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

Excipients: lactose monohydrate 36.5 mg, pregelatinized starch 9.0 mg, microcrystalline cellulose 50.0 mg, sodium lauryl sulfate 1.5 mg, silicon colloidal 1.0 mg, magnesium stearate 1.0 mg, opadrai white 20Н 58983 - 2,500 mg (hypromellose - 1,540 mg, titanium dioxide - 0,370 mg, propylene glycol - 0,308 mg, giprolose - 0,154 mg, talc - 0,128 mg).

Tablets, film-coated, 2 mg:

Each film-coated tablet contains Active substance: risperidone 2.0 mg.

Excipients: lactose monohydrate - 73.0 mg pregelatinized starch - 18.0 mg Microcrystalline cellulose - 100.0 mg Sodium lauryl sulfate - 3.0 mg Colloidal silicon dioxide - 2.0 mg magnesium stearate - 2.0 mg Opadry orange II 31G 53291 - 5,000 mg (Hypromellose - 1,700 mg lactose monohydrate - 1.200 mg of titanium dioxide - 1.176 mg macrogol 4000 - 0.450 mg of macrogol-400 - 0,250 mg, sunset yellow dye - 0.024 mg).

Tablets, film-coated, 3 mg:

Each film-coated tablet contains Active substance: risperidone 3.0 mg.

Excipients: lactose monohydrate - 109.5 mg pregelatinized starch - 27.0 mg Microcrystalline cellulose - 150.0 mg Sodium lauryl sulfate - 4.5 mg Colloidal silicon dioxide - 3.0 mg magnesium stearate - 3.0 mg Opadry yellow II 31G 52408 - 7,500 mg (Hypromellose - 2,550 mg lactose monohydrate - 1.800 mg of titanium dioxide - 1.620 mg macrogol 4000 - 0.675 mg of macrogol-400 - 0,300 mg, quinoline yellow dye - 0,180 mg talc - 0.375 mg).

Pills, coated with a film coating, 4 mg:

Each film-coated tablet contains Active substance: risperidone 4.0 mg.

Excipients: lactose monohydrate 146.0 mg, pregelatinized starch 36.0 mg, microcrystalline cellulose 200.0 mg, sodium lauryl sulfate 6.0 mg, silicon colloidal 4.0 mg, magnesium stearate 4.0 mg, opadrai green II 31G 51195 - 10,00 mg (hypromellose - 3,400 mg, lactose monohydrate 2,400 mg, titanium dioxide 2,058 mg, macrogol-4000 0.900 mg, macrogol-400 0.400 mg, quinoline yellow color 0.228 mg, talc 0.500 mg, indigo carmine - 0.060 mg).

Description:

Tablets, film-coated, 1 mg

Pills capsular Forms covered with a film shell of white color, with separating risk from both sides of the tablet and engraving "RSN" and "1" on one side of the pill on both sides of the separation hazard. Type of tablets at break: homogeneous pressed mass from white to almost white.

Tablets, film-coated, 2 mg

Capsule-shaped capsules coated with a film-colored light orange color, with a separation risk from both sides of the tablet and engraved "RSN" and "2" on one side of the pill on either side of the separation hazard. Type of tablets at break: homogeneous pressed mass from white to almost white.

Tablets, film-coated, 3 mg

Pills capsular Forms covered with a film coating of yellow color, with separating risk from both sides of the tablet and engraving "RSN" and "3" on one side of the pill on both sides of the separation hazard. Type of tablets at break: homogeneous pressed mass from white to almost white.

Tablets, film-coated, 4 mg

Capsule-shaped capsules coated with a filmy coat of light green color, with a dividing risk from both sides of the tablet and engraving "RSN" and "4" on one side of the pill on either side of the separation hazard. Type of tablets at break: homogeneous pressed mass from white to almost white.

Pharmacotherapeutic group:antipsychotic agent (antipsychotic).

ATX: & nbsp

N.05.A.X Other antipsychotics

N.05.A.X.08 Risperidone

Pharmacodynamics:

An antipsychotic agent (neuroleptic), a benzisoxazole derivative. Has a high affinity for 5-HT₂serotonin and D₂dopamine receptors. Communicates with α₁-adrenoceptors and, with a slightly less affinity, with H₁-histamine and α₂-adrenoceptors. Has no affinity for cholinergic receptors. Although risperidone is a powerful blocker D₂dopamine receptors (which is believed to be the main mechanism for reducing the productive symptoms of schizophrenia), it causes less pronounced inhibition of motor activity and to a lesser degree induces catalepsy than typical neuroleptics. A balanced central antagonism to serotonin and dopamine can reduce the propensity to extrapyramidal side effects and extend the therapeutic effect of the drug to cover the negative and affective symptoms of schizophrenia. Risperidone can induce a dose-dependent increase in prolactin concentration in the blood plasma. Risperidone has a sedative and hypothermic effect.

Pharmacokinetics:

After oral administration risperidone completely absorbed from the gastrointestinal tract, the maximum concentration in the blood plasma is achieved within 1-2 hours. Food has no effect on the absorption of risperidone. Absolute bioavailability of risperidone after oral administration 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.

The equilibrium concentration of risperidone in the body in most patients is reached within 1 day. The equilibrium concentration of 9-hydroxyrisperidone is reached within 4-5 days. The concentration of risperidone in the blood plasma is proportional to the dose (in the range of therapeutic doses).

Risperidone is rapidly distributed in the body, the volume of distribution is 1-2 l / kg. In the plasma risperidone binds to albumin and α₁acid glycoprotein. The binding of risperidone to plasma proteins is 90%, 9-hydroxyrisperidone - 77%.

Risperidone is metabolized in the liver with the participation of the isoenzyme CYP2D6 system of cytochrome P450 with the formation of 9-hydroxyrisperidone, which has a similar pharmacological action to risperidone. The active antipsychotic effect is due to the pharmacological activity of risperidone and 9-hydroxyrisperidone. Isozyme CYP2D6 is subject to genetic polymorphism. In patients with high isoenzyme activity CYP2D6 risperidone is rapidly converted to 9-hydroxyrisperidone, while in patients with low isoenzyme activity CYP2D6 this transformation is much slower.Although patients with high isoenzyme activity CYP2D6 have a lower concentration of risperidone and a higher concentration of 9-hydroxyrisperidone than patients with low isoenzyme activity CYP2D6, the total pharmacokinetics of risperidone and 9-hydroxyrisperidone (the active antipsychotic fraction) after receiving one or more doses in these patient groups is almost the same. Another way of metabolizing risperidone is N-dealkylation. Research in vitro on microsomes of the human liver showed that risperidone in clinically significant concentrations, in general, does not inhibit the metabolism of drugs that undergo biotransformation with P450 isoenzymes, including CYP1A2, CYP2A6, CYP2C8/9/10, CYP2D6, CYP2E1, CYP3A4 and CYP3A5.

After oral administration in patients with psychoses, the half-life of risperidone is 3 hours. The half-life of the active antipsychotic fractionrisperidone and 9-hydroxyrisperidone) is 24 hours.

After 1 week of admission, 70% is excreted by the kidneys, 14% is excreted by the intestine. In urine, the total content of risperidone and 9-hydroxyrisperidone is 35-45% of the dose. The remaining amount falls on inactive metabolites.

With a single dose of risperidone in elderly patients, the concentration of the active antipsychotic fraction in the blood plasma is higher (by 43%), the half-life lasts 38% longer and a slower (longer by 30%) elimination. In patients with renal insufficiency, an increase in plasma concentration and a decrease in the clearance of the active antipsychotic fraction is observed on average by 60%. Hepatic insufficiency in patients taking risperidone, does not affect the concentration of risperidone in the blood plasma.

Children

The pharmacokinetics of risperidone, 9-hydroxyrisperidone and the active antipsychotic fraction in children are comparable to that of adult patients.

Influence of sex, race and 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;

- treatment of manic episodes of moderate to severe severity, due to or associated with bipolar disorders.

Contraindications:

- hypersensitivity to risperidone or other excipients of the drug;

- children's age till 18 years;

- lactation period;

- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

Carefully:

Use with caution in patients with diseases of the cardiovascular system (including heart failure, myocardial infarction, cardiac muscle conduction abnormalities), as well as during dehydration, hypovolemia or cerebrovascular disorders. In this category of patients, the dose should be increased gradually.

Caution should be applied risperidone in patients with Parkinson's disease, since it is theoretically possible the deterioration of the course of the disease.

It should be used with caution in case of convulsions (including anamnesis), severe renal or hepatic insufficiency, drug abuse or drug dependence, in conditions predisposing to the development of tachycardia such as pirouette (bradycardia, electrolyte imbalance, concomitant medication , extending the interval QT on an electrocardiogram (ECG)), with a brain tumor, intestinal obstruction, in old age with dementia, when used in combination with furosemide, with thrombophlebitis,with hyperglycemia, in case of acute drug overdose, with Reye's syndrome (antiemetic effect of risperidone may mask the symptoms of these conditions), during pregnancy.

Risperidone should be used with caution in combination with other drugs of central action.

Pregnancy and lactation:

Use in pregnancy is possible if the expected benefit of therapy for the mother exceeds the potential risk to the fetus, while it should be borne in mind that the abolition of the drug in the case of pregnancy should be done gradually. Risperidone can be used in the third trimester of pregnancy, but it is necessary to take into account the possible risk of developing extrapyramidal disorders in newborns and / or withdrawal syndrome (agitation, muscle hypertension, muscle hypotension, tremor, drowsiness, respiratory distress syndrome, suppression of the sucking reflex).

If it is necessary to use lactation, breastfeeding should be discontinued, since risperidone and 9-hydroxyrisperidone penetrate into breast milk.

Influence on reproductive function

Due to the fact that risperedon can increase the concentration of prolactin in the blood plasma,hyperprolactinemia can inhibit the production of GnRH (gonadotropin-releasing hormone) by 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

The dose may be given once or twice a day. The initial dose of risperidone 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 adjusted 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. Maximum dose: when using risperidone at a dose of more than 10 mg per day, there is no increase in efficacy compared with lower doses, but the risk of developing extrapyramidal symptoms increases. The safety of the use of risperidone in doses greater than 16 mg per day has not been studied, therefore further increase in the dose is not recommended.

Elderly age: in schizophrenia for elderly patients, an initial dose of 0.5 mg twice daily is recommended. If necessary, the dose can be increased to 1-2 mg twice a day. When appointing and correcting the dose of risperidone, elderly patients should be aware that they may be more sensitive to the action of risperidone due to delayed metabolism.

Manic episodes of moderate to severe severity, due to or associated with bipolar disorders

The recommended dose of risperidone is 2 mg once a day. If necessary, the daily dose may be increased no more than 1 mg per day by more than 24 hours. For most patients, the optimal dose is 1-6 mg per day. Safety of doses above 6 mg per day in patients for treatment according to this indication has not been studied. The duration of the use of risperidone in patients for treatment of this indication should be determined and justified in accordance with the current pattern of the disease.

Elderly age: The recommended initial dose of risperidone is 0.5 mg twice daily. If necessary, this dose can be increased to a daily dose of 1-2 mg twice daily.Caution should be exercised when prescribing risperidone to elderly patients for treatment according to this indication, since clinical trials are limited.

Diseases of the liver and kidneys

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. Preparation Rezalen should be administered with caution in this category of patients.

Side effects:

The frequency of a side effect is determined 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: often - urinary tract infections, nasopharyngitis, upper respiratory tract infections, sinusitis, pneumonia, phlegmon; infrequently - ear infections, viral infections,pharyngitis, tonsillitis, eye infections, localized infections, cystitis, onychomycosis, acrodermatitis, bronchopneumonia, respiratory infections, tracheobronchitis.

Hematologic disorders and disorders of the lymphatic system: infrequently - neutropenia, anemia, thrombocytopenia; rarely - granulocytopenia; very rarely - agranulocytosis.

From the immune system: infrequently hypersensitivity; highly rarely anaphylactic shock.

From the endocrine system: infrequently hyperprolactinemia, diabetic coma; rarely - a violation of the production of antidiuretic hormone.

Metabolic and nutritional disorders: often - decreased appetite, increased appetite, increased levels of cholesterol and triglycerides in the blood; infrequently - polydipsia, anorexia; very rarely - diabetic ketoacidosis, diabetes mellitus, hypoglycemia, water intoxication; frequency is not known - weight gain.

Mental disorders: very often insomnia; often - anxiety, nervousness, sleep disturbances, confusion; infrequent - excitation, flattening of affect, weakening of libido, anorgasmia, mania.

From the nervous system: very often - Parkinsonism (including extrapyramidal disorders *, cogwheel syndrome, akinesia, bradykinesia, hypokinesia, muscle rigidity), headache; often akathisia (including restlessness), drowsiness, dizziness, sedation, tremor, dystonia (including muscle spasms, involuntary muscle contractions, muscle contractions, involuntary eyeball movements, tongue paralysis), lethargy, postural dizziness, dyskinesia (including muscle twitching, chorea and choreoathetosis), fainting, depressed condition; infrequent - lack of response to irritants, impaired coordination, loss of consciousness, speech impairment, hypoesthesia; rarely - movement disorders, tardive dyskinesia, cerebral ischemia, cerebrovascular disorders, malignant neuroleptic syndrome.

Ophthalmic disorders: often - violation of visual acuity; infrequently - conjunctivitis, conjunctival hyperemia, visual impairment, eyelid edema, periorbital edema, crust formation on the edges of the eyelids, dry eyes, increased lacrimation, photophobia, increased intraocular pressure, eye pain; rarely - glaucoma, involuntary rotation of eyeballs.

From the ear and the labyrinth: infrequently - pain in the ears, tinnitus; rarely - chronic otitis media.

From the side of the cardiovascular system: often - tachycardia, hypotension / orthostatic hypotension, lowering of arterial pressure, transient ischemic attack, myocardial infarction, stroke; infrequent - bradycardia / sinus bradycardia, sinus tachycardia, palpitations, lengthening of the interval QT on ECG, atrioventricular block, blockage of the right and left legs of the bundle of the Hisnia, atrioventricular blockade, "tides" of blood to the skin of the face; very rarely - atrial fibrillation; when using risperidone with other antipsychotic drugs; very rarely - ventricular tachycardia, ventricular arrhythmia, ventricular fibrillation and flutter, cardiac arrest, sudden death; frequency unknown - embolism and thrombosis of veins, deep vein thrombosis, pulmonary embolism.

Respiratory, thoracic disorders and disorders of the mediastinum: often - stuffy nose, shortness of breath, epistaxis, sinus congestion, cough, rhinorrhea, bronchitis; infrequently - wheezing, aspiration pneumonia, dysphonia, productive cough,obstruction of the respiratory tract, wet wheezing, respiratory failure, edema of the nose, laryngism (stridor); very rarely - sleep apnea syndrome, hyperventilation.

From the gastrointestinal tract: often - nausea, constipation, indigestion, vomiting, diarrhea, hypersecretion of the salivary glands, dryness of the oral mucosa, dyspepsia, abdominal pain, infrequently - dysphagia, fecaloma, encopresis, gastritis; rarely - edema of the lips, cheilitis, hypo secretion of the salivary glands; very rarely - intestinal obstruction, pancreatitis.

Hepatobiliary disorders: very rarely - jaundice.

From the skin and subcutaneous tissues: often - a rash, erythema; infrequent - dry skin, seborrheic dermatitis, hyperkeratosis, skin pigmentation disorder, erythematous rashes, papular rashes, generalized rash, maculopapular rash, alopecia areata; very rarely - Quincke's edema, dandruff.

From the osteomuscular system and connective tissue: often - back pain, arthralgia, pain in the extremities, torticollis; infrequent - abnormalities of gait, swelling of the joints, myalgia, muscle pain in the chest, joint stiffness, muscle weakness; rarely rhabdomyolysis.

From the side of the kidneys and urinary tract: often - urinary incontinence; infrequently - pain when urinating, urinary retention, dysuria, frequent urination.

From the side of the reproductive system and mammary glands: infrequent - menstruation disorder, amenorrhea, galactorrhea, gynecomastia, vaginal discharge, erectile dysfunction, ejaculation, lack of ejaculation, retrograde ejaculation, sexual dysfunction; very rarely - priapism.

Common violations: often - fatigue, asthenia, fever, pain in the chest, peripheral edema; infrequent - thirst, flu-like condition, swelling, poor health, swelling of the face, chills, cold extremities; rarely - hypothermia, general edema, withdrawal syndrome.

Violations of laboratory and instrumental indicators: often - an increase in the activity of creatine phosphokinase, an increase in heart rate, an increase in body temperature; infrequently, an increase in alanine aminotransferase activity, an ECG disorder, an increase in the number of eosinophils in the blood, an increase in the activity of aspartate aminotransferase, an increase / decrease in the number of leukocytes in the blood, an increase in the concentration of glucose in the blood,a decrease in hemoglobin concentration, a decrease in hematocrit, a decrease in blood pressure, an increase in the activity of transaminases; very rarely - interval lengthening QT on the ECG.

Class Effects

Interval lengthening QT on the ECG

When risperidone is used, the lengthening of the interval QT on ECG was observed in the post-marketing period of observation in very rare cases. Due to the lengthening of the interval QT on the ECG against the background of the use of antipsychotic agents, the following side effects from the cardiovascular system were recorded: ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac arrest and polymorphic ventricular pirouette tachycardia.

Venous thromboembolism

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

Weight gain

In 6-8 weeks of placebo-controlled trials in patients with schizophrenia, 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 placebo-controlled clinical trials in adults with acute mania, 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 and adolescents with antisocial manifestations and other 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 the age of 12-16, the increase in body weight was 3-5 kg per year for girls and about 5 kg per year for boys. **

Additional information about specific patient groups

Side effects that have been observed with a greater frequency in elderly patients with dementia and in children than in adult patients are described below:

Older 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 adverse effects were observed in elderly patients with dementia with a frequency of ≥5% and at a frequency at least two times greater than that in other groups of patients: a urinary tract infection, peripheral edema, lethargy, and cough.

Patients of childhood

The following adverse effects were observed in pediatric patients (5 to 17 years) with a frequency of ≥5% and at a frequency at least two times greater than that in other groups of patients in clinical trials: drowsiness / sedation, tiredness, headache , increased appetite, vomiting, upper respiratory tract infection, nasal congestion, abdominal pain, dizziness, cough, fever, tremors, diarrhea, urinary incontinence. **

* Extrapyramidal disorders - a complex of motor disorders of neurological complications. They include parkinsonism (tremor, muscle rigidity, postural instability, bradykinesia), muscle dystonia, tremor (rapid rhythmic movements of limbs or trunk caused by muscle contractions), chorea (irregular irregular jerky movements)athetosis (slow tonic convulsions of limbs, face, trunk), akathisia (a feeling of inner motor restlessness), tics (rapid transient stereotypical violent elementary movements), myoclonus (involuntary short-term reduction of part or all of the muscles), stereotypies (sustainable aimless repetition of moves) .

** Application Rezalen drug in pediatric patients under 18 years is contraindicated due to the inability to ensure adequate dosing regimen.

Overdose:

Symptoms: drowsiness, oppression of consciousness, sedation, tachycardia, lowering of blood pressure (BP), extrapyramidal disorders, rarely - lengthening of the interval QT on an electrocardiogram, convulsions.

Treatment: Provide free airway to ensure adequate oxygen supply and ventilation. During the first hour after washing the stomach overdose carried out (after intubation, if the patient is unconscious) and assignment of activated carbon with laxatives. Immediately begin monitoring the ECG to identify possible arrhythmias and continue it until the symptoms of intoxication disappear completely.There is no specific antidote. It is necessary to carry out symptomatic therapy aimed at maintaining vital body functions. With a decrease in blood pressure and a vascular collapse, intravenously inject infusion solutions and / or α-adrenomimetics. In the case of development of acute extrapyramidal symptoms - the introduction of central m-holinoblokatorov. Continuous medical surveillance and monitoring should continue until the symptoms of intoxication disappear.

When combined overdose with paroxetine, ventricular tachycardia such as pirouette may develop.

Interaction:

With the simultaneous use of inducers of microsomal enzymes of the liver (rifampicin, phenytoin, phenobarbital), a decrease in the concentration of risperidone in the blood plasma is possible.

When used simultaneously with carbamazepine, the concentration of risperidone in the blood plasma is significantly reduced.

With simultaneous use with phenothiazine derivatives, tricyclic antidepressants and β-adrenoblockers, an increase in the concentration of risperidone in the blood plasma, but not an active antipsychotic fraction, is possible. Amitriptyline and erythromycin do not affect the pharmacokinetics of either risperidone or the active antipsychotic fraction. Cimetidine and ranitidine increase the bioavailability of risperidone, but not the active antipsychotic fraction.

The combined use of risperidone with psychostimulants (methylphenidate) in children does not affect the pharmacokinetics of risperidone. *

With simultaneous application risperidone reduces the effects of levodopa and other dopamine receptor agonists.

The use of risperidone with paliperidone is not recommended, as their combined use leads to the potentiation of antipsychotic effects.

When used simultaneously with fluoxetine or paroxetine, an increase in the concentration of risperidone in the blood plasma is possible.

As 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.

Caution should be exercised in the combined use of risperidone with drugs that extend the interval QT on the ECG.

Topiramate, preparations of lithium, valproic acid and digoxin moderately reduce the bioavailability of risperidone, but not the active antipsychotic fraction. This interaction is not considered clinically significant.

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

Verapamil increases the concentration of risperidone in the blood plasma.

Galantamine and donepezil have no clinically significant effect on the pharmacokinetics of risperidone and the active antipsychotic fraction.

When used with furosemide, as well as with other strong diuretics, one should keep in mind the risk of increased mortality (the pathophysiological mechanism is not known).

* Use of the drug Rezalen in patients under 18 years of age is contraindicated because it is impossible to provide an adequate dosage regimen.

Special instructions:

The risk of developing orthostatic hypotension is especially elevated in the initial period of dose selection. If hypotension occurs, consider lowering the dose.

Transition from therapy with other antipsychotic drugs. In schizophrenia, at the beginning of risperidone treatment, it is recommended that the previous therapy be gradually phased out if clinically justified.In this case, if patients are transferred from the therapy of depot forms of antipsychotics, then risperidone therapy should be started instead of the next scheduled injection. Periodically, the need to continue current therapy with antiparkinsonian drugs should be evaluated.

Elderly patients with dementia

The effect of risperidone on elderly patients with dementia has not been studied, therefore, risperidone not shown for this group of patients. Risperidone is not licensed to treat behavioral disorders caused by dementia.

Increased mortality in elderly patients with dementia. In a meta-analysis of 17 controlled studies, an increase in mortality was found in the group receiving atypical antipsychotics (including risperidone for oral administration), compared with the placebo group. Mortality in the group receiving risperidone, was 4.0%, and in the placebo group, 3.1%. The odds ratio (95% accurate confidence interval) was 1.21 (0.7, 2.1). The average age of the deceased patients was 86 years (from 67 to 100 years). Data from two large studies showed that elderly patients,who took standard antipsychotics, also have a slightly increased risk of death compared with a group of patients who did not take standard antipsychotics. To accurately assess the magnitude of the risk, as well as the causes that cause this risk, there is not enough data.

Simultaneous application of furosemide. In a study of placebo-controlled studies of risperidone oral use, a higher mortality rate was observed among patients taking risperidone and furosemide (7.3%, mean age 89 years, 75 to 97 years) compared with patients receiving only risperidone (3.1%, average age 84 years, 70 to 96 years) or only furosemide (4.1%, the average age is 80 years, from 67 to 90 years). Of the four clinical studies conducted, such data were obtained in two studies. When studying the results of simultaneous reception of risperidone with other diuretics (mainly thiazide diuretics in small doses), similar data were not obtained.

A pathophysiological mechanism that could explain such an increase in mortality is not identified. Certain regularities in the causes of death were also not revealed.Nevertheless, care must be taken and the risk and benefit of using a combination of risperidone with strong diuretics should be correlated. Regardless of the treatment, dehydration is a common risk of death, which must be carefully avoided in the treatment of elderly patients with dementia.

Cerebrovascular disorders

Data from a randomized, placebo-controlled clinical trial suggest a threefold increase in the risk of cerebrovascular disorders among patients with dementia who are treated with some atypical antipsychotics. The generalized data from six placebo-controlled studies in predominantly elderly (> 65 years) patients with dementia show the incidence of cerebrovascular disorders of varying degrees of 3.3% (33/1009) in patients treated with risperidone and 1.2% (8/712), who received a placebo. The risk ratio (the exact confidence interval of 95%) was 2.96 (1.34, 7.50). The mechanism of increasing the risk is unknown. Increased risk can not be ruled out for other antipsychotics or for other populations of patients. Risperidone should be used with caution in patients at risk of stroke.

Orthostatic hypotension

In connection with α-adrenoblocking activity of risperidone, orthostatic hypotension may occur, especially at the onset of treatment. Clinically significant hypotension was observed in the postmarketing study with simultaneous use of risperidone with antihypertensive agents. Risperidone should be used with caution in patients with cardiovascular disease (heart failure, myocardial infarction, conduction disorders, dehydration, hypovolemia, or cerebrovascular disease). In patients with clinically significant hypotension, the risk-to-benefit ratio of risperidone should be assessed.

Leukopenia, neutropenia and agranulocytosis

When using antipsychotic drugs, including risperidone, cases of leukopenia, neutropenia and agranulocytosis were observed. Agranulocytosis was very rare (<1 / 100,000 patients) with post-marketing surveillance.

Patients with a clinically significant decrease in the number of blood leukocytes or with drug-induced leukopenia / neutropenia should be observed during the first few months of treatment.At the first signs of a decrease in the number of white blood cells (in the absence of other causes), the question of the abolition of risperidone should be considered.

Patients with a clinically significant decrease in the number of white blood cells should be observed for possible fever or other signs of infection. Patients with severe neutropenia (absolute number of neutrophils less than 1 x 10⁹/ l) require the withdrawal of risperidone and in observation until the recovery of neutrophil count.

Late dyskinesia / extrapyramidal symptoms

Means with the properties of dopamine receptor antagonists can cause tardive dyskinesia characterized by rhythmic involuntary movements, predominantly of the tongue and / or facial muscles. The occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. When the appearance of tardive dyskinesia, it is necessary to cancel all antipsychotics.

Malignant neuroleptic syndrome

Malignant neuroleptic syndrome, whose development is known after taking antipsychotic drugs, is characterized by hyperthermia, muscle stiffness, autonomic nervous system disorder, impaired consciousness and increased activity of creatine phosphate kinase.There may also be myoglobinuria (rhabdomyolysis) and acute renal failure. In this case, all antipsychotics, including risperidone, should be canceled.

Parkinson's disease and dementia with Levi bodies

The physician should carefully weigh the risk-benefit ratio of antipsychotics (including risperidone) in patients with Parkinson's disease or dementia with Levy bodies. Parkinson's disease can be exacerbated by the use of risperidone. Both groups of patients have an increased risk of malignant neuroleptic syndrome, as well as people with increased sensitivity to antipsychotics. These patients were excluded from clinical trials. The manifestation of hypersensitivity to antipsychotics can be manifested by confusion, stunning, postural instability with frequent falls and extrapyramidal symptoms.

Hyperglycemia and diabetes mellitus

There are cases of hyperglycemia, diabetes mellitus and exacerbation of existing diabetes mellitus during treatment with risperidone. In some cases, a primary increase in body weight has been reported,which can be a predisposing factor of these undesirable phenomena. In rare cases, it was reported about ketoacidosis and in very rare cases - about diabetic coma. Patients after taking any atypical antipsychotics, including risperidone, should be observed for possible symptoms of hyperglycemia (polydipsia, polyuria, polyphagia and weakness). Patients with diabetes need constant monitoring of blood glucose.

Weight gain

During the treatment with risperidone, binge eating should be avoided, since there are cases of a significant increase in body weight after its application. Regular weight control is recommended.

Hyperprolactinemia

Cells of the breast tumor are stimulated with prolactin. Although there is no clear connection between the appointment of antipsychotics and the development of breast tumors, it is necessary to prescribe risperidone with caution to patients with initial hyperprolactinemia and patients with a possible prolactin-dependent tumor.

Increase the interval QT

As with other antipsychotics, caution should be exercised in prescribing risperidone to patients with cardiac arrhythmias or previous history, patients with congenital lengthening of the interval QT on ECG and when combined with drugs that extend the interval QT on the ECG.

Infringements of regulation of body temperature

As a result of taking antipsychotic drugs, including risperidone, one should keep in mind the risk of thermoregulation of the body and exercise caution in conditions of heat and dehydration, intense physical activity, and also when taking anticholinergic drugs.

Venous thromboembolism

When using risperidone in patients with risk factors for embolism and venous thrombosis, caution should be taken, as embolism and venous thrombosis are one of the side effects of risperidone with an unknown incidence.

Intraoperative syndrome of trembling iris

This syndrome was observed in operations for cataracts in patients who received drugs that are antagonists α₁_a-adrenergic receptors (including risperidone).

Syndrome of trembling iris can increase the risk of eye complications during and after eye operations. The operating ophthalmologist should be advised of the admission to the patients α₁_a-antagonists. Using α₁-blocks before surgery for cataracts in patients who received α₁_A-antagonists, not studied.

Antiemetic effect

An antiemetic effect was observed in preclinical studies of risperidone. This effect in humans can mask the signs and symptoms of an overdose of certain drugs, as well as symptoms of such conditions as intestinal obstruction, hepatocerebral syndrome or brain tumor.

Patients of childhood

Before appointing risperidone patients in this age group should carefully evaluate the physical (pain) and social (environment) the adequacy of the level of requirements, etc., causes of aggression or other destructive behavior, should be carefully monitored learning ability and concentration of attention of patients in this age group due to sedation effect of risperidone and adjust the recommended time of taking the drug in accordance with the patient's day regimen. Because of this side effect, when taking risperidone as prolactinemia, you should regularly monitor the patient's hormonal status and monitor changes in body weight, height, puberty,regularity of the menstrual cycle and compliance of these indicators with age norms. *

During treatment with risperidone, children should be monitored regularly and regularly checked for extrapyramidal symptoms. * * The use of Resalen in children under 18 years of age is contraindicated because it is impossible to provide an adequate dosing regimen.

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

In the period of treatment, before clarifying individual sensitivity to risperidone, patients should avoid driving motor vehicles and other activities that require high concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 1 mg, 2 mg, 3 mg, 4 mg.

Packaging:

10 tablets in a blister of aluminum foil, coated with a PVC / PVDC film.

2, 3 or 6 blisters with instructions for use in a cardboard bundle.

Storage conditions:

In a dry place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001364

Date of registration:16.12.2011

The owner of the registration certificate:Ranbaxy Laboratories LimitedRanbaxy Laboratories Limited India

Manufacturer: & nbsp

RANBAXY LABORATORIES, Ltd. India

Representation: & nbspRABBAYS LABORATORY LIMITEDRABBAYS LABORATORY LIMITED

Information update date: & nbsp21.10.2015

Illustrated instructions

Instructions

Rezalen (Rezalen)