Rispolept Kviklet

General characteristics. Structure:

Active agent: рисперидон – 1 mg.

Excipients: pitch the poly(acrylic (полиакрилекс) – 6 mg, gelatin of type A – 6,5 mg, Mannitolum – 8 mg, glycine – 6 mg, симетикон – 0,02 mg, carbomer of 34 000 - 0,15 mg, sodium hydroxide – 0,078 mg, aspartame – 0,5 mg, dye ferrous oxide red – 0,00625 mg, a peppermint of leaves oil – 0,3 mg.

Active agent: рисперидон – 2 mg.

Excipients: pitch the poly(acrylic (полиакрилекс) – 12 mg, gelatin of type A – 6,5 mg, Mannitolum – 8 mg, glycine – 6 mg, симетикон – 0,02 mg, carbomer 934P - 0,15 of mg, sodium hydroxide – 0,078 mg, aspartame – 0,75 mg, dye ferrous oxide red – 0,0625 mg, xanthane gum – 0,025 mg, a peppermint of leaves oil – 0,3 mg.

Pharmacological properties:

Pharmacodynamics.

Risperidon is a selection monoaminergichesky antagonist, has high affinity to serotonergic 5-HT2 and dofaminergichesky D2 receptors. Risperidon communicates also with α1-адренергическими receptors and, slightly more weakly, with H1-gistaminergichesky and α2-адренергическими receptors. Risperidon does not possess a tropnost 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 oral administration is completely absorbed, reaching the maximum concentration in 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 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 CYP 2D6 isoenzyme to a 9-gidroksirisperidon who possesses pharmacological action similar to a risperidon. Risperidon and 9-gidroksirisperidon make active antipsychotic fraction. The isoenzyme of CYP 2D6 is subject to genetic polymorphism. At patients with intensive metabolism on CYP 2D6 isoenzyme рисперидон quickly turns in 9-гидроксирисперидон 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 of CYP 2D6.

Some other way metabolism of a risperidon N-dealkylation 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 P450 system isoenzymes including CYP 1A2, CYP 2A6, CYP 2C8/9/10, CYP 2D6, CYP 2E1, CYP 3A4 and CYP 3A5. 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 oral administration at patients with psychosis рисперидон about 3 hours are brought out of an organism with an elimination half-life (T1/2). T1/2 9-gidroksirisperidon and active antipsychotic fraction make 24 hours.

Linearity.

Concentration of a risperidon in 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 plasma were on average 43% more, the elimination half-life lasted for 38% longer, and the clearance decreased by 30%. At patients with a renal failure increase in plasma concentration an iponizheniye of clearance of active antipsychotic fraction on average for 60% was observed. At patients with a liver failure of concentration of a risperidon in 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:

- treatment of schizophrenia at adults and children of 13 years;

- treatment of the maniacal episodes connected with bipolar disorder, average and heavy degree at adults and children of 10 years;

- short-term (up to 6 weeks) 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 or other persons;

- short-term (up to 6 weeks) a symptomatic treatment of continuous aggression in the structure of disorder of behavior at children of 5 mentally retarded years 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:

Schizophrenia.

Adults.

Рисполепт® Kviklet can be appointed one or two times a day. An initial dose of the drug Rispolept® of Kviklet – 2 mg a day. For the second day it is possible 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 both lower 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 not recommended 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 by 0,5 mg twice a day to 1-2 mg twice a day.

Children of 13 years.

The initial dose of 0,5 mg on reception once a day in the morning or is recommended in the evening. If necessary it is possible to increase a dosage 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.

The maniacal episodes connected with bipolar disorder.

Adults. The recommended initial dose of drug – 2 mg a day at one time. If necessary this dose can be raised not less than in 24 hours on 1 mg a day. For most of patients an optimum dose are 1-6 mg a day. Use of doses higher than 6 mg a day at patients with maniacal episodes was not studied. As well as for any other symptomatic therapy, expediency of continuation of treatment Kviklet has to be estimated and confirmed by the drug Rispolept® regularly.

Elderly patients. The initial dose of 0,5 mg on reception twice a day is recommended. It is possible to increase a dosage individually by 0,5 mg twice a day to 1-2 mg twice a day. It is necessary to be careful in connection with limited experience of use of drug for elderly patients.

Children of 10 years. The initial dose of 0,5 mg on reception once a day in the morning or is recommended in the evening. If necessary it is possible to increase a dosage 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.

Continuous aggression at patients with dementia caused by Alzheimer's disease.

The initial dose on 0,25 mg on 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. Рисполепт® by Kviklet it should not be applied more than 6 weeks at continuous aggression at patients with dementia caused by Alzheimer's disease. During treatment the condition of patients has to be estimated on a regular basis, also as well as need of continuation of therapy.

Continuous aggression in structure of disorder of behavior.

Children from 5 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 raised on 0,5 mg a day, not more often than every other day. For most of patients an optimum dose is the dose of 1 mg a day. However reception on 0,5 mg a day whereas some need increase in a dose up to 1,5 mg a day is more preferable to some patients.

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 raised on 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 a day. 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. As well as for any other symptomatic therapy, expediency of continuation of treatment Kviklet has to be estimated and confirmed by the drug Rispolept® regularly. Use for children is younger than 5 years it is not recommended in view of lack of data.

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.

Рисполепт® it is necessary to appoint Kviklet with care at this category of patients.

Route of administration.

Inside. Meal does not exert impact on drug absorption. It is necessary to open the blister just before reception of tablets. It is necessary to remove accurately a foil for extraction of a tablet. It is impossible to squeeze out a tablet as it can be damaged. It is necessary to take a tablet from the blister dry hands then immediately to place it on language. The tablets Rispolept® of Kviklet begin to break up in a mouth within several seconds. If necessary it is possible to use water.

In need of use of doses less than 1,0 mg are recommended to use the drug Rispolept®, solution for intake.

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 the drug Rispolept® of Kviklet recommends 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 therapy by the drug Rispolept® of Kviklet is recommended to be begun instead of the following planned injection. Periodically it is necessary to estimate need of continuation of the current therapy by protivoparkinsonichesky drugs.

Features of use:

Use for elderly patients with dementia.

The increased mortality at 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). The data collected as a result of two extensive observation researches show that the elderly patients with dementia undergoing treatment by typical antipsychotic drugs also have a little increased risk of death in comparison with the patients who are not undergoing treatment. Not enough data for exact assessment of this risk are at the moment collected. Also the reason of increase in this risk is unknown. Also degree in which increase in mortality can be applicable to antipsychotic drugs, but not to features of this group of patients is not defined.

Combined use with furosemide.

At elderly patients with dementia the increased mortality at a concomitant use of furosemide and a risperidon was observed orally (7,3%, average age of 89 years, range of 75-97 years) in comparison with the group accepting only рисперидон (3,1%, middle age 84 years, the range of 70-96 years) and the group accepting only furosemide (4,1%, average age of 80 years, range of 67-90 years). Increase in mortality of the patients accepting рисперидон together with furosemide was observed during the 2nd of 4 clinical trials. Combined use of a risperidon with other diuretics (generally with thiazide diuretics in small doses) was not followed by increase in mortality.

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. Before appointment it is necessary to estimate carefully a ratio risk/advantage. 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.

At elderly patients with dementia increase in side effects from cerebrovascular system (acute and passing disorders of cerebral circulation) was observed, including fatal cases at patients (average age of 85 years, range of 73-97 years) at use of a risperidon in comparison with placebo.

Cardiovascular effects. In placebo - controlled clinical trials at the patients with dementia accepting some atypical antipsychotic drugs increase in risk of cerebrovascular side effects approximately by 3 times was observed. The integrated data of 6 placebos - the controlled researches including generally elderly patients with dementia (age more 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. Рисполепт® by Kviklet it has to be applied with care at patients with risk factors of developing of a stroke.

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

Doctors should estimate a ratio risk/advantage of use of the drug Rispolept® of Kviklet for 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 cardiovascular events immediately: such as sudden weakness or immovability/nonsensitivity in a face, legs, hands, and also difficulty of the speech and a problem with sight. At the same time all possible options of treatment, including the termination of reception of a risperidon have to be considered.

Рисполепт® Kviklet 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. It is necessary to estimate constantly a condition of patients and need of continuation of therapy risperidony.

Orthostatic hypotension. Risperidon has the alpha blocking activity and therefore can cause in some patients orthostatic hypotension, especially during initial selection of a dose. Clinically significant hypotension it was observed in the post-marketing period at combined use with anti-hypertensive drugs. Рисполепт® Kviklet needs to apply with care at patients with the known cardiovascular diseases (for example, heart failure, a myocardial infarction, disturbances of conductivity of a cardiac muscle, dehydration, a hypovolemia or a cerebrovascular disease). The corresponding dose adjustment is also necessary. It is recommended to estimate a possibility of a dose decline in case of developing of hypotension.

Late dyskinesia and extrapyramidal frustration. The drugs having properties of antagonists of dopamine receptors can cause late dyskinesia which is characterized by the rhythmic involuntary movements, preferential language and/or mimic muscles. Emergence of extrapyramidal symptoms is risk factor of development of late dyskinesia. At emergence at the patient of the objective or subjective symptoms indicating late dyskinesia it is necessary to consider expediency of cancellation of all antipsychotic drugs, including Kviklet's Rispolept®.

Malignant Antipsychotic Syndrome (MAS). Antipsychotic drugs, including рисперидон, can cause a zlokachestvennyyneyroleptichesky syndrome (ZNS) which is characterized by a hyperthermia, muscle tension, instability of function of the autonomic nervous system, consciousness oppression, and also increase in serum of concentration of a kreatinfosfokinaza. At patients with ZNS can arise also a myoglobinuria (рабдомиолиз) and an acute renal failure. At emergence at the patient of objective or subjective symptoms of ZNS it is necessary to cancel immediately all antipsychotic drugs, including Kviklet's Rispolept®.

Parkinson's disease and dementia with Levi's little bodies. Purpose of antipsychotic drugs, including Kviklet's Rispolept®, to patients with Parkinson's disease or dementia with Levi's little bodies has to be carried out with care since at both groups of patients the risk of development of an antipsychotic malignant syndrome is increased and sensitivity to antipsychotic drugs is increased (including obtusion of painful sensitivity, confusion of consciousness, postural instability with frequent falling and extrapyramidal symptoms). At reception of a risperidon deterioration in disease of Parkinson is possible.

Hyperglycemia and diabetes mellitus. At treatment the drug Rispolept® of Kviklet observed a hyperglycemia, a diabetes mellitus and an aggravation of already available diabetes mellitus. It is probable that the increase in body weight preceding treatment also is the factor contributing to it. Very seldom ketoacidosis can be observed and it is rare – a diabetic coma. At all patients it is necessary to carry out clinical control on existence of symptoms of a hyperglycemia (such as polydipsia, polyuria, polyphagia and weakness). At patients with a diabetes mellitus regular observation regarding deterioration in control of level of glucose has to be made.

Increase in body weight. At treatment the drug Rispolept® of Kviklet observed significant increase in body weight. It is necessary to carry out control of body weight of patients.

Giperprolaktinemiya. On the basis of results of researches on cultures of fabrics the assumption is made that growth of tumor cells of a breast can be stimulated with prolactin. In spite of the fact that in clinical and epidemiological trials accurate communication of a giperprolaktinemiya with reception of antipsychotic drugs is not revealed, it is necessary to be careful at purpose of a risperidon to patients with the burdened anamnesis. The drug Rispolept® of Kviklet has to be used with care at patients with the existing giperprolaktinemiya and at patients with possible prolactin - dependent tumors.

Lengthening of an interval of QT. Lengthening of an interval of QT was very seldom observed in the post-marketing period of observation. As well as for other antipsychotic means, patients should be careful at purpose of the drug Rispolept® of Kviklet with the known cardiovascular diseases, lengthening of an interval of QT in the family anamnesis, bradycardia, disturbances of electrolytic balance (a hypopotassemia, a hypomagnesiemia) as it can increase risk of aritmogenny effect; and at combined use with the drugs extending QT interval.

Spasms. Рисполепт® by Kviklet it has to be applied with care at patients with spasms in the anamnesis or with other medical states at which the snizhatsyasudorozhny threshold can.

Priapism. The priapism can arise at reception of a risperidon because of alpha and adrenoceptor blocking effects.

Regulation of body temperature. Such undesirable effect as disturbance of ability of an organism to regulate temperature is attributed to antipsychotic drugs. It is necessary to be careful at purpose of the drug Rispolept® of Kviklet 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.

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 come to light prior to the beginning of and during treatment by Kviklet drug Rispolept®, and the warning measures have to be taken.

Children and teenagers. Before purpose of the drug Rispolept® of Kviklet 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 from - for possible influences 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 risperidony regular verification of presence of extrapyramidal symptoms and other motor disturbances has to be carried out.

Excipients.

Tablets of the drug Rispolept® of Kviklet contain aspartame. Aspartame is a source of phenylalanine which can constitute danger to people with a fenilketonuriya.

Influence on ability to manage vehicles and mechanisms.

Рисполепт® Kviklet can make impact on ability to manage vehicles and mechanisms in small or moderate degree. Patients should recommend to refuse driving of the car and work with mechanisms before clarification of their individual sensitivity to drug.

Side effects:

The most often observed side effects (emergence frequency ≥ 10%) were: parkinsonism, headache and sleeplessness.

Side effects of the drug Rispolept® of Kviklet are given in therapeutic doses with distribution on frequencies and systems of bodies. Frequency of side effects was classified as follows: very frequent (≥1/10 cases), frequent (≥1/100 <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).

In each frequency group side effects are presented as reduction of their importance.

Disturbances of laboratory and tool indicators:

- often – increase in level prolaktina1, increase in body weight;

- infrequently – lengthening of an interval of QT on 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 level of hemoglobin, increase in level of a kreatinfosfokinaza;

- seldom – fall of temperature of a body.

From cardiovascular system:

- often – tachycardia;

- infrequently – an atrioventricular block, blockade of a ventriculonector, fibrillation of auricles, a sinus bradycardia, heartbeat.

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 (2), a headache;

- often – an akathisia (2), dizziness (2), a tremor (2), dystonia (2), drowsiness, sedation, a lethargy, dyskinesia (2);

- 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, an incoordination, 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.

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, 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 (3), anorexia, a polydipsia, a hyperglycemia;

- seldom – a hypoglycemia;

- very seldom – diabetic ketoacidosis;

- with an unknown frequency – water intoxication. Infections: often – pneumonia, flu, bronchitis, upper respiratory tract infections, infections of urinary tract;

- infrequently – 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.

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 hypersensitivity;

- with an unknown frequency – anaphylactic reaction.

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 periods, allocations 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.

(1) – the giperprolaktinemiya in certain cases can lead to a gynecomastia, disturbances of a menstrual cycle, an amenorrhea and a galactorrhoea.

(2) – extrapyramidal frustration can be shown as: parkinsonism (hypersalivation, musculoskeletal constraint, parkinsonism, hypersalivation, rigidity as "cogwheel", a bradykinesia, a hypokinesia, the maskopodobny person, tension of muscles, an akineziya, a stiff neck, muscular rigidity, parkinsonichesky gait, disturbances of a glabellar reflex), an akathisia (an akathisia, concern, a hyperkinesia and a syndrome of "uneasy" legs), a tremor, dyskinesia (dyskinesia, twitching of muscles, a choreoathetosis, an athetosis and a myoclonus), dystonia.

Dystonia includes dystonia, muscular spasms, a hypertension, a wryneck, involuntary muscular contractions, a muscular contracture, a nictitating spasm, the movements of an eyeglobe, a glossolysis, a front spasm, a laryngospasm, a myatonia, an opisthotonos, an orofaringealny spasm, плеврототонус, a glossospasm and a lockjaw. The tremor includes a tremor and a parkinsonichesky tremor of rest. Also it should be noted that there is wider number of symptoms which not always have an extrapyramidal origin.

(3) – in placebo-kontrolirumykh researches the diabetes mellitus was observed at 0,18% of the patients accepting рисперидон in comparison with 0,11% of patients in group of placebo. The general frequency of emergence of a diabetes mellitus by results of all clinical tests made 0,43% of all patients accepting рисперидон.

The side effects observed during clinical trials of the prolonged injection form of a risperidon – Rispolept Konsta®, but not shown at use of peroral dosage forms of a risperidon are listed in addition below. This list does not include the side effects connected with structure or an injection way of administration of drug:

Disturbances of laboratory indicators: body degrowth, increase in level gamma глутамилтрансферазы, increase in liver enzymes.

From cardiovascular system: bradycardia.

From blood and lymphatic system: neutropenia.

From a nervous system: paresthesia, convulsions.

From eyes: nictitating spasm.

From an ear and a labyrinth: вертиго.

From digestive tract: dentagra, glossospasm.

From skin and hypodermic fabrics: eczema.

From a musculoskeletal system and connecting fabric: buttock pains. Infections: lower respiratory tract infections, infections, gastroenteritis, hypodermic abscess.

Injuries and poisonings: falling.

Vascular disorders: arterial hypertension.

The general disturbances and the phenomena caused by administration of drug: pains.

Mental disturbances: depression.

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 - the 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 (frequency is unknown).

Increase in body weight. During placebo - controlled researches at patients with schizophrenia, body povysheniyemassa not less than 7% in 6-8 weeks were observed at 18% of the patients accepting Kviklet drug Rispolept® and at 9% of the patients accepting placebo. 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 Kviklet drug Rispolept® (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. 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 the size of increase in body weight has to make 3-5 kg a year for girls and about 5 kg a year 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 ≥ 5% and 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.

Interaction with other medicines:

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

Influence of administration of drug of Rispolept® of Kviklet on other medicines.

Рисполепт® Kviklet should be applied with care in combination with other drugs and substances of the central action, especially with alcohol, opiates, antihistaminic drugs and benzodiazepines because of the increased risk of sedation. Рисполепт® Kviklet can reduce efficiency of a levodopa and other agonists of dopamine. If reception of this combination, especially on an end-stage of a disease of Parkinson is necessary, it is necessary to appoint the smallest effective dose of each of drugs.

At use of a risperidon together with anti-hypertensive drugs in the post-marketing period clinically significant hypotension was observed. Risperidon has no clinically significant effect on pharmacokinetics of lithium, Valproatum, digoxin or a topiramat.

Influence of reception of other medicines on Kviklet drug Rispolept®.

When using carbamazepine decrease in concentration of active antipsychotic fraction of a risperidon in plasma was noted. Similar effects can be observed when using other inductors of liver enzymes and P-of a glycoprotein (for example, rifampicin, Phenytoinum, phenobarbital). At appointment and after cancellation of carbamazepine or other inductors of liver enzymes and a P-glycoprotein it is necessary to correct a drug Rispolept® dose of Kviklet.

Fluoxetine and пароксетин, being CYP 2D6 isoenzyme inhibitors, increase concentration of a risperidon in plasma, but to a lesser extent concentration of active antipsychotic fraction. It is supposed that other inhibitors of an isoenzyme of CYP 2D6 (for example, quinidine) influence concentration of a risperidon in the same way. At appointment and after cancellation of fluoxetine or a paroksetin it is necessary to correct a drug Rispolept® dose of Kviklet.

The verapamil which is inhibitor of an isoenzyme of CYP 3A4 and P-glycoprotein increases concentration of a risperidon in plasma.

Galantaminum and donepezil do not render clinically significant effect on pharmacokinetics of a risperidon and its active antipsychotic fractions.

Fenotiazina, tricyclic antidepressants and some β-adrenoblockers can increase concentration of a risperidon in plasma, 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, CYP 3A4 isoenzyme inhibitor, does not influence pharmacokinetics of a risperidon and aktivnoyantipsikhotichesky fraction.

Combined use of psychostimulants (for example, methylphenidate) and Kviklet drug Rispolept® at children does not change pharmacokinetic parameters and efficiency of a risperidon.

It is not recommended to apply рисперидон together with paliperidony in view of the fact that палиперидон is an active metabolite of a risperidon, and use of such combination can lead to increase in concentration of active antipsychotic fraction.

Contraindications:

 individual hypersensitivity to a risperidon or any other ingredient of this drug;

- fenilketonuriya.

With care:

- diseases of cardiovascular system (chronic heart failure, the postponed myocardial infarction, disturbances of conductivity of a cardiac muscle);

- dehydration and hypovolemia;

- disturbances of cerebral circulation;

- Parkinson's disease;

- spasms (including in the anamnesis);

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

- abuse of medicines or medicinal dependence;

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

- 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);

- risk factors of development of a thromboembolism of venous vessels;

- disease of diffusion little bodies of Levi;

- patients of advanced age with cerebrovascular dementia;

- pregnancy.

Overdose:

Symptoms.

In general, observed symptoms of overdose represented already known pharmacological effects of a risperidon in the strengthened form: drowsiness, sedation, tachycardia, arterial hypotension, extrapyramidal symptoms. Lengthening of an interval of QT and a spasm was observed. Bidirectional ventricular tachycardia was noted in joint reception of the raised dose of a risperidon and a paroksetin. In case of acute overdose the possibility of overdose from reception of several drugs has to be considered.

Treatment.

It is necessary to achieve and maintain free passability of respiratory tracts for ensuring adequate supply with oxygen and ventilation. A gastric lavage (after an intubation if the unconscious patient) and reception of absorbent carbon together with laxative has to see off only if drug was accepted no more than a one hours ago. It is necessary to begin immediately monitoring of an ECG for detection of possible arrhythmias. The specific antidote does not exist, the corresponding symptomatic therapy has to be carried out. Arterial hypotonia and a vascular collapse should be eliminated with intravenous infusions of liquid and/or sympathomimetic drugs. At development of heavy extrapyramidal symptoms it is necessary to appoint anticholinergic drugs. Constant medical observation and monitoring should be continued before disappearance of symptoms of intoxication.

Storage conditions:

To store at a temperature of 15-30 °C in the dry place. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

The tablets dispersed in an oral cavity, 1 mg, 2 mg. On 4 tablets in the blister from a film and aluminum foil. On 7 or 14 blisters together with the application instruction in a pack from a cardboard.