Rispolept Konsta

General characteristics. Structure:

Active component: рисперидон in the form of microgranules of the prolonged release (381 mg of a risperidon in 1 g of microgranules).

Excipients: milk and glycolic acids copolymer – 619 mg.

Solvent: a karmelloza of sodium 40 мПа∙с – 22,5 mg, polysorbate of 20 - 1,0 mg, hydrophosphate sodium a dihydrate – 1,27 mg, citric acid anhydrous – 1,0 mg, sodium chloride – 6,0 mg, sodium hydroxide – 0,54 mg, water for injections – to 1 ml. 

Description. Solvent: transparent colourless solution, free from visible mechanical inclusions

Pharmacological properties:

Pharmacodynamics.

Risperidon is a selective monoaminergichesky antagonist. It has high affinity to serotonergic 5-HT2-retseptoram and dofaminergichesky D2 receptors. Besides, рисперидон contacts alfa1-adrenergic receptors and, to a lesser extent, H1-gistaminergichesky and alfa2-adrenergic receptors. Risperidon does not contact cholinergic receptors. In spite of the fact that рисперидон is a powerful antagonist of D2 receptors thanks to what it improves positive symptoms of schizophrenia, this drug, in comparison with typical neuroleptics, to a lesser extent oppresses a physical activity and less often causes a katalepsy. Thanks to the balanced central antagonism concerning serotoninovy and dopamine receptors рисперидон causes extrapyramidal side effects less often and has therapeutic effect on negative and affective symptoms of schizophrenia.

Pharmacokinetics.

Risperidon is metabolized by CYP2D6 isoenzyme to a 9-gidroksirisperidon who has the same pharmacological activity as рисперидон. Risperidon and 9-гидроксирисперидон form active antipsychotic fraction. Some other way metabolism of a risperidon N-dealkylation is.

At bystry metabolizator the clearance of active antipsychotic fraction and a risperidon makes 5,0 and 13,7 l/h respectively, and at weak metabolizator – 3,2 and 3,3 l/h respectively.

General characteristics of a risperidon after an injection to patients of drug Rispolept Konsta®.

At single intramuscular administration of drug Rispolept Konsta® the profile of release of a risperidon consists of a small initial phase (<1% of a dose) which the interval lasting 3 weeks follows. After an intramuscular injection the main release of a risperidon begins in 3 weeks, is supported from the 4th to the 6th week and decreases by 7th week. In this regard, the patient has to accept additional antipsychotic drug within the first 3 weeks after an initiation of treatment drug Rispolept Konsta®.

The combination of a profile of release of a risperidon and the mode of dosing (an intramuscular injection once in two weeks) provides maintenance in plasma of therapeutic concentration of a risperidon. Therapeutic concentration remain to 4-y-6-y weeks after the last injection of drug Rispolept Konsta®. The phase of elimination comes to the end approximately in 7–8 weeks after the last injection. Risperidon is completely absorbed from suspension Rispolept Konsta®. Risperidon is quickly distributed in body tissues. The volume of distribution makes 1–2 l/kg. In plasma рисперидон contacts albumine and an alfa1-acid glycoprotein. Communication with proteins of plasma of a risperidon makes 90%, and a 9-gidroksirisperidon – 77%.

After intramuscular injections of drug Rispolept Konsta® in doses of 25 or 50 mg once in two weeks average values of the minimum and maximum concentration in plasma of active antipsychotic fraction make 9,9–19,2 ng/ml and 17,9–45,5 ng/ml respectively. At such mode of dosing the pharmacokinetics of a risperidon has linear character. In prolonged use (12 months) at patients to whom once in two weeks administered the drug Rispolept Konsta® in doses of 25-50 mg cumulation of a risperidon was not observed.

Studying of use of a single dose of a peroral form of a risperidon showed higher concentration in plasma and the reduced clearance of active antipsychotic fraction for 30% at elderly patients and for 60% at patients with a renal failure. Concentration of a risperidon at patients with a liver failure were in plasma normal, but average value of free fraction in plasma increased by 35%.

Indications to use:

Treatment and prevention of exacerbations of schizophrenia and schizoaffective disorders.

Route of administration and doses:

At patients who did not receive рисперидон earlier it is recommended to define portability of peroral dosage forms of a risperidon before starting treatment by drug Rispolept Konsta®.

Rispolept Konsta® enter once in 2 weeks by means of a deep injection into a gluteus, using for this purpose the sterile needle attached to the syringe. Injections should be done alternately in the right and left buttocks. The drug cannot be administered intravenously. Application instructions are given in the section "Instructions on Use".

Adults.

The recommended dose makes 25 mg intramusculary once in 2 weeks. Some patients need higher doses: 37,5 or 50 mg. In clinical trials increase in efficiency at use of 75 mg was not observed. The maximum dose should not exceed 50 mg once in 2 weeks.

During the 3 weeks period after the first administration of drug Rispolept Konsta® the patient has to accept effective antipsychotic remedy. The dose of drug can be raised not more often than once in 4 weeks. The effect of such increase in a dose should be expected not earlier, than in 3 weeks after the first injection of the increased dose.

Elderly patients.

The recommended dose makes 25 mg intramusculary once in 2 weeks. During the 3 weeks period after the first injection of drug Rispolept Konsta® the patient has to accept effective antipsychotic remedy.

Patients with abnormal liver functions or kidneys.

There are no data on use of drug Rispolept Konsta® for patients with abnormal liver functions or kidneys now.

If nevertheless the patient with abnormal liver functions or kidneys needs to be treated drug Rispolept Konsta®, then in the first week it is recommended to accept in 0,5 mg two times a day a peroral dosage form of a risperidon. Within the second week the patient can accept 1 mg two times a day or 2 mg once a day. If the patient well transfers a peroral dose not less than 2 mg, then he can enter intramusculary 25 mg of drug Rispolept Konsta® once in 2 weeks.

Instructions on use.

Use of drug of Rispolept Konst demands strict observance of instructions to a suspension poprigotovleniye to provide exact administration of drug and izbezhatvozmozhny mistakes.

For preparation of suspension from Rispolept Konst's microgranules of the prolonged action which are in a bottle it is possible to use only the solvent which is in previously filled syringe. Ready suspension is entered intramusculary only into a rump. It is impossible to replace the components which are in packaging with any drugimiizdeliya. For ensuring use of a full dose of a risperidon all contents of a bottle have to be entered. Introduction of a part of contents of a bottle cannot provide the patient of the necessary dose of drug. The drug should be administered at once after suspension preparation. Get packaging of drug of Rispolept of Konsta® from the refrigerator and before preparation of suspension let's it heat up to room temperature within 30 minutes.

1. Remove a color plastic cover from a bottle. Do not delete a gray rubber bung. Wipe not opened bottle with a spirit napkin and let's dry. 

2. Open the blister packaging and take the needleless Alaris SmartSite device, holding it between a white lyuerovsky cap and "skirt". It is impossible to touch an acute tip of the device at all.

3. It is very important that the needleless SmartSite device was correctly installed on a bottle, otherwise solvent can leak at receipt in a bottle. Put a bottle on a firm surface. Hold the bottle basis. Direct the needleless SmartSite device to a bottle vertically so that the acute tip was located in the center of a rubber bung of a bottle.

Pressing from top to down, push an acute tip of the needleless SmartSite device through the center of a rubber bung of a bottle before reliable fixing of the device on an upper part of a bottle.

4. Before connection of the syringe to the needleless SmartSite device, holding the bottle basis, wipe the place of fastening of the device with the syringe (a blue circle) a spirit napkin and let's dry. 

5. Previously filled syringe has a white tip, two-piece: white collar and glossy white cap. To open the syringe, you hold the syringe for a white collar and break off a glossy white cap (the white cap cannot be turned off or cut off). Remove a white cap together with the rubber tip which is in it.

At all stages of assembly you hold the syringe only for the white collar located on a syringe tip. Fixing of a white collar will help to protect a collar from department and guarantees good connection with the syringe. Be accurate and do not overwind components at assembly since at the same time parts of the syringe can come off it.

6. Holding the syringe for a white collar, insert the syringe into a blue circle of the needleless device, press and turn clockwise the syringe strongly connected to the needleless device (it is necessary to avoid twisting).

For prevention of rotation of the needleless device during connection with the syringe strongly hold "skirt".

The syringe and the needleless device have to be on one line.

7. Enter into a bottle all contents of the syringe with solvent.

8. Holding the syringe piston with a thumb, vigorously stir up bottle contents not less than 10 seconds before formation of homogeneous suspension.

After the correct hashing suspension becomes homogeneous, dense, milk color. 

Microgranules can be visible in liquid, but has to remain the dry microgranules moistened with solvent. 

You do not store a bottle after suspension preparation as suspension can be stratified.

9. Turn a bottle a bottom up and slowly involve all contents of a bottle in the syringe. Separate a part of the label from a bottle through perforation and paste it to the syringe (for identification).

10. Holding the syringe for a white collar, disconnect the syringe from the needleless device. Utilize a bottle and the needleless device according to local rules on destruction of such waste.

11. Open the blister packaging of a needle of Needle-Pro®. It is impossible to touch a part of the needle joining the syringe. Take a needle from packaging, holding it for a transparent case.

12. For prevention of hit of microbes do not concern a lyuerovsky tip of the orange protection device of a needle of Needle-Pro. Holding the syringe for a white collar, attach a lyuerovsky cannula of the orange protection device of a needle of Needle-Pro to the syringe easy turn clockwise. 

13. Continuing to hold the syringe for a white collar, clamp a transparent case of a needle and densely fix a needle in the Needle-Pro protection device by pressing and turn clockwise. Fixing of a needle can guarantee safe connection between a needle and the protection device of a needle Needle-Pro during the following stages.

14. Just before introduction Rispolept Konst's drug needs to be resuspended as after preparation of suspension a part of microgranules can settle in a bottle. For resuspending of microgranules vigorously stir up the syringe. 

15. Holding the syringe for a white collar, remove a transparent case from a needle. Do not bend a case since at the same time connection of a lyuerovsky tip can be broken.

16. Slightly knock with a finger on the syringe that the vials of air which are in it rose up. Slightly advancing the piston up, remove vials of air from the syringe and a needle, holding the syringe so that the needle was directed vertically up. Enter all contents of the syringe into an upper external quadrant of a rump.

Suspension cannot be entered intravenously!

Caution: in order to avoid traumatizing medical personnel the used needle:

• Do not touch a free hand the device of protection of a needle Needle-Pro of its priprizhimaniya to a flat surface.

• Do not disassemble the device of protection of a needle Needle-Pro.

• Do not try to straighten a needle and do not concern the device of protection of a needle Needle-Pro if it iglapognutsya or it is damaged.

• Use the device of protection of a needle Needle-Pro only for designated purpose, otherwise the needle to mozhetvystupit from a protective cap.

17. After performance of an injection enter a needle into the orange device of protection of a needle Needle-Pro one hand. For this purpose accurately press the orange device of protection of a needle Needle-Pro to a flat surface. As soon as the orange device of protection of a needle Needle-Pro is pressed, the needle has to enter the device of protection of a needle Needle-Pro densely. Before throwing out a needle, be convinced that the needle is densely fixed in the orange device of protection of a needle Needle-Pro. Utilize according to local rules on destruction of such waste. 

Do not reuse: This device is intended only for disposable. Any attempt of the subsequent reuse can adversely affect integrity of the device or lead to deterioration in its work.

Features of use:

At patients who did not receive рисперидон earlier it is recommended to define portability of peroral dosage forms of a risperidon before starting treatment by drug Rispolept Konsta®.

Use for elderly patients with dementia.

Use of drug Rispolept Konsta® was not investigated at elderly patients with dementia as it is not shown for this group of patients. Drug Rispolept Konsta® is not intended for treatment of the disorders of behavior connected with dementia.

The increased mortality at elderly patients with dementia.

At elderly patients with dementia at treatment atypical antipsychotic means observed the increased mortality in comparison with group of placebo at meta-analysis of 17 controlled researches of atypical antipsychotic means, including a peroral risperidon. In placebo - controlled researches of peroral forms 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 group of 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.

Simultaneous 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.

Side effects from cerebrovascular system.

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. Rispolept Konsta® has to be applied with care at patients with risk factors of developing of a stroke.

Orthostatic hypotension.

Risperidon has the alpha blocking activity and therefore can cause in some patients orthostatic hypotension, especially at the beginning of therapy. Clinically significant hypotension it was observed in the post-marketing period at combined use with anti-hypertensive drugs. Risperidon it is necessary 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 advantage/risk at assessment of a possibility of continuation of therapy is recommended to estimate carefully a ratio drug Rispolept Konsta®.

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.

Malignant Antipsychotic Syndrome (MAS).

Antipsychotic drugs, including рисперидон, can cause the malignant antipsychotic syndrome (MAS) 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 symptoms of ZNS it is necessary to cancel immediately all antipsychotic drugs, including Rispolept Konsta®.

Parkinson's disease and dementia with Levi's little bodies.

Purpose of antipsychotic drugs, including Rispolept Konsta®, 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 drug Rispolept Konsta® 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 drug Rispolept Konsta® 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. Drug Rispolept Konsta® 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 drug Rispolept Konsta® 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.

Rispolept Konsta® has to be applied with care at patients with spasms in the anamnesis or with other medical states at which the convulsive threshold can decrease.

Priapism.

The priapism can arise at use 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 drug Rispolept Konsta® 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 drug Rispolept Konsta®, and the warning measures have to be taken.

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-adrenoceptors including drug Rispolept Konsta®.

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 Rispolept Konsta® 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.

It is necessary to be careful in order to avoid accidental administration of drug Rispolept Konsta® in a blood vessel.

It is impossible to subject drug to influence of temperatures above 25 °C. In the absence of the refrigerator drug Rispolept Konsta® before use can be stored at a temperature not above 25 °C no more than 7 days.

After suspension preparation: suspension physically is also chemically stable during 24 h at a temperature of 25 °C. From the microbiological point of view, it is desirable to use suspension at once after preparation. If suspension is not used right after preparation, then it is possible to store it no more than 6 h at a temperature of 25 °C.

Risperidon can reduce the speed of mental and physical reactions and therefore patients should recommend to abstain from driving of the car and work with mechanisms.

Incompatible combinations.

Rispolept Konsta® cannot mix or part with any other drugs and liquids in addition to the special solvent which is contained in packaging.

Side effects:

The most frequent side effects (≥1/10) are: sleeplessness, uneasiness, headache, infections of upper parts of respiratory system, parkinsonism, depression and akathisia. In the post-marketing period of observation serious reactions in the place of an injection, including a necrosis, abscess, an inflammation of a hypodermic fatty tissue, an ulceration, a hematoma, a cyst and nodules are noted. Frequency of emergence of these reactions is unknown (it is impossible to estimate frequency from available data). In certain cases surgical intervention was required.

Side effects of drug Rispolept Konsta® which were observed during clinical trials and in the post-marketing period of observation are included below. Frequency of side effects was classified as follows: very frequent (≥1/10), frequent (≥1/100 and <1/10), infrequent (≥1/1000 and <1/100), rare (≥1/10000 and <1/1000), very rare (<1/10000) and with an unknown frequency (it is impossible to estimate frequency from available data).

In each frequency group side effects are given in a gravity reduction order.

Side effects are given with distribution on the frequency and system and organ classes.

Disturbances of laboratory and tool indicators:

- often – disturbances of an ECG, increase in level of prolactin (1), increase in activity of microsomal enzymes of a liver, increase in activity of transaminases, increase or a degrowth of a body;

- infrequently – lengthening of an interval of QT on the electrocardiogram.

Disturbances from cardiovascular system:

- often – an atrioventricular block, tachycardia;

- infrequently – blockade of a ventriculonector, fibrillation of auricles, bradycardia, sinus bradycardia, a heart consciousness.

Hematologic disturbances and disturbances of lymphatic system:

- often – anemia;

- infrequently – thrombocytopenia, a neutropenia;

- very seldom – an agranulocytosis.

Disturbances from a nervous system:

- very often – parkinsonism (2), an akathisia (2), a headache;

- often – dizziness, sedation, drowsiness, a tremor, dystonia (2), late dyskinesia, dyskinesia (2);

- infrequently – spasms, a faint, postural dizziness, a hypesthesia, paresthesia, a lethargy, a hypersomnia.

Disturbances from an organ of sight:

- often – the sight illegibility, konjyuktivit;

- seldom – a syndrome of a flabby iris (intraoperative) (4);

- with an unknown frequency – retina artery occlusion.

Disturbances from an acoustic organ and a labyrinth:

- often – вертиго; infrequently – ear pain.

Respiratory, thoracic disturbances and disturbances of a mediastinum:

- often – short wind, cough, a congestion of nasal bosoms, pharyngolaryngeal pain;

- seldom – an apnoea syndrome in a dream.

Disturbances from digestive tract:

- often – vomiting, diarrhea, a lock, nausea, pain in a stomach, dyspepsia, a dentagra, dryness in a mouth, discomfort in a stomach, gastritis;

- seldom – mechanical intestinal impassability, pancreatitis;

- very seldom – intestinal impassability.

Disturbances from kidneys and urinary tract:

- often – an urine incontience;

- infrequently – an urination delay.

Disturbances from skin and hypodermic fabrics:

- often – rash, eczema;

- infrequently – a Quincke's edema, an itch, an acne, an alopecia, a xeroderma.

Disturbances from a musculoskeletal system and connecting fabric:

- often – an arthralgia, a dorsodynia, extremity pain, a mialgiya;

- infrequently – muscular weakness, pain in a neck, pain in buttocks, musculoskeletal pain in a breast.

Disturbances from endocrine system:

- seldom – disturbance of secretion of antidiuretic hormone.

Disturbances of metabolism and food:

- often – a hyperglycemia;

- infrequently – a diabetes mellitus (3), increase in appetite, a loss of appetite;

- seldom – a hypoglycemia; very seldom – diabetic ketoacidosis;

- with an unknown frequency – water intoxication.

Infections:

- very often – upper respiratory tract infections;

- often – pneumonia, flu, lower respiratory tract infections, bronchitis, infections of urinary tract, ear infections, sinusitis, viral infections;

- infrequently – cystitis, a gastroenteritis, infections, the localized infections, hypodermic abscess.

Injuries, poisonings and complications connected with the procedure of administration of drug:

- often – falling;

- infrequently – pain during the procedure of administration of drug.

Vascular disorders:

- often – hypertensia, hypotension;

- infrequently – orthostatic hypotension.

The general disturbances and disturbances in the field of administration of drug:

- often – a pyrexia, peripheral hypostasis, pain in a breast, fatigue, pains, pain in the field of administration of drug, an adynamy, a grippopodobny state;

- infrequently – consolidation in the field of administration of drug, consolidation, reactions in the field of administration of drug, discomfort in a breast, sluggishness, feeling sick;

- seldom – a hypothermia.

Disturbances from immune system:

- infrequently – hypersensitivity;

- with an unknown frequency – anaphylactic reactions.

Gepatobiliarny disturbances:

- seldom – jaundice.

Disturbances from reproductive system and mammary glands:

- often – an amenorrhea, erectile dysfunction, a galactorrhoea;

- infrequently – sexual dysfunction, a gynecomastia; with an unknown frequency – a priapism.

Mental disturbances:

- very often – a depression, sleeplessness, concern;

- often – agitation, frustration of a dream; infrequently – manias, reduction of a libido, nervousness.

(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, bone muscular 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.

(4) – it was observed only in the post-marketing period.

The side effects observed during clinical trials of peroral dosage forms of a risperidon, but which are not shown at use of the prolonged injection form of a risperidon – Rispolept Konsta® are listed in addition below.

Side effects are given with distribution on system and organ classes:

Disturbances of laboratory indicators: fervescence, increase in quantity of ezonofil, increase in quantity of leukocytes, reduction of level of hemoglobin, increase in level of a kreatinfosfokinaza, fall of temperature of a body.

Infections: tonsillitis, inflammation of a hypodermic fatty tissue, average otitis, infections of eyes, acariasis, respiratory infections, onychomycosis, chronic average otitis.

From blood and lymphatic system: granulocytopenia.

From immune system: hypersensitivity to drug.

Disturbances of metabolism and food: anorexia, polydipsia.

Mental disturbances: confusion of consciousness, slackness, anorgazmiya, affective flattening.

From a nervous system: lack of reaction to irritants, loss of consciousness, malignant antipsychotic syndrome, diabetic coma, stroke, consciousness oppression, cerebral ischemia, cerebrovascular disturbances, passing ischemic attack, dysarthtia, disturbance of attention, balance disturbance, disturbance of the speech, lack of coordination, disturbance of movements.

Ophthalmologic disturbances: an ocular hyperemia, allocations from eyes, area hypostasis around eyes, a xerophthalmus, the strengthened dacryagogue, a photophobia, decrease in visual acuity, involuntary rotations of eyeglobes, glaucoma.

From an ear and a labyrinth: a ring in ears.

Vascular disorders: inflows.

Respiratory, thoracic disturbances and disturbances of a mediastinum: goose breathing, aspiration pneumonia, stagnation in lungs, breath disturbance, rattles, nasal bleeding, a nose congestion, a hyperventilation, a dysphonia.

From digestive tract: dysphagy, incontience calla, fekaloma, hypostasis of lips, cheilitis.

From skin and hypodermic fabrics: damage of skin, disturbance of integuments, disturbance of coloring of skin, seborrheal dermatitis, hyperkeratosis, dandruff, erythema.

From a musculoskeletal system and connecting fabric: рабдомиолиз, swelling of joints, disturbances of a pose, constraint in joints.

From kidneys and urinary tract: enuresis, dysuria, pollakiuria.

From reproductive system and mammary glands: erectile dysfunction, allocations from a vagina, disturbance of periods.

The general disturbances and the phenomena caused by administration of drug: general hypostasis, face edema, gait disturbance, thirst, fever, cold snap of extremities, syndrome of "cancellation".

Class effects.

As well as at use of other antipsychotic drugs, very exceptional cases of lengthening of an interval of QT were celebrated in the post-marketing period of observation. A class the effects from cardiovascular system observed at use of antipsychotic drugs which extend QT interval include others: 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 12 weeks placebo - controlled researches at 9% of the patients accepting drug Rispolept Konsta® in comparison with 6% of the patients accepting placebo increase in body weight not less than 7% at the time of completion of a research was observed. In other clinical trial, lasting 1 year, changes in body weight for certain patients were made by ±7% of an average; at 25% of patients increase in body weight not less than for 7% was observed.

Interaction with other medicines:

Rispolept Konsta® increases expressiveness of the oppressing influence on TsNS of opioid analgetics, hypnagogues, anxiolytics, tricyclic antidepressants, means for the general anesthesia, alcohol.

Rispolept Konsta® can weaken action of a levodopa and other agonists of dopamine receptors.

Clinically significant arterial hypotension is observed at combined use of a risperidon with anti-hypertensive means.

It is necessary to be careful at combined use of Rispolept Konsta® with the medicines increasing QT interval.

It is established that carbamazepine reduces the content in plasma of active antipsychotic fraction of a risperidon. Similar effects can call also other inductors of microsomal enzymes of a liver. At appointment and after cancellation of carbamazepine or other inductors of microsomal enzymes of a liver it is necessary to correct a dose of drug Rispolept Konsta®. Fluoxetine and пароксетин, inhibitors of microsomal enzymes of a liver, increase concentration of a risperidon in plasma, but to a lesser extent concentration of active antipsychotic fraction. At appointment and after cancellation of fluoxetine or a paroksetin it is necessary to correct a dose of drug Rispolept Konsta®.

Topiramat moderately reduces bioavailability of a risperidon, but not active antipsychotic fraction. This interaction is not considered clinically significant.

Fenotiazina, tricyclic antidepressants and some beta adrenoblockers can increase concentration of a risperidon in plasma, but to a lesser extent concentration of active antipsychotic fraction. Cimetidinum and ranitidine increase bioavailability of a risperidon, but in the minimum degree influence concentration of active antipsychotic fraction. Erythromycin, inhibitor of inductors of microsomal enzymes of a liver does not influence pharmacokinetics of a risperidon and active antipsychotic fraction. Cholinesterase inhibitors (Galantaminum and donepezil) have no clinically significant effect on pharmacokinetics of a risperidon and active antipsychotic fraction. At joint reception with the drugs possessing a high svyazyvayemost with proteins of plasma clinically significant replacement of drug from proteins of plasma is not observed. Risperidon has no clinically significant effect on pharmacokinetics of lithium, valproic acid, digoxin or topiramat.

See the section "Special Instructions" on the increased mortality of elderly patients with dementia at combined use of furosemide and peroral forms of a risperidon.

Contraindications:

Hypersensitivity to a risperidon or to any other ingredient of this drug.

Lactation period.

Children's age up to 18 years.

With care:

To apply with care at the following states:

− 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 and epilepsy (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);

− pregnancy.

Overdose:

When using parenteral dosage forms of a risperidon the overdose is less probable, than at use of peroral forms (a tablet, film coated, and solution for intake) and therefore here information concerning peroral forms is provided.

Symptoms: The symptoms observed at overdose are the strengthened known pharmacological effects. They include sedation, drowsiness, tachycardia, lowering of arterial pressure and extrapyramidal frustration. Lengthening of an interval of QT and a spasm was observed. Bidirectional ventricular tachycardia was noted at a concomitant use of the raised dose of a peroral risperidon and a paroksetin. In case of overdose the possibility of involvement of several drugs has to be considered.

Treatment: Provide and maintain passability of respiratory tracts, adequate oxygenation and ventilation. Monitoring of function of cardiovascular system which has to include constant control of an ECG for detection of possible arrhythmias is necessary. Рисполепт® has no specific antidote and therefore treatment has to be directed to maintenance of the TsNS function and cardiovascular system, and also disintoxication therapy has to be carried out. At heavy extrapyramidal symptoms it is necessary to administer the anticholinergic drugs. Medical observation and monitoring needs to be continued before disappearance of signs of overdose.

Storage conditions:

To store at a temperature from 2 to 8 °C in the place protected from light. Not to subject to influence of temperatures above 25 °C. In the absence of the refrigerator drug before use can be stored at a temperature not above 25 °C no more than 7 days. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Powder for preparation of suspension for intramuscular introduction of the prolonged action of 25 mg, 37,5 mg, 50 mg.