Risperidon

General characteristics. Structure:

Active ingredient: 1 mg or 2 mg of a risperidon in 1 tablet.

Excipients: lactoses monohydrate, cellulose microcrystallic, magnesium stearate.

Cover: Опадрай II 85F28751 white (polyvinyl alcohol, titanium dioxide, macrogoal, talc.

Pharmacological properties:

Pharmacodynamics. Risperidon is the selection monoaminergichesky antagonist with unique properties. It has high affinity to serotonergic 5-HT2-retseptoram and dofaminergichesky D2 receptors. Risperidon also communicates with (α1-адренергическими receptors and, slightly more weakly, with H1-gistaminergichesky and α2-адренергическими receptors. Risperidon has no affinity to cholinergic receptors. Risperidon reduces productive symptomatology of schizophrenia, causes smaller suppression of motor activity and to a lesser extent induces a katalepsy, than classical neuroleptics. The balanced central antagonism to serotonin and dopamine probably reduces tendency to extrapyramidal side effects and expands therapeutic influence of drug with coverage of negative and affective symptoms of schizophrenia.

Pharmacokinetics. Absorption. Risperidon after intake is completely absorbed, reaching the maximum concentration in a blood plasma in 1-2 hours. Absolute bioavailability of a risperidon after intake makes 70%. Relative bioavailability after intake of a risperidon in the form of tablets makes 94% when comparing with risperidony in the form of solution. Food does not exert impact on drug absorption therefore рисперидон it is possible to appoint irrespective of meal. Equilibrium concentration of a risperidon in an organism at most of patients is reached within 1 day. Equilibrium concentration of a 9-gidroksirisperidon is reached within 4-5 days.

Distribution. Risperidon is quickly distributed in an organism. The volume of distribution makes 1-2 l/kg. In a blood plasma рисперидон contacts albumine and an alfa1-acid glycoprotein. Risperidon for 90% communicates proteins of plasma, 9-gidroksirisperidon - for 77%.

Metabolism and removal. 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 reduced metabolism much more slowly. Though patients with intensive metabolism have lower concentration of a rispsrndon 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 of CYP2D6.

Some other way metabolism of a risperidon N-dszalkilirovaniye is. The researches in vitro on microsomes of a liver of the person showed what рисперидон in clinically significant concentration, in general, does not inhibit metabolism of the medicines which are exposed to biotransformation isoenzymes of system of P450 cytochrome including CYP1A2, CYP2A6, CYP2C8/9/10, CYP2D6, CYP2E1, CYP3A4 and CYP3A5. In a week after the beginning of administration of drug of 70% of a dose 14% - with a stake are removed with urine. In urine рисперидон together with 9-gidroksirisperidony make 35-45% of a dose. Other quantity is made by inactive metabolites. After intake at patients with psychosis рисперидон about 3 hours are brought out of an organism with an elimination half-life (T1/2). T1/2 of a 9-gidroksirisperidon and active antipsychotic fraction makes 24 hours.

Linearity. Concentration of a risperidon in a blood plasma is directly proportional to the accepted dose in the therapeutic range of doses.

Elderly patients and patients with a liver and renal failure. After a single dose of a risperidon at elderly patients of concentration of active antipsychotic fraction in a blood plasma were on average 43% more, T1/2 lasted for 38% longer, and the clearance decreased by 30%. At patients with a renal failure increase in plasma concentration and decrease in clearance of active antipsychotic fraction on average by 60% was observed. At patients with a liver failure of concentration of a risperidon in a blood plasma did not change, however average concentration of free fraction of a risperidon increased by 35%.

Children. The pharmacokinetics of a risperidon, 9-gidroksirisperidon and active antipsychotic fraction at children is comparable to that at adult patients.

Influence of a floor, race and smoking. The population pharmacokinetic analysis did not reveal visible effect of a floor, race or smoking on pharmacokinetics of a risperidon and active pharmacokinetic fraction.

Indications to use:

- schizophrenia at adults;

- the maniacal episodes connected with bipolar disorder, average and heavy degree at adults;

- short-term (up to 6 weeks) a symptomatic treatment of continuous aggression at patients with the dementia caused by Alzheimer's disease, average and heavy degree, which is not giving in to not pharmacological methods of correction and when there is a risk of infliction of harm by the patient to itself and other persons;

- short-term (up to 6 weeks) a symptomatic treatment of the continuous aggression at disorders of behavior at children of 5 years and mentally retarded teenagers diagnosed according to DSM-IV (The guide to diagnosis and statistics of mental disorders, the 4th edition, the USA) 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, washing down with water.

The termination of administration of drug is recommended to be carried out gradually. Acute symptoms of "cancellation", including nausea, vomiting, sweating and sleeplessness, were observed very seldom after the sharp termination of reception of high doses of antipsychotic drugs.

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.

Schizophrenia. Adults. Risperidon can be appointed one or two times a day. An initial dose inside - 2 mg a day. For the second day it is necessary to increase a dose to 4 mg a day. From this point the dose can or be kept at the previous level, or to correct individually if necessary. 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.

Elderly patients. The initial dose of 0,5 mg on reception twice a day is recommended. It is possible to increase a dosage individually on 0,5 mg twice a day to 1-2 mg twice a day.

Children. Due to the lack of data on safety and efficiency, drug Risperidon is not recommended for use to the children up to 18 years having schizophrenia.

The maniacal episodes connected with bipolar disorder of average and heavy degree. Adults. The recommended initial dose of drug - 2 mg a day on one reception.

If necessary this dose can be raised not earlier than in 24 hours on 1 mg, an optimum dose, in most cases, are 1-6 mg a day. Use of doses higher than 6 mg a day was not studied. As well as at any symptomatic therapy during treatment it is necessary to estimate expediency of continuation of treatment by drug Risperidon.

Elderly patients. Due to the insufficient experience of use for elderly it is necessary to use with care drug in this age group. The initial dose of 0,5 mg on reception twice a day is recommended. If necessary it is possible to increase a dosage individually on 0,5 mg twice a day to 1-2 mg twice a day.

Continuous aggression at patients with dementia caused by Alzheimer's disease of average and heavy degree

The initial dose on 0,25 mg of a pas reception twice a day is recommended. If necessary it is possible to increase a dosage individually on 0,25 mg 2 times a day, not more often than every other day. For most of patients an optimum dose are 0,5 mg twice a day. However reception on 1 mg 2 times a day is shown to some patients. On reaching an optimum dose administration of drug can be recommended once a day. Rispsridon should not be applied longer than 6 weeks.

Continuous aggression at disorder of behavior at children from 5 to 18 mentally retarded years, diagnosed according to DSM-IV

Patients with the body weight of 50 kg and more: an initial dose - 0,5 mg of 1 times a day. Increase in a dose - on 0,5 mg/days not more often than every other day. An optimum dose - 1 mg/days.

Patients with body weight less than 50 kg: an initial dose - 0,25 mg of 1 times a day. Increase in a dose - on 0,25 mg/days, not more often than every other day. An optimum dose - 0,5 mg/days. However reception on 0,25 mg a day whereas some need increase in a dose up to 0,75 mg a day is more preferable to some patients. Long reception of Risperidon at teenagers has to be carried out under constant control of the doctor.

As well as for any other symptomatic therapy, expediency of continuation of treatment Risperidon has to be estimated and confirmed by drug regularly.

Diseases of a liver and kidneys. At patients with diseases of kidneys ability of removal of active antipsychotic fraction in comparison with other patients is reduced. At patients with diseases of a liver the increased concentration of free fraction of a risperidon in a blood plasma is observed.

The initial and maintenance dose according to indications has to be reduced twice, increase in a dose at patients with diseases of a liver and kidneys has to be carried out more slowly. Risperidon it is necessary to appoint with care at this category of patients.

Features of use:

Pregnancy and lactation. Safety of a risperidon at pregnant women was not studied. If the woman accepted antipsychotic drugs (including рисперидон) in the third trimester of pregnancy, newborns have a risk of emergence of extrapyramidal frustration and/or a withdrawal of varying severity. These symptoms can include agitation, a hypertension, hypotonia, a tremor, drowsiness, respiratory disturbances and disturbance of feeding.

At pregnancy рисперидон it is possible to use only if the advantage for mother exceeds risk of development of side effects in a fruit and the child. In need of the termination of administration of drug during pregnancy it is necessary to carry out cancellation of a preprat gradually.

As рисперидон and 9-gidroksirisperidon get into breast milk, the women using drugs of a risperidon should not nurse.

Fertility. As well as in cases of use of other antagonists of D2-retseptorov of a dopamine, рисперидон increases the content of prolactin in a blood plasma. Giperprolaktinemiya can suppress production of hypothalamic gonadotrophin-releasing-hormone that leads to reduction of secretion of a pituitary gonadotrophin. It, in turn, can oppress reproductive function by disturbance of synthesis of sex hormones both at women, and at men.

During preclinical trials the corresponding phenomena were not observed.

When developing orthostatic hypotension, especially in an initial stage of selection of a dose, it is necessary to consider a question of a dose decline.

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. Average age of the died patients makes 86 years (range of 67-100 years).

For the elderly patients with dementia taking the peroral forms of a risperidon the increased mortality at the patients accepting furosemide and рисперидон was observed (7,3%; average age of 80 years. range of 67-90 years). It is not installed the pathophysiological mechanisms explaining this observation. It is necessary to observe extra care at purpose of drug in such cases. Increase in mortality at the patients accepting other diuretics along 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. In placebo - controlled randomized clinical trials at the patients with dementia accepting some atypical antipsychotic drugs increase in risk of cerebrovascular side reactions approximately by 3 times was observed. The integrated data of 6 placebos - the controlled researches including generally elderly patients with dementia (the age is more senior than 65 years), show that cerebrovascular side effects (serious and frivolous) arose at 3,3% (33/1009) patients accepting рисперидон and at 1,2% (8/712) patients accepting placebo. The ratio of risks made 2,96 (1,34; 7,50) at a confidence interval of 95%. The mechanism of increase in risk is unknown. Increase in risk is not excluded also for other antipsychotic drugs, and also for other populations of patients. Drug Risperidon has to be used with care at patients with risk factors of developing of a stroke.

The risk of emergence of cerebrovascular side reactions is much higher at patients with dementia of the mixed or vascular type, in comparison with patients with Altsgeymerovsky dementia. Therefore patients with dementia of any type, except Altsgeymerovskaya, should not accept drug Risperidon.

Doctors should estimate a ratio risk/advantage of use of drug Risperidon at elderly patients with dementia, in view of harbingers of risk of a stroke individually at each patient. The patients and persons who are looking after them have to be warned that it is necessary to report about signs and symptoms of cerebrovascular events immediately: such as sudden weakness or numbness in a face, legs, hands, and also difficulty of the speech and a vision disorder. At the same time all possible options of treatment, including the termination of administration of drug have to be considered. Drug Risperidon can be used only for short-term treatment of continuous aggression at patients with dementia caused by Alzheimer's disease, average and heavy degree as addition to not pharmacological methods of correction, in case of their inefficiency or limited efficiency and when there is a risk of infliction of harm by the patient to itself or other persons.

Assessment of a condition of patients and need of continuation of therapy risperidony has to be carried out by the doctor regularly.

Orthostatic hypotension. Due to the α-blocking action of a risperidon there can be orthostatic hypotension, 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. At 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 (see the section "Route of Administration and Doses").

Leukopenia, neutropenia, agranulocytosis. The leukopenia, a neutropenia, an agranulocytosis were noted at use of antipsychotic means, including at drug use Risperidon. The agranulocytosis was noted very seldom during post-marketing observations. To patients with clinically significant reduction of quantity of leukocytes in the anamnesis or about drug - the dependent leukopenia / neutropenia recommends carrying out an integrated analysis of blood within the first months of therapy, the treatment termination by drug Risperidon has to be considered at the first clinically significant reduction of quantity of leukocytes in the absence of other possible reasons. Patients with clinically significant neutropenia are recommended to be observed regarding temperature increase or emergence of symptoms of an infection and to begin treatment immediately at emergence of such symptoms. Patients with a severe form of a neytropepiya (absolute quantity of neutrophils less than 1Õ109/l) have to stop drug use рисперидон until the quantity of leukocytes is not normalized.

Venous thromboembolism. At use of antipsychotic drugs cases of a venous thromboembolism were noted. 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.

Late dyskinesia and extrapyramidal frustration. The drugs having properties of antagonists of dopamine receptors can cause поздню dyskinesia which is characterized by the rhythmic involuntary movements, preferential language and/or mimic muscles. There are messages that emergence of these symptoms is risk factor for development of late dyskinesia. Risperidon less than classical neuroleptics, emergence of extrapyramidal symptoms causes. The 13th case of emergence of signs and symptoms of late dyskinesia it is necessary to consider a question of cancellation of all antipsychotic drugs.

Malignant antipsychotic syndrome. At development of the malignant antipsychotic syndrome which is characterized by a hyperthermia, muscular rigidity, instability of autonomous functions, disturbances of consciousness and increase in activity of a kreatinfosfokinaza (the myoglobinuria - рабдомиолиз - and an acute renal failure can be also observed), it is necessary to cancel all antipsychotic medicines, including Risperidon.

Parkinson's disease and dementia with Levi's little bodies. Purpose of antipsychotic drugs, including рисперидон, to patients with Parkinson's disease or dementia with Levi's little bodies has to be carried out with care as at both groups of patients the risk of development of a malignant antipsychotic syndrome is increased and sensitivity to antipsychotic drugs is increased (including obtusion of painful sensitivity, confusion of consciousness, postural instability with frequent falling and ekstrapiramidiy symptoms).

Hyperglycemia and diabetes mellitus. At treatment drug Risperidon observed a hyperglycemia, development of a diabetes mellitus and an aggravation of already available diabetes mellitus. Establishment of interrelation between use of atypical antipsychotic drugs and disturbance of exchange of glucose is complicated by the increased risk of development of a diabetes mellitus in patients with schizophrenia and prevalence of a diabetes mellitus in the general population. Considering these factors, interrelation between use of atypical antipsychotic drugs and development of the side effects connected with a hyperglycemia it is established not completely. At all patients it is necessary to carry out clinical control on existence of symptoms of a hyperglycemia and diabetes mellitus (see the section "Side effect").

Giperprolaktinemiya. In researches on cultures of fabrics it is shown 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 about potentially prolactin - dependent tumors.

Increase in body weight. At treatment drug Risperidon observed significant increase in body weight. It is necessary to carry out control of body weight of patients at therapy by drug. Patients should recommend to refrain from an overeating in connection with a possibility of increase in body weight.

Lengthening of QT of an interval. As well as in case of other antipsychotic means, patients should be careful at purpose of drug Risperidon with cardiac arrhythmias in the anamnesis, to patients with inborn lengthening of an interval of QT and at combined use with the drugs increasing QT interval.

Priapism. The drugs having alpha and adrenoceptor blocking effects can cause a priapism. In post-market researches of drug Risperidon messages on development of a priapism were received.

Regulation of body temperature. Disturbance of ability of an organism to regulate temperature very much is attributed to antipsychotic drugs as undesirable effect. It is necessary to be careful at purpose of drug Risperidon to patients with states which can promote increase in internal body temperature, to which the intensive exercise stress, organism dehydration, influence of high external temperatures or simultaneous use of drugs with anticholinergic activity belong.

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

Spasm/threshold of convulsive activity. Ability of atypical neuroleptics to reduce a threshold of convulsive activity is known. Risperidon has to be applied with care at patients with epilepsy and spasms in the anamnesis or with other medical states at which the convulsive threshold can decrease.

Intraoperative Syndrome of a Flabby Iris (ISFI). ISDR was observed during performing surgery concerning existence of a cataract at the patients receiving therapy by the drugs having activity of antagonists α1-адренорецепторов including drugs of a risperidon. 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 antagonists 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.

Renal and liver failure. In spite of the fact that drug Risperidon was not investigated at patients with a renal or liver failure, it is necessary to be careful at use of drug for such groups of patients.

Sinddr of cancellation. At the termination of treatment the gradual dose decline is recommended. Withdrawal symptoms: very seldom - nausea, vomiting, perspiration and sleeplessness at the sharp termination of reception of high doses of antipsychotic drugs.

Use for children and teenagers. Before purpose of drug Risperidon children or mentally retarded teenagers need to carry out careful assessment of their state regarding existence of the physical or social reasons of an agressive behavior, such as pain or inadequate requirements of the social environment. Sedation of a risperidon has to be traced carefully in this population because of possible influence on ability to training. Change of time of reception of a risperidon can improve control of influence of sedation on attention of teenagers and children. Use of a risperidon was connected with average increase in body weight and an index of body weight. Changes of growth during the long-term researches were within the expected age norms. Influence of long-term reception of a risperidon on sexual development and growth is completely not studied. Due to the possible influence of a long giperprolaktinemiya on growth and sexual development at children and teenagers, regular clinical assessment of the hormonal status, including measurement of growth, weight, observation of sexual development, a menstrual cycle and others possible prolactin - dependent effects has to be carried out. During treatment by Risperidon's drug regular verification of presence of extrapyramidal symptoms and other motor disturbances has to be carried out.

Excipients. Drug Risperidon, tablets, film coated, contains lactose. Patients with the rare hereditary diseases connected with intolerance of a galactose, deficit of lactase or glyukozo-galaktozny malabsorption should not appoint drug Risperidon, tablets, film coated.

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

Side effects:

Side effects of drug Risperidon are given in therapeutic doses with distribution on frequencies and system and organ classes. Frequency of side effects was classified as follows: very frequent (≥ 1/10 cases), frequent (≥ 1/100 and <1/10 cases), infrequent (≥ 1/1000 and <1/100 cases), rare (≥ 1/10000 and <1/1000 cases), very rare (<1/10000 cases) and with an unknown frequency (it is impossible to estimate frequency from available data).

The most often observed undesirable reactions (emergence frequency ≥ 10%) were: parkinsonism, headache and sleeplessness, sedation/drowsiness. Dozozavisimy undesirable reactions: parkinsonism and akathisia.

Infections: very often - elderly people with dementia have infections of urinary tract; often - pneumonia, flu, bronchitis, upper respiratory tract infections, infections of urinary tract; infrequently - pharyngitis, sinusitis, viral infections, ear infections, tonsillitis, an inflammation of a hypodermic fatty tissue, average otitis, infections of eyes, the localized infections, an acariasis, respiratory infections, cystitis, an onychomycosis; seldom - chronic average otitis.

Disturbances of laboratory and tool indicators: often - increase in level of prolactin, increase in body weight; infrequently - lengthening of an interval of QT of a pas to the electrocardiogram, disturbance of an ECG, increase in level of transaminases, reduction of quantity of leukocytes in blood, fervescence, increase in quantity of eosinophils in blood, reduction of an urovnyagemoglobin. increase in level kreatinfosfokbnazy, increase in level of triglycerides; seldom - fall of temperature of a body.

From cardiovascular system: often - tachycardia; infrequently - an atrioventricular block, blockade of the right or left legs of a ventriculonector, bradycardia, heartbeat, disturbance of conductivity of heart, a sinus arrhythmia; fibrillation of auricles.

Hematologic disturbances and disturbances of lymphatic system: infrequently - anemia, thrombocytopenia; seldom - a granulocytopenia; with an unknown frequency - an agranulocytosis.

From a nervous system: very often - parkinsonism, a headache, drowsiness/sedation; often - an akathisia, dizziness, a tremor, dystonia, a lethargy, dyskinesia; infrequently - lack of reaction to irritants, a loss of consciousness, a syncope, dejectedness, a stroke, the passing ischemic attack, a dysarthtia, disturbance of attention, a hypersomnia, postural dizziness, balance disturbance, late dyskinesia, disturbance of the speech, a lack of coordination, вертиго, a hypesthesia; seldom - a malignant antipsychotic syndrome, a diabetic coma, cerebrovascular disturbances, cerebral ischemia, disturbance of movements.

Ophthalmologic disturbances: often - indistinct sight; infrequently - conjunctivitis, an ocular hyperemia, a vision disorder, allocations from eyes, area hypostasis around eyes, a xerophthalmus, the strengthened dacryagogue, a photophobia; seldom - decrease in visual acuity, involuntary rotations of eyeglobes, glaucoma; with an unknown frequency - an intraoperative syndrome of a sluggish iris.

From an ear and a labyrinth: infrequently - ear pain, a sonitus.

Respiratory, thoracic disturbances and disturbances of a mediastinum: often - short wind, nasal bleeding, cough, a nose congestion, pain in a throat and a throat; infrequently - goose breathing, aspiration pneumonia, stagnation in lungs, breath disturbance, wet rattles, obstruction of respiratory tracts, a dysphonia; seldom - an apnoea syndrome in a dream, a hyperventilation.

From digestive tract: often - vomiting, diarrhea, a lock, nausea, pains in a stomach, dyspepsia, dryness in a mouth, discomfort in a stomach; infrequently - a dysphagy, gastritis, a meteorism, an incontience a calla, hypersalivation, a fekaloma; seldom - impassability of intestines, pancreatitis, hypostasis of lips, a cheilitis.

From kidneys and urinary tract: often - enuresis; infrequently - an urination delay, a dysuria, an urine incontience, a pollakiuria.

From skin and hypodermic fabrics: often - rash, an erythema; infrequently - a Quincke's edema, damage of skin, disturbance of integuments, an itch, an acne, disturbance of coloring of skin, an alopecia, seborrheal dermatitis, a xeroderma, a hyperkeratosis; seldom - dandruff.

From a musculoskeletal system and connecting fabric: often - an arthralgia, dorsodynias, extremity pains; infrequently - muscular weakness, a mialgiya, neck pains, swelling of joints, disturbances of a pose, constraint in joints, muscular stethalgias; seldom - рабдомиолиз.

From endocrine system: seldom - disturbance of production of antidiuretic hormone.

Disturbances of metabolism and food: often - increase in appetite, a loss of appetite; infrequently - a diabetes mellitus, anorexia, a polydipsia, a hyperglycemia; seldom - a hypoglycemia; very seldom - diabetic ketoacidosis; with an unknown frequency - water intoxication.

Vascular disorders: infrequently - hypotension, orthostatic hypotension, "inflows".

The general disturbances and the phenomena caused by administration of drug: often - a pyrexia, fatigue, peripheral hypostasis, an adynamy, pains in a thorax; infrequently - a face edema, gait disturbance, feeling sick, sluggishness, a grippopodobny state, thirst, discomfort in a thorax, a fever; seldom - the general hypostasis, a hypothermia, a syndrome of "cancellation", a cold snap of extremities.

From immune system: infrequently - hypersensitivity; seldom - medicinal гиперчувствителыюсть; with an unknown frequency - anaphylactic reaction, toksiko-allergic dermatitis.

Gepatobiliarny disturbances: seldom - jaundice.

From reproductive system and mammary glands: infrequently - an amenorrhea, sexual dysfunction, erectile dysfunction, disturbance of an ejaculation, a galactorrhoea, a gynecomastia, disturbance of a menstrual cycle, allocation from a vagina; with an unknown frequency - a priapism.

Mental disturbances: very often - sleeplessness; often - concern, excitement, sleep disorders; infrequently - confusion of consciousness, a mania, decrease a libido, slackness, nervousness; seldom - an anorgazmiya, affect flattening.

Class effects. As well as at use of other antipsychotic drugs, very exceptional cases of increase in a tooth of QT were celebrated in the post-marketing period of observation. Others a class effects from cardiovascular system, observed at use of antipsychotic drugs which increase QT tooth, include: ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac standstill and bidirectional ventricular tachycardia.

Venous thromboembolism. Cases of a venous thromboembolism, including a pulmonary embolism and cases of a deep vein thrombosis, were observed when using antipsychotic drugs.

Increase in body weight. In placebo - controlled clinical trials at patients with maniacal episodes the number of cases of increase in body weight for 7% and more after 3 weeks of treatment was comparable in the group accepting drug of a risperidon (2,5%) and in the group accepting placebo (2,4%), and in group of active control there was a little more (3,5%). At children with disorders of behavior during long-term clinical trials body weight increased on average by 7,3 kg after 12 months of therapy whereas the expected increase in body weight at children of 5-12 years with normal development makes 3-5 kg a year. From 12-16 years increase in body weight made 3-5 kg a year for girls and about 5 kg for boys.

Additional information on special populations of patients. Side effects which were noted with a bigger frequency at elderly patients with dementia and at children, than than at adult patients are described below:

Elderly patients with dementia. The passing ischemic attack and a stroke were observed during clinical trials with a frequency of 1,4% and 1,5% respectively at elderly patients with dementia. Besides, the following side effects were noted at elderly patients with dementia with a frequency ≥ 5% and with a frequency, at least, twice exceeding that in other populations of patients: infections of urinary tract, peripheral hypostasis, lethargy and cough.

Children. The following side effects were noted at children from 5 to 17 years with a frequency, at least, twice exceeding that in other populations of patients during clinical trials: drowsiness/sedation, fatigue, a headache, increase in appetite, vomiting, upper respiratory tract infections, a nose congestion, pain in a stomach, dizziness, cough, a pyrexia, a tremor, diarrhea, enuresis.

One of the undesirable reactions which are most often found at children is fervescence.

Interaction with other medicines:

As well as in a case with other antipsychotic drugs it is necessary to be careful at joint purpose of drug Risperidon with the drugs extending QT interval, for example, with antiarrhytmic drugs (for example, quinidine, Disopyramidum, procaineamide, пропафенон, Amiodaronum, соталол), tricyclic antidepressants (for example, amitriptyline), tetracyclic antidepressants (for example, Maprotilinum), some antihistaminic drugs, other antipsychotic drugs, some antimalarial drugs (quinine, мефлохин, etc.), the drugs causing an electrolytic imbalance (a hypopotassemia, a hypomagnesiemia), bradycardia or the drugs inhibiting hepatic metabolism of a risperidon. This list is not exhaustive.

Taking into account that рисперидон has effect 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, opiates, antihistaminic drugs and benzodiazepines (.хлордиазепоксид) because of the increased risk of sedation. Risperidon reduces efficiency of a levodopa and other agonists of dopamine.

Clozapine reduces clearance of a risperidon.

Use of a risperidon with paliperidony is not recommended as it leads to potentiation of antipsychotic effects.

When using carbamazepine decrease in concentration of active antipsychotic fraction of a risperidon in plasma is noted. Similar effects can be observed when using other inductors of liver enzymes of P450 cytochrome (an isoenzyme of CYP3A4 and R-glikoiroteina) - phenobarbital, Phenytoinum, rifampicin. At appointment and after cancellation of carbamazepine or other inductors of an isoenzyme SYRZA4/R glycoprotein it is necessary to correct a drug dose Risperidon.

The haloperidol inhibits an isoenzyme of CYP2D6 of P450 cytochrome and can interfere with formation of a 9-gidroksirisperidon, strengthen (mutually) effect. When sharing care is necessary.

Fenotiazina concentration of a risperidon in plasma can raise (Chlorpromazinum), tricyclic antidepressants (Imipraminum) and some β-adrenoblockers, however it does not influence concentration of active antipsychotic fraction.

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

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

Erythromycin, CYP3A4 isoenzyme inhibitor, does not influence pharmacokinetics of a risperidon and active antipsychotic fraction.

Fluoxetine and пароксетин. Inhibitors of an izofermeit CYP2D6 can increase concentration of a risperidon in plasma (to a lesser extent - active antipsychotic fraction). At appointment and after fluoxetine cancellation / пароксетина it is necessary to correct a drug dose Risperidon. Other inhibitors of an isoenzyme of CYP2D6 (quinidine) can change similarly concentration of a risperidon in plasma.

Verapamil - inhibitor of an isoenzyme CYP3A4 and R-glycoprotein - increases concentration of a risperidon in plasma.

At simultaneous use of a risperidon with furosemide, and also with other diuretics, it must be kept in mind risk of the increased mortality (the pathophysiological mechanism is unknown).

Topiramat moderately reduces bioavailability of a risperidon, but not active antipsychotic fraction.

Cholinesterase inhibitors (Galantaminum and donepezil) have no clinically significant effect on pharmacokinetics of a risperidon and active antipsychotic fraction.

The combined use of a respiridon with psychostimulants (methylphenidate) at children does not influence pharmacokinetics and efficiency of a risperidon.

At use of a risperidon together with other drugs highly contacting proteins of plasma, clinically expressed replacement of any drug from protein fraction of plasma is not observed.

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

Risperidon has no clinically significant effect on pharmacokinetics of lithium, valproic acid, digoxin or topiramat.

Contraindications:

- hypersensitivity to drug components;

- deficit of lactase, lactose intolerance, glyukozo-galaktozny malabsorption;

- at treatment of continuous aggression at disorder of behavior at mentally retarded children of average and heavy degree - children's age up to 5 years; at other indications - children's age up to 15 years.

With care:
- at patients with diseases of cardiovascular system (chronic heart failure, the postponed myocardial infarction, disturbances of conductivity of heart);

- at dehydration and a hypovolemia, simultaneous use of furosemide;

- at patients with disturbance of cerebral circulation;

- at patients with Parkiison's disease;

- at spasms (including in the anamnesis);

- at patients with a heavy renal or liver failure (see the section "Route of Administration and Doses");

- at abuse of medicines or medicinal dependence;

- at the states contributing to development of tachycardia like "pirouette" (bradycardia, disturbance of electrolytic balance, the accompanying reception of the medicines extending QT interval);

- patients with the phenomena have neutropenias;

- at patients with a diabetes mellitus;

- at a hyperglycemia;

- at patients with a giperprolaktinemiya;

- before cataract surgery;

- at patients with a brain tumor, intestinal impassability, at acute overdose of drugs, with a syndrome to Reja (the antiemetic effect of a risperidon can mask symptoms of these states);

- patients with existence of risk factors have development of a thromboembolism of venous vessels;

- at patients with dementia with Levi's little bodies;

- at patients of advanced age with cerebrovascular dementia;

- during pregnancy and breastfeeding.

Overdose:

Symptoms: strengthening of pharmacological effects - drowsiness, sedation, consciousness oppression, tachycardia, arterial hypotension, extrapyramidal frustration, spasms. Bidirectional "piruetny" 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: creation of conditions for free passability of respiratory tracts for ensuring adequate oxygenation and ventilation, a gastric lavage (after an intubation, if the unconscious patient) and purpose of absorbent carbon in a combination to purgatives. The symptomatic therapy directed to maintenance of the vital functions of an organism.

At a lowering of arterial pressure and a vascular collapse - intravenously to administer infusion solutions and/or the sympathomimetic drugs. In case of development of acute extrapyramidal symptoms - anticholinergic medicines. For timely diagnosing of possible disturbances of a heart rhythm it is necessary to begin monitoring of the electrocardiogram (ECG) as soon as possible. Constant medical observation and monitoring of an ECG will see to total disappearance of symptoms of intoxication. The specific antidote is absent.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 1 mg, 2 mg. Packaging: on 10 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 50 or 100 tablets in bank of polymeric. On 1 or 2 blister strip packagings or 1 bank polymeric together with the application instruction in a pack from a cardboard.