Instruction for use: Rispolept CONSTA

Dosage form: powder

Active substance: Risperidone*

ATX

N05AX08 Risperidone

Pharmacological group:

Neuroleptics

The nosological classification (ICD-10)

F20 Schizophrenia: Schizophrenic Conditions; An exacerbation of schizophrenia; Schizophrenia; Chronic schizophrenia; Dementia praecox; Bleuler's disease; Psychotic discordant; Dementia early; The febrile form of schizophrenia; Chronic schizophrenic disorder; Psychosis of the schizophrenic type; Acute form of schizophrenia; Acute schizophrenic disorder; Cerebral Organic Insufficiency in Schizophrenia; Acute attack of schizophrenia; Schizophrenic psychosis; Acute schizophrenia; Sluggish schizophrenia; Sluggish schizophrenia with apathoabulic disorders; Acute stage of schizophrenia with agitation

F25 Schizoaffective disorders: Schizoaffective disorders; Schizoaffective psychosis; Schizoaffective disorder

Composition

Powder for the preparation of suspension for intramuscular administration of prolonged action 1 fl.

active substance:

risperidone (in the form of sustained release micro-granules) 25 mg; 37.5 mg; 50 mg

(381 mg of risperidone in 1 g of microgranules)

auxiliary substances: lactic and glycolic acid copolymer - 619 mg (in 1 g microgranules)

solvent: carmellose sodium (40 mPa.s) - 22.5 mg; polysorbate 20 - 1 mg; sodium hydrogen phosphate dihydrate - 1.27 mg; citric acid anhydrous - 1 mg; sodium chloride - 6 mg; sodium hydroxide - 0.54 mg; water for injection - up to 1 ml

Description of dosage form

Powder: white or almost white powder, free from visible foreign impurities.

Solvent: Clear, colorless solution, free from visible mechanical impurities.

Suspension: the preparation should easily form a suspension in a solvent, the slurry should not have lumps or visible inclusions. Suspension must pass through the needle smoothly, with little resistance or no resistance.

Pharmachologic effect

Pharmacological action - antipsychotic.

Pharmacodynamics

Risperidone is an selective monoaminergic antagonist. It has a high affinity for serotonergic 5-HT2 receptors and dopaminergic D2 receptors. In addition, risperidone binds to α1-adrenergic receptors and, to a lesser extent, to H1-histaminergic and α2-adrenergic receptors. Risperidone does not bind to cholinergic receptors. Despite the fact that risperidone is a potent antagonist of D2 receptors, due to which it improves the positive symptoms of schizophrenia, this drug, in comparison with typical neuroleptics, to a lesser extent inhibits motor activity and less often causes catalepsy. Due to a balanced central antagonism for serotonin and dopamine receptors, risperidone rarely causes extrapyramidal side effects and has a therapeutic effect on the negative and affective symptoms of schizophrenia.

Pharmacokinetics

Risperidone is metabolized by the isoenzyme CYP2D6 to 9-hydroxyrisperidone, which has the same pharmacological activity as risperidone itself. Risperidone and 9-hydroxyrisperidone form an active antipsychotic fraction. Another way of metabolizing risperidone is N-dealkylation.

In fast metabolizers, the clearance of active antipsychotic fraction and risperidone is 5 and 13.7 l / h, respectively, and in weak metabolizers - 3.2 and 3.3 l / h, respectively.

In long-term use (12 months) in patients who received Rispolept Konsta® in doses of 25-50 mg once every 2 weeks, no risperidone cumulation was observed. The study of single dose application of the oral form of risperidone showed higher plasma concentrations and reduced clearance of the active antipsychotic fraction by 30% in elderly patients and by 60% in patients with renal insufficiency. The concentrations of risperidone in plasma in patients with hepatic insufficiency were normal, but the mean free plasma fraction increased by 35%.

Indications Rispolept CONSTA®

Treatment and prevention of exacerbations of schizophrenia and schizoaffective disorders.

Contraindications

hypersensitivity to risperidone or any other ingredient of this drug;

lactation period;

children's age till 18 years.

With care: diseases of the cardiovascular system (chronic heart failure, suffered myocardial infarction, conduction disorders of the heart muscle); dehydration and hypovolemia; disorders of cerebral circulation; Parkinson's disease; convulsions and epilepsy (including in the anamnesis); severe renal or hepatic insufficiency (see "Method of administration and dose"); drug abuse or drug dependence; conditions predisposing to the development of tachycardia such as "pirouette" (bradycardia, electrolyte imbalance, concomitant drug use, prolonging the QT interval); brain tumor, intestinal obstruction, cases of acute drug overdose, Reye's syndrome (antiemetic effect of risperidone may mask the symptoms of these conditions); pregnancy.

Application in pregnancy and lactation

There are no data on the safety of risperidone in pregnant women. In animal experiments, risperidone had no direct toxic effect on the reproductive system, but caused some indirect effects mediated through prolactin and the central nervous system. In none of the studies did risperidone have a teratogenic effect. In the case of a woman taking antipsychotics (including Rispolept®) in the third trimester of pregnancy, newborns are at risk of extrapyramidal disorders and / or withdrawal syndrome of varying severity. These symptoms may include agitation, hypertension, hypotension, tremor, drowsiness, respiratory disorders, and breast-feeding disorders. The drug Rispolept® Consta® can be used during pregnancy only in those cases where the potential benefit for a woman outweighs the possible risk to the fetus.

In experiments on animals, risperidone and 9-hydroxyrisperidone are excreted with milk. It was also found that risperidone and 9-hydroxyrisperidone are excreted with human milk. Therefore, women taking Rispolept® Consta® should not breast-feed.

Side effects

The most frequent side effects (≥1 / 10) are: insomnia, anxiety, headache, upper respiratory system infections, parkinsonism, depression and akathisia.

In the postmarketing period of observation, serious reactions at the injection site were noted, including necrosis, abscess, inflammation of subcutaneous fat, ulceration, hematoma, cyst and nodular thickening. The frequency of occurrence of these reactions is unknown (it is impossible to estimate the frequency from the available data). In some cases, surgical intervention was required.

The side effects of Rispolept Consta®, which were observed during clinical trials and in the post-marketing period of follow-up, are given below. The incidence of side effects was classified as follows: very often (≥1 / 10); often (≥1 / 100 and <1/10); infrequently (≥1 / 1000 and <1/100); rarely (≥1 / 10000 and <1/1000); very rarely (<1/10000) and with unknown frequency (it is impossible to estimate the frequency from the available data).

In each frequency group, side effects are given in order of decreasing severity. Side effects are given with frequency distribution and system-organ classes.

Changes in laboratory and instrumental indicators: often - ECG disorders, increased prolactin level, 1 increased activity of microsomal liver enzymes, increased activity of transaminases, increased or decreased body weight; infrequent - prolongation of the QT interval on the ECG.

From the CVS: often - AV blockade, tachycardia; infrequently - blockade of the bundle of the Guiss, atrial fibrillation, bradycardia, sinus bradycardia, palpitation.

Hematologic disorders and disorders of the lymphatic system: often anemia; infrequently - thrombocytopenia, neutropenia; very rarely - agranulocytosis.

From the nervous system: very often - parkinsonism2, akathisia2, headache; often - dizziness, sedation, drowsiness, tremor, dystonia2, tardive dyskinesia, dyskinesia2; infrequently - convulsions, fainting, postural dizziness, hypoesthesia, paresthesia, lethargy, hypersomnia.

From the side of the organ of vision: often - blurred vision, conjunctivitis; rarely - flabby iris syndrome (intraoperative) 4; with an unknown frequency - the occlusion of the artery of the retina.

From the side of the kidneys and urinary tract: often - urinary incontinence; infrequently urinary retention.

From the skin and subcutaneous tissues: often - rash, eczema; infrequently - Quincke's edema, itching, acne, alopecia, dry skin.

From the musculoskeletal system and connective tissue: often - arthralgia, back pain, pain in the extremities, myalgia; infrequently - muscle weakness, pain in the neck, pain in the buttocks, musculoskeletal pain in the chest.

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

Metabolic and nutritional disorders: often - hyperglycemia; infrequently - diabetes mellitus3, increased appetite, decreased appetite; rarely - hypoglycemia; very rarely diabetic ketoacidosis; with unknown frequency - water intoxication.

Infections: very often - infections of the upper respiratory tract; often - pneumonia, influenza, lower respiratory tract infections, bronchitis, urinary tract infections, ear infections, sinusitis, viral infections; infrequently - cystitis, gastroenteritis, infections, localized infections, subcutaneous abscess.

Injuries, poisoning and complications associated with the procedure for administering the drug: often - falling; infrequently - pain during the procedure of drug administration.

Vascular disorders: often - hypertension, hypotension; infrequently - orthostatic hypotension.

General violations and violations in the field of drug administration: often - pyrexia, peripheral edema, pain in the chest, fatigue, pain, pain in the area of drug administration, asthenia, influenza-like condition; infrequent - compaction in the area of drug administration, densification, reactions in the area of drug administration, discomfort in the chest, sluggishness, poor health; rarely - hypothermia.

From the immune system: infrequently - hypersensitivity; with an unknown frequency - anaphylactic reactions.

Hepatobiliary disorders: rarely - jaundice.

On the part of the reproductive system and mammary glands: often - amenorrhea, erectile dysfunction, galactorrhea; infrequently - sexual dysfunction, gynecomastia; with an unknown frequency - priapism.

Mental disorders: very often - depression, insomnia, anxiety; often - agitation, sleep disorders; infrequently - mania, decreased libido, nervousness.

1- Hyperprolactinemia in some cases can lead to gynecomastia, menstrual cycle disorders, amenorrhea and galactorrhea.

2- extrapyramidal disorders may manifest as: parkinsonism (hypersalivation, musculoskeletal stiffness, parkinsonism, drooling, rigidity as a cogwheel, bradykinesia, hypokinesia, masculine face, muscle tension, akinesia, stiff neck, muscle rigidity, parkinsonian gait, disorders glabellar reflex), akathisia (akathisia, restlessness, hyperkinesia and restless leg syndrome), tremor, dyskinesia (dyskinesia, muscle twitching, choreoathetosis, athetosis and myoclonus), dystonia. Dystonia includes dystonia, muscle spasms, hypertension, torticollis, involuntary muscle contractions, muscle contracture, blepharospasm, eyeball movements, paralysis of the tongue, facial spasm, laryngospasm, myotonia, opisthotonus, oropharyngeal spasm, pleurototonus, spasm of the tongue and trismus. Tremor includes tremor and Parkinson's tremor tremor.

3 - in placebo-controlled studies, diabetes was observed in 0.18% of patients taking risperidone compared with 0.11% of patients in the placebo group. The total incidence of diabetes by the results of all clinical trials was 0.43% of all patients taking risperidone.

4 - was observed only in the postmarketing period.

The following side effects are further described in the clinical studies of oral dosage forms of risperidone, but not with the use of a prolonged injection of risperidone - Rispolept Konsta®. Side effects are given with the distribution of system-organ classes.

Changes in laboratory parameters: increased body temperature, an increase in the number of ezonophiles, an increase in the number of leukocytes, a decrease in the level of hemoglobin, an increase in the level of CK, a decrease in body temperature.

Infections: tonsillitis, inflammation of subcutaneous fat, otitis media, eye infections, acrodermatitis, respiratory tract infections, onychomycosis, chronic otitis media.

From the side of blood and lymphatic system: granulocytopenia.

From the immune system: hypersensitivity to the drug.

Metabolic and nutritional disorders: anorexia, polydipsia.

Mental disorders: confusion, lethargy, anorgasmia, affective flattening.

From the side of the nervous system: lack of response to stimuli, loss of consciousness, malignant neuroleptic syndrome, diabetic coma, stroke, depression, cerebral ischemia, cerebrovascular disorders, transient ischemic attack, dysarthria, attention disturbance, imbalance, speech impairment, impaired coordination movements.

Ophthalmic disorders: ocular hyperemia, discharge from the eyes, edema around the eyes, dry eyes, increased lacrimation, photophobia, decreased visual acuity, involuntary eyeball rotation, glaucoma.

From the side of the ear and the labyrinth: ringing in the ears.

Vascular disorders: hot flushes.

Respiratory, thoracic disorders and disorders of the mediastinum: wheezing, aspiration pneumonia, congestion in the lungs, respiratory failure, wheezing, epistaxis, nasal congestion, hyperventilation, dysphonia.

From the digestive tract: dysphagia, fecal incontinence, fecaloma, edema of lips, cheilitis.

From the skin and subcutaneous tissues: skin lesions, skin disorders, skin discoloration, seborrheic dermatitis, hyperkeratosis, dandruff, erythema.

From the musculoskeletal system and connective tissue: rhabdomyolysis, swelling of the joints, impaired posture, stiffness in the joints.

From the side of the kidneys and urinary tract: enuresis, dysuria, pollakiuria.

On the part of the reproductive system and mammary glands: erectile dysfunction, vaginal discharge, menstruation.

General disorders and phenomena caused by the administration of the drug: general edema, edema of the face, gait disturbance, thirst, chills, cold extremities, withdrawal syndrome.

Class-effects. As with the use of other antipsychotics, very rare cases of prolongation of the QT interval were observed in the post-marketing period of observation. Other CCC-class effects observed with the use of antipsychotics that extend the QT interval include: ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac arrest, and bidirectional ventricular tachycardia.

Venous thromboembolism. Cases of venous thromboembolism, including pulmonary embolism and cases of deep vein thrombosis, were observed with the use of antipsychotics (the frequency is unknown).

Increase in body weight. In a 12-week, placebo-controlled study, 9% of patients taking Rispolept Consta® received an increase of at least 7% at the end of the study compared with 6% of patients taking placebo. In another clinical study, lasting 1 year, changes in body weight for individual patients were ± 7% of the mean; In 25% of patients, an increase in body weight of at least 7% was observed.

Interaction

Rispolept Consta® increases the severity of oppressive effects on the CNS of opioid analgesics, hypnotics, anxiolytics, tricyclic antidepressants, agents for general anesthesia, alcohol.

Rispolept Consta® can weaken the action of levodopa and other dopamine receptor agonists.

Clinically significant arterial hypotension is observed with the combined use of risperidone with antihypertensive agents.

Caution should be exercised when using the drug Rispolept Consta® with medications that increase the QT interval.

It was found that carbamazepine reduces the plasma content of the active antipsychotic fraction of risperidone. Similar effects may be caused by other inducers of microsomal liver enzymes. When appointing and after the withdrawal of carbamazepine or other inducers of microsomal liver enzymes, the dose of Rispolept Consta® should be adjusted.

Fluoxetine and paroxetine, inhibitors of microsomal liver enzymes, increase the concentration of risperidone in plasma, but to a lesser extent - the concentration of the active antipsychotic fraction. When appointing and after the abolition of fluoxetine or paroxetine, the dose of Rispolept Consta® should be adjusted.

Topiramate moderately reduces the bioavailability of risperidone, but not the active antipsychotic fraction. This interaction is not considered clinically significant.

Phenothiazines, tricyclic antidepressants and some β-adrenoblockers can increase plasma concentrations of risperidone, but to a lesser extent, the concentration of the active antipsychotic fraction.

Cimetidine and ranitidine increase the bioavailability of risperidone, but have a minimal effect on the concentration of the active antipsychotic fraction.

Erythromycin, an inhibitor of inducers of microsomal liver enzymes does not affect the pharmacokinetics of risperidone and the active antipsychotic fraction.

Cholinesterase inhibitors (galantamine and donepezil) do not have a clinically significant effect on the pharmacokinetics of risperidone and the active antipsychotic fraction.

When combined with drugs that have a high binding to plasma proteins, there is no clinically significant displacement of the drug from plasma proteins.

Risperidone does not have a clinically significant effect on the pharmacokinetics of lithium, valproic acid, digoxin or topiramate.

When furosemide and oral forms of risperidone are used together, there is an increase in deaths in elderly patients with dementia (see "Special instructions").

Dosing and Administration

IM, 1 time in 2 weeks, deep into the gluteal muscle using a sterile needle attached to the syringe. Injections should be done alternately in the right and left buttocks. The drug can not be administered iv.

In patients who have not previously received risperidone, it is recommended to determine the tolerability of oral dosage forms of risperidone before initiating treatment with Rispolept Consta®.

Adults. The recommended dose is 25 mg once every 2 weeks. Some patients need higher doses - 37.5 or 50 mg. In clinical studies, there was no increase in efficacy with 75 mg. The maximum dose should not exceed 50 mg once every 2 weeks.

In the 3-week period after the first administration of Rispolept®, the patient should take an effective antipsychotic.

The dose of the drug can be increased no more than once in 4 weeks. The effect of such a dose increase should be expected not earlier than 3 weeks after the first injection of the increased dose.

Elderly patients. The recommended dose is 25 mg once every 2 weeks. In the 3-week period after the first injection of Rispolept®, the patient should take an effective antipsychotic.

Patients with impaired hepatic or renal function. At present, there is no data on the use of Rispolept Consta® in patients with impaired hepatic or renal function.

If it is necessary to treat patients with impaired hepatic or renal function with Rispolept Consta® in the first week, it is recommended to take 0.5 mg 2 times per day oral dosage form of risperidone. During the second week the patient can take 1 mg 2 times a day or 2 mg 1 time per day. If the patient well tolerates an oral dose of at least 2 mg, then he can inject 25 mg of Rispolept Consta ® 1 time every 2 weeks.

Instructions for use

The use of Rispolept® Constan® requires strict adherence to the instructions for preparing the suspension in order to ensure accurate administration of the preparation and avoid possible errors.

To prepare the suspension from the Ripolept Consta® micro-granules in the vial of the prolonged action, only the solvent in the pre-filled syringe can be used. Ready suspension is administered intramuscularly only in the gluteal region. Do not replace the components in the packaging with any other products. To ensure the use of a full dose of risperidone, the entire contents of the vial should be administered. The introduction of part of the contents of the vial can not ensure that the patient receives the correct dose of the drug. The drug should be administered immediately after the preparation of the suspension.

First, you need to get the package of Rispolept Consta® from the refrigerator and let it warm to room temperature before the suspension is prepared for 30 minutes.

The composition of the package is shown in the figure below:

• 1.Remove the colored plastic cover from the bottle. Do not remove the gray rubber stopper. Wipe unopened vial with alcohol wipe and allow to dry.

• 2.Open the blister pack and remove the Alaris ™ Smart Site® needle-less device, holding it between the white luer cap and the "skirt". Never touch the sharp tip of the device.

• 3.It is very important that the Smart Site® needleless device is correctly installed on the bottle, otherwise the solvent may leak when it enters the bottle. Place the vial on a hard surface. Hold the bottom of the bottle. Direct the Smart Site® needleless device onto the bottle vertically so that the sharp tip is located in the center of the vial of the vial.

Right

Don’t right

Pressing downwards, push the sharp tip of the needleless device Smart Site® through the center of the rubber bottle stopper until the device is securely attached to the top of the bottle.

• 4.Before attaching the syringe to the needleless device Smart Site®, holding the base of the vial, wipe the place of attachment of the device with a syringe (blue circle) with an alcoholic cloth and allow to dry.

5. The pre-filled syringe has a white tip consisting of two parts: a white collar and a glossy white cap. In order to open the syringe, you should hold the syringe by the white collar and break off the glossy white cap (the white cap can not be unscrewed or cut off). Then remove the white cap with the rubber tip inside.

At all stages of assembly it is necessary to keep the syringe just behind the white collar located on the tip of the syringe. Fixing the white collar will help to protect the collar from separation and ensures a good connection with the syringe. Care must be taken not to twist components during assembly, because while parts of the syringe can come off of it.

• 6.While holding the syringe by the white collar, insert the syringe into the blue circle of the needleless device, press and turn clockwise, so that the syringe is firmly connected to the needleless device (avoid twisting). To prevent rotation of the needleless device during the connection with the syringe, you must firmly hold the "skirt". The syringe and the needleless device must be on the same line.

• 7.Insert the contents of the syringe with the solvent into the vial.

• 8.While holding the plunger of the syringe with your thumb, vigorously shake the contents of the vial for at least 10 seconds until a homogeneous suspension forms. After proper mixing, the suspension becomes homogeneous, thick, milky in color. The microgranules can be seen in the liquid, but should not remain dry by the solvent of the dry microgranules. Do not store the vial after the suspension has been prepared, since the suspension may be exfoliated.

9. Turn the bottle upside down and slowly draw all the contents of the vial into the syringe. Separate part of the label from the vial along the perforation line and glue it to the syringe (for identification).

10. Holding the syringe by the white collar, disconnect the syringe from the needleless device. Dispose of the bottle and needleless device in accordance with local regulations for the disposal of this type of waste.

11. Open the blister pack of Needle-Pro® needle. Do not touch the part of the needle that joins the syringe. Remove the needle from the package, holding it by the transparent case.

12. To prevent germs from entering, do not touch the Lener tip of the orange needle safety device Needle-Pro®. Holding the syringe by the white collar, attach the Luer cannula of the orange Needle-Pro® needle safety device to the syringe by slightly turning it clockwise.

13. Continuing to hold the syringe by the white collar, clamp the transparent case of the needle and tighten the needle firmly in the Needle-Pro® protective device by pressing and turning it clockwise. Securing the needle can ensure a safe connection between the needle and the Needle-Pro® needle guard during the following steps.

14. Immediately prior to administration, Rispolept® Konsta® must be resuspended, since after the suspension is prepared in the vial, some of the microgranules may settle. To resuspend the microgranules, vigorously shake the syringe.

15. Holding the syringe by the white collar, remove the transparent case from the needle. Do not bend the case; the junction of the luer tip can be violated.

16. Lightly tap with your finger on the syringe so that the air bubbles in it go up. Slightly pushing the piston upward, remove air bubbles from the syringe and needle, holding the syringe so that the needle is directed vertically upwards. Enter the entire contents of the syringe into the upper outer quadrant of the gluteal region.

Suspension can not be administered intravenously!

Caution: To avoid injuring medical personnel with a used needle:

- Do not touch the needle protection device Needle-Pro® while pressing it against a flat surface;

- Do not disassemble Needle-Pro® needle protection;

- Do not attempt to straighten the needle and touch the Needle-Pro® needle guard unless the needle is bent or damaged;

- Use needle protection device Needle-Pro® only for the purpose, otherwise the needle may protrude from the protective cap.

17. After the injection, insert the needle into the orange Needle-Pro® needle protection device with one hand. To do this, gently press the orange needle protection device Needle-Pro® onto a flat surface.

18. Once the Needle-Pro® orange needle protector has been pressed, the needle must fit tightly into the Needle-Pro® needle guard. Before discarding the needle, make sure that the needle is firmly attached to the orange needle protection device Needle-Pro®. Dispose of in accordance with local regulations for the destruction of this type of waste.

Do not reuse: this device is intended for single use only. Any attempt at subsequent reuse may adversely affect the integrity of the device itself or lead to a deterioration in its operation.

Overdose

When using parenteral dosage forms of risperidone, an overdose is less likely than with the use of oral forms (film-coated tablets and oral solution), and therefore information on oral forms is provided.

Symptoms: Observed with overdose symptoms, are enhanced known pharmacological effects. These include sedation, drowsiness, tachycardia, lowering blood pressure, and extrapyramidal disorders. There was an extension of the QT interval and convulsions. Bi-directional ventricular tachycardia was noted with simultaneous administration of an increased dose of oral risperidone and paroxetine. In case of an overdose, the possibility of involving several drugs should be considered.

Treatment: provide and maintain airway patency, adequate oxygenation and ventilation. It is necessary to monitor the function of the CAS, which should include continuous ECG monitoring to identify possible arrhythmias. Rispolept® does not have a specific antidote, and therefore treatment should be aimed at maintaining the function of the central nervous system and the CVS, and detoxification therapy should also be carried out. In severe extrapyramidal symptoms, anticholinergic drugs should be prescribed. Medical surveillance and monitoring should continue until the signs of an overdose disappear.

Special instructions

In patients who have not previously received risperidone, it is recommended to determine the tolerability of oral dosage forms of risperidone before initiating treatment with Rispolept Consta®.

Use in elderly patients with dementia

The use of Rispolept Consta® was not investigated in elderly patients with dementia, it is not indicated for this group of patients. The drug Rispolept® Consta® is not intended to treat behavioral disorders associated with dementia.

Increased mortality in elderly patients with dementia

In elderly patients with dementia, atypical antipsychotics, an increased mortality was observed compared to the placebo group in the meta-analysis of 17 controlled trials of atypical antipsychotics, including oral risperidone. In placebo-controlled trials of oral risperidone for this population, the incidence of death was 4% for patients taking risperidone, compared with 3.1% for the placebo group. The average age of the deceased patients is 86 years (range - 67-100 years). The data collected from two extensive observational studies show that elderly patients with dementia who are treated with typical antipsychotics also have a slightly increased risk of death compared to patients who do not receive treatment. At the moment, there is insufficient data to accurately assess this risk. The cause of this risk increase is also unknown. Also, the extent to which an increase in mortality may not be applicable to antipsychotics, nor to the characteristics of this group of patients, has been determined.

Simultaneous application with furosemide

In elderly patients with dementia, increased mortality was observed with furosemide and risperidone taken concurrently (7.3%, mean age 89 years, range 75-97 years) compared with the risperidone-only group (3.1%, mean age 84 year, range - 70-96 years) and the group taking only furosemide (4.1%, mean age 80 years, range - 67-90 years). Increased mortality of patients taking risperidone with furosemide was observed in 2 of 4 clinical trials. Joint use of risperidone with other diuretics (mainly with thiazide diuretics in small doses) was not accompanied by an increase in mortality.

There are no pathophysiological mechanisms that explain this observation. Nevertheless, special care should be taken when prescribing the drug in such cases. Before appointment, the risk / benefit ratio must be carefully assessed. There was no increase in mortality in patients taking other diuretics simultaneously with risperidone. Regardless of treatment, dehydration is a common risk factor for mortality and should be carefully monitored in elderly patients with dementia.

Side effects from the cerebrovascular system

In placebo-controlled clinical trials in patients with dementia, taking some atypical antipsychotics, an increased risk of cerebrovascular side effects was approximately 3-fold. Combined data from six placebo-controlled trials, including mainly elderly patients with dementia (age over 65 years), demonstrated that cerebrovascular side effects (serious and non-serious) occurred in 3.3% (33/1009) of patients taking risperidone and in 1.2% (8/712) of patients taking placebo. The risk ratio was 2.96 (1.34, 7.5 at a confidence interval of 95%). The mechanism of increasing the risk is unknown. Increased risk is not excluded for other antipsychotics, as well as for other patient populations. Rispolept Konsta® should be used with caution in patients with risk factors for stroke.

Orthostatic hypotension

Risperidone has α-adrenoblocking activity, and therefore can cause orthostatic hypotension in some patients, especially at the beginning of therapy. Clinically significant hypotension was observed in the postmarketing period when combined with antihypertensive drugs. Risperidone should be used with caution in patients with known cardiovascular diseases (eg, heart failure, myocardial infarction, cardiac muscle conduction disorders, dehydration, hypovolemia or cerebrovascular disease). It is recommended that the benefit / risk ratio be evaluated carefully when assessing the possibility of continuing therapy with Rispolept Konsta®.

Late dyskinesia and extrapyramidal disorders

Drugs that have the properties of dopamine receptor antagonists can cause tardive dyskinesia, which is characterized by rhythmic involuntary movements, predominantly of the tongue and / or facial musculature. The occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. If the patient has objective or subjective symptoms indicating late dyskinesia, it is necessary to consider the feasibility of the abolition of all antipsychotics.

Malignant neuroleptic syndrome (CNS)

Antipsychotic drugs, including risperidone, can cause CNS, which is characterized by hyperthermia, rigidity of muscles, instability of the autonomic nervous system function, depression of consciousness, and an increase in serum concentrations of CK. In patients with ZNS, myoglobinuria (rhabdomyolysis) and acute renal failure may also occur. If a patient develops symptoms of the NSA, all antipsychotics should be immediately discontinued, including Ryspolept Consta®.

Parkinson's disease and dementia with Levi bodies

The administration of antipsychotics, including Ryspolept Consta®, to patients with Parkinson's disease or dementia with Levy bodies should be carried out with caution, since in both groups of patients, the risk of developing CNS increased and sensitivity to antipsychotic drugs increased (including blunting of pain sensitivity, confusion, postural instability with frequent falls and extrapyramidal symptoms). When taking risperidone, there may be a worsening of the course of Parkinson's disease.

Hyperglycemia and diabetes mellitus

When treating the drug Rispolept Consta®, hyperglycemia, diabetes mellitus and exacerbation of already existing diabetes mellitus were observed. It is likely that the previous increase in body weight is also predisposing to this factor. It is very rare to have ketoacidosis and rarely - a diabetic coma. All patients need to be clinically monitored for symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia, and weakness). Patients with diabetes should be monitored regularly for impaired glucose control.

Weight gain

In the treatment with Rispolept® Consta®, a significant increase in body weight was observed. It is necessary to monitor the body weight of patients.

Hyperprolactinemia

Based on the results of studies on tissue cultures, it has been suggested that the growth of breast tumor cells can be stimulated by prolactin. Although clinical and epidemiological studies have not revealed a clear association between hyperprolactinaemia and antipsychotic medications, caution should be exercised in prescribing risperidone to patients with a history of history. The drug Rispolept® Consta® should be used with caution in patients with existing hyperprolactinemia and in patients with possible prolactin-dependent tumors.

QT interval extension

The prolongation of the QT interval was very rare in the post-marketing period. As with other antipsychotics, caution should be exercised when prescribing Rispolept Konsta® to patients with known cardiovascular diseases, prolonged QT interval in a family history, bradycardia, electrolyte balance disorders (hypokalemia, hypomagnesemia this may increase the risk of arrhythmogenic effect; and when combined with drugs that extend the QT interval.

Convulsions

Rispolept Consta® should be used with caution in patients with a history of seizures or with other medical conditions in which the convulsive threshold may be reduced.

Priapism

Priapism may occur with the use of risperidone due to alpha-adrenergic blocking effects.

Regulation of body temperature

Antipsychotic drugs attributed to such an undesirable effect as a violation of the ability of the body to regulate the temperature. Caution should be exercised when prescribing Rispolept Consta® to patients with conditions that can contribute to an increase in internal body temperature, such as intense physical activity, dehydration, exposure to high external temperatures, or simultaneous use of drugs with anticholinergic activity.

Venous thromboembolism

When using antipsychotic drugs, cases of venous thromboembolism were noted. Because patients taking antipsychotics often have a risk of developing venous thromboembolism, all possible risk factors should be identified before and during treatment with Rispolept Consta®, and precautionary measures should be taken.

Intraoperative syndrome of sagging iris (ISDR)

ISDR was observed during operative intervention for the presence of cataracts in patients receiving therapy with drugs that have α 1 -adrenoreceptor antagonist activity, including Rispolept Consta® preparation.

ISDR increases the risk of complications associated with the organ of vision, during and after an operation. The physician conducting such an operation should be informed in advance that the patient has or is currently taking drugs that have α 1 -adrenoreceptor antagonist activity. The potential benefit of the abolition of α1-adrenergic antagonists before surgery is not established, and should be evaluated taking into account the risks associated with the abolition of antipsychotic medications.

Renal and hepatic impairment

Despite the fact that Rispolept® Konsta® has not been studied in patients with renal or hepatic insufficiency, caution should be exercised when using the drug in such patient groups.

Care must be taken to avoid inadvertent administration of Rispolept® Constan® into the blood vessel.

Do not expose the product to temperatures above 25 ° C.

In the absence of a refrigerator, the preparation Rispolept Konsta® before use can be stored at a temperature of no higher than 25 ° C for not more than 7 days.

After the suspension is prepared: the suspension is physically and chemically stable for 24 hours at 25 ° C. From the microbiological point of view, it is desirable to use the suspension immediately after preparation. If the suspension is not used immediately after preparation, it can be stored for no more than 6 hours at a temperature of 25 ° C.

Incompatible combinations

Rispeplet Consta® can not be mixed or diluted with any other medicines and fluids other than the special solvent contained in the package.

Influence on the ability to drive and work with machinery. Risperidone can reduce the rate of mental and physical reactions, and therefore patients should be advised to refrain from driving the car and working with mechanisms.

Release form

Powder for suspension for intramuscular administration of prolonged action, 25 mg, 37.5 mg, 50 mg.

Package Content: 1 fl. with a powder containing sustained release micro-granules of Ryspolept Consta® at 25, 37.5 or 50 mg of risperidone; 1 pre-filled syringe with 2 ml solvent; 1 Alaris ™ Smart Site® needleless device for suspension preparation; 1 Needle-Pro® safety needle (with protective device) for the first injection.

The color of the vial plug differs depending on the dosage of the drug: for 25 mg - pink, for 37.5 mg - green, for 50 mg - blue.

The components are packaged in a contoured cell pack of PVC film coated with a transparent PE film. 1 contour pack in a cardboard box.

Conditions of leave from pharmacies

On prescription.

Storage conditions for Rispolept CONSTA

In the dark place at a temperature of 2-8 ° C.

Keep out of the reach of children.

Shelf life of Rispolept CONSTA

3 years.

Do not use after the expiry date printed on the package.