Risperidon

General characteristics. Structure:

Active ingredient: 0,25 mg, 1 mg, 2 mg, 3 mg or 4 mg of a risperidon.

Excipients: lactoses monohydrate; cellulose microcrystallic; starch corn; silicon dioxide colloid; magnesium stearate.

Film cover: [a gipromelloza, talc, titanium dioxide, a macrogoal 4000 (polyethyleneglycol 4000)] or [the dry mix for a film covering containing a gipromelloza (60%), talc (20%), titanium dioxide (11%), a macrogoal 4000 (polyethyleneglycol 4000) (9%)].

The antipsychotic means rendering also sedative, antiemetic and hypothermal action.

Pharmacological properties:

Pharmacodynamics. Risperidon - derivative a benzizoksazola. Risperidon is the selection monoaminergichesky antagonist showing high affinity to 5HT2-serotoninovy and D2 - to dopamine receptors. Risperidon contacts also alfa1-adrenoceptors and, slightly more weakly, H1-histamine receptors and alfa2-adrenoceptors. Risperidon does not possess a tropnost to cholinergic receptors. Antipsychotic action is caused by blockade of D2 - dopamine receptors of mesolimbic and mesocortical system. Sedative action is caused by blockade of adrenoceptors of a reticular formation of a trunk of a brain; antiemetic action – blockade of D2 - dopamine receptors of a trigger zone of the emetic center; hypothermal action – blockade of dopamine receptors of a hypothalamus.

Risperidon reduces productive symptomatology of schizophrenia (nonsense, hallucinations), aggression, automatism, it causes smaller suppression of a physical activity and to a lesser extent induces a katalepsy, than typical neuroleptics. The balanced central antagonism to serotonin and dopamine can reduce tendency to extrapyramidal side effects and expand therapeutic influence of drug with coverage of negative and affective symptoms of schizophrenia.

Pharmacokinetics. Absorption. Risperidon after oral administration is completely absorbed, reaching the maximum concentration in a blood plasma in 1-2 hours. Food does not exert impact on absorption of a risperidon therefore it is possible to appoint it irrespective of meal.

Distribution. Risperidon is quickly distributed in an organism, gets into the central nervous system and breast milk. The volume of distribution makes 1-2 l/kg. In a blood plasma рисперидон contacts albumine and α1-кислым a glycoprotein.

Risperidon for 88% communicates proteins of plasma, 9-gidroksirisperidon – for 77%. Equilibrium concentration of a risperidon in an organism at most of patients is reached within one day. Equilibrium concentration of a 9-gidroksirisperidon is reached in 4-5 days. Concentration of a risperidon in a blood plasma is proportional to a drug dose (within therapeutic doses).

Metabolism. Risperidon is metabolized by CYP2D6 isoenzyme to a 9-gidroksirisperidon who possesses pharmacological action similar to a risperidon. Risperidon and 9-gidroksirisperidon make active antipsychotic fraction. The isoenzyme of CYP2D6 is subject to genetic polymorphism. At patients with intensive metabolism on CYP2D6 isoenzyme рисперидон quickly turns in 9-gidroksirisperidon while at patients this transformation happens to weak metabolism much more slowly. Though patients with intensive metabolism have lower concentration of a risperidon and higher concentration of a 9-gidroksirisperidon, than patients with weak metabolism, the total pharmacokinetics of a risperidon and 9-gidroksirisperidon (active antipsychotic fraction) after reception of one or several doses is similar at patients with intensive and to weak metabolism in CYP2D6 isoenzyme.

Some other way metabolism of a risperidon N-dealkylation is.

Removal. An elimination half-life (T1/2) of a risperidon after oral administration at patients with psychosis about 3 hours. T1/2 of a 9-gidroksirisperidon and active antipsychotic fraction make 24 hours.

In a week of administration of drug of 70% of the accepted dose 14% – through intestines are removed by kidneys. In urine рисперидон and 9-gidroksirisperidon make 35-45% of the accepted dose. Other quantity is made by inactive metabolites.
The research of a single dose of a risperidon revealed higher concentration in a blood plasma and slower removal at elderly patients and at patients with a renal failure. Concentration of a risperidon in a blood plasma at patients with a chronic liver failure did not change, however average concentration of free fraction of a risperidon increased by 35%.

Indications to use:

- treatment of schizophrenia at adults and children aged from 13 up to 17 years;
- treatment of the maniacal episodes connected with bipolar disorder, average and heavy severity at adults and children aged from 10 years;
- short-term (up to 6 weeks) treatment of continuous aggression at patients with dementia caused by Alzheimer's disease, the average and heavy degree which is not giving in to not pharmacological methods of correction and with risk of infliction of harm by the patient to itself and/or other persons;
- short-term (up to 6 weeks) a symptomatic treatment of continuous aggression in the structure of disorder of behavior at children aged from 5 years and mentally retarded teenagers diagnosed according to DSM-IV at which, in the gravity of aggression or other destructive behavior, drug treatment is required.

The pharmacotherapy has to be a part of wider program of treatment, including psychological and educational actions. Risperidon has to be appointed the specialist in the field of children's neurology and children's psychiatry or the doctor well familiar with treatment of disorders of behavior at children and teenagers.

Route of administration and doses:

Inside, irrespective of meal.
Schizophrenia. Adults. An initial dose of a risperidon for all patients (at acute displays of a disease and a chronic current) – 2 mg a day (in one or two receptions). For the second day the dose can be increased to 4 mg a day; further if necessary the dose can be increased or reduced on 1-2 mg with week an interval. Usually optimum dose are 4-6 mg a day. In some cases slower increase in a dose and lower the initial and supporting doses can be justified.

Doses higher than 10 mg a day did not show higher performance in comparison with smaller doses and can cause emergence of extrapyramidal symptoms. Because safety of doses higher than 16 mg a day was not studied, doses are higher than this level it is impossible to apply.

Risperidony it is possible to add benzodiazepines to therapy if additional sedation is required.

Elderly patients. The recommended initial dose on 0,5 mg two times a day. It is possible to increase a dosage gradually to 1-2 mg by reception two times a day.

Use for children of 13 years. The recommended initial dose of 0,5 mg on reception once a day in the morning or in the evening. If necessary it is possible to increase a dose not less than in 24 hours by 0,5-1 mg a day to the recommended dose of 3 mg a day at good tolerance. Despite the efficiency shown at treatment of schizophrenia at teenagers by doses of 1-6 mg a day additional efficiency at doses was not observed higher than 3 mg a day, and higher doses caused more side effects. Use of doses higher than 6 mg a day was not studied.

Patients at whom steady drowsiness is observed are recommended to accept a half of a daily dose 2 times a day.

Manias at bipolar disorders. Adults. An initial dose of a risperidon for all patients (at acute displays of a disease and a chronic current) – 2-3 mg a day (in one or two receptions). Dose adjustment needs to be carried out not earlier than in 24 hours on 1 mg a day. Usually optimum dose varies from 1 mg to 6 mg a day. Use of a risperidon in a daily dose higher than 6 mg at treatment of manias at bipolar disorders was not studied. The long symptomatic treatment risperidony has to be reasonable.

Elderly patients. The recommended initial dose on 0,5 mg two times a day. It is possible to increase a dosage gradually to 1-2 mg by reception two times a day.

Use for children of 10 years. The recommended initial dose of 0,5 mg on reception once a day in the morning or in the evening. If necessary it is possible to increase a dose not less than in 24 hours by 0,5-1 mg a day to the recommended dose of 1-2,5 mg a day at good tolerance. Despite the efficiency shown at treatment of the maniacal episodes connected with bipolar disorder at children doses of 0,5-6 mg a day additional efficiency at doses was not observed higher than 2,5 mg a day, and higher doses caused more side effects. Use of doses higher than 6 mg a day was not studied.

Patients at whom steady drowsiness is observed are recommended to accept a half of a daily dose 2 times a day.

Behavioural frustration at patients with Alzheimer's dementia. The recommended initial dose on 0,25 mg twice a day. If necessary increase in a dose by 0,25 mg 2 times a day not is possible more often than every other day. For most of patients an optimum dose are 0,5 mg twice a day. At some patients, however, the effective dose can make on 1 mg two times a day.

Drug Risperidon should not be used more than 6 weeks at patients with constant aggression at Alzheimer's dementia. During treatment risperidony frequent and regular assessment of a condition of the patient is necessary for the solution of a question of need of continuation of treatment.

Disorders of behavior. Children and teenagers aged from 5 up to 18 years. Patients with the body weight of 50 kg and more – the recommended initial dose of drug – 0,5 mg once a day. If necessary this dose can be increased by 0,5 mg a day not more often than every other day. For most of patients the optimum dose makes 1 mg once a day. However reception is more preferable than 0,5 mg to some patients a day whereas other patients need increase in a dose up to 1,5 mg a day.

Patients with body weight less than 50 kg – the recommended initial dose of drug – 0,25 mg once a day. If necessary this dose can be increased by 0,25 mg a day not more often than every other day. For most of patients an optimum dose is the dose of 0,5 mg once a day. However reception on 0,25 mg is more preferable to some patients once a day whereas others need increase in a dose up to 0,75 mg once a day.

During treatment risperidony frequent and regular assessment of a condition of the patient is necessary for the solution of a question of need of continuation of treatment.

Long reception of a risperidon at teenagers has to be carried out under constant control of the doctor.

Use for children is younger than 5 years was not studied.

Use for patients with a renal and/or liver failure. At patients with a renal failure removal of active antipsychotic fraction is slowed down. At a liver failure concentration of metabolites of a risperidon in a blood plasma increases. Therefore at patients with a renal and/or liver failure initial and effective doses are recommended to be lowered by 50%, increase in a dose has to be carried out more slowly. Risperidon it is necessary to appoint with care at this category of patients.

At a renal failure (clearance of creatinine less than 30 ml/min.) or a liver failure (10-15 points on a scale of Chayld-Pyyu) the initial dose of a risperidon should not exceed 0,5 mg two times a day. If necessary the dose can be increased by 0,5 mg at use 2 times a day. For doses of 1,5 mg and more, twice a day, it is necessary to increase an interval up to 1 week or more.

Transition to treatment risperidony. Gradual cancellation of earlier being accepted neuroleptic is recommended. If earlier the neuroleptic depot was applied to parenteral administration, the first dose of drug рисперидон should be accepted instead of an injection according to the mode of introduction of a neuroleptic depot.

At sharp cancellation of a risperidon there can be a syndrome of "cancellation" (including nausea, sleeplessness, the increased perspiration) therefore it is recommended to stop drug use gradually.

Features of use:

Use at pregnancy and during breastfeeding. Controlled researches of use of a risperidon during pregnancy were not conducted. In experiments on animals рисперидон had no direct toxic effect on reproductive system, but caused some indirect effects mediated by influence on the central nervous system (CNS) and concentration of prolactin. In one of researches рисперидон did not possess teratogenic action. Reversible extrapyramidal symptoms at newborns whose mothers accepted рисперидон during the third trimester of pregnancy were observed. The potential risk for the person is unknown. Use of a risperidon during pregnancy is possible only if the estimated advantage for mother exceeds potential risk for a fruit. It is necessary to stop use of a risperidon during pregnancy gradually. As рисперидон and 9-gidroksirisperidon get into breast milk, in need of administration of drug by nursing mothers it is necessary to resolve an issue of the breastfeeding termination.

Because рисперидон can increase concentration of prolactin in a blood plasma, the giperprolaktinemiya can suppress production of gonadotrophin-rileasing-hormone a hypothalamus that leads to reduction of secretion of a gonadotrophin a hypophysis. It, in turn, can reduce reproductive function because of disturbance of a steroidogenesis in gonads at patients both women's, and a male.

Transition from therapy by other antipsychotic drugs. In an initiation of treatment drug Risperidon is recommended to cancel gradually previous therapy if it is clinically justified. At the same time if patients are transferred from therapy of depot forms of antipsychotic drugs, then drug Risperidon is recommended to begin therapy instead of the following planned injection. Periodically it is necessary to estimate need of continuation of the current therapy by protivoparkinsonichesky drugs.

Use for elderly patients with dementia. At elderly patients with dementia at treatment atypical antipsychotic means observe the increased mortality in comparison with placebo in researches of atypical antipsychotic means, including рисперидон. At use of a risperidon for this population the frequency of fatal cases made 4,0% for the patients accepting рисперидон in comparison with 3,1% for placebo. The reason of increase in this risk is at the moment unknown. Causes of death were various, the main reasons – cardiovascular (disturbances of a rhythm, a sudden cardiac death, the increased risk of strokes, thromboembolisms) and infectious diseases (pneumonia). Average age of the died patients makes 86 years (range of 67-100 years).

For elderly patients with dementia the increased mortality at simultaneous use of furosemide and a risperidon was observed (7,3%, average age of 89 years, range of 75-97 years) in comparison with the group accepting only рисперидон (4,1%, middle age 84 years, the range of 75-96 years) and the group accepting only furosemide (3,1%, average age of 80 years, range of 67-90 years). It is not installed the pathophysiological mechanisms explaining this observation. Nevertheless, it is necessary to observe extra care at purpose of drug in such cases. Increase in mortality at the patients who are at the same time accepting other diuretics together with risperidony is not revealed. Irrespective of treatment, dehydration is the general risk factor of mortality and has to be controlled carefully at elderly patients with dementia.

Cerebrovascular disturbances. At elderly patients with dementia at treatment atypical antipsychotic means observe increase in risk of cerebrovascular undesirable reactions in randomized placebos - controlled clinical trials. The generalized analysis of results of six placebos - controlled researches of a risperidon generally at patients of advanced age (65 years are more senior) with dementia showed that cerebrovascular undesirable reactions (serious and frivolous, combined) were shown at 3,3% (33/1009) patients receiving рисперидон and at 1,2% (8/712) patients receiving placebo. Relation of chances 2,96 (95% confidence interval). The mechanism of this risk is not studied. The increased risk cannot be excluded for other antipsychotic drugs and other groups of patients. Risperidon it is necessary to apply with care at patients with risk factors of a stroke.

Risk of development of undesirable cerebrovascular reactions above at patients with dementia of the mixed or vascular type, than with Alzheimer's dementia is reliable. Therefore patients with dementia of the mixed or vascular type are not recommended to appoint рисперидон. It is necessary to estimate risks and therapeutic advantages of use of a risperidon for patients of advanced age with dementia, considering predictive risk factors of a stroke at the specific patient. The patient and his environment should be warned about need of the urgent address to the doctor at emergence of signs of disturbance of cerebral circulation, such as sudden weakness or numbness of the person, hands or legs, disturbance of the speech or sight. In this case urgently consider all therapeutic options, including cancellation of a risperidon.

Drug Risperidon should be used only at short-term treatment of continuous aggression at patients with dementia caused by Alzheimer's disease, average and heavy degree as an additional method of treatment at inefficiency of not pharmacological treatment or with potential danger of infliction of harm to and/or surrounding people.

During treatment risperidony frequent and regular assessment of a condition of the patient is necessary for the solution of a question of need of continuation of treatment.

Orthostatic hypotension. Due to the α-adrenoceptor blocking action of a risperidon there can be an expressed lowering of arterial pressure (hypotension, including orthostatic), especially during initial selection of a dose. Clinically significant lowering of arterial pressure is observed at joint purpose of a risperidon with anti-hypertensive drugs. When developing a lowering of arterial pressure it is necessary to consider a question of a dose decline. At patients with diseases of cardiovascular system, and also at dehydration, a hypovolemia or cerebrovascular disturbances the dose should be increased gradually, according to recommendations.

Lengthening of QT of an interval. As well as for other antipsychotic drugs patients should be careful at Risperidon's appointment with arrhythmias in the anamnesis, with inborn lengthening of an interval of QT and at combined use with the drugs increasing QT interval. And also at bradycardia or electrolytic disturbances (a hypopotassemia, a hypomagnesiemia) as it can increase risk of development of arrhythmia.

Late dyskinesia and extrapyramidal frustration. Use of the medicines capable to block dopamine receptors can be followed by induction of late dyskinesia (the involuntary rhythmic movements, preferential language and/or the person). There are messages that emergence of extrapyramidal symptoms is risk factor of late dyskinesia. If there are signs and symptoms of late dyskinesia, it is necessary to consider a question of cancellation of all antipsychotic drugs.

Malignant antipsychotic syndrome. At emergence of the malignant antipsychotic syndrome which is characterized by a hyperthermia, muscular rigidity, vegetative instability, the changed consciousness and increase in activity of a kreatinfosfokinaza (the myoglobinuria can be also observed (owing to a rabdomioliz) and an acute renal failure), it is necessary to cancel all antipsychotic drugs, including рисперидон.

Parkinson's disease and dementia with Levi's little bodies. At use of neuroleptics, including a risperidona, at patients with Parkinson's disease or dementia with Levi's little bodies the doctor has to estimate a ratio advantage/risk. Disease of Parkinson at use of a risperidon can worsen. Both groups of patients have a risk of development of a malignant antipsychotic syndrome, and also hypersensitivity to antipsychotic medicines. In addition to extrapyramidal symptoms, confusion of consciousness, sensitivity obtusion, postural instability with frequent falling can be hypersensitivity manifestations.

Threshold of convulsive activity. At patients with a low threshold of convulsive readiness drug Risperidon should be used with care as the risk of development of spasms increases.

Hyperglycemia and diabetes mellitus. At treatment by drug Risperidon emergence of a hyperglycemia, diabetes mellitus or an aggravation of already existing diabetes mellitus is possible. Development of ketoacidosis and a diabetic coma is in rare instances possible. The family anamnesis of a diabetes mellitus and obesity are the contributing factors to emergence of a hyperglycemia and diabetes mellitus. At all patients it is necessary during treatment by drug Risperidon to carry out clinical control on existence of symptoms of a hyperglycemia and diabetes mellitus, and control of body weight.

Regulation of body temperature. At use of antipsychotic medicines disturbance of the central regulation of body temperature is possible. It is recommended to watch patients at use of a risperidon, especially at emergence of the states promoting fervescence (for example, an exercise stress, visit of a bath/sauna), at simultaneous use of drugs with anticholinergic action or at patients with dehydration.

Antiemetic effect. In preclinical trials the antiemetic effect of a risperidon was revealed. This effect, in case of its emergence at people, can mask objective and subjective symptoms of overdose of some antipsychotic drugs, and also such diseases as impassability of intestines, a syndrome to Reja and a brain tumor.

Venous thromboembolism. At use of antipsychotic drugs cases of development of a venous thromboembolism were described. As the patients accepting antipsychotic drugs often have risk of development of a venous thromboembolism, all possible risk factors have to be revealed to and during treatment by drug Risperidon and the warning measures have to be taken.

Giperprolaktinemiya. Researches on cultures of fabrics showed that growth of cells can be stimulated in tumors of a mammary gland with prolactin. Risperidon it is necessary to apply with care at patients with a giperprolaktinemiya and at patients about potentially prolactin - dependent tumors.

Intraoperative syndrome of a flabby iris. The Intraoperative Syndrome of a Flabby Iris (ISFI) was observed during performing surgery concerning existence of a cataract at the patients receiving therapy by drugs of group of antagonists α1-адренорецепторов.

ISDR increases risk of emergence of the complications connected with an organ of sight in time and after carrying out operational intervention. The doctor performing such operation has to be beforehand informed that the patient accepted or accepts the drugs having activity of agonists α1-адренорецепторов now.

The potential advantage of cancellation of therapy by antagonists α1-адренорецепторов before an operative measure is not established, and has to be estimated taking into account the risks connected with therapy cancellation by antipsychotic drugs.
During treatment by drug Risperidon is recommended regular inspection of the TsNS function on extrapyramidal and other motor disturbances.

Priapism. Due to the blocking action of a risperidon on α-adrenoceptors, during treatment by drug the priapism can appear.

Leukopenia, neurosinging, agranulocytosis. At use of antipsychotic medicines, including Risperidona, emergence of a leukopenia/neutropenia, and also agranulocytosis is possible. Therefore before drug use Risperidon, especially at patients with risk factors is development of a leukopenia/neutropenia, it is necessary to make clinical blood test with calculation of a leukocytic formula. Patients with clinically significant decrease in quantity of leukocytes in blood or with a medicinal leukopenia / neutropenia have to be observed within the first several months of treatment. At identification at the patient of the expressed neutropenia it is necessary to control carefully fervescence or other symptoms of development of an infection. To patients with a heavy neutropenia (absolute number of neutrophils less than 1000/mm3) in the absence of other reasons drug Risperidon is recommended to stop treatment to a complete recovery of quantity of leukocytes.

Drowsiness. Drowsiness is the most frequent side effect at use of a risperidon and its expressiveness depends on a dose.

Aspiration pneumonia. At use of antipsychotic medicines, including a risperidona, it was reported about disturbance of motility of a gullet and aspiration.

Aspiration pneumonia is the most common cause of incidence and mortality at patients with dementia caused by Alzheimer's disease. Risperidon it is necessary to apply with care at patients with risk of development of aspiration pneumonia.

Increase in body weight. Because Risperidon can lead drug use to significant increase in body weight, it is necessary to carry out control of body weight of patients at therapy by drug Risperidon and to make recommendations to the patient on a diet during treatment.

When developing orthostatic hypotension, especially in an initiation of treatment, it is necessary to consider a question of a drug dose decline. At patients with diseases of cardiovascular system, and also at dehydration, a hypovolemia or cerebrovascular disturbances the dose of drug should be increased gradually.

At cancellation of carbamazepine and other inductors of "hepatic" enzymes the dose of a risperidon has to be lowered.

Withdrawal. Gradual cancellation of a risperidon since after the sharp termination of treatment by high doses of neuroleptics development of a syndrome of "cancellation" is possible is recommended.

Symptoms of a syndrome of "cancellation": nausea, vomiting, perspiration, sleeplessness are very seldom described.

Children and teenagers. Before рисперидон it is appointed to the child or the teenager with behavioural frustration, it is necessary to estimate completely the reasons of an agressive behavior, to exclude pain, social problems. Sedation of a risperidon should be traced attentively at children and teenagers in connection with possible decline in the ability to training. Change of time of use of a risperidon can strengthen sedation and reduce attention at children and teenagers.

Because of possible effects of influence of a long giperprolaktinemiya on growth and puberty of children and teenagers regular clinical and laboratory assessment of the endocrinological status is necessary: growth, weight, puberty, control of a menstrual cycle, and also other potential effects of prolactin.

Influence on ability to control of vehicles and mechanisms. During treatment risperidony it is necessary to be careful at control of vehicles and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Classification of frequency of development of side effects (WHO): very often > 1/10; often  from> 1/100 to <1/10; infrequently from> 1/1000 to <1/100; seldom  from> 1/10000 to <1/1000; very seldom <1/10000, including separate messages.

Infections: very often – elderly patients with dementia have infections of urinary tract; often – a nasopharyngitis, upper respiratory tract infections, sinusitis, infections of urinary tract; elderly patients with dementia have a pneumonia, phlegmon; children have a rhinitis, grippopodobny diseases; infrequently – ear infections, viral infections, pharyngitis, tonsillitis, bronchitis, infections of eyes, the localized infections, cystitis, an onychomycosis, an acrodermatitis, bronchial pneumonia, respiratory infections, a tracheobronchitis.

From system of blood: often – anemia; infrequently – a granulocytopenia, a neutropenia; very seldom – thrombocytopenia, an agranulocytosis.

From immune system: infrequently – hypersensitivity; very seldom – an acute anaphylaxis.

From endocrine system: infrequently – a giperprolaktinemiya, a diabetic coma; very seldom – disturbance of secretion of antidiuretic hormone.

Disturbances of metabolism and food: often – elderly patients with dementia have a loss of appetite; children have an increase in appetite; infrequently – a polydipsia, anorexia; seldom – diabetic ketoacidosis, a diabetes mellitus, a hypoglycemia, water intoxication.

Mental disturbances: very often – sleeplessness; often – concern, nervousness; elderly patients with dementia have a confusion of consciousness; children have a slackness; infrequently – excitement, flattening of affect, a sleep disorder, weakening of a libido, an anorgazmiya; very seldom – manias.

From a nervous system: very often – parkinsonism (including extrapyramidal frustration, a syndrome of "cogwheel", an akineziya, a bradykinesia, a hypokinesia, muscular rigidity); children have a drowsiness, headaches, sedative action; often – an akathisia (including concern), drowsiness, dizziness, sedation, a tremor, dystonia (including muscular spasms, involuntary muscular contractions, a contracture of muscles, a glossolysis), a lethargy, postural dizziness, dyskinesia (including twitchings of muscles, a chorea and a choreoathetosis), a syncope; elderly patients with dementia have a dejectedness; children have a dysarthtia, disturbance of attention, gait disturbance; infrequently – lack of reaction to irritants, a lack of coordination, a loss of consciousness, disturbance of the speech, a hypesthesia, disturbance of movements, late dyskinesia, brain ischemia, cerebrovascular disturbances, a malignant antipsychotic syndrome, a rhythmical kivaniye the head.

Ophthalmologic disturbances: often – visual acuity disturbance; elderly patients with dementia have a conjunctivitis; infrequently – a conjunctiva hyperemia, a vision disorder, involuntary rotations of eyeglobes, puffiness a century, periorbital hypostasis, crusting at edges a century, a xerophthalmus, the strengthened dacryagogue, a photophobia, increase in intraocular pressure.

From an ear and a labyrinth: often – ear pain; infrequently – a sonitus.

From cardiovascular system: often – tachycardia, orthostatic hypotension, a lowering of arterial pressure; elderly patients with dementia have a passing ischemic attack, a myocardial infarction, a stroke; children have a heart consciousness; infrequently – a sinus bradycardia, sinus tachycardia, a heart consciousness, an atrioventricular block of the I degree, blockade of the right and left legs of a ventriculonector, "inflows" of blood to the person, lengthening of an interval of QT, a syncope; very seldom – fibrillation of auricles.

From respiratory system, bodies of a thorax and a mediastinum: often – a nose congestion, an asthma, nasal bleeding, a congestion of bosoms of a nose; elderly patients with dementia have a cough, a rhinorrhea; children have a cough, a rhinorrhea, pain in a throat and drinks, stagnation in lungs; infrequently – goose breathing, aspiration pneumonia, a dysphonia, productive cough, obstruction of respiratory tracts, wet rattles, breath disturbance, a rhinedema, a hyperventilation; very seldom – an apnoea syndrome in a dream.

From digestive tract: often – nausea, a lock, dyspepsia, vomiting, diarrhea, hypersalivation, dryness of a mucous membrane of an oral cavity, discomfort in a stomach, pain in a stomach; elderly patients with dementia have a dysphagy, a fekaloma; infrequently – энкопрез, gastritis, hypostasis of lips, a cheilitis, an aptializm, a dysgeusia, formation of a fecal concrement, a hypoptyalism; very seldom – impassability of intestines, pancreatitis, jaundice.

From skin and hypodermic fabrics: often – skin rash, a xeroderma, dandruff, seborrheal dermatitis, a hyperkeratosis; elderly patients with dementia have an erythema; children have an itch, an acne; infrequently – disturbance of a xanthopathy, erythematic rashes, papular rashes, generalized rash, makulopapulezny rash; very seldom – a Quincke's edema, an alopecia.

From a musculoskeletal system: often – a dorsodynia, an arthralgia, extremity pain; elderly patients with dementia have gait disturbances, swelling of joints; children have a mialgiya, pain in a neck; infrequently – muscular weakness, a swelling of joints, disturbance of a bearing, rigidity of joints, muscular stethalgias, рабдомиолиз.

From kidneys and urinary tract: often – an urine incontience; children have an enuresis, a pollakiuria; infrequently – an urodynia; very seldom – an urination delay.

From reproductive system and mammary glands: often – lack of an ejaculation; children have a galactorrhoea; infrequently – disturbance of a menstrual cycle, an amenorrhea, a gynecomastia, allocations from a vagina, erectile dysfunction, disturbances of an ejaculation, increase in mammary glands, sexual dysfunction, a retrograde ejaculation; very seldom – a priapism.

Influence on the course of pregnancy, puerperal and perinatal states: very seldom – a syndrome of "cancellation" at newborns.

General disturbances: often – fatigue, an adynamy, fever, pains in a thorax; elderly patients with dementia have a peripheral hypostasis; children have sluggishness, discomfort in a thorax; infrequently – thirst, a grippopodobny state, hypostases, feeling sick, a face edema, the general hypostasis, a fever, a cold snap of extremities, a syndrome of "cancellation"; very seldom – a hypothermia.

Disturbances of laboratory and tool indicators: often – increase in activity of a kreatinfosfokinaza, increase of a cordial rhythm; elderly patients with dementia have a fervescence; children have an increase in body weight, increase in concentration of prolactin; infrequently – increase in activity of alaninaminotranspherase, disturbance of an ECG, increase in quantity of eosinophils in blood, increase in activity of aspartate aminotransferase, increase in quantity of leukocytes in blood, increase in concentration of glucose in blood, reduction of concentration of hemoglobin, reduction of a hematocrit, increase in concentration of cholesterol in blood, increase in level of triglycerides in blood; very seldom – lengthening of an interval of QT.

Interaction with other medicines:

It is necessary to be careful at combined use of drug Risperidon with the drugs increasing QT interval such as antiarrhytmic drugs Ia of a class (for example, quinidine, procaineamide, Disopyramidum), the III class (for example, Amiodaronum, соталол), tricyclic antidepressants (for example, Maprotilinum), some antihistaminic drugs, other antipsychotic drugs, some antimalarial drugs (for example, мефлохин).

Cimetidinum and ranitidine increase bioavailability of a risperidon, but in the minimum degree influence concentration of active antipsychotic fraction.

Risperidon reduces efficiency of a levodopa and other agonists of dopamine. In need of simultaneous use it is recommended to use minimum effective doses of drugs.

Hypotensive medicines increase expressiveness of a lowering of arterial pressure against the background of reception of a risperidon.

Carbamazepine and other inductors of "hepatic" enzymes (for example, rifampicin, Phenytoinum, phenobarbital) reduce concentration of active fraction of a risperidon in plasma. At appointment and after carbamazepine cancellation the drug dose Risperidon should be corrected.

At a concomitant use of fluoxetine / пароксетина concentration of a risperidon in a blood plasma decreases, however the level of antipsychotic fraction increases slightly. It is expected that other CYP2D6 inhibitors, such as quinidine, can reduce plasma concentration of a risperidon.

Verapamil (CYP3A4 inhibitor and the R-glycoprotein) increases concentration of a risperidon in plasma.

Taking into account that рисперидон makes impact first of all on the central nervous system, it should be applied with care in combination with other drugs of the central action and with alcohol.

At simultaneous use of a risperidon with furosemide at elderly patients with dementia the risk of mortality increases.

Simultaneous use of a risperidon and paliperidon is not recommended as the last is an active metabolite of a risperidon, and strengthening of antipsychotic effect is possible.

Fenotiazinovy neuroleptics, tricyclic antidepressants and some
β-adrenoblockers at simultaneous use with risperidony can increase its concentration in a blood plasma, however it does not influence concentration of active antipsychotic fraction.

Amitriptyline does not influence pharmacokinetics of a risperidon and active antipsychotic fraction.

Clinically significant interaction at simultaneous use of a risperidon with lithium drugs, sodium Valproatum, digoxin, topiramaty, the selection inhibitors of anti-cholinesterase (for example, Galantaminum, donepezil), amitriptyline, erythromycin, psychogogic drugs was not revealed (for example, methylphenidate).

Contraindications:

- hypersensitivity to a risperidon or any other components of drug;
- rare hereditary forms of intolerance of a galactose;
- deficit of lactase or disturbance of absorption of a glucose/galactose (since lactose is a part of drug);
- breastfeeding period;
- children's age up to 5 years at behavioural frustration at children;
- children's age up to 13 years at treatment of schizophrenia;
- children's age up to 10 years at treatment of the maniacal episodes connected with bipolar disorder, average and heavy severity;
- age up to 18 years according to other indications.

To apply with care at the following states: 
- heavy renal or liver failure;
- cardiovascular diseases (chronic heart failure, the postponed myocardial infarction, disturbances of endocardiac conductivity, including an atrioventricular block); 
- dehydration and hypovolemia; 
- the states contributing to development of tachycardia like "pirouette" (bradycardia, disturbance of electrolytic balance, the accompanying administration of drugs, QT extending an interval);
- disturbances of cerebral circulation; 
- Parkinson's disease;
- spasms and epilepsy (including in the anamnesis); 
- abuse of medicines or medicinal dependence (see the section "Route of Administration and Doses"); 
- a brain tumor, intestinal impassability, cases of acute overdose of drugs, a syndrome to Reja (the antiemetic effect of a risperidon can mask symptoms of these states); 
- advanced age at patients with dementia;
- use in combination with furosemide;
- hyperglycemia;
- risk factors of development of a thromboembolism of venous vessels;
- combined use with drugs of the central action;
- disease of diffusion little bodies of Levi;
- pregnancy.

Overdose:

Symptoms. Drowsiness, sedation, tachycardia, lowering of arterial pressure, extrapyramidal symptoms, consciousness oppression. Seldom – lengthening of an interval of QT, a spasm. Bidirectional ventricular tachycardia was noted at joint reception of the raised dose of a risperidon and a paroksetin.

In case of overdose the possibility of overdose from reception of several drugs has to be considered.

Treatment. At acute overdose it is necessary to provide free passability of respiratory tracts for ensuring adequate supply with oxygen and ventilation, monitoring of an ECG, performing the symptomatic therapy directed to maintenance of the vital functions of an organism, a gastric lavage. Purpose of absorbent carbon and laxatives should be carried out only if there passed no more than one hour from the moment of administration of drug.

At the expressed lowering of arterial pressure or a vascular collapse it is necessary to enter intravenous infusion solutions and/or to use sympathomimetic medicines. At development of extrapyramidal symptoms appoint anticholinergic medicines (for example, trigeksifenidit). Constant medical observation should be continued before total disappearance of symptoms of intoxication. There is no specific antidote.

Storage conditions:

To store in the place protected from light at a temperature not over 25 ºС. To store in the place, unavailable to children. Period of validity 3 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 0,25 mg, 1 mg, 2 mg, 3 mg and 4 mg. 5, 10, 15, 20 or 30 tablets in a blister strip packaging from a film of polyvinyl chloride and aluminum foil. 20, 30, 60 or 90 tablets in bank from polyethylene of high density. 4 blister strip packagings on 5 tablets, 2, 3, 6 or 9 blister strip packagings on 10 tablets, 2, 4 or 6 blister strip packagings on 15 tablets, 1 or 3 blister strip packagings on 20 tablets, 1, 2 or 3 blister strip packagings on 30 tablets or one bank together with the instruction on a medical use in a pack from a cardboard.