Rispolept Consta, vial, 25mg

Composition

Active ingredient:

risperidone (in the form of extended-release microgranules);

Auxiliary substances:

lactic and glycolic acid copolymer — 619 mg (in 1 g of microgranules);

Solvent:

carmellose sodium (40 MPa * s) – 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;

Pharmacological action

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 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 powerful D2-receptor antagonist, thanks to which it improves the positive symptoms of schizophrenia, this drug, compared to typical antipsychotics, inhibits motor activity to a lesser extent and less often causes catalepsy. Due to its balanced central antagonism against serotonin and dopamine receptors, risperidone is less likely to cause extrapyramidal side effects and has a therapeutic effect on the negative and affective symptoms of schizophrenia.

Pharmacokinetics

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

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 in patients with Rispolept Consta®

With a single intravenous injection of Rispolept Consta®, the risperidone release profile consists of a small initial phase (r.

The combination of risperidone release profile and dosage regimen (i/m injection 1 time in 2 weeks) ensures maintenance of therapeutic risperidone concentrations in plasma. Therapeutic concentrations are maintained until 4-6 weeks after the last injection of Rispolept Consta®. The elimination phase is completed approximately 7-8 weeks after the last injection.

Risperidone is completely absorbed from the Rispolept Consta®suspension. Risperidone is rapidly distributed in the body’s tissues. Vd is 1-2 l/kg. In plasma, risperidone binds to albumin and α1-acid glycoprotein. The plasma protein binding of risperidone is 90%, and that of 9-hydroxyrisperidone is 77%. After intravenous injections of Rispolept Consta® in doses of 25 or 50 mg once every 2 weeks, the average values of Cmin and Cmax in the plasma of the active antipsychotic fraction are 9.9-19.2 and 17.9–45.5 ng / ml, respectively.

With this dosage regimen, the pharmacokinetics of risperidone are linear. In long-term use (12 months), no accumulation of risperidone was observed in patients who were administered Rispolept Consta® in doses of 25-50 mg once every 2 weeks.

A study of the use of a single dose of oral 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%.

Indications

Treatment and prevention of exacerbations of schizophrenia and schizoaffective disorders.

Contraindications

• hypersensitivity to risperidone or any other ingredient of this drug;
• lactation period;
• children under 18 years of age.

With caution:  diseases of the cardiovascular system (chronic heart failure, previous myocardial infarction, cardiac muscle conduction disorders); dehydration and hypovolemia; cerebral circulation disorders; Parkinson’s disease; seizures and epilepsy (including in the anamnesis); severe renal or hepatic insufficiency; substance abuse Drugs or drug dependence; conditions predisposing to the development of pirouette-type tachycardia (bradycardia, electrolyte imbalance, concomitant use of drugs that prolong the QT interval); brain tumor, intestinal obstruction, cases of acute drug overdose, Reye’s syndrome (the antiemetic effect of risperidone can mask the symptoms of these conditions); pregnancy.

Side effects

Changes in laboratory and instrumental indicators:  often — ECG disorders, an increase in prolactin 1 levels, an increase in the activity of microsomal liver enzymes, an increase in transaminase activity, an increase or decrease in body weight; infrequently-prolongation of the QT interval on the ECG.

From the CCC side:  often — AV block, tachycardia; infrequently-bundle branch block, atrial fibrillation, bradycardia, sinus bradycardia, palpitation sensation.

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

Nervous system disorders:  very often-parkinsonism 2, akathisia 2, headache; often-dizziness, sedation, drowsiness, tremor, dystonia 2, tardive dyskinesia, dyskinesia 2; infrequently-convulsions, syncope, postural vertigo, hypesthesia, paresthesia, lethargy, hypersomnia.

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

From the side of the organ of hearing and labyrinth:  often-vertigo; infrequently-ear pain.

Respiratory, thoracic and mediastinal disorders:  often — shortness of breath, cough, sinus congestion, pharyngolaryngeal pain; rarely — sleep apnea syndrome.

From the gastrointestinal tract:  often — vomiting, diarrhea, constipation, nausea, abdominal pain, dyspepsia, toothache, dry mouth, stomach discomfort, gastritis; rarely-mechanical intestinal obstruction, pancreatitis; very rarely-intestinal obstruction.

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

Skin and subcutaneous tissue disorders:  often — rash, eczema; infrequently-angioedema, itching, acne, alopecia, dry skin.

Musculoskeletal and connective tissue disorders:  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-violation of the secretion of antidiuretic hormone.

Metabolic and nutritional disorders:  often — hyperglycemia; infrequently – diabetes mellitus 3, increased appetite, decreased appetite; rarely-hypoglycemia; very rarely-diabetic ketoacidosis; with unknown frequency-water intoxication.

Infections:  very often-upper respiratory tract infections; often-pneumonia, flu, 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 related to the drug use procedure:  often-falling; infrequently-pain during the drug use procedure.

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

General disorders and disorders in the area of drug use:  often-pyrexia, peripheral edema, chest pain, fatigue, pain, pain in the area of drug use, asthenia, flu-like condition; infrequently-compaction in the area of drug use, compaction, reactions in the area of drug use, chest discomfort, slowness, poor health; rarely-hypothermia.

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

Hepatobiliary disorders:  rarely-jaundice.

From the side 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.

Interaction

Rispolept Consta ® increases the severity of the depressing effect on the central nervous system of opioid analgesics, sleeping pills, anxiolytics, tricyclic antidepressants, general anesthesia, alcohol.

Rispolept Consta may weaken the effects 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 Rispolept Consta® is co-administered with medicinal products that increase the QT interval.

Carbamazepine was found to reduce the plasma level of the active antipsychotic fraction of risperidone. Other inducers of microsomal liver enzymes may have similar effects. When carbamazepine or other inducers of microsomal liver enzymes are prescribed and discontinued, 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 modestly reduces the bioavailability of risperidone, but not the active antipsychotic fraction. This interaction is not considered clinically significant.

Phenothiazines, tricyclic antidepressants, and some beta-blockers may 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 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 co-administered with drugs with high binding to plasma proteins, 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.

How to take, course of use and dosage

IV, once every 2 weeks, deep into the gluteal muscle, using a sterile needle attached to the syringe. Injections should be made 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-37.5 or 50 mg. In clinical studies, no increase in efficacy was observed with the use of 75 mg. The maximum dose should not exceed 50 mg once every 2 weeks.

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

The dose of the drug can be increased no more than 1 time in 4 weeks. The effect of such an increase in the dose should be expected no earlier than 3 weeks after the first injection of an 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 agent.

Patients with impaired liver or kidney function. Currently, there are 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® in the first week, it is recommended to take an oral dosage form of risperidone 0.5 mg 2 times a day. 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 25 mg of Rispolept Consta® can be administered intravenously once every 2 weeks.

Instructions for use

The use of Rispolept Consta ® requires strict compliance with the instructions for preparing the suspension to ensure accurate use of the drug and avoid possible errors.

Only the solvent contained in the pre-filled syringe can be used to prepare the suspension from the microgranules of Rispolept Consta®with prolonged action in the vial. The finished suspension is administered intramuscularly only in 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 should be administered. 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 preparation of the suspension.

First, remove the package of Rispolept Consta® from the refrigerator and allow it to warm up to room temperature for 30 minutes before preparing the suspension.

Overdose

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

Treatment: provide and maintain airway patency, adequate oxygenation and ventilation. Monitoring of CVS function is necessary, which should include continuous monitoring of ECG to detect 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 be performed. In case of severe extrapyramidal symptoms, anticholinergic drugs should be prescribed. Medical supervision and monitoring should continue 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

Application of Rispolept Konsta® It has not been studied in elderly patients with dementia, as 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 experienced increased mortality compared to the placebo group in a meta-analysis of 17 controlled trials of atypical antipsychotics, including oral risperidone. In placebo-controlled studies 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-67-100 years). Data collected from two extensive observational studies show that elderly patients with dementia who are treated with typical antipsychotic medications also have a slightly increased risk of death compared to patients who are not treated. 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 can be attributed to antipsychotic drugs, rather than to the characteristics of this group of patients, has not been determined.

Concomitant use with furosemide

Elderly patients with dementia experienced increased mortality when furosemide and risperidone were co-administered orally (7.3%, mean age 89 years, range 75-97 years). compared to the risperidone — only group (3.1%, mean age 84 years, range 70-96 years) and the furosemide — only group (4.1%, mean age 80 years, range 67-90 years). An increase in mortality in patients taking risperidone together with furosemide was observed in 2 out of 4 clinical trials. Concomitant use of risperidone with other diuretics (mainly low-dose thiazide diuretics) was not associated with increased 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, the risk/benefit ratio should be carefully evaluated. There was no increase in mortality in patients taking other diuretics concomitantly 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, patients with dementia taking certain atypical antipsychotic medications experienced an approximately 3-fold increased risk of cerebrovascular side effects. Combined data from 6 placebo-controlled trials, which included mainly elderly patients with dementia (over 65 years of age), show that cerebrovascular side effects (serious and non-serious) occurred in 3.3% (33/1009) of patients taking risperidone and 1.2% (8/712) of patients taking placebo. The risk ratio was 2.96 (1.34; 7.5 with 95% confidence interval). 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 alpha-blocking 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 co-administered with antihypertensive drugs. Risperidone should be used with caution in patients with known cardiovascular diseases (for example, heart failure, myocardial infarction, cardiac 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 that have the properties of dopamine receptor antagonists 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 tardive dyskinesia. If a patient has objective or subjective symptoms that indicate tardive dyskinesia, discontinuation of all antipsychotic medications should be considered.

Neuroleptic malignant syndrome (NMS)

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

Parkinson’s disease and dementia with Lewy bodies

Antipsychotic medications, including Rispolept Consta®, should be used with caution in patients with Parkinson’s disease or Lewy body dementia, as both groups of patients have an increased risk of developing NMS and increased sensitivity to antipsychotic medications (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 pre – existing diabetes mellitus were observed during treatment with Rispolept Consta®. It is likely that pre-treatment weight gain is also a predisposing factor. Ketoacidosis is 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 should be regularly monitored for deterioration in glucose control.

Weight gain

When treated 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 is suggested that the growth of breast tumor cells can be stimulated by prolactin. Despite the fact that clinical and epidemiological studies have not shown a clear association of hyperprolactinemia with antipsychotic medications, caution should be exercised when prescribing risperidone to patients with a burdened medical history. Rispolept Consta® should be used with caution in patients with pre-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 follow-up period. As with other antipsychotic agents, caution should be exercised when prescribing Rispolept Consta® to patients with known cardiovascular diseases, a family history of QT prolongation, bradycardia, electrolyte disturbances (hypokalemia, hypomagnesemia), as this may increase the risk of arrhythmogenic effects; and when used in combination with drugs that prolong the QT interval.

Convulsions

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

Priapism

Priapism may occur with risperidone due to alpha-blocking 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, such as intense physical activity, 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 medications are often at 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 loose iris syndrome (ISDR)

ISDR was observed during cataract surgery in patients receiving therapy with drugs that have the activity of alpha-1-adrenergic antagonists, including Rispolept Consta®.

ISDR increases the risk of visual organ-related complications 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 that have the activity of alpha-1-adrenergic antagonists. The potential benefit of discontinuing alpha-1-adrenergic antagonist therapy prior to surgery has not been established, and should be evaluated taking into account the risks associated with discontinuing antipsychotic therapy.

Renal and hepatic insufficiency

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

Care should be taken to avoid accidental use of Rispolept Consta® into a blood vessel.

Do not expose the product 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 suspension preparation: the suspension is physically and chemically stable for 24 hours at a temperature of 25 °C. From a 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

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

Influence on the ability to drive a car and work with mechanisms. Risperidone may reduce the speed of mental and physical reactions, and therefore the patient may not be able to take any medication.

Form of production

Powder for the preparation of a suspension for intramuscular use of prolonged action

Storage conditions

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

Shelf life

3 years

Active ingredient

Risperidone

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection