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

Composition:Dosage 0.5 mg:
One film-coated tablet contains:
active substance: risperidone 0.5 mg;
Excipients: lactose monohydrate 59.5 mg, microcrystalline cellulose 38.75 mg, silicon dioxide colloid 0.5 mg, magnesium stearate 0.75 mg;
composition of the shell: opadray green 03В51373 3,58 mg [hypromellose-6 сР 62,5%, titanium dioxide 26,4%, macrogol 6.25%, dye quinoline yellow 4%, indigocarmine 0,85%].
Dosage 1 mg:
One film-coated tablet contains:
active ingredient: risperidone 1 mg;
Excipients: lactose monohydrate 59 mg, cellulose microcrystalline 38.75 mg, silicon dioxide colloid 0.5 mg, magnesium stearate 0.75 mg;
composition of the shell: opadray white Y-1-7000 3,57 mg [hypromellose-5cP 62.5%, titanium dioxide 31.25%, macrogol 6.25%].
Dosage 2 mg:
One film-coated tablet contains:
active substance: risperidone 2 mg;
Excipients: lactose monohydrate 118 mg, cellulose microcrystalline 77.5 mg, silicon colloidal dioxide 1 mg, magnesium stearate 1.5 mg;
composition of the shell: orange opahedra 03B53576 7.14 mg [hypromellose-6cR 62.5%, titanium dioxide 29.704%, macrogol 6.25%, iron dye oxide red 0.35%, iron dye oxide yellow 1.154%, iron oxide dye black 0.042%] .
Dosage 3 mg:
One film-coated tablet contains:
active substance: risperidone 3 mg;
Excipients: lactose monohydrate 177 mg, microcrystalline cellulose 116.25 mg, silicon dioxide colloid 1.5 mg, magnesium stearate 2.25 mg;
composition of the shell: opadray yellow 03V52852 10.71 mg [hypromellose-6cR 62.5%, titanium dioxide 28.75%, macrogol 6.25%, dye quinoline yellow 2.5%].
Dosage 4 mg:
One film-coated tablet contains:
active substance: risperidone 4 mg;
Excipients: lactose monohydrate 236 mg, microcrystalline cellulose 155 mg, silicon dioxide colloid 2 mg, magnesium stearate 3 mg;
composition of the shell: opadray green 03V51373 14.29 mg [hypromellose-6cR 62.5%, titanium dioxide 26.4%, macrogol 6.25%, dye quinoline yellow 4%, indigocarmine 0.85%].
Dosage 6 mg:
One film-coated tablet contains:
active substance: risperidone 6 mg;
Excipients: lactose monohydrate 234 mg, microcrystalline cellulose 155 mg, silicon dioxide colloid 2 mg, magnesium stearate 3 mg;
composition of the shell: opadray white Y-1-7000 14.29 mg [hypromellose-5cP 62.5%, titanium dioxide 31.25%, macrogol 6.25%].

Description:Dosage 0.5 mg: The capsule-shaped form, biconvex tablets coated with a film shell, green, with an engraving "A" on one side and a risk between the engraving "50" on the other side.

Dosage 1 mg: The capsule-shaped form, biconvex tablets coated with a film shell, white, with an engraving "A" on one side and a risk between the engraving "51" on the other side.

Dosage 2 mg: The capsule-shaped form, biconvex tablets coated with a film shell, light orange, with an engraving "A" on one side and a risk between the engraving "52" on the other side.

Dosage 3 mg: The capsule-shaped form, biconvex tablets coated with a film membrane, yellow, with an engraving "A" on one side and a risk between engraving "53" on the other side.

Dosage 4 mg: The capsule-shaped form, biconvex tablets coated with a film shell, green, with an engraving "A" on one side and a risk between the engraving "54" on the other side.

Dosage 6 mg: The capsule-shaped form, biconvex tablets coated with a film shell, white, engraved "A" on one side and engraved "55" on the other side.

Pharmacotherapeutic group:Antipsychotic agent (antipsychotic) (APS)

ATX: & nbsp

N.05.A.X Other antipsychotics

N.05.A.X.08 Risperidone

Pharmacodynamics:

Risperidone is a selective monoaminergic antagonist with a high affinity for serotonin 5-HT₂ and dopamine D₂receptors. Risperidone also communicates from α₁-adrenoceptors and, to a lesser extent, H₁-histamine and α₂-adrenoceptors. Risperidone does not possess affinity to cholinergic receptors. Although risperidone is a potent antagonist D₂-receptors, and therefore eliminates the productive symptoms in schizophrenia,it causes less motor and depressive disorders and less potentiates catalepsy than classical neuroleptics. Balanced antagonism against central serotonin and dopamine receptors reduces the likelihood of developing extrapyramidal disorders and increases the therapeutic breadth of the drug with respect to influencing the negative and productive symptoms of schizophrenia.

Pharmacokinetics:

- suction. Absorption is fast and complete (food does not affect the completeness and absorption rate). Absolute bioavailability of risperidone is 70%, the relative bioavailability of risperidone tablets is 94% compared to oral solution. The maximum concentration (Cmah) in blood plasma is achieved after 1-2 hours. The concentration of risperidone in the blood plasma depends on the dose taken. The equilibrium concentration of risperidone in the body of most patients is established within 1 day, and its main active metabolite (9-hydroxyrisperidone) - for 4-5 days.

- distribution. Quickly and well distributed in the body. The volume of distribution is 1-2 l / kg body weight. In the blood plasma risperidone binds to albumin and α₁glycoprotein. The binding of risperidone to plasma proteins is 88%, and 9-hydroxyrisperidone - 77%.

- metabolism. Metabolized in the liver with the participation of isoenzyme CYP2D6. The main pathway of biotransformation is hydroxylation to form the main active metabolite, 9-hydroxyrisperidone, which has similar pharmacological properties with risperidone. Another way of biotransformation, which has a minimum value - N-dealkylation. 9-hydroxyrisperidone and risperidone form an active antipsychotic fraction (AAPF). Although hydroxylation of risperidone is susceptible to genotypic polymorphism, the differences in pharmacokinetics and the effect of active metabolites in different phenotypes are minimal.

- excretion. Half-life (T_1/2) risperidone with active metabolism is 3 hours, at a slow - 20 hours, T _1/29-hydroxyrisperidone with active metabolism - 21 hours, at a slow - 30 hours. T_1/2 AAPF in different phenotypes is 24 hours.

After one week of admission, 70% of the taken risperidone is excreted by the kidneys, 14% by the intestine. 35-45% of the fraction excreted by the kidneys consists of unchanged risperidone and 9-hydroxyrisperidone. Pharmacokinetics the special patient groups

Renal insufficiency

In patients with renal insufficiency, the clearance of the AAPF decreases by 60%.

Liver failure

In patients with hepatic insufficiency, the concentration of risperidone in plasma did not differ from other patients, despite the fact that the mean free fraction of risperidone was increased by approximately 35%.

Elderly patients

With a single admission in the blood plasma of elderly patients there is a decrease in clearance of AAPF by 30% and an increase in T_1/2 on 38%.

Children

The pharmacokinetics of risperidone in adults and children does not differ.

Sex, race and tobacco

Population pharmacokinetic analysis did not reveal a distinct effect of sex, race or tobacco on the pharmacokinetics of risperidone and its AAPF.

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 aged 5-18 with moderate and severe mental retardation,due to the severity of which pharmacological correction methods are required (as part of complex therapy).

Contraindications:

Hypersensitivity to risperidone or any other component of the drug, lactation period, galactosemia, lactase deficiency, glucose-galactose malabsorption syndrome, children under 18 years of age (in the treatment of schizophrenia and manic episodes in the structure of bipolar disorder), children under 5 years of age (in treatment incessant aggression in behavioral disorders in children with moderate and severe mental retardation).

Carefully:

Diseases of the cardiovascular system (chronic heart failure, suffered myocardial infarction, conduction disorders heart muscle); dehydration and hypovolemia; disorders of cerebral circulation; Parkinson's disease; convulsions (including in the anamnesis); severe renal and / or hepatic insufficiency; drug abuse or drug dependence; conditions predisposing to the development of tachycardia such as "pirouette" (bradycardia, electrolyte imbalance, simultaneous use of drugs that extend the interval QT); elderly age (in the treatment of manic episodes in the structure of bipolar disorder), advanced age with dementia; simultaneous application with furosemide; thrombophlebitis; hyperglycemia; brain tumor; intestinal obstruction, cases of acute drug overdose, Reye's syndrome (the antiemetic effect of risperidone may mask the symptoms of these conditions).

Pregnancy and lactation:

The safety of risperidone in pregnant women is not known. The use of the drug is possible only if the expected benefit for the mother exceeds the potential risk to the fetus.

When using risperidone in the third trimester of pregnancy, there is a risk of developing extrapyramidal disorders and / or withdrawal syndrome in newborns. In newborns, excitement, tremor, respiratory distress syndrome, eating disorders, and violation of muscle tone may appear. These symptoms are usually reversible, but sometimes require prolonged therapy.

Because the risperidone and 9-hydroxyrisperidone penetrate into breast milk, women receiving risperidone, it is necessary to refrain from breastfeeding.

Dosing and Administration:

Inside, regardless of food intake.

Schizophrenia

Adults

Risperidone may be given once or twice a day.

The initial dose is 2 mg / day. On the second day, the dose can be increased to 4 mg / day. After that, the dose can be maintained unchanged or, if necessary, individually adjusted. For most patients, the optimal dose is 4-6 mg / day. Some patients may need a slow titration phase, in which case low initial and maintenance doses are prescribed.

Doses higher than 10 mg per day did not show higher efficacy compared with smaller doses, but they can cause the appearance of extrapyramidal symptoms. The safety of doses above 16 mg / day has not been studied, so doses above this level can not be used.

Elderly patients

The recommended initial dose is 0.5 mg 2 times a day. It is possible to individually increase the dose from 0.5 mg 2 times a day to 1-2 mg 2 times a day.

Children

Children under 18 with schizophrenia risperidone Do not appoint in connection with the lack of data on the effectiveness of the application.

Manic episodes in the structure of bipolar disorder of the middle and

severe

Adults

The recommended initial dose of the drug is 2 mg / day. If necessary, this dose can be increased at least every 24 hours for 1 mg / day. For individual optimization of efficacy and tolerability of patients, risperidone can be administered with non-persistent doses in the range of 1-6 mg / day. Safety of doses above 6 mg / day has not been studied.

Elderly patients

The initial dose of the drug is 0.5 mg twice a day. Further individual correction is carried out by increasing the dose of 0.5 mg 2 times per day to 2 mg 1-2 times a day. Since the clinical experience of using risperidone in elderly patients is limited, the drug should be administered with caution.

Children

The drug is not prescribed for children under 18 with bipolar mania due to lack of data on the effectiveness of the application.

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

The recommended initial dose is 0.25 mg twice a day. If necessary, the dose may be individually adjusted, increasing it for 1 times in the 0.25 mg 2 times a day, but not more than 1 time per day. For most patients, the optimal dose is 0.5 mg 2 times a day, but some patients may require doses of up to 1 mg 2 times a day.Duration of treatment should not exceed 6 weeks. During treatment, patients should be constantly monitored and analyzed for their decision to continue therapy.

Continued aggression in behavioral disorders the patients with mental retardation

Children aged 5-18 years

Patients with a body weight of 50 kg and above are recommended an initial dose of 0.5 mg / day. If necessary, this dose can be individually adjusted, increasing not more than 1 time per day by 0.5 mg. For most patients, the optimal dose is 1 mg / day. In this case, one patient may have a sufficient dose of 0.5 mg / day, while others require 1,5 mg / day.

For patients with a body weight of less than 50 kg, an initial dose of 0.25 mg / day is recommended. If necessary, this dose can be individually adjusted, increasing not more than once a day by 0.25 mg. For most patients, the optimal dose is 0.5 mg / day. At the same time, in some patients there may be a sufficient dose of 0.25 mg / day, and in others - 0.75 mg / day.

Children under 5 years

The drug is not recommended for use in children under 5 due to lack of experience in treating this disorder in this age group.

Patients with impaired hepatic and renal function

In patients with kidney disease, the ability to excrete an AAPF drug 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.

Regardless of the indications, the initial and subsequent corrective doses should be reduced 2 times; the dose increase in patients with liver and kidney disease should be slower.

Risperidone should be administered with caution in this category of patients.

Side effects:

Very often -> 10%; often -> 1% and <10%; infrequently -> 0.1% and <1%; rarely -> 0.01% and <0.1%; very rarely - <0.01%; frequency is unknown - insufficient data for estimating the frequency of the phenomenon in the population.

Disorders from the cardiovascular system: often - tachycardia; infrequently - atrioventricular blockade, palpitations, sinus bradycardia, orthostatic hypotension, blockage of the branch of the gastric atrial bundle of the Guiss, "tides"; rarely - transient ischemic attack (in elderly patients with dementia associated with psychosis); frequency unknown - venous thromboembolism.

Violations from the blood and lymphatic system: infrequently - anemia, neutropenia, thrombocytopenia; rarely - granulocytopenia; frequency is unknown - agranulocytosis.

Impaired nervous system: very often - insomnia, parkinsonism^a, headache; often - akathisia^a, dizziness, drowsiness, sedation, tremor^a, dystonia^a, lethargy, dyskinesia^a; infrequent - lack of response to irritants, coordination disorders, transient ischemic attack, fainting, speech disorders, hypoesthesia, impaired concentration, tardive dyskinesia; often - anxiety, agitation, sleep disorders; infrequently - confusion of consciousness, mania, weakening of libido, agitation, apathy, stroke, nervousness; rarely - malignant neuroleptic syndrome, cerebral ischemia, cerebrovascular disorders, movement disorders, diabetic coma, anorgasmia, dullness of emotions.

Disorders from the side of the organ of vision: often - blurring of vision; infrequently - conjunctivitis, hyperemia of the eyes, dry eyes, increased lacrimation, orbital edema, photophobia; rarely - reduced visual acuity, glaucoma, rotational nystagmus.

Hearing disorders and labyrinthine disturbances: infrequently - pain in the ears, noise in the ears.

Disturbances from the respiratory system, chest and mediastinal organs: often - shortness of breath, nosebleed, cough, nasal congestion, sore throat; infrequently - rhinitis, respiratory failure, dysphonia, "wheezing" breathing, aspiration pneumonia, productive cough, blockage of the respiratory tract, wet wheezes, swelling of the nose; rarely - hyperventilation, sleep apnea syndrome.

Disorders from the gastrointestinal tract: often - vomiting, diarrhea, constipation, nausea, abdominal pain, indigestion, dry mouth, stomach discomfort; infrequently - dysphagia, gastritis, fecal matter; rarely - intestinal obstruction, jaundice, pancreatitis, edema of the lips, cheilitis, aptialism.

Disorders from the kidneys and urinary tract: often - enuresis; infrequently - dysuria, urinary incontinence, pollakiuria.

Disturbances from the skin and subcutaneous tissues: often - erythema, skin rash; infrequently - angioedema, skin damage, erythematous rashes, itching, acne, skin pigmentation disorder, alopecia, seborrheic dermatitis, dry skin, hyperkeratosis; rarely - dandruff.

Disturbances from the musculoskeletal and connective tissue: often - arthralgia, back pain, pain in the limbs; infrequently - muscle weakness, myalgia, pain in the neck, swelling of the joints, violation of posture, joint stiffness, chest pain; rarely rhabdomyolysis.

Disorders from the endocrine system: rarely - a violation of the secretion of antidiuretic hormone.

Disorders from the metabolism and nutrition: often - increased or decreased appetite; infrequently - diabetes mellitus, anorexia, polydipsia; very rarely diabetic ketoacidosis; frequency unknown - water intoxication.

Infectious and parasitic diseases: often - pneumonia, influenza, bronchitis, upper respiratory tract infections, urinary tract infections; infrequently - sinusitis, viral infections, ear infections, tonsillitis, cellulitis, otitis media, eye infections, localized infections, acarobacteria, respiratory infections, cystitis, onychomycosis; rarely - chronic otitis media.

Other: often - hyperthermia, fatigue, peripheral edema, asthenia; infrequently - edema of the face, gait disturbance, sensitivity disturbance, lethargy, flu-like condition, thirst, chest discomfort, chills; rarely - generalized edema, hypothermia, withdrawal syndrome, cold extremities.

Immune system disorders: infrequently - hypersensitivity; rarely - hypersensitivity to medicines; frequency unknown - anaphylactic reaction.

Violations of the genitals and breast: infrequently - amenorrhea, sexual dysfunction, erectile dysfunction, ejaculation disorder, galactorrhea, gynecomastia, menstrual disorder, vaginal discharge; frequency is unknown - priapism.

Laboratory and instrumental data: often - an increase in the concentration of prolactin in the blood plasma^b, weight gain; infrequent - lengthening of the interval QT on electrocardiogram (ECG), hyperglycemia, increased activity of "liver" transaminases, eosinophilia, decreased hemoglobin, increased cholesterol levels in blood plasma, increased triglyceride levels in blood plasma, increased body temperature; rarely - hypoglycemia, weight loss.

^aThe following extrapyramidal disorders are possible: parkinsonism (increased secretion of saliva, decreased skeletal muscle mobility, rigidity in the form of a cogwheel, bradykinesia, hypokinesia, face mask, muscle tension, akinesia, stiff neck, muscle stiffness,Parkinsonian gait and violation of the glabular reflex), akathisia (akathisia, excitability, hyperkinesia and restless legs syndrome), tremor, dyskinesia (dyskinesia, muscle cramps, choreoathetosis, athetosis and myoclonus), dystonia.

Dystonia can manifest itself with dystonia proper, muscular spasms, hypertension, spasmodic torticollis, unauthorized muscle contractions, muscle contraction, tonic blepharospasm, eyeball movements, paralysis of the tongue, spasm of the face, larynx, myotonia, opisthotonus, oropharyngeal spasm, bend of the trunk toward greater muscle contraction , spasm of the tongue and trism. By tremor means actually tremor and parkinsonic tremor at rest. It should be noted that a broader spectrum of symptoms is given, which need not necessarily be extrapyramidal in nature.

^bIn certain cases, hyperprolactinemia can lead to gynecomastia, menstrual cycle disorders, amenorrhea, galactorrhea.

Class Effects

As with other APS, in the post-marketing studies of risperidone, very rare cases of lengthening of the interval QT. At APS, which extend the interval QT, the following class-related cardiovascular disorders were recorded: ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac arrest and ventricular pirouette tachycardia.

Venous thromboembolism

Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis, have been reported in APS (frequency unknown).

Weight gain

During 6- and 8-week placebo-controlled clinical trials of adult patients with schizophrenia, a 7% or more increase in body weight with risperidone showed a statistically correct increase in body weight by 18% in patients taking risperidone, and 9% in those taking placebo.

During a 3-week, placebo-controlled clinical trial of treatment of adult patients with manic episodes, a 7% or more increase in body weight with risperidone, showed the same increase in body weight in patients taking risperidone, and those taking placebo, 2.5% and 2.4%, respectively, and 3.5% of patients in the active control group.

In long-term studies of treatment of children and adolescents with behavioral disorders, body weight averaged 7.3 kg after 12 months of treatment. A normal increase in body weight for children aged 5-12 years is 3-5 kg per year. For adolescents aged 12-16 years, an increase in body weight of 3-5 kg per year is maintained for girls, and for boys is 5 kg per year.

Additional information about individual patient populations

Below are the undesirable drug reactions, of which among older patients with dementia and in children reported with a higher frequency than among adults.

Older patients with dementia

In clinical trials among elderly patients with dementia, undesirable pharmacological reactions in the form of a transient ischemic attack and stroke were reported at a frequency of 1.4% and 1.5%, respectively. In addition, among elderly patients with dementia about the following undesirable side effects reported with frequency ≥ 5% or at least twice as often as in the adult population of young patients: urinary tract infections, peripheral edema, drowsiness, and cough.

Children

Among patients in the pediatric group (aged 5-17), the following undesirable side effects in clinical trials were reported with frequency ≥ 5 % or at least twice as often as in the adult population: lethargy / sedation, fatigue, headache, increased appetite, vomiting, upper respiratory tract infection, nose congestion, abdominal pain, dizziness, cough, fever, tremor, diarrhea and enuresis .

Overdose:

Symptoms: drowsiness, sedation, depression of consciousness, tachycardia, arterial hypotension, extrapyramidal disorders; in rare cases - lengthening the interval QT.

Treatment: ensuring free airway patency for adequate oxygenation and ventilation; gastric lavage (after intubation, if the patient is unconscious) and the appointment of activated charcoal in combination with laxatives. Symptomatic therapy is aimed at maintaining vital body functions.

For timely diagnosis of a possible heart rhythm disturbance, it is necessary to start ECG monitoring as soon as possible.Careful medical supervision and monitoring of the ECG is performed until the symptoms of intoxication disappear completely.

There is no specific antidote. With a reduction in blood pressure and vascular collapse, intravenous infusion solutions and / or adrenostimulators are recommended. In case of development of acute extrapyramidal symptoms, m-holinoblockers should be prescribed.

Interaction:

Given that APS, including risperidone, have an impact, primarily on the central nervous system, they should be used with caution in combination with other drugs of central action. APS strengthen the action of ethanol, opiates, antihistamines and benzodiazepines. For the treatment with risperidone, benzodiazepines can be added if an additional sedative effect is required.

When therapy with a combination of risperidone with other APS, lithium, antidepressants, antiparkinsonics, drugs with a central anticholinergic effect increases the risk of developing tardive dyskinesia.

Risperidone reduces the effectiveness of levodopa and other dopamine agonists.A similar effect is possible with the use of risperidone with other drugs that induce the metabolism of microsomal enzymes of cytochrome P450, such as barbiturates, rifampicin, phenytoin and St. John's wort. In this case, the dose of risperidone should be reviewed or reduced.

Do not use risperidone simultaneously with carbamazepine to patients with mania in bipolar disorder. When carbamazepine was used, there was a decrease in the plasma concentration of AAPF in risperidone.

Clozapine reduces the clearance of risperidone.

Phenothiazines, tricyclic antidepressants and some β-adrenoceptors may increase the concentration of risperidone in blood plasma, but this does not affect the concentration of AAPF.

Quinidine, fluoxetine, paroxetine, terbinafine and other isoenzyme inhibitors CYP2D6 may increase the concentration of risperidone in blood plasma, but to a lesser extent the concentration of AAPF.

Carbamazepine, rifampicin, St. John's wort, phenytoin, phenobarbital are isoenzyme inducers CYP3A4 and P-glycoprotein, and reduce the plasma concentration of risperidone AAPF.With the withdrawal of carbamazepine and other isoenzyme inducers CYP3A4 and P-glycoprotein, the dose of risperidone should be reduced. Verapamil, being an inhibitor CYP3A4 and P-glycoprotein, increases the concentration of risperidone in blood plasma.

Cimetidine and ranitidine increase the concentration of risperidone in blood plasma, but the antipsychotic effect does not increase, because the adhesion of active metabolites is reduced.

α₁-the adrenoblocking effect of risperidone can increase blood pressure, reducing the effectiveness of phenoxybenzamine, labetalol and other antihypertensive agents of central action. In contrast, the antihypertensive effect of guanitidine is blocked.

The attention and caution of simultaneous reception of risperidone with drugs that extend the interval QT, such as other antipsychotics, antiarrhythmics IA and III classes, moxifloxacin, methadone, mefloquine, erythromycin, tricyclic antidepressants, lithium and cisapride.

It is necessary to be careful when taking risperidone simultaneously with drugs that can cause disturbances in electrolyte metabolism, such as thiazide diuretics (hypokalemia). This combination increases the risk of developing a malignant arrhythmia.

When using risperidone along with other drugs that bind to a high degree with blood plasma proteins, there is no clinically pronounced displacement of any active substance from the protein fraction of blood plasma.

Special instructions:

Transition from therapy with other APS to risperidone

When schizophrenia, at the beginning of treatment with risperidone, it is recommended to gradually cancel the previous therapy, if it is clinically justified. If patients are transferred from depot therapy to APS, it is advisable to start the treatment instead of the next scheduled injection. Periodically, the need to continue current therapy with antiparkinsonian drugs should be evaluated.

Older patients with dementia

A meta-analysis of 17 controlled trials of atypical APS (also of risperidone) showed an increased, compared with placebo, mortality among elderly patients with dementia in their treatment with active drugs. Testing risperidone in this population in a placebo-controlled regimen showed a risk of developing a fatal outcome in the risperidone group of 4.0% compared with 3.1% in the placebo group.The average age (range) of patients with a lethal outcome was 86 (67-100) years.

Simultaneous application with furosemide

In risperidone, placebo-controlled trials in elderly patients with dementia, an increased risk of death was noted with the simultaneous use of furosemide with risperidone (7.3 %; mean age 89 years, range 75-97), compared with patients treated with risperidone alone (3.1%, mean age 84 years, range 70-96) or furosemide (4.1%, mean age 80 years, range 67-90). The increase in mortality in patients who used the combination furosemide+ risperidone, were noted in two out of four trials. Simultaneous reception risperidone with other diuretics (especially with thiazide diuretics in low doses) was not associated with similar changes. Pathophysiological mechanisms of such changes were not revealed, and there was no regularity in the causes of these lethal cases. Therefore, care should be taken and treatment should be prescribed only after careful study of the potential risks and therapeutic benefits of such combinations or concomitant administration with other potent diuretics.

Among patients taking with other riseridone other diuretics, the risk of developing a lethal outcome was not increased. Regardless of treatment, the common risk factor for death is dehydration, which requires prophylactic measures among elderly patients with dementia.

Cerebrovascular undesirable reactions

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 dementia of a different type (not Alzheimer's) 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. Patients and their environment should be warned about the urgency of reporting symptoms and signs of potential cerebrovascular unwanted reactions, in particular the sudden weakness or numbness of the face, upper and lower extremities,violation of speech or sight. In this case, all therapeutic options are urgently considered, including the abolition of the drug.

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 evaluation of patients, as well as the rationale for the need for further treatment.

Orthostatic hypotension

Activity of risperidone as a blocker α-adrenoreceptors can cause arterial hypotension (orthostatic), especially when taking the initial dose and during the titration period. Postmarketing observations revealed clinically significant hypotension with simultaneous use of risperidone with antihypertensive drugs. Risperidone should be used with caution in patients with known cardiovascular diseases (for example, with heart failure, myocardial infarction, conduction disorders, dehydration,hypovolemia or cerebral vascular disease) and it is necessary to gradually increase the dose. When arterial hypotension occurs, the possibility of dose reduction is considered.

Extrapyramidal syndrome and tardive dyskinesia

Drugs with the properties of dopamine receptor antagonists are associated with the appearance of late dyskinesia, characterized by rhythmic spontaneous movements, mainly of language and face. If there are signs or symptoms of tardive dyskinesia, consider the possibility of canceling all APS.

Malignant neuroleptic syndrome

When APS was used, cases of malignant neuroleptic syndrome, characterized by hyperthermia, rigidity of muscles, vegetative disorders, changes in the state of consciousness and increased activity of creatine phosphokinase (CK) in blood plasma were reported. Among other symptoms, myoglobinuria (acute necrosis of skeletal muscles) and acute renal failure can be noted. In this case, all the MTAs are stopped, including risperidone.

Parkinson's disease and dementia with Levi bodies

In appointing risperidone, patients with Parkinson's disease or dementia with Levy bodies should evaluate the risk ratio with the expected therapeutic benefits. Taking the drug may cause an exacerbation of Parkinson's disease. Among the manifestations of hypersensitivity are confusion, stunning (one of the stages of coma) and impaired coordination of movements with frequent falls and extrapyramidal symptoms.

Hyperglycaemia

In the treatment with risperidone, there have been reports of rare cases of hyperglycemia and exacerbation of diabetes mellitus. Therefore, among patients with diabetes mellitus and risk factors for the development of diabetes, appropriate clinical monitoring is recommended.

Hyperprolactinemia

Studies of tissue cultures have shown that prolactin is able to stimulate the division of tumor cells of the female breast. Although clinical and epidemiological studies have not revealed a direct link with the use of APS, caution should be exercised in the treatment of patients with appropriate medical history.

Risperidone should be used with caution in patients with hyperprolactinaemia, or in which prolactin-dependent tumors are not excluded.

Interval lengthening QT

Post-marketing studies reported individual cases of lengthening the interval QT. As with any other APS, caution should be exercised in prescribing risperidone to patients with known cardiovascular diseases, a hereditary etiology of prolongation of the interval QT, bradycardia and electrolyte balance disorders (hypokalemia, hypomagnesemia), since such treatment may increase the risk of arrhythmogenic effects. Also caution is needed when prescribing combinations with drugs that can lengthen the interval QT.

Thromboembolism of veins

In the treatment of APS reported cases of venous thromboembolism. Patients who need APS treatment often note acquired risk factors for venous thromboembolism, so before prescribing risperidone (and in treating it), it is necessary to identify all potential risk factors for venous thromboembolism and to take possible preventive measures.

Epileptic seizures

Risperidone should be used with caution in patients with epileptic seizures in the anamnesis or with other disorders that lead to a decrease in the convulsive threshold.

Priapism

As a result, α-adrenergic blocking effects, treatment with risperidone may be accompanied by the occurrence of priapism.

Regulation of body temperature

With the use of APS bind the violation of thermoregulation of the body. Caution is advised when prescribing risperidone to patients whose lifestyle is associated with exposures that increase internal body temperature, for example, intense physical activity, exposure to high temperatures, concomitant medication with anticholinergic activity, and a state of dehydration.

The withdrawal syndrome

At the end of treatment it is recommended to gradually reduce the dose. After a sudden administration of APS in high doses, individual cases of acute withdrawal syndrome were described, including nausea, vomiting, increased sweating and insomnia. It is also possible to restore psychotic symptoms, and reported cases of uncontrolled movements (in particular akathisia, dystonia and dyskinesia).

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

During the period of application of risperidone, it is necessary to refrain from driving vehicles and taking other potentially hazardous activities,requiring increased concentration and speed of psychomotor reactions, due to the possibility of developing dizziness, impaired concentration and other side effects.

Form release / dosage:

Film coated tablets 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg, 6 mg.

Packaging:

10 tablets in a three-layer blister PVC/PE/PVdC film / aluminum foil. 1, 2, 3 or 5 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

In dry, the dark place at a pacenot higher than 25 ° С. Store in inaccessible to children.

Shelf life:

2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002142

Date of registration:12.07.2013

The owner of the registration certificate:Aurobindo Pharma Co., Ltd.Aurobindo Pharma Co., Ltd. India

Manufacturer: & nbsp

AUROBINDO PHARMA, Ltd. India

Representation: & nbspAurobindo Pharma, ZAOAurobindo Pharma, ZAO

Information update date: & nbsp16.10.2015

Illustrated instructions

Instructions

Risperidone (Risperidone)