Expiration date: 02/2026

Composition

Active ingredient: risperidone (in the form of microgranules of prolonged release),

Excipients: lactic and glycolic acid copolymer 619 mg (in 1 g of microgranules),

Solvent: sodium carmellose (40 MPa·, c) 22.5 mg, polysorbate 20 1 mg, sodium hydrophosphate 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,

Pharmacodynamics

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

In fast metabolizers, the clearance of the 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.

General characteristics of risperidone after injection of Rispolept Consta to patients

With a single intravenous administration of Rispolept Consta, the risperidone release profile consists of a small initial phase.

The combination of risperidone release profile and dosage regimen (intramuscular injection once every 2 weeks) ensures maintenance of therapeutic risperidone concentrations in plasma. Therapeutic concentrations persist until the 4th to 6th week after the last injection of Rispolept Consta. The elimination phase ends approximately 78 weeks after the last injection.

Risperidone is completely absorbed from the suspension of Rispolept Consta. Risperidone is rapidly distributed in the tissues of the body. The Vd is 12 l/kg. In plasma, risperidone binds to albumin and 1-acid glycoprotein. The plasma protein binding of risperidone is 90%, and 9-hydroxyrisperidone is 77%. After intramuscular injection of Rispolept Consta at doses of 25 or 50 mg once every 2 weeks, the average values of Cmin and Cmax in plasma of the active antipsychotic fraction are 9.919.2 and 17.945.5 ng /ml, respectively. With this dosage regimen, the pharmacokinetics of risperidone is linear. In long-term use (12 months) in patients who were administered Rispolept Consta at doses of 2550 mg once every 2 weeks, no accumulation of risperidone was observed. A study of the use of a single dose 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. Plasma concentrations of risperidone in patients with hepatic insufficiency were normal, but the average value of the free fraction in plasma increased by 35%.

Pharmacokinetics

Risperidone is a selective monoaminergic antagonist. It has a high affinity for serotonergic 5-HT2 receptors and dopaminergic D2 receptors. In addition, risperidone binds to 1-adrenergic receptors and, to a lesser extent, to H1-histaminergic and 2-adrenergic receptors. Risperidone does not bind to cholinergic receptors. Despite the fact that risperidone is a powerful antagonist of D2 receptors, due to which it improves the positive symptoms of schizophrenia, this drug, compared with typical neuroleptics, inhibits motor activity to a lesser extent and less often causes catalepsy. Due to the balanced central antagonism against serotonin and dopamine receptors, risperidone less often causes extrapyramidal side effects and has a therapeutic effect on the negative and affective symptoms of schizophrenia.

Indications for use

Treatment and prevention of schizophrenia and schizoaffective disorders.

Contraindications

• lactation (breastfeeding),
• children and adolescents under 18 years of age,
• hypersensitivity to Rispolept Consta.

Due to the alpha-adrenoblocking activity of risperidone, orthostatic hypotension may occur in patients, especially during the initial period of treatment, and therefore risperidone should be used with caution in patients with cardiovascular diseases (for example, heart failure, myocardial infarction, cardiac muscle conduction disorders / for example, AV block, dehydration, hypovolemia or cerebrovascular disorders). In such patients, the dose should be increased gradually. With the continuation of clinically significant hypotension, it is necessary to assess the risk/benefit of further treatment with Rispolept Consta.

Caution should be exercised when prescribing Rispolepta Consta to patients with Parkinson's disease (since, theoretically, risperidone can cause an exacerbation of this disease), as well as to patients with epilepsy.

Use during pregnancy and lactation

The safety of Rispolept Consta in human pregnancy has not been studied.

In experimental animal studies, risperidone did not have a 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.

Thus, Rispolept Consta can be used during pregnancy only if the expected benefit of therapy for the mother exceeds the potential risk to the fetus.

Since risperidone and 9-hydroxy-risperidone penetrate into breast milk, if necessary, breastfeeding should be discontinued during lactation.

Side effects

Rispolept Consta in therapeutic doses causes the following adverse events:

Often (>1/100) weight gain (by 2.7 kg or more in 1 year), depression, increased fatigue and extrapyramidal symptoms. Against the background of taking Rispolept Consta (in doses up to 50 mg), the frequency of extrapyramidal symptoms is similar to that of patients receiving placebo.

Rarely (>0.1/100) weight gain, increased irritability, sleep disorders, apathy, decreased concentration, late dyskinesia, seizures, neuroleptic malignant syndrome, visual impairment, hypotension, tachycardia, fainting, skin rash, itching, peripheral edema, injection site reaction.

Symptoms of hyperprolactinemia, such as non-labor-related lactation, amenorrhea, gynecomastia, menstrual disorders, impaired sexual function, impaired ejaculation, decreased libido and impotence.

Hematological disorders: an increase or decrease in the number of leukocytes or platelets, an increase in the activity of liver enzymes.

In addition, the following undesirable phenomena are possible: insomnia, agitation, anxiety, headache, constipation, abdominal pain, rhinitis, urinary incontinence, priapism, drowsiness, dizziness, dyspepsia, nausea, vomiting, thermoregulation disorders, as well as hypervolemia caused by polydipsia or insufficient secretion of ADH syndrome. During treatment with Rispolept Consta, disorders of cerebral circulation sometimes occur. Hyperglycemia or worsening of the course of diabetes mellitus is very rarely observed during treatment with Rispolept Consta.

Interaction

Rispolept Consta increases the severity of the depressive effect on the central nervous system of opioid analgesics, hypnotics, anxiolytics, tricyclic antidepressants, general anesthesia, alcohol.

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

Clinically significant arterial hypotension is observed when risperidone is co-administered with antihypertensive agents.

Caution should be exercised when using Rispolept Consta in combination with drugs that increase the QT interval.

Carbamazepine has been found to reduce the plasma content of the active antipsychotic fraction of risperidone. Similar effects can be caused by other inducers of microsomal liver enzymes. When prescribing and after discontinuation 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 prescribing and after discontinuation 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 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) have no clinically significant effect on the pharmacokinetics of risperidone and the active antipsychotic fraction.

When taken together with drugs with high plasma protein binding, there is no clinically significant displacement of the drug from plasma proteins.

Risperidone has no clinically significant effect on the pharmacokinetics of lithium, valproic acid, digoxin or topiramate.

Method of administration and dosage

I/m, 1 time every 2 weeks, deep into the gluteal muscle, using a sterile needle attached to the syringe. Injections should be given alternately in the right and left buttocks. The drug should not be administered intravenously.

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

Adults. The recommended dose is 25 mg once every 2 weeks. Some patients need higher doses of 37.5 or 50 mg. In clinical studies, there was no increase in efficacy when using 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 Consta, the patient should take an effective antipsychotic.

The dose of the drug can be increased no more than once every 4 weeks. The effect of such an increase in dose should be expected no 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 Consta, the patient should take an effective antipsychotic.

Patients with impaired liver or kidney function. Currently, there is no data on the use of Rispolept Consta in patients with impaired liver or kidney function.

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

Instructions for use

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

To prepare a suspension from the microgranules of Rispolept with Prolonged action in the vial, only a solvent located in a pre-filled syringe can be used. The finished suspension is injected intramuscularly only into the gluteal region. Do not replace the components in the package with any other products. To ensure the use of the full dose of risperidone, the entire contents of the vial must be injected. The introduction of part of the contents of the vial cannot ensure that the patient receives the desired 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 heat up to room temperature for 30 minutes before preparing the suspension.

Overdose

Symptoms: the symptoms observed in overdose are enhanced by known pharmacological effects. They include sedation, drowsiness, tachycardia, lowering blood pressure and extrapyramidal disorders. Prolongation of the QT interval and seizures were observed. Bidirectional ventricular tachycardia was observed with simultaneous administration of an increased dose of oral risperidone and paroxetine. In case of overdose, the possibility of involving multiple drugs should be considered.

Treatment: provide and maintain airway patency, adequate oxygenation and ventilation. It is necessary to monitor the function of the cardiovascular system, which should include constant 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 CVS, and detoxification therapy should also be performed. In severe extrapyramidal symptoms, anticholinergic drugs should be prescribed. Medical supervision and monitoring should be continued until the signs of 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 starting treatment with Rispolept Consta.

Use in elderly patients with dementia

The use of Rispolept Consta has not been studied in elderly patients with dementia, because it is not indicated for this group of patients. Rispolept Consta is not intended for the treatment of dementia-related behavioral disorders.

Increased mortality in elderly patients with dementia

Elderly patients with dementia treated with atypical antipsychotics had increased mortality compared to the placebo group in a meta-analysis of 17 controlled trials of atypical antipsychotics, including oral risperidone. In placebo-controlled trials of oral forms of risperidone for this population, the death rate was 4% for patients taking risperidone, compared with 3.1% for the placebo group. The average age of deceased patients is 86 years (range 67100 years). Data collected from two extensive observational studies show that elderly dementia patients treated with typical antipsychotic medications also have a slightly increased risk of death compared to non-treated patients. Currently, insufficient data has been collected to accurately assess this risk. The reason for the increase in this risk is also unknown. Also, the extent to which the increase in mortality may be applicable to antipsychotic drugs, and not to the characteristics of this group of patients, has not been determined.

Simultaneous use with furosemide

Elderly patients with dementia had increased mortality when taking furosemide and risperidone orally at the same time (7.3%, mean age 89 years, range 7597 years) compared with the group taking only risperidone (3.1%, average age 84 years, range 7096 years) and the group taking only furosemide (4.1%, average age 80 years, range 6790 years). An increase in mortality in patients taking risperidone together with furosemide was observed in 2 out of 4 clinical trials. The combined use of risperidone with other diuretics (mainly thiazide diuretics in small doses) was not accompanied by an increase in mortality.

No pathophysiological mechanisms have been established to explain this observation. However, special care should be taken when prescribing the drug in such cases. Before prescribing, it is necessary to carefully assess the risk/benefit ratio. There was no increase in mortality in patients taking other diuretics together with risperidone at the same time. 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, patients with dementia taking some atypical antipsychotic drugs had an increased risk of cerebrovascular side effects by about 3 times. Combined data from 6 placebo-controlled trials, which included mainly elderly patients with dementia (age over 65 years), demonstrate 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 with a confidence interval of 95%). The mechanism of increased risk is unknown. An increase in risk is not excluded for other antipsychotic drugs, as well as for other patient populations. Rispolept Consta should be used with caution in patients with risk factors for stroke.

Orthostatic hypotension

Risperidone has adrenoblocking activity, and therefore may cause orthostatic hypotension in some patients, especially at the beginning of therapy. Clinically significant hypotension was observed in the post-marketing period when combined with antihypertensive drugs. Risperidone should be used with caution in patients with known cardiovascular diseases (e.g. heart failure, myocardial infarction, cardiac muscle conduction disorders, dehydration, hypovolemia or cerebrovascular disease). It is recommended to carefully evaluate the benefit/risk ratio when evaluating the possibility of continuing therapy with Rispolept Consta.

Tardive dyskinesia and extrapyramidal disorders

Drugs with dopamine receptor antagonist properties can cause tardive dyskinesia, which is characterized by rhythmic involuntary movements, mainly of the tongue and/or facial muscles. The occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. If a patient has objective or subjective symptoms indicating tardive dyskinesia, it is necessary to consider the expediency of discontinuing all antipsychotic drugs.

Neuroleptic malignant syndrome (NMS)

Antipsychotic drugs, including risperidone, can cause NMS, which is characterized by hyperthermia, muscle rigidity, instability of the autonomic nervous system, depression of consciousness, as well as an increase in serum concentrations of CKF. Myoglobinuria (rhabdomyolysis) and acute renal failure may also occur in patients with NMS. If a patient has symptoms of NMS, all antipsychotic medications, including Rispolept Consta, should be discontinued immediately.

Parkinson's disease and dementia with Lewy bodies

The administration of antipsychotic drugs, including Rispolept Consta, to patients with Parkinson's disease or dementia with Levi's corpuscles should be carried out with caution, since both groups of patients have an increased risk of developing NMS and increased sensitivity to antipsychotic drugs (including blunted pain sensitivity, confusion, postural instability with frequent falls and extrapyramidal symptoms). When taking risperidone, the course of Parkinson's disease may worsen.

Hyperglycemia and diabetes mellitus

Hyperglycemia, diabetes mellitus and exacerbation of existing diabetes mellitus were observed during treatment with Rispolept Consta. It is likely that an increase in body weight prior to treatment is also a predisposing factor to this. Ketoacidosis can be very rare and diabetic coma is rare. All patients should be clinically monitored for symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia and weakness). Patients with diabetes mellitus should be monitored regularly for deterioration of glucose control.

Weight gain

A significant increase in body weight was observed during treatment with Rispolept Consta. 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. Despite the fact that clinical and epidemiological studies have not revealed a clear link between hyperprolactinemia and taking antipsychotic drugs, caution should be exercised when prescribing risperidone to patients with a burdened medical history. Rispolept Consta should be used with caution in patients with existing hyperprolactinemia and in patients with possible prolactin-dependent tumors.

Prolongation of the QT interval

Prolongation of the QT interval was very rarely observed in the post-marketing observation period. As with other antipsychotics, caution should be exercised when prescribing Rispolept Consta to patients with known cardiovascular diseases, family history of QT prolongation, bradycardia, electrolyte imbalance (hypokalemia, hypomagnesemia), because this may increase the risk of arrhythmogenic effect, and when combined with drugs that prolong the QT interval.

Seizures

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

Priapism

Priapism may occur when using risperidone due to alpha-adrenoblocking effects.

Regulation of body temperature

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

Venous thromboembolism

Cases of venous thromboembolism have been reported with the use of antipsychotic drugs. Since patients taking antipsychotic drugs often have a risk of developing venous thromboembolism, all possible risk factors should be identified before and during treatment with Rispolept Consta, and preventive measures should be taken.

Intraoperative flabby iris syndrome (ISDR)

ISDR was observed during surgery for the presence of cataracts in patients receiving therapy with drugs with the activity of 1-adrenergic receptor antagonists, including Rispolept Consta.

ISDR increases the risk of complications related to the organ of vision during and after surgery. The doctor performing such an operation should be informed in advance that the patient has taken or is currently taking drugs with the activity of 1-adrenergic receptor antagonists. The potential benefit of discontinuing therapy with 1-adrenergic receptor antagonists before surgery has not been established, and should be evaluated taking into account the risks associated with discontinuation of antipsychotic therapy.

Kidney and liver failure

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

Care must be taken to avoid accidental injection of Rispolept Consta into a blood vessel.

Do not expose the drug to temperatures above 25 C.

In the absence of a refrigerator, Rispolept Consta can be stored at a temperature of no more than 25 C for no more than 7 days before use.

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

Incompatible combinations

Rispolept Consta should not be mixed or diluted with any other drugs and liquids other than the special solvent contained in the package.

Influence on the ability to drive vehicles and manage mechanisms

Risperidone can reduce the rate of mental and physical reactions, and therefore the patient

Conditions of release from pharmacies

Available by prescription

Storage conditions

In a place protected from light, at a temperature of 28 C

Shelf life

3 years