment of positive and negative syndromes (PANSS). In an 8-week comparative study of five fixed doses of risperidone (1, 4, 8, 12 and 16 mg / day, 2 times a day), risperidone in groups of 4, 8 and 16 mg / day was more effective than risperidone 1 mg / day on the PANSS scale. In a 4-week, comparative placebo-controlled study of two fixed doses of risperidone (4 and 8 mg / day, once daily), risperidone in both groups was more effective than placebo on several points of the PANSS scale.
Manic episodes with bipolar disorder
The efficacy of risperidone in monotherapy of acute manic episodes in type I bipolar disorder was demonstrated in three double-blind, placebo-controlled trials involving about 820 patients with type I bipolar disorder, according to the DSM-IV scale. In these three studies risperidone in doses of 1-6 mg / day (initial dose of 3 mg in two studies and 2 mg in one study) was statistically superior to placebo at the primary endpoint,that is, by changing the score on the Yang's estimate mania scale (YMRS) in 3 weeks compared to the original one. The results for the secondary endpoints of efficacy are generally consistent with the results for the primary endpoint. The percentage of patients with a> 50% decrease in the YMRS score after 3 weeks compared with baseline was significantly higher for risperidone than for the placebo group.
The efficacy of risperidone, in combination with mood controllers in the treatment of mania, was demonstrated in two three-week, double-blind studies in approximately 300 patients meeting the criteria of bipolar disorder of the first type in the DSM-IV system. In a 3-week study risperidone in doses from 1 to 6 mg / day, the initial dose of 2 mg / day in combination with lithium or valproate was more effective than lithium or valproate only at the end of the study according to the primary given criterion, that is, the change in the sum of points on the YMRS scale compared with the initial in the third week.
Long-term aggression in dementia
The efficacy of risperidone in the treatment of psycho-behavioral symptoms of dementia, including behavioral problems such as aggression, agitation,psychosis, activity and affective disorders were demonstrated in three double-blind, placebo-controlled studies in 1150 patients with moderate and severe dementia. One study was conducted in fixed doses of 0.5, 1 and 2 mg / day. Two studies examined non-fixed doses, including those with risperidone doses of 0.5 to 4 mg / day and 0.5 to 2 mg / day, respectively. Risperidone showed clinically and statistically high efficacy in the treatment of aggression, and, to a lesser extent, excitation and psychosis in elderly patients with dementia (on the BEHAVE-AD behavioral pathology scale and Cogen Mansfield for Citation).
Behavioral disorders
The efficacy of risperidone in short-term treatment of aggressive behavior was demonstrated in placebo-controlled studies in approximately 240 patients aged 5 to 12 years with devastating behavioral disorders in accordance with the DSM-IV system and intellectual functioning below the average or with mild mental retardation or moderate impairment training. In both studies risperidone in doses from 0.02 to 0.06 mg / kg / day was significantly more effective than placebo at a pre-determined primary endpoint of efficacy.

Pharmacokinetics:Risperidone after oral intake is completely absorbed, reaching the maximum concentrations in the plasma after 1-2 hours. Absolute oral bioavailability of risperidone is 70%.
Food does not affect the absorption of risperidone, so it can be administered regardless of food intake.
Risperidone is rapidly distributed in the body. The volume of distribution is 1-2 l / kg. In the plasma risperidone binds to albumin and alpha-1-acid glycoprotein.
Risperidone is 90% bound by plasma proteins, 9-hydroxyrisperidone - by 77%.
The equilibrium concentration of risperidone in the body in most patients is reached within 1 day. The equilibrium concentration of 9-hydroxyrisperidone is reached after 4-5 days. The concentrations of risperidone in plasma are proportional to the dose of the drug (within therapeutic doses).
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. Metabolism depends on the genetic polymorphism of the isoenzyme CYP2D6.
Another way of metabolizing risperidone is N-dealkylation.
After oral administration in patients with psychosis risperidone is excreted from the body with a half-life (T 1/2) of 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 excreted in the urine, 14% - with feces. In the urine risperidone plus 9-hydroxyrisperidone constitute 35-45% of the dose. The rest is made up of inactive metabolites.
Special patient groups
The study of a single dose of the drug revealed a higher concentration in the plasma and a slower elimination in the elderly and in patients with renal insufficiency. The concentrations of risperidone in plasma in patients with hepatic insufficiency were normal. The pharmacokinetics of risperidone and 9-hydroxyrisperidone in children are similar to pharmacokinetics in adult patients. There is no influence of sex, nationality or smoking on the pharmacokinetics of risperidone.

Indications:Treatment of schizophrenia.
Treatment of manic episodes in the structure of bipolar disorder of moderate and severe severity.
Short-term (up to 6 weeks) treatment of persistent aggression in patients with dementia due to Alzheimer's disease of medium and severe degree - with ineffectiveness of non-pharmacological methods of correction and the threat of harm to the patient or others. Short-term (up to 6 weeks) symptomatic treatment of persistent aggression in behavioral disorders in children 5-16 years of age with moderate and severe mental retardation, due to the severity of which pharmacological correction methods are required (as part of complex therapy).

Contraindications:- Individual hypersensitivity to risperidone or any other ingredient of this drug;
- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
- in the treatment of persistent aggression in behavioral disorder in children with mental retardation of moderate to severe degree, children under 5 years of age (experience is insufficient);
- for other indications, children under 18 years of age.

Carefully:Use with caution under the following conditions:
- 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 and epilepsy (including in the anamnesis);
- severe renal or hepatic insufficiency (see section "Method of administration and dose");
- Drug abuse or drug dependence (see section "Method of administration and dose");
- conditions predisposing to the development of tachycardia such as "pirouette" (bradycardia, electrolyte imbalance, concomitant medication prolonging 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);
- pregnancy and lactation.

Pregnancy and lactation:There are no data on the safety of risperidone in pregnant women. In animal experiments risperidone did not have a direct toxic effect on the reproductive system, but caused some indirect effects mediated through prolactin and the central nervous system. None of the studies risperidone did not possess a teratogenic effect. In the case of a woman taking antipsychotic drugs (including Risperidone) in the third trimester of pregnancy, neonates have a risk of extrapyramidal disorders and / or withdrawal syndrome of varying severity. These symptoms may include agitation, hypertension, hypotension, tremor, drowsiness, respiratory disorders, and breast-feeding disorders.
A drug Risperidone can be used during pregnancy only in those cases where the potential benefit for a woman outweighs the possible risk to the fetus.
Because the risperidone and 9-hydroxyrisperidone penetrate into breast milk, to women using Risperidone, do not breast-feed.

Dosing and Administration:

Inside, regardless of food intake.

1. Schizophrenia

Adults. Risperidone may be given once or twice a day. Initial dose of the drug Risperidone - 2 mg per day. On the second day, the dose should be increased to 4 mg per day. From this moment, the dose can either be keep at the same level, or individually adjust if necessary. Usually, the optimal dose is 4 to 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.

Elderly patients. Recommended initial dose of 0.5 mg per reception twice a day. The dose can be individually increased by 0.5 mg twice a day to a dose of 1 to 2 mg twice a day.
Children
Information on the use of the drug for the treatment of schizophrenia in children under 18 years is absent.
2. Manic episodes in the structure of bipolar disorder of moderate and severe severity
Adults. The recommended initial dose of the drug is 2 mg per day at a time. If necessary, this dose can be increased at least 24 hours per 1 mg per day. For most patients, the optimal dose is from 1 -6 mg per day.
Elderly patients. Recommended initial dose of 0.5 mg per reception twice a day. If necessary, the dose can individually be increased by 0.5 mg twice a day to a dose of 1 to 2 mg twice a day. Care should be taken when prescribing elderly patients.
Children
Information on the use of the drug for the treatment of manic episodes in the structure of bipolar disorder of moderate and severe degree in children under 18 years is absent.
3. Continuous aggression in patients with dementia due to moderate and severe Alzheimer's disease
Recommended initial dose of 0.25 mg per reception twice a day. If necessary, the dose can be individually increased by 0.25 mg twice a day, not more often than every other day. For most patients, the optimal dose is 0.5 mg twice daily. However, some patients receive 1 mg 2 times a day. Risperidone should not be used for longer than 6 weeks in the treatment of persistent aggression in patients with dementia due to moderate and severe Alzheimer's disease.
4. Continuing aggression in behavioral disorders in children aged 5-16 years with moderate and severe mental retardation
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, not more often than every other day. For most patients, the optimal dose is a dose of 1 mg 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.
Patients weighing less than 50 kg - The recommended initial dose of the drug is 0.25 mg once a day. If necessary, this dose can 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 per day. However, for some patients it is preferable to take 0.25 mg per day, while some require an increase in the dose to 0.75 mg per day.
Prolonged intake of the drug Risperidone in adolescents should be carried out under the constant supervision of a doctor.
A drug Risperidone is not recommended for children under 5 years of age, since there are no data on such violations in children under the age of 5 years.
Renal and hepatic impairment
In patients with kidney disease, the ability to excrete the active antipsychotic fraction is reduced compared to other patients. In patients with liver disease, there is an increased concentration of free fraction of risperidone in the blood plasma.
The initial and maintenance dose in accordance with the indications should be reduced 2 times, increasing the dose in patients with liver and kidney disease should be slower.
Risperidone should be administered with caution in this category of patients.

Side effects:

Side effects of the drug Risperidone in therapeutic doses are given with a frequency distribution and system-organ classes. The frequency of side effects was classified as follows: very frequent (≥1 / 10 cases), frequent (≥1 / 100 and <1/10 cases), infrequent (≥ 1/1000 and <1/100 cases), rare (≥1 / 10000 and <1/1000 cases) and very rare (<1/10000 cases).

Infections:

very often - in elderly patients with dementia - urinary tract infections;

often - nasopharyngitis, upper respiratory tract infection, bronchitis, sinusitis, urinary tract infections, rhinitis, influenza-like diseases; in elderly patients with dementia - pneumonia, phlegmon;

infrequently - ear infections, viral infections, tonsillitis, eye infections, localized infections, cystitis, onychomycosis, acrodermatitis, respiratory tract infections.

Hematologic disorders and disorders of the lymphatic system:

infrequently - thrombocytopenia, anemia, neutropenia, leukopenia, decreased hematocrit;

rarely - granulocytopenia, agranulocytosis.

From the immune system:

infrequently - hypersensitivity;

very rarely - anaphylactic reactions, anaphylactic shock.

From the endocrine system:

often - hyperprolactinemia;

rarely - a violation of the secretion of antidiuretic hormone, a diabetic coma.

Metabolic and nutritional disorders:

often - increased appetite, in elderly patients with dementia - decreased appetite;

infrequently - polydipsia, anorexia, diabetes mellitus; rarely - hypoglycemia, water intoxication;

very rarely diabetic ketoacidosis.

Mental disorders:

very often insomnia;

often - anxiety, sleep disorders, nervousness, lethargy, in elderly patients with dementia - confusion;

infrequent - flattening of affect, mania, weakening of libido, depression, nightmares;

very rarely - anorgasmia.

From the nervous system:

very often - Parkinsonism (hypersalivation, cogwheel syndrome, akinesia, bradykinesia, hypokinesia, musculoskeletal rigidity, masculine face), drowsiness, headaches, sedation, dizziness;

often akathisia (including anxiety), tremors, dystonia (including muscle spasms, involuntary muscle contractions, muscle contractions, involuntary movements of the eyeballs, paralysis of the tongue), lethargy, postural dizziness,dyskinesia (including muscle twitching, chorea and choreoathetosis), dysarthria, salivation, attention impairment, gait disturbance, increased drowsiness; in elderly patients with dementia - depressed state, drooling, cerebrovascular disorders;

infrequent - lack of response to irritants, impaired coordination of movements, loss of consciousness, fainting, speech disorders, hypesthesia, parestenesis, psychomotor hyperactivity, tardive dyskinesia, cerebrovascular disorders;

rarely - malignant neuroleptic syndrome, extrapyramidal symptoms (tremor, rigidity, hypersalivation, bradykinesia, akathisia, acute dystonia), rhythmic nodding.

Ophthalmic disorders:

often - reduced visual acuity, in elderly patients with dementia - conjunctivitis;

infrequent congestion of the conjunctiva, involuntary sprains of the eyeballs, crust formation at the edges of the eyelids, dry eyes, increased lacrimation, photophobia, increased intraocular pressure.

From the ear and the labyrinth:

infrequently - a noise in the ears, pain in the ear, vertigo, chronic otitis media.

From the side of the cardiovascular system:

often - tachycardia, orthostatic hypotension, lowering of arterial pressure, palpitation, in elderly patients with dementia - transient ischemic attack;

infrequent - bradycardia, sinus arrhythmia, atrial fibrillation, atrioventricular blockade, "hot flashes" of blood, impaired conduction of the heart muscle;

very rarely - deep vein thrombosis, pulmonary embolism, venous thromboembolism.

Respiratory, Thoracic disorders and disorders of the mediastinum:

often - nasal congestion, shortness of breath, nosebleed, nasal congestion, cough, rhinorrhea, pain in the larynx and pharynx, stagnation in the lungs, in elderly patients with dementia - cough, rhinorrhea; infrequently - wheezing, aspiration pneumonia, dysphonia, blockage of the respiratory tract, wet wheezing, respiratory failure; rarely - sleep apnea syndrome, hyperventilation.

From the gastrointestinal tract:

often - nausea, constipation, indigestion, vomiting, diarrhea, drooling, dry mouth, stomach discomfort, abdominal pain, elderly patients with dementia - dysphagia, fecaloma;

infrequently - fecal incontinence, flatulence, gastroenteritis, toothache, edema of the tongue, cheilitis, dysgeusia;

very rarely - intestinal obstruction, pancreatitis.

Hepatobiliary disorders:

rarely - jaundice.

From the skin and subcutaneous tissues:

often - rash, itching, acne, in elderly patients with dementia - erythema;

infrequently - eczema, dry skin, seborrheic dermatitis, hyperkeratosis, skin pigmentation disorder, skin inflammation, skin damage, Quincke's edema, alopecia;

rarely - dandruff.

From the osteomuscular system and connective tissue:

often - musculoskeletal pain, back pain, arthralgia, pain in the extremities, myalgia, neck pain, in elderly patients with dementia -

gait disorders, swelling of the joints;

infrequent - stiffness in the joints, muscle weakness;

rarely rhabdomyolysis.

From the side of the kidneys and urinary tracts:

often - urinary incontinence, enuresis, pollakiuria; infrequent - the delay of urination, dysuria.

On the part of the reproductive system and mammary glands:

often - absence of ejaculation, galactorrhea;

infrequent - menstruation, amenorrhea, gynecomastia, vaginal discharge, erectile dysfunction, ejaculation, breast enlargement, sexual dysfunction, discharge from the breast;

very rarely - priapism.

Influence on the course of pregnancy, postpartum and perinatal conditions:

very rarely - withdrawal syndrome in newborns.

Common violations:

often - fatigue, asthenia, fever, pain in the chest, weight gain, sluggishness, in elderly patients with dementia - peripheral edema, gait disturbance, mild edema; infrequently - thirst, lowering of temperature, malaise, edema of the face, chills; rarely - hypothermia, withdrawal syndrome, cold extremities.

Violations of laboratory and instrumental indicators:

often - more frequent cardiac rhythm, in elderly patients with dementia - increased body temperature;

infrequent increase in the number of eosinophils in the blood, an increase in the activity of creatine phosphokinase, a decrease in the number of leukocytes in the blood, an increase in the activity of liver enzymes, an increase in the activity of gamma-glutamyltransferase, a decrease in hematocrit, an increase in the activity of transaminases, an increase in the concentration of blood cholesterol, an increase in the concentration of triglycerides in the blood, granulocytopenia, hyperglycemia, weight loss, lengthening of the interval QT on an electrocardiogram, change on a cardiogram.

Class Effects

In post-marketing studies of risperidone, very rare cases of lengthening of the interval QT. In addition, effects such as ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac arrest, flutter and flicker were noted.

Venous thromboembolism

With the use of neuroleptics, cases of venous thromboembolism, including cases of pulmonary embolism, as well as deep vein thrombosis (the frequency is unknown) have been documented.

Weight gain

In a 6-8-week, placebo-controlled study in adults with schizophrenia with risperidone and placebo, a clinically significant increase in body weight of 7% or more was observed in the risperidone group (18%), higher than in the placebo group (9% ). In a 3-week placebo-controlled study in adults with acute mania, an increase in body weight of 7% or more at the end of the study was adequate in the risperidone group (2.5%) and placebo (2.4%) and slightly more the control group (3.5%).

In children and adolescents with antisocial manifestations and other behavioral disorders in long-term studies, the average body weight increased by 7.3 kg after 12 months of treatment.The expected increase in body weight in healthy children aged 5-12 years is between 3 and 5 kg per year. Girls 12-16 years old add 3 to 5 kg per year, and boys about 5 kg per year.

Elderly patients with dementia

Side effects in elderly patients with dementia in clinical trials were: transient ischemic attack, stroke; urinary tract infections, peripheral edema, drowsiness, cough.

Children

Types of adverse reactions in children are similar to those observed in adult patients.

The following adverse events were recorded at a frequency of 5% in children (5 to 17 years of age) and at least twice the frequency observed in adult clinical trials: drowsiness, sedation, fatigue, headache, increased appetite, vomiting, upper respiratory tract infections, nasal congestion, abdominal pain, dizziness, cough, fever, tremor, diarrhea and enuresis.

With long-term treatment with risperidone, the effect on puberty has not been studied.

Overdose:

Symptoms: drowsiness, sedation, tachycardia, lowering of arterial pressure, extrapyramidal symptoms. The lengthening of the interval QT and convulsions. Bi-directional ventricular tachycardia was noted in the joint intake 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. It is necessary to achieve and maintain a free airway to ensure adequate oxygen delivery and ventilation, gastric lavage (after intubation if the patient is unconscious) and appoint Activated carbon together with a laxative. Immediately begin monitoring the ECG to identify possible arrhythmias.

Specific antidote does not exist, appropriate symptomatic therapy should be conducted. Reduction of blood pressure and collapse should be eliminated by intravenous fluid infusions and / or sympathomimetic drugs. In case of development of acute extrapyramidal symptoms, m-holinoblokatory (for example, trihexyphenidyl). Continuous medical surveillance and monitoring should continue until the symptoms of intoxication disappear.

Interaction:

Given that Risperidone has an effect primarily on the central nervous system, it should be used with caution with alcohol, opiates, antihistamines and benzodiazepines because of the increased risk of sedation.

Risperidone reduces the effectiveness of levodopa and other dopamine receptor agonists. However, if simultaneous use is necessary, especially at the terminal stage of Parkinson's disease, the minimum effective dose of each treatment should be prescribed. Care should be taken when using the drug together Risperidone with drugs that increase the interval QT, for example, with antiarrhythmic drugs of class Ibut (for example, quinidine, disopyramide, procainamide), antiarrhythmic drugs of class III (for example, amiodarone, sotalol), tricyclic antidepressants (amitriptyline), tetracyclic antidepressants (maprotiline), some antihistamines, other antipsychotics, some antimalarial drugs (quinine and mefloquine), and some drugs that cause electrolyte disorders (hypokalemia, hypomagnesemia), bradycardia, or suppressing the hepatic metabolism of risperidone.

Clozapine reduces the clearance of risperidone.

When carbamazepine was used, a decrease in the concentration of the active antipsychotic fraction of risperidone in plasma was noted. Similar effects can be observed with the use of other isoenzyme inducers CYP3A4 and P-glycoprotein. With the appointment and after the withdrawal of carbamazepine or other inducers of the isoenzyme CYRPA4 / P-glycoprotein should adjust the dose of the drug Risperidone.

Fluoxetine and paroxetine, inhibitors of isoenzyme CYP2D6, increase the concentration of risperidone in plasma, but to a lesser extent the concentration of the active antipsychotic fraction. When the appointment and after the abolition of fluoxetine or paroxetine should adjust the dose of the drug Risperidone. Other inhibitors of isoenzyme CYP2D6, such as quinidine, can change the concentration of risperidone in plasma in the same way. Verapamil, inhibitor of isoenzyme CYP3A4 and P-glycoprotein, increases the concentration of risperidone in plasma.

Topiramate moderately reduces the bioavailability of risperidone, but not the active antipsychotic fraction. This interaction is not considered clinically significant. Phenothiazine derivatives, tricyclic antidepressants and some (β- adrenoblockers may increase plasma concentrations of risperidone, 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. Cimetidine and ranitidine increase the bioavailability of risperidone, but have a minimal effect on the concentration of the active antipsychotic fraction. Erythromycin, inhibitor of isoenzyme CYP3A4, does not affect the pharmacokinetics of risperidone and the active antipsychotic fraction. Cholinesterase inhibitors (galantamine and donepezil), do not have a clinically significant effect on the pharmacokinetics of risperidone and the active antipsychotic fraction.

When using the drug Risperidone together with other drugs, highly binding to plasma proteins, there is no clinically pronounced displacement of any drug from the plasma protein fraction.

Hypotensive drugs increase the degree of reduction in blood pressure in the background of risperidone.

Risperidone does not have a clinically significant effect on the pharmacokinetics of lithium, valproic acid, digoxin or topiramate.Eating does not affect the absorption of risperidone.

Special instructions:

Transition from therapy with other antipsychotic drugs. At a schizophrenia at the beginning of treatment by a preparation Risperidone it is recommended to gradually cancel the previous therapy, if it is clinically justified. In this case, if patients are transferred from depot therapy to forms of antipsychotics, then drug therapy Risperidone it is recommended to start instead of the next scheduled injection. Periodically, the need to continue 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. The average age of the deceased patients is 86 years (range 67-100 years).

For elderly patients with dementia who take oral forms of risperidone, there was an increased mortality in patients taking furosemide and risperidone (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). 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 patients with dementia treated with atypical antipsychotics, there is an approximately 3-fold increase in the 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,that cerebrovascular unwanted reactions (serious and non-serious, combined) appeared in 3.3% (33/1009) 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 in patients 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 report symptoms and signs of potential cerebrovascular unwanted reactions, in particular about sudden weakness or numbness of the face, upper and lower extremities, speech or vision impairment.In this case, all therapeutic options are urgently considered, including the discontinuation of risperidone.

With persistent aggression in patients with Alzheimer's dementia risperidone is intended only for short-term use as an adjunct to non-pharmacological interventions if they are ineffective or limited in the absence of potential danger to the patient or his environment. Need constant monitoring and assessment of the patient's condition, as well as the rationale for the need for further treatment.

Orthostatic hypotension. In connection with αthe blocking action of risperidone may cause orthostatic hypotension, especially during the initial dose selection. Clinically significant reduction in blood pressure is observed with the joint appointment of risperidone with antihypertensive drugs. With a decrease in blood pressure should consider reducing 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 recommendations.

Leukopenia, neutropenia, agranulocytosis

Leukopenia, neutropenia and agranulocytosis were observed when applying antipsychotics, including when using the drug Risperidone. Agranulocytosis was very rare during postmarketing observations. Patients with clinically significant decrease in the number of leukocytes in the preparation or history-dependent leukopenia / neutropenia holding CBC recommended during the first months of therapy, discontinuation of drug treatment Risperidone should be considered at the first clinically significant decrease in the number of leukocytes in the absence of other possible causes. Patients with clinically significant neutropenia recommended monitored for temperature increase or the occurrence of the symptoms of infection and begin treatment immediately in the event of such symptoms. Patients with severe neutropenia (absolute number of neutrophils less than 1 x 10⁹/ l) should stop using the drug Risperidone until the number of leukocytes is normalized.

Venous thromboembolism

When using antipsychotic drugs, cases of venous thromboembolism were noted.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.

Late dyskinesia and extrapyramidal disorders

Drugs that have the properties of dopamine receptor antagonists can cause tardive dyskinesia, which is characterized by rhythmic involuntary movements, predominantly of the tongue and / or facial musculature. There are reports that the occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. Risperidone rarely causes the appearance of extrapyramidal symptoms than classical neuroleptics. If signs and symptoms of tardive dyskinesia occur, you should consider withdrawing all antipsychotics.

Malignant neuroleptic syndrome

In the case of malignant neuroleptic syndrome characterized by hyperthermia, muscle rigidity, instability of autonomic functions,impaired consciousness and increased activity of creatine phosphokinase (also can be observed myoglobinuria (rhabdomyolysis) and acute renal failure), it is necessary to cancel all antipsychotic drugs, including Risperidone.

Parkinson's disease and dementia with Levi bodies

The use of antipsychotics, including RisperidonePatients with Parkinson's disease or dementia with Levy bodies should be treated with caution, since in both groups of patients, the risk of malignant neuroleptic syndrome increased and sensitivity to antipsychotic drugs increased (including blunting of pain sensitivity, confusion, postural instability with frequent falls and extrapyramidal symptoms).

Hyperglycemia and diabetes mellitus

When treating the drug Risperidone hyperglycemia, development of diabetes mellitus and exacerbation of existing diabetes mellitus. Establishing the relationship between the use of atypical antipsychotics and impaired glucose metabolism is complicated by an increased risk of developing diabetes in patients with schizophrenia and the prevalence of diabetes mellitus in the general population.Given these factors, the relationship between the use of atypical antipsychotics and the development of side effects associated with hyperglycemia has not been fully established. In all patients, it is necessary to conduct clinical monitoring for the presence of symptoms of hyperglycemia and diabetes mellitus, (see section "Side effect").

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.

Weight gain

When treating the drug Risperidone a significant increase in body weight was observed. It is necessary to monitor the body weight of patients with drug therapy Risperidone.

Elongation QT interval

As with other antipsychotics, caution should be exercised when prescribing the drug Risperidone patients with a history of cardiac arrhythmias, patients with congenital lengthening of the interval QT and when combined with drugs that increase the interval QT.

Priapism

Drugs that have alpha-adrenergic blocking effects can cause priapism. In post-marketing studies of the drug Risperidone were reported on the development of priapism.

Regulation of body temperature

Antipsychotic drugs attributed to such an undesirable effect as a violation of the body's ability to regulate body temperature. Care should be taken when prescribing the drug Risperidone patients with conditions that can contribute to an increase in internal body temperature, which include intense physical activity, dehydration, exposure to high external temperatures, or simultaneous use of drugs with anticholinergic activity.

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 certain drugs, as well as diseases such as intestinal obstruction, Reye's syndrome and brain tumors.

Threshold of convulsive activity

The ability of typical neuroleptics to lower the threshold of convulsive activity is known.It should be used with caution Risperidone patients with epilepsy.

The withdrawal syndrome

When discontinuing treatment, a gradual dose reduction is recommended. Symptoms of withdrawal: very rarely described nausea, vomiting, sweating and insomnia with a sudden discontinuation of high doses of antipsychotic drugs.

Children and teens

It is necessary to carefully monitor the sedative effect of risperidone, possibly changing the time of taking the drug Risperidone.

It is necessary to control body weight. A regular evaluation of the endocrine function, extrapyramidal symptoms, and movement disorders is required.

Effect on the ability to drive transp. cf. and fur:

Risperidone can have an impact on activities that require a quick reaction: patients should be advised not to drive a car and do not work with the equipment until they find out their individual sensitivity to the drug.

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

Packaging:10 tablets per contour cell pack.
For 30 or 100 tablets in a can of polymer or a bottle of polymer.
For 2, 3 contour mesh packages, jar or bottle together with the instruction for use are placed in a cardboard box.

Storage conditions:In a dry, the 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 the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002328

Date of registration:13.12.2013

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Information update date: & nbsp13.10.2015

Illustrated instructions

Instructions

Risperidone (Risperidone)