Is it possible to take Rispolept 1 mg. "Rispolept": reviews. "Rispolept": application, description, side effects. Composition and release form

Rispolept is a drug with antipsychotic action.

Release form and composition

Rispolept is available in the following forms:

• solution for oral administration: colorless, transparent (in dark glass bottles of 30 or 100 ml, 1 bottle in a cardboard box complete with a graduated pipette);
• film-coated tablets: biconvex, oblong, scored, with a break – white; 2 mg each - light orange, on one side the inscription “2” and “Ris”; 4 mg each - green, on one side the inscription “4” and “Ris” (10 pieces in blisters, 2 or 6 blisters in a cardboard pack);
• film-coated tablets: biconvex, oblong, scored: 1 mg - white, on one side the inscription “1” and “Ris”; 2 mg each - light orange, on one side the inscription “2” and “Ris”; 3 mg each - yellow, on one side the inscription “3” and “Ris”; 4 mg each - green, on one side the inscription “4” and “Ris” (10 pieces in blisters, 2 or 6 blisters in a cardboard pack).

Composition of 1 ml oral solution:

• active ingredient: risperidone – 1 mg;
• excipients: sodium hydroxide – up to pH 3.0±0.1; benzoic acid – 2 mg; tartaric acid – 7.5 mg; purified water – up to 1 ml.

Composition of 1 film-coated tablet:

• active ingredient: risperidone – 2 or 4 mg;
• excipients: magnesium stearate, lactose, corn starch, hypromellose, microcrystalline cellulose, anhydrous colloidal silicon dioxide, propylene glycol, sodium lauryl sulfate, titanium dioxide, talc; additionally for 2 mg tablets – orange-yellow S (E110); additionally for 4 mg tablets – indigotin disulfonate, choline yellow.

Composition of 1 film-coated tablet:

• active ingredient: risperidone – 1, 2, 3 or 4 mg;
• excipients (1/2/3/4 mg): lactose monohydrate – 131/130/195/260 mg, corn starch – 44/44/66/88 mg, hypromellose 2910 15 mPa×s – 2/2/3/ 4 mg, sodium lauryl sulfate – 0.4/0.4/0.6/0.8 mg, microcrystalline cellulose – 20/20/30/40 mg, magnesium stearate – 1/1/1.5/2 mg, colloidal silicon dioxide – 0.6/0.6/0.9/1.2 mg;
• shell (1/2/3/4 mg): hypromellose 2910 5 mPa×s – 4/4/5.2/6.8 mg, propylene glycol – 1/1/1.3/1.7 mg, titanium dioxide – 0/2/2.6/3.4 mg, talc – 0/1.2/1.56/2.04 mg, sunset yellow dye (E110) – 0/0.05/0/0 mg, yellow quinoline dye (E104) – 0/0/0.052/0.068 mg, indigo carmine (E132) – 0/0/0/0.068 mg.

Indications for use

• schizophrenia – treatment of patients over 13 years of age;
• moderate to severe manic episodes associated with bipolar disorder - treatment of patients from 10 years of age;
• persistent aggression in patients with moderate and severe dementia caused by Alzheimer's disease, which is not amenable to non-pharmacological methods of correction, and also if there is a possibility of harm by the patient to other persons or to himself - short-term treatment (up to 6 weeks);
• persistent aggression in the structure of conduct disorder in children over 5 years of age diagnosed in accordance with DSM-IV mental retardation in which, due to the severity of aggression or other destructive behavior, it is indicated drug treatment– short-term symptomatic treatment (up to 6 weeks), which should be part of a broader program that includes educational and psychological activities. The drug can be prescribed by a specialist in the field of child psychiatry/neurology or a doctor familiar with the treatment of behavioral disorders in adolescents and children.

Contraindications

• phenylketonuria;
• hypersensitivity to the components of the drug.

Prescribing Rispolept requires caution in the presence of the following diseases/conditions:

• hypovolemia and dehydration;
• cerebrovascular accidents;
• diseases of the cardiovascular system (myocardial infarction, chronic heart failure, cardiac muscle conduction disorders);
• Parkinson's disease;
• convulsions, incl. in the anamnesis;
• severe renal or liver failure;
• drug dependence or abuse medicines;
• conditions predisposing to the occurrence of tachycardia of the “pirouette” type (electrolyte imbalance, bradycardia, combined use with drugs that prolong the QT interval);
• Reye's syndrome, intestinal obstruction, brain tumor, cases of acute drug overdose (the antiemetic effect of the drug may hide the symptoms of these conditions);
• dementia with Lewy bodies;
• the presence of risk factors for venous thromboembolism;
• pregnancy;
• old age in the presence of cerebrovascular dementia.

Due to the lack of sufficient data, the use of Rispolept by pregnant and lactating women is possible after assessing the benefit-risk ratio.

Directions for use and dosage

Rispolept is taken orally regardless of food intake.

If the single dose is less than 1 mg, Rispolept should be taken as an oral solution.

Therapy for schizophrenia:

• adults: initial daily dose – 2 mg in 1 or 2 doses. On the second day, the dose is doubled. In the future, it is maintained at this level or adjusted individually. The average optimal daily dose is 4-6 mg. In some cases, a slower dose increase and lower initial and maintenance doses may be warranted. Doses higher than 10 mg per day have not been shown to be more effective and may result in extrapyramidal symptoms. More than 16 mg of Rispolept per day is not prescribed (the safety profile has not been studied). In case of persistent drowsiness, it is recommended to reduce the daily dose by 2 times; the drug should be taken 2 times a day. Elderly patients are prescribed 0.5 mg 2 times a day, it is possible to increase the dose to 1-2 mg per day without changing the frequency of administration;
• children over 13 years of age: initial daily dose – 0.5 mg in 1 dose (morning or evening). If necessary and if well tolerated, it can be increased by 0.5-1 mg per day to the recommended 3 mg (with a break of at least 24 hours). The use of doses higher than 3 mg per day has not shown greater effectiveness, in addition, this may lead to an increase in the frequency of adverse reactions. More than 6 mg of Rispolept per day is not prescribed (the safety profile has not been studied).

Treatment for manic episodes associated with bipolar disorder:

• adults: initial daily dose – 2 mg in 1 dose. If necessary, the dose can be increased by 1 mg (with a break of at least 24 hours). In most cases, the optimal daily dose is 1-6 mg. The safety profile of use above 6 mg per day has not been studied. The advisability of continuing therapy should be regularly assessed. In case of persistent drowsiness, it is recommended to reduce the daily dose by 2 times; the drug should be taken 2 times a day. Elderly patients are prescribed 0.5 mg 2 times a day, the dose can be increased to 1-2 mg per day (without changing the frequency of administration). Due to limited experience with elderly patients, Rispolept should be taken with caution;
• children over 10 years of age: initial daily dose – 0.5 mg (in 1 dose in the morning or evening). If necessary and if well tolerated, it can be increased by 0.5-1 mg per day to the recommended 1-2.5 mg (with a break of at least 24 hours). The use of doses higher than 2.5 mg per day has not been shown to be more effective; in addition, this may lead to an increase in the incidence of adverse reactions. More than 6 mg of Rispolept per day is not prescribed (the safety profile has not been studied).

In the treatment of persistent aggression in patients with dementia due to Alzheimer's disease, the drug is prescribed 2 times a day, 0.25 mg. Once every 2 days, it is possible to increase the dose by 0.25 mg. In most cases, the optimal dose is 0.5 mg 2 times a day; in some cases, 2 mg per day in 2 divided doses is optimal. Duration of therapy is up to 6 weeks. Regular assessment of the condition and the need for continued therapy is required.

The recommended regimen for using the drug for persistent aggression in the structure of behavior disorder in children 5-18 years old weighing up to/more than 50 kg: initial daily dose - 0.25/0.5 mg in 1 dose; possible increase - by 0.25/0.5 mg (no more than 1 time every 2 days); optimally - 0.5/1 mg, in some cases it is preferable to take an increased (0.75/1.5 mg) or reduced (0.25/0.5 mg) daily dose. Regular assessment of the condition and the need for continued therapy is required.

In the presence of kidney and liver diseases, Rispolept is prescribed with caution in initial and maintenance doses reduced by 2 times (they should be increased more slowly).

Treatment should be discontinued gradually. In rare cases, withdrawal symptoms may occur in the form of nausea, vomiting, sweating and insomnia.

At the beginning of the course of Rispolept, it is recommended to gradually discontinue previous therapy with other drugs.

Side effects

While taking Rispolept, the development of disorders such as parkinsonism, insomnia and headache was most often observed (≥10% of cases).

Possible adverse reactions (≥1/10 - very common, ≥1/100 and<1/10 – часто, ≥1/1000 и <1/100 – нечасто, ≥1/10 000 и <1/1000 – редко, <1/10 000 – очень редко, при невозможности оценить частоту развития – с неустановленной частотой):

• cardiovascular system: often – tachycardia, arterial hypertension; infrequently - palpitations, His bundle block, orthostatic and arterial hypotension, hot flashes, atrioventricular block, atrial fibrillation, cardiac conduction disorders; rarely - pulmonary embolism, sinus bradycardia, deep vein thrombosis;
• immune system: uncommon – hypersensitivity; rarely – anaphylactic reactions, drug hypersensitivity;
• organ of vision and hearing: often – conjunctivitis, blurred vision; uncommon – discharge from the eyes, redness and dryness of the eyes, blurred vision, swelling of the area around the eyes, increased lacrimation, photophobia, tinnitus, ear pain; rarely - decreased visual acuity, glaucoma, involuntary rotation of the eyeballs, intraoperative floppy iris syndrome;
• hematopoietic system: uncommon – anemia, thrombocytopenia; rarely – agranulocytosis, granulocytopenia;
• nervous system: very often – parkinsonism, drowsiness, headache, sedation; often – lethargy, dizziness, akathisia, tremor, dystonia, dyskinesia; uncommon – dysarthria, lack of response to stimuli, fainting, impaired consciousness, stroke, transient ischemic attack, postural dizziness, tardive dyskinesia, hypesthesia, convulsions, taste perversion, taste disorders, cerebral ischemia, disturbances of attention, balance, speech, coordination of movements; rarely - head tremor, neuroleptic malignant syndrome, cerebrovascular disorders, diabetic coma;
• digestive system: often - nausea, dry mouth, abdominal pain, vomiting, diarrhea, constipation, dyspepsia, stomach discomfort, hypersalivation; uncommon – gastroenteritis, fecaloma, dysphagia, fecal incontinence, gastritis, flatulence; rarely – cheilitis, intestinal obstruction, lip swelling, pancreatitis;
• respiratory system: often - nasal congestion, shortness of breath, cough, nosebleeds, pain in the larynx and pharynx; uncommon – airway obstruction, breathing, pulmonary congestion, wheezing, aspiration pneumonia, moist rales, dysphonia; rarely – hyperventilation, sleep apnea syndrome;
• reproductive system: uncommon - ejaculation disorders, sexual dysfunction, erectile dysfunction, gynecomastia, galactorrhea, amenorrhea, vaginal discharge, menstrual disorders; rarely - priapism;
• liver and biliary tract: rarely – jaundice;
• subcutaneous tissues and skin: often – erythema, rash; uncommon – acne, acne, itching, hyperkeratosis, alopecia, seborrheic dermatitis, dryness, lesions and discoloration of the skin; rarely – dandruff; very rarely - Quincke's edema;
• kidneys and urinary tract: often – enuresis; uncommon – urinary incontinence, urinary retention, dysuria, pollakiuria;
• connective tissues and musculoskeletal system: often – arthralgia, pain in the limbs and back; uncommon – poor posture, muscle weakness, neck pain, myalgia, joint swelling, muscle pain in the chest, stiffness in the joints; rarely - rhabdomyolysis;
• pregnancy, neonatal and postpartum period: rarely - withdrawal syndrome in newborns;
• psyche: very often – insomnia; often – anxiety, agitation, restlessness, sleep disturbances; infrequently - mania, confusion, lethargy, decreased libido, nervousness; rarely – affective flattening, anorgasmia;
• infections: often - sinusitis, pneumonia, flu, bronchitis, ear, upper respiratory and urinary tract infections; uncommon – tonsillitis, otitis media, cystitis, viral infections, acarodermatitis, inflammation of subcutaneous fat, eye infections, localized infections, respiratory tract infections, onychomycosis; rarely – chronic otitis media;
• metabolism: often – change in appetite; uncommon – diabetes mellitus, polydipsia, anorexia, hyperglycemia; rarely - water intoxication, hypoglycemia, impaired production of antidiuretic hormone; very rarely - diabetic ketoacidosis;
• laboratory/instrumental indicators: often - weight gain, increased prolactin levels; infrequently - ECG abnormalities, prolongation of the QT interval on the ECG, decrease in the number of leukocytes in the blood and hemoglobin level, increase in body temperature, increase in the level of transaminases, the number of eosinophils in the blood, CPK level, cholesterol concentration; rarely - increased triglyceride concentrations, decreased body temperature;
• general disorders: often - pyrexia, fatigue, slowness, generalized or peripheral edema, asthenia, chest pain; uncommon – gait disturbances, facial swelling, poor health, flu-like condition, thirst, chills, chest discomfort; rarely – withdrawal syndrome, hypothermia, cold extremities.

Violations identified during clinical studies of the use of Rispolept Konsta - an injectable prolonged form of risperidone (adverse reactions not related to the route of administration and composition):

• vestibular apparatus, organs of hearing and vision: vertigo, retinal artery occlusion, blepharospasm;
• cardiovascular system: bradycardia, arterial hypertension;
• digestive system: tongue spasm, toothache;
• musculoskeletal system and connective tissues: pain in the buttocks;
• laboratory indicators: weight loss, increase in liver enzymes and gamma-glutamyltransferase levels;
• nervous system: convulsions, paresthesia;
• hematopoietic system: neutropenia;
• skin and subcutaneous tissues: eczema;
• injuries: falls;
• psyche: depression;
• infections: lower respiratory tract infections, gastroenteritis, infections, subcutaneous abscess;
• general disorders: pain.

special instructions

When using Rispolept in combination with furosemide in elderly patients with dementia, caution should be exercised (there is evidence of increased mortality).

The likelihood of developing cerebrovascular adverse reactions is significantly higher in patients with vascular or mixed dementia compared to patients with Alzheimer's dementia, and therefore Rispolept is not prescribed for dementia of any type except Alzheimer's.

Taking Rispolept may cause orthostatic hypotension in some patients, especially during the initial dose selection period.

If symptoms (objective or subjective) develop that indicate tardive dyskinesia, it may be necessary to discontinue all antipsychotic medications, including Rispolept.

In case of existing hyperprolactinemia, in patients with probable prolactin-dependent tumors, as well as in patients with a history of seizures or other conditions in which the seizure threshold may be lowered, therapy is prescribed with caution.

All patients should be clinically monitored for symptoms of hyperglycemia.

Caution must be exercised when prescribing Rispolept against the background of conditions in which an increase in body temperature is possible, including dehydration and intense physical activity.

Until individual sensitivity to the action of the drug is determined, it is recommended to refrain from driving a car or working with machinery.

Drug interactions

The combined use of Rispolept with certain drugs/substances can lead to the development of the following effects:

• drugs that prolong the QT interval, tricyclic/tetracyclic antidepressants, some antihistamines, other antipsychotics, some antimalarials, drugs that cause bradycardia, electrolyte imbalance or inhibit the hepatic metabolism of risperidone: interaction (the combination requires caution);
• paroxetine, fluoxetine: an increase in the plasma concentration of risperidone in plasma, and to a lesser extent - the concentration of the active antipsychotic fraction (when prescribing/discontinuing these drugs, the dose of Rispolept must be adjusted);
• antihypertensive drugs: development of severe arterial hypotension (noted in the post-marketing period);
• levodopa and other dopamine agonists: decrease in their effectiveness (if it is necessary to use a combination, especially in the terminal stage of Parkinson’s disease, the minimum effective doses of each drug must be used);
• verapamil: increased plasma concentrations of risperidone;
• other centrally acting drugs/substances, especially ethanol, opiates, antihistamines, benzodiazepines: increased likelihood of sedation (combination requires caution);
• carbamazepine and other inducers of liver enzymes and P-glycoprotein: a decrease in the plasma concentration of the active antipsychotic fraction of risperidone (when prescribing/discontinuing these drugs, the dose of Rispolept must be adjusted);
• tricyclic antidepressants, phenothiazines and some beta-blockers: increased plasma concentrations of risperidone;
• paliperidone: increasing the concentration of the active antipsychotic fraction (the combination is not recommended);
• ranitidine, cimetidine: increased bioavailability of risperidone, minimal effect on the concentration of the active antipsychotic fraction.

Terms and conditions of storage

Store out of the reach of children at a temperature of 15-30 °C.

Shelf life – 3 years.

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Pharmacological.

Risperidone is a selective monoaminergic antagonist with unique properties. It exhibits high affinity for serotonergic 5-HT 2 and dopaminergic D 2 receptors. Risperidone also binds to α 1 adrenergic receptors and, with less affinity, to H 1 -histamine and α 2 adrenergic receptors. Risperidone does not show affinity for cholinergic receptors. Although risperidone is a potent D2 antagonist, which is associated with its effectiveness in relation to the productive symptoms of schizophrenia, it does not cause significant suppression of motor activity and induces catalepsy to a lesser extent compared to classical antipsychotics. Balanced central antagonism of serotonin and dopamine reduces the tendency for extrapyramidal side effects and expands the therapeutic effect of the drug to cover the negative and affective symptoms of schizophrenia.

Pharmacokinetics.

Rispolept ® is in the form of tablets, dispersible in the oral cavity, and film-coated tablets are bioequivalent to the oral solution.

Risperidone is metabolized to 9-hydroxy, which has similar pharmacological effects to risperidone.

Suction.

After administration, risperidone is completely absorbed and reaches peak plasma concentrations within 1-2 hours, in elderly patients - within 2-3 hours. Bioavailability after oral administration of risperidone is 70% (CV = 25%). Food does not affect the absorption of the drug, so risperidone can be administered regardless of food intake. Bioavailability is 66% in fast metabolizers, and 82% in slow metabolizers.

Distribution.

Risperidone is rapidly distributed in the body. The volume of distribution is 1-2 l/kg. In plasma, risperidone binds to albumin and acidic α 1 glycoproteins. Risperidone is 90% bound to plasma proteins, 9-hydroxy is 77%. The equilibrium concentration of risperidone in the body is achieved within 1 day in most patients. The equilibrium concentration of 9-hydroxy is achieved within 4-5 days.

Metabolism and excretion.

Risperidone is metabolized by cytochrome CYP2D6 to 9-hydroxy, which has pharmacological effects similar to risperidone. Risperidone and 9-hydroxy active antipsychotic fraction. Cytochrome CYP2D6 is subject to genetic polymorphism. In CYP2D6 extensive metabolizers, risperidone is rapidly converted to 9-hydroxy, whereas in poor metabolizers, risperidone is converted much more slowly. Although concentrations of risperidone and 9-hydroxy are lower in extensive metabolizers than in poor metabolizers, the pharmacokinetics of risperidone and 9-hydroxy in combination (i.e., the active antipsychotic fraction) after single and multiple doses in extensive and poor metabolizers of cytochrome CYP2D6 are similar.

Another route of metabolism for risperidone is N-dealkylation. In vitro studies on human liver microsomes have shown that risperidone at clinically relevant concentrations does not significantly inhibit the metabolism of drugs that are metabolized by cytochrome P450 isoenzymes, including CYP1A2, CYP2A6, CYP2C8/9/10 CYP2D6, CYP2E1, CYP3A4 and CYP3A5. A week after using the drug, 70% of the dose is excreted in the urine, 14% in feces. The concentration of risperidone and 9-hydroxy in the urine is equal to 35-45% of the dose taken. The rest consists of inactive metabolites. After administration in patients with psychosis, the half-life is approximately 3:00. The half-life of 9-hydroxy risperidone reaches 24 hours, and in elderly patients - 34 hours.

Linearity.

Plasma concentrations of risperidone are proportional to the dose of the drug (within therapeutic doses).

Elderly patients and patients with impaired renal and liver function.

A study of a single dose of the drug in elderly patients and patients with renal failure revealed a high level of plasma concentration (AUC and Cmax 2-2.5 times higher) and a decrease in clearance of the active antipsychotic fraction by 30% in elderly patients and by 60% in patients with renal failure (see section "Peculiarities of application").

In patients with impaired liver function, a lower degree of binding of risperidone to plasma proteins was observed.

In patients with hepatic impairment, normal plasma risperidone concentration levels were observed, but the mean plasma free fraction of risperidone was increased by 35%.

The pharmacokinetics of risperidone and 9-hydroxy risperidone in children are similar to those in adults.

Gender, race and smoking.

Population pharmacokinetic analysis revealed no apparent influence of gender, age, or smoking habit on the pharmacokinetics of risperidone or the active antipsychotic fraction.

Indications

• Treatment of schizophrenia and other mental disorders, including maintenance therapy in patients who have responded to therapy, in order to prevent relapse of the disease;
• short-term treatment of severe aggression or severe psychiatric symptoms in patients with dementia when there is a threat of harm to themselves or others;
• treatment of manic episodes in bipolar disorders (adjuvant therapy in combination with mood stabilizers as initial treatment or as monotherapy for up to 12 weeks)
• symptomatic treatment of defiant oppositional disorders or other disorders of social behavior in children, adolescents and adults with below average mental development or mental retardation who have manifestations of destructive behavior (impulsivity, auto-aggression)
• symptomatic treatment of autistic disorders in children over 5 years of age whose symptoms range from hyperactivity to irritability (including aggression, self-harm, anxiety and pathological cycling).

Contraindications

Hypersensitivity to the active component or excipient of the drug.

Dementia and symptoms of Parkinson's disease (rigidity, bradykinesia and parkinsonian postural disorders).

Dementia and suspected dementia with Lewy bodies (except for symptoms of dementia, less than two of the following symptoms: parkinsonism, visual hallucinations, unsteadiness of gait).

Interaction with other drugs and other types of interactions.

In vitro metabolism studies have shown that the breakdown of risperidone to 9-hydroxy-risperidone can be inhibited by phenothiazines, tricyclic antidepressants and some beta blockers that bind to CYP 2D6. Such suppression may result in increased plasma concentrations of risperidone and a decrease in the active metabolite 9-hydroxy. Although clinical data from 12 patients showed that amitriptyline did not inhibit the breakdown of risperidone to 9-hydroxy, analysis of data from a small number of patients taking these drugs concomitantly confirms that the clinical effect is not affected.

Risperidone is a weak inhibitor of CYP 2D6 in vitro. Therefore, it is expected that Rispolept ® will significantly suppress the excretion of drugs metabolized by these enzymes.

With simultaneous use of drugs that are enzyme inducers, the metabolism of risperidone may increase. Carbamazepine reduces the concentration of the active antipsychotic fraction in the blood plasma. Clinical data showed that in patients taking carbamazepine concomitantly, plasma concentrations of risperidone and 9-hydroxy were 1.7-3.7 times lower. Similar effects (decreased plasma concentrations of the active antipsychotic fraction) may be observed with the use of other inducers of CYP 3A4 liver enzymes, such as rifampicin, phenytoin and phenobarbital. When discontinuing or resuming the use of carbamazepine or other inducers of CYP 3A4 enzymes, the dosage of rispolept ® should be re-evaluated and, if necessary, adjusted. In rare cases, toxic serum concentrations of carbamazepine have been observed during concomitant use of carbamazepine and risperidone.

Rispolept ® may exhibit antagonistic effects to levodopa and other dopamine antagonists.

If such a combination is considered necessary, especially in end-stage Parkinson's disease, the most effective dose of each drug should be prescribed.

Phenothiazines, tricyclic antidepressants and some beta-blockers may increase plasma concentrations of risperidone, but not the concentration of the antipsychotic fraction.

Cimetidine 400 mg twice daily and ranitidine 150 mg twice daily increased the AUC of risperidone (risperidone and 9-hydroxy) by 8% and 20%, respectively, although this was not clinically significant.

Fluoxetine (20 mg/day) and paroxetine (20 mg/day) were found to increase plasma risperidone concentrations by 2.5-2.8 and 3-9 times, respectively. Fluoxetine does not affect plasma 9-hydroxy concentrations. Paroxetine on average reduces plasma 9-hydroxy concentrations by 13%. In general, risperidone concentrations increase by 50% when fluoxetine and paroxetine are administered concomitantly. If treatment with fluoxetine and paroxetine is started or discontinued during Rispolept ® therapy, the physician should reconsider the dose of Rispolept ® . The effect of discontinuation of treatment with fluoxetine and paroxetine on the pharmacokinetics of risperidone or 9-hydroxy has not been studied.

Erythromycin (CYP 3A4 inhibitor) does not affect the pharmacokinetics of risperidone and the active antipsychotic fraction.

In the post-marketing period, cases of clinically significant hypotension have been observed with simultaneous use of risperidone and antihypertensive drugs.

As with other antipsychotics, caution should be exercised when prescribing risperidone with drugs that prolong the QT interval, such as class Ia antiarrhythmics (quinidine, procainamide), class III antiarrhythmics (amiodarone, solatol), tricyclic antidepressants (amitriptyline), tetracyclics antidepressants (maprolitine), some antihistamines, other antipsychotics, some antimalarials (quinine, mefloquine), and with drugs that cause electrolyte imbalance (hypokalemia, hypomagnesemia), bradycardia, or drugs that inhibit the hepatic metabolism of risperidone. This list is not complete.

Cholinesterase inhibitors, galantamine and donezepil do not show clinically significant effects on the pharmacokinetics of risperidone and the active antipsychotic fraction.

A clinical study involving 13 patients showed that the pharmacokinetic parameters of lithium did not change significantly when the concomitant antipsychotic was replaced by Rispolept ® at a dose of 3 mg twice daily. The compatibility of risperidone with lithium has not been studied. With the simultaneous use of antipsychotics and lithium, cases of encephalopathy, extrapyramidal disorders and neuroleptic malignant syndrome have been observed. During clinical trials, extrapyramidal disorders and hyperkinesia were reported more frequently when lithium was used with antipsychotics than when lithium was used alone.

Rispolept ® had no clinically significant effects on the pharmacokinetics of valproate in a parallel group study and of digoxin in a crossover interaction study.

Topiramate significantly reduces the effectiveness of risperidone, but only slightly reduces the effectiveness of risperidone. Therefore, it is unlikely that this interaction is clinically important.

Clonazepam, gabapentin, lamotrigine, methylphenidate: despite the pharmacokinetics of risperidone and these active ingredients, interactions between them are not expected. Although no relevant studies have been conducted.

The risks of using Rispolept ® concomitantly with other drugs have not been systematically studied. Theoretically, interactions with all active substances that affect the central nervous system are possible. Until additional research data are available, caution should be exercised when prescribing risperidone concomitantly with other drugs.

For information about increased mortality when used concomitantly with furosemide in elderly patients with dementia, see the section "Peculiarities of use."

Risperidone should be used with caution in combination with other centrally acting substances, including alcohol, opiates, antihistamines and benzodiazepines, due to an increased risk of sedation.

Verapamil, an inhibitor of CYP3A4 and P-glycoprotein, increases the concentration of risperidone in the blood plasma.

Concomitant use of oral Rispolept ® with paliperidone is not recommended because paliperidone is the active metabolite of risperidone, and their combination may lead to additional exposure to the active antipsychotic fraction.

Features of application

Elderly patients with dementia.

Increased mortality rate.

Among elderly patients with dementia who were treated with atypical antipsychotics, there was an increased mortality rate compared with patients in the placebo group in meta-17 controlled trials of atypical antipsychotics, including Rispolept ® . In a placebo-controlled study using the drug Rispolept ® to patients in this category, the mortality rate was 4.0% compared to 3.1% in the placebo group. The mean age of patients who died was 86 years (range, 67–100 years). The specific profile of risk factors for mortality in the group of patients taking Rispolept ® has not been determined. Causes of death were typical for this age group (65 years and older) and included: cardiovascular and cerebrovascular diseases, tumors, infections (eg, pneumonia) and diabetes.

Simultaneous use with furosemide.

In placebo-controlled studies in elderly patients with dementia, an increased mortality rate was observed when risperidone was given concomitantly with furosemide (7.3%; mean age 89 years, range 75-97 years) compared with patients treated with risperidone alone (3.1%, mean age 84 years, range 70-96 years) or furosemide alone (4.1%, mean age 80 years, range 67-90 years). An increased mortality rate among patients treated concomitantly with risperidone and furosemide was observed in two of four clinical studies. There was no increased mortality observed among patients taking risperidone concomitantly with other diuretics.

Pathophysiological mechanisms to explain this fact have not been established. The cause of death was also not uniform. However, extreme caution should be exercised when prescribing the drug in such cases, and an assessment of the risks and benefits of this combination with other potential diuretics should be carried out before prescribing the drug. Regardless of treatment, dehydration was a common risk factor for mortality and should be closely monitored in patients with dementia.

Cerebrovascular adverse reactions.

In placebo-controlled clinical trials, patients with dementia treated with Rispolept ® experienced a higher rate of fatal cerebrovascular adverse events (stroke and transient ischemic attack) compared with those treated with placebo (mean age 85 years, range - 73-97 years old).

Combined data from six placebo studies in elderly patients with dementia (over 65 years of age) demonstrated the occurrence of cerebrovascular disorders (including severe) in 3.3% (33/989) of patients treated with Rispolept ® compared to 1.2 % (8/693) of patients receiving placebo. The ratio between the Rispolept ® and placebo groups (odds ratio; 95% CI) was 2.96 (1.33; 7.45), in the subgroup of patients with vascular dementia - 5.26 (1.18; 48.11).

The risk of cerebrovascular side effects is significantly higher in patients with mixed or vascular dementia compared with Alzheimer's dementia. The risks and benefits of prescribing Rispolept ® to elderly patients with dementia should be carefully weighed, especially the risk of stroke. Rispolept ® should be prescribed with extreme caution to patients with dementia who have arterial hypertension, diseases of the cardiovascular system, and patients with vascular dementia. Patients and their caregivers should be instructed to immediately report signs of possible cardiovascular attacks, such as sudden weakness, numbness of the face, arms, or legs, and disturbances in speech or vision. All possible treatment options, including interruption of Rispolept ® therapy, should be considered without delay.

Before prescribing Rispolept ® to children, the risk-benefit ratio should be carefully weighed. The need for continued treatment should be carefully assessed regularly. The indications “symptomatic treatment of social behavior disorders, oppositional defiant disorders and or other social behavior disorders” and “autistic disorders” were studied only from the age of 5 years. Therefore, Rispolept ® should not be prescribed to children under the age of 5 years for the following indications.

There is no experience with the use of Rispolept ® in children under 15 years of age for the treatment of schizophrenia and in children under 10 years of age for the treatment of manic episodes in bipolar disorders.

For children, the available data are based on clinical studies lasting 1 year. These data indicate that there are no effects on growth and development. The effect on growth and development with treatment lasting more than one year is unknown. Therefore, clinical monitoring of the endocrine system should be performed, including measurement of height and weight, monitoring of sexual development, potential prolactin-induced effects, examination of extrapyramidal symptoms and other movement disorders.

Drowsiness.

During placebo studies, somnolence was frequently observed in children with autism. Most cases were mild to moderate in severity. Somnolence was observed predominantly at the beginning of treatment, with the greatest frequency during the first two weeks of treatment, and went away on its own, with an average duration of 16 days. In patients with drowsiness, a change in dosage regimen may be considered.

Orthostatic hypotension.

Due to the α 1 -lytic activity of risperidone, orthostatic hypotension may occur, especially at the beginning of treatment. In post-marketing experience, clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive agents. Rispolept ® should be used with caution in patients with cardiovascular disease (such as heart failure, myocardial infarction, conduction disorders, dehydration, hypovolemia or cerebrovascular disease). In these cases, the dose should be gradually adjusted (see Section "Dosage and Administration"). If hypotension occurs, dose reduction should be considered.

Prolongation of the QT interval.

QT prolongation was not associated with risperidone during clinical studies.

Cases of QT prolongation have been very rarely reported in post-marketing experience. Rispolept ®, like other antipsychotics, should be used with caution in patients with cardiovascular disease, electrolyte disturbances (hypokalemia, hypomagnesemia) or a family history of QT interval prolongation. Caution should also be exercised during concomitant use with drugs that prolong the QT interval.

Leukopenia, neutropenia, agranulocytosis.

Cases of leukopenia, neutropenia and agranulocytosis have been observed with the use of antipsychotics, including risperidone. In the post-marketing period, agranulositosis has been observed very rarely (<1/10 000 пациентов).

Patients with a history of significant decreases in white blood cell counts or drug-induced leukopenia/neutropenia should be monitored closely during the first few months of treatment and risperidone should be discontinued if signs of a significant decrease in white blood cell counts occur and there is no other reason for the decrease.

Patients with clinically significant neutropenia should be monitored for the occurrence of fever and other signs of infection and treated appropriately if symptoms are detected. In case of severe neutropenia (<чем 1 × 10 9 / л) лечение рисперидоном следует прекратить и следить за количеством лейкоцитов к восстановлению.

Venous thromboembolism.

Cases of venous thromboembolism have been described when using antipsychotic drugs. Since patients treated with antipsychotic drugs often have acquired risk factors for venous thromboembolism, all possible factors for the development of thromboembolism must be identified before and during treatment with Rispolept ® and appropriate preventive measures taken.

Tardive dyskinesia/extrapyramidal symptoms.

When using drugs with dopamine receptor antagonist properties, tardive dyskinesia, characterized by involuntary rhythmic movements (mainly of the tongue and/or face), was observed. The occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. If signs and symptoms of tardive dyskinesia occur, discontinuation of all antipsychotic medications should be considered.

Parkinson's disease and dementia with Lewy bodies.

Physicians must weigh the risks and benefits when prescribing antipsychotics, including Rispolept ® to patients with Parkinson's disease or dementia with Lewy bodies. Risperidone may worsen Parkinson's disease. Patients with any of the above conditions may have an increased risk of neuroleptic malignant syndrome, as well as increased sensitivity to antipsychotic drugs (eg, confusion, dullness of pain sensitivity, and postural instability with frequent falls in addition to extrapyramidal symptoms).

Neuroleptic malignant syndrome.

When using classical antipsychotic drugs, cases of neuroleptic malignant syndrome, characterized by hyperthermia, muscle rigidity, instability of autonomic functions, impaired consciousness and increased CPK levels, are rarely reported. Additional features include myoglobinuria (rhabdomyolysis) and acute renal failure. In case of development of neuroleptic syndrome, it is necessary to discontinue all antipsychotic drugs, including Rispolept ® .

Hyperglycemia and diabetes mellitus.

Hyperglycemia, diabetes mellitus, or exacerbation of existing diabetes have been reported during treatment with Rispolept ® . Assessing the association between the use of atypical antipsychotics and abnormal glucose levels is difficult due to the increased risk of diabetes mellitus in patients with schizophrenia and the increased incidence of diabetes mellitus in the general population. Thus, the relationship between the use of atypical antipsychotic drugs and adverse reactions associated with hyperglycemia is not completely clear. Although epidemiological studies indicate an increased risk of hyperglycemia-related adverse reactions in patients treated with atypical antipsychotics. Each patient using atypical antipsychotics should be monitored for symptoms of hyperglycemia and diabetes mellitus.

Increase in body weight.

Cases of weight gain have been reported when using the drug Rispolept ®. Recommended body weight control.

Priapism.

There is a possibility of priapism occurring during treatment with Rispolept ® due to its alpha-adrenergic blocking effect. Cases of priapism have been reported post-marketing.

Regulation of body temperature.

Antipsychotics may interfere with the body's ability to lower core body temperature. Appropriate care is recommended for patients treated with Rispolept ® if they will be exposed to conditions that may cause an increase in core body temperature, such as intense physical exercise, exposure to high ambient temperatures, concomitant therapy with drugs with anticholinergic activity, or the effects of dehydration.

Antiemetic effect.

In preclinical studies of the properties of risperidone, an antiemetic effect was noted. This property may mask symptoms of overdose of some drugs or conditions such as intestinal obstruction, Reye's syndrome and brain tumors.

Cramps.

Rispolept should be used with caution in patients with a history of seizures or other conditions that potentially lower the seizure threshold.

Intraoperative atonic iris syndrome (ISAR).

During cataract operations, intraoperative atonic iris syndrome was observed in patients treated with α1-adrenergic receptor antagonists, incl. Rispoleptom ®.

ISAR may increase the risk of eye surgery complications during and after surgery. The ophthalmic surgeon should be informed about the use of antipsychotic drugs in the past or during the operation. The potential benefits of stopping therapy with α1-blocking drugs before surgery have not been established, and the risk of stopping treatment with antipsychotics should be weighed.

Impaired liver and kidney function.

For patients with impaired liver and kidney function, it is recommended to prescribe half the initial and maintenance doses (see Section "Dosage and Administration").

Hyperprolactinemia.

Tissue culture studies indicate that cell growth in human breast tumors may be stimulated by prolactin. Although clinical and epidemiological studies have not yet established a clear connection with the use of antipsychotic drugs, it is recommended to prescribe risperidone with caution to patients with a history of corresponding pathology. Rispolept ® should be used with caution in patients with hyperprolactinemia and in patients with probable prolactin-associated tumors, such as pituitary prolactinoma, or probable prolactin-associated tumors, such as epithelial breast tumors.

Use during pregnancy or breastfeeding.

Pregnancy.

There are no controlled studies in pregnant women. Although no teratogenic effects were identified in animal studies, an indirect effect on prolactin levels was observed.

Neonates whose mothers used antipsychotics (including risperidone) during the last trimester of pregnancy are at risk of developing reversible extrapyramidal symptoms and/or drug withdrawal syndrome. These symptoms include agitation, unusually increased or decreased muscle tone, tremors, drowsiness, breathing problems, or feeding problems. These complications can vary in severity. In some cases, they disappeared on their own after a certain period of time, in some cases monitoring of the infants' condition in the intensive care unit or long-term hospitalization was necessary.

Breastfeeding.

In animal studies, risperidone and 9-hydroxy were excreted into breast milk. There are observations that risperidone and 9-hydroxy may also be excreted in breast milk. In some cases, 4.3% of the dose used by the mother in the form of the active antipsychotic fraction of the active substance was determined in breast milk. If it is necessary to take the drug, breastfeeding should be stopped.

The ability to influence the reaction rate when driving a vehicle or working with other mechanisms.

Rispolept ® may have a slight or moderate effect on the ability to drive vehicles, as a result of potential effects on the nervous system and visual organs (see section “Adverse Reactions”). During treatment, it is recommended to refrain from driving vehicles or operating other machinery until the patients' sensitivity to the drug is known.

Directions for use and doses

usual dose

Rispolept ® can be used once or twice a day. Doses greater than 8 mg should be divided into two doses (morning and evening). Eating does not affect the absorption of the drug Rispolept ®.

Gradual cessation of treatment is recommended. Acute withdrawal symptoms, including nausea, vomiting, sweating, and insomnia, have been observed very rarely after abrupt cessation of high-dose antipsychotic medications. Relapse of psychotic symptoms may also occur, and involuntary movements (eg, akathisia, dystonia, and dyskinesia) have been reported.

schizophrenia

adults

Rispolept ® can be prescribed once or twice a day.

You should start taking it with 2 mg of rispolept ® per day, on the second day the dose can be increased to 4 mg. After this, the dose can be maintained unchanged or, if necessary, adjusted individually. For most patients, the recommended dose is 4-6 mg per day. Some patients may need a gradual dose increase or a reduction in the starting dose.

Doses above 10 mg per day have not been found to be as effective as lower doses, but they may cause extrapyramidal symptoms. Since the safety of doses exceeding 16 mg per day has not been studied, such doses should not be used.

If additional sedation is necessary, a benzodiazepine may be used concomitantly.

The recommended starting dose is 0.5 mg twice daily. If necessary, the dose can be increased to 1-2 mg twice a day, increasing by 0.5 mg twice a day. If additional sedation is necessary, a benzodiazepine may be used concomitantly.

Manic episodes in bipolar disorders

Adults.

The recommended starting dose of Rispolept ® is 2 mg once a day, in the evening. The dose can be individually increased by adding 1 mg/day no more than every 24 hours. The recommended dose range is from 2 to 6 mg per day.

As with other types of symptomatic treatment, with long-term use of Rispolept ® it is necessary to periodically review the doses and adjust them throughout therapy. There are no data on the effectiveness of Rispolept ® in the treatment of acute bipolar mania lasting more than 12 weeks. If Rispolept ® is used in combination with normoticamams, therapy can be stopped earlier, since the onset of the effect of treatment can be expected in the first weeks of therapy. Even after a response to treatment appears, the possibility of reoccurrence of depressive symptoms should be taken into account due to the nature of the disease and adverse reactions of the medications used for treatment, including Rispolept ®.

Elderly patients (over 65 years old).

The recommended starting dose is 0.5 mg twice daily. If necessary, the dose can be increased to 1-2 mg twice a day, increasing by 0.5 mg twice a day. Since experience in elderly patients is limited, caution is recommended.

Children aged 10 years and older.

The recommended starting dose is 0.5 mg once daily, morning or evening. The dose can be individually increased by adding 0.5 to 1 mg/day no more than every 24 hours until the recommended dose of 2.5 mg/day is reached. The effectiveness of treatment has been demonstrated in the dose range from 0.5 to 6 mg/day; doses above 6 mg/day have not been studied.

As with other types of symptomatic treatment, with long-term use of Rispolept ® it is necessary to periodically review the doses and adjust them throughout therapy.

There is no experience with the use of Rispolept ® for the treatment of manic episodes in bipolar disorders in children under 10 years of age.

Short-term treatment of severe aggression or severe psychiatric symptoms in patients with dementia

The recommended starting dose is 0.25 mg twice daily. If necessary, the dose can be increased by increasing the dose of 0.25 mg twice a day no more than every other day. For most patients, the optimal dose is 0.5 mg twice daily. However, for some patients the effective dose can be increased to 1 mg twice daily. Once the optimal dose has been achieved, you may consider taking the daily dose once a day. As with other types of symptomatic treatment, with long-term use of Rispolept ® it is necessary to periodically review the doses and adjust them throughout therapy.

Cancellation of treatment with Rispolept ® should take place no later than three months after the start of therapy; therapy can be resumed only if behavioral disorders reappear.

Symptomatic treatment of social behavior disorders or aggressive behavior

The recommended starting dose is 0.5 mg once daily. If necessary, the dose should be adjusted by adding 0.5 mg once a day, no more than every other day. The optimal dose for most patients is 1 mg once daily. However, for some patients, no more than 0.5 mg once daily is sufficient to achieve benefit, while others may require 1.5 mg once daily.

Patients with weight<50 кг

The recommended starting dose is 0.25 mg once daily. If necessary, the dose can be adjusted by adding 0.25 mg once a day, no more than every other day. The optimal dose for most patients is 0.5 mg once daily. However, for some patients, no more than 0.25 mg once daily is sufficient to achieve benefit, while others may require 0.75 mg once daily.

As with other types of symptomatic treatment, long-term use of Rispolept ® must be periodically reviewed and adjusted throughout therapy.

There is no experience with the use of Rispolept ® for the symptomatic treatment of social behavior disorders or aggressive behavior in children under 5 years of age.

Autism (children from 5 years old)

The dose should be adjusted individually depending on the patient's condition and clinical response.

Patients with weight<50 кг

The recommended starting dose is 0.25 mg once daily. From day 4, the dose can be increased by 0.25 mg. The dose should be maintained at 0.5 mg and clinical response assessed on day 14. Dose increases of 0.25 mg at 2-week intervals should only be considered for patients with insufficient clinical response.

Patients weighing ≥ 50 kg

The recommended starting dose is 0.5 mg once daily. From day 4, the dose can be increased by 0.5 mg. The 1 mg dose should be maintained and clinical response assessed on day 14. Dose increases of 0.5 mg at 2-week intervals should only be considered for patients with insufficient clinical response.

Doses of Rispolept ® for children with autism (daily dose in mg/day)

*Patients weighing more than 45 kg may require larger doses; the maximum dose used in clinical studies was 3.5 mg/day.

Correspondence of doses of Rispolept ® in mg and ml

Rispolept ® can be used once or twice a day.

For patients who experience drowsiness after taking the drug, it is better to take a daily dose of Rispolept ® at bedtime or in two doses. During clinical studies, approximately two-thirds of children with autism complained of weakness, especially during the initial phase of treatment.

Once an adequate clinical response is achieved, a gradual dose reduction should be considered to achieve an optimal balance of clinical efficacy and safety.

Information obtained from controlled clinical studies is insufficient to determine the recommended duration of treatment with Rispolept ® in patients with autism. Therefore, an experienced specialist should carefully monitor the patient's condition.

If severe adverse reactions occur (for example, extrapyramidal disorders, tardive dyskinesia, or uncontrolled weight gain), the dose of Rispolept ® should be reduced or treatment should be discontinued.

There is no experience with the use of Rispolept ® for the symptomatic treatment of autism in children under 5 years of age.

Instructions for opening the bottle yourself and using the dispenser pipette

Bottle 30 ml

To open the bottle and use the pipette, follow these steps (see Figure 1-4):

Rice. 3. Hold the lower rim and remove the dispenser pipette from the bottle. Pour the contents of the dropper into any non-alcoholic drink other than tea by pressing the plunger of the dropper. Close the bottle and rinse the dispenser pipette with water. Place the pipette in its designated location. Rice. 4. Release the paper holder. Attach the holder to the bottle with the tab pointing down.

100 ml bottle

To open the bottle and use the pipette, follow these steps (see Figure 1-3):

Rice. 1. The bottle has a child-proof cap and opens as follows: press the plastic cap down until it stops and turn it counterclockwise. Remove the cover. Rice. 2. Remove the dispenser pipette from the case and insert it into the bottle. While holding the lower rim of the pipette, pull the plunger of the pipette to the appropriate milliliter or milligram mark. Rice. 3. Hold the lower rim and remove the dispenser pipette from the bottle. Pour the contents of the dropper into any non-alcoholic drink other than tea by pressing the plunger of the dropper. Close the bottle and rinse the dispenser pipette with water. Place the pipette in its designated location.

Patients with liver and kidney diseases.

In patients with impaired renal function, risperidone is eliminated from the body more slowly than in patients with healthy kidneys. In patients with impaired liver function, the concentration of the free fraction of risperidone in the blood plasma increases.

Regardless of the indication, these patients are prescribed half the initial and maintenance doses, and dose titration should be slow.

Rispolept ® should be used with caution in this category of patients.

Transition from therapy with other antipsychotic drugs.

If clinically justified, during therapy with Rispolept ® it is recommended to gradually discontinue previous therapy with other drugs. Moreover, if the patient is transferred from therapy with antipsychotic drugs in the “depot” form, it is recommended to start using the drug Rispolept ® instead of the next scheduled injection. The need to continue current antiparkinsonian drug therapy should be periodically assessed.

Risperidone is used to treat social behavior disorders or aggressive behavior, as well as autistic disorders in children aged 5 years and older; for the treatment of manic episodes in bipolar disorders in children over 10 years of age.

Overdose

Symptoms

Signs and symptoms of overdose that have been observed are known adverse reactions of the drug that appear in an enhanced form: drowsiness and sedation, tachycardia and arterial hypotension, as well as extrapyramidal symptoms. QT prolongation and seizures have been reported in overdose. Flutter-flicker has been reported associated with an overdose of Rispolept ® in combination with paroxetine.

The airway must be established and maintained to ensure adequate ventilation and oxygenation. Consider gastric lavage (after intubation if the patient is unconscious) and the administration of activated charcoal along with a laxative if less than an hour has passed since taking the drug. Monitoring of cardiovascular activity is indicated, including continuous ECG recording to identify possible arrhythmias.

Risperidone does not have a specific antidote. Therefore, appropriate supportive measures should be taken. In case of acute overdose, the possibility of interaction of several drugs should be analyzed. Hypotension and vascular collapse should be treated with measures such as intravenous fluids and/or sympathomimetic drugs. If acute extrapyramidal symptoms develop, anticholinergic drugs should be prescribed. Constant medical monitoring should be continued until the patient recovers completely.

Adverse reactions

The most common adverse reactions reported (incidence ≥ 10%) are parkinsonism, sedation/drowsiness, headache and insomnia. Parkinsonism and akathisia are dose-dependent adverse reactions.

The adverse reactions listed below include those reported during clinical trials and post-marketing experience. Incidence of adverse reactions: very common (≥1/10), common (≥1/100 to<1/10), нечасто (≥1 / 1000 до <1/100), редко (≥1 / 10000 до <1 / 1000), очень редко (<1/10000) и неизвестно (частоту нельзя установить из доступных данных).

In each group, adverse reactions are presented in decreasing order of severity.

Infections and infestations
often	pneumonia, bronchitis, upper respiratory tract infections, sinusitis, urinary tract infections, ear infections, flu
infrequently	respiratory tract infections, cystitis, eye infections, tonsillitis, onychomycosis, inflammation of the subcutaneous tissue, localized infection, viral infection, acarodermatitis
rarely	infection
From the blood and lymphatic system
infrequently	neutropenia, decreased white blood cell count, thrombocytopenia, anemia, decreased hematocrit, increased eosinophil count
rarely	agranulocytosis with
From the immune system
infrequently	hypersensitivity
rarely	anaphylactic reactions with
From the endocrine system
often	hyperprolactinemia a
rarely	impaired ADH secretion, presence of glucose in the urine
Metabolism and digestion
often	weight gain, increased appetite, decreased appetite
infrequently	diabetes mellitus b, hyperglycemia, polydipsia, weight loss, anorexia, increased cholesterol
rarely	water intoxication c, hypoglycemia, hyperinsulinemia c, increased triglyceride levels in the blood
Very rarely	diabetic ketoacidosis
From the mental side
Often	insomnia d
often	sleep disorders, agitation, depression, anxiety
infrequently	mania, confusion, decreased libido, nervousness, nightmares
rarely	dulled affect, anorgasmia
From the nervous system
Often	sedation/drowsiness, parkinsonism d, headache
often	akathisia d, dystonia d, dizziness, dyskinesia d, tremor
infrequently	tardive dyskinesia, cerebral ischemia, lack of response to stimuli, loss of consciousness, depressed level of consciousness, convulsions, syncope, psychomotor hyperactivity, balance disorders, impaired coordination, postural dizziness, impaired attention, dysarthria, taste disorders, hypoesthesia, paresthesia
rarely	neuroleptic malignant syndrome, cerebrovascular disorders, diabetic coma, rhythmic head bobbing
From the organs of vision
often	blurred vision, conjunctivitis
infrequently	photophobia, dry eyes, increased lacrimation, red eyes
rarely	glaucoma, eye movement disorders, rotatory nystagmus, crust formation on the edge of the eyelid, intraoperative atonic iris syndrome with
From the hearing organs
infrequently	vertigo, tinitis, ear pain
From the side of cardiac activity
often	tachycardia
infrequently	atrial fibrillation, AV block, cardiac conduction disturbances, prolongation of the QT interval on the ECG, bradycardia, abnormalities on the ECG, palpitations
rarely	sinus arrhythmia
unknown	postural orthostatic tachycardia syndrome
From the vascular system
often	arterial hypertension
infrequently	hypotension, orthostatic hypotension, hot flashes
rarely	pulmonary embolism, venous thrombosis
From the respiratory system
often	shortness of breath, pharyngolaryngeal pain, cough, epitaxy, nasal congestion
infrequently	aspiration pneumonia, pulmonary congestion, deterioration of airway conduction, wheezing, wheezing, dysphonia, respiratory failure
rarely	sleep apnea syndrome, hyperventilation
often	abdominal pain, abdominal discomfort, vomiting, nausea, constipation, diarrhea, dyspepsia, dry mouth, toothache
infrequently	fecal incontinence, fecaloma, gastroenteritis, dysphagia, bloating
rarely	pancreatitis, gastrointestinal obstruction, tongue swelling, cheilitis
Very rarely	intestinal obstruction
From the digestive system
infrequently	increased levels of transaminases, increased levels of gammaglutamyl transferase, increased levels of liver enzymes
rarely	jaundice
From the skin and subcutaneous tissue
often	rashes, erythema
infrequently	urticaria, itching, alopecia, hyperkeratosis, eczema, dry skin, skin discoloration, acne, seborrheic dermatitis, skin diseases, skin damage
rarely	drug rashes, dandruff
Very rarely	angioedema
From the musculoskeletal system
often	muscle spasms, musculoskeletal pain, back pain, arthralgia
infrequently	increased CPK levels, poor posture, joint stiffness, joint swelling, muscle weakness, neck pain
rarely	rhabdomyolysis
From the urinary system
often	urinary incontinence
infrequently	polakiuria, urinary retention, dysuria
Pregnancy, puerperium and neonatal conditions
Very rarely	extrapyramidal symptoms and/or drug withdrawal syndrome in neonates with
From the reproductive system and mammary glands
infrequently	erectile dysfunction, ejaculation disorders, amenorrhea, menstrual cycle disorders, gynecomastia, galactorrhea, sexual dysfunction, breast pain, vaginal discharge
rarely	priapism c, delayed menstruation, engorgement of the mammary glands, enlargement of the mammary glands, discharge from the mammary glands
general disorders
often	edema d, fever, chest pain, asthenia, fatigue, pain
infrequently	facial swelling, chills, increased body temperature, gait disturbance, thirst, chest discomfort, fever, unusual sensations, discomfort
rarely	hypothermia, decreased body temperature, feeling of coldness in the extremities, drug withdrawal syndrome, compactions with
Damage and poisoning
often	a fall
infrequently	pain after surgery

a Hyperprolactinemia in some cases can lead to gynecomastia, menstrual disorders, amenorrhea, galactorrhea.

b In placebo studies, diabetes mellitus was reported in 0.18% of patients receiving risperidone compared with 0.11% in the placebo group. The overall incidence across all clinical trials was 0.43% in patients treated with risperidone. c NOT observed in clinical studies of rispolept®, but was detected during post-marketing surveillance.

d Extrapyramidal disorders include: parkinsonism (hypersecretion of saliva, muscle rigidity, parkinsonism, drooling, cogwheel phenomenon, bradykinesia, hypokinesia, masked face, muscle tension, akinesia, nuchal rigidity, muscle rigidity, parkinsonian gait, impaired glabellar reflex, parkinsonian tremor), akathisia (akathisia, restlessness, hyperkinesia, restless legs syndrome), tremor, dyskinesia (dyskinesia, muscle twitching, choreoathetosis, athetosis, myoclonus), dystonia.

Dystonia includes dystonia, hypertension, torticollis, involuntary muscle contractions, myogenic contractures, blepharospasm, eyeball movement, tongue paralysis, tic (in the face), laryngospasm, myotonia, opisthotonus, oropharyngeal spasm, pleurotonus, tongue spasm, trismus. A larger list of symptoms is included, not necessarily of extrapyramidal origin. Insomnia includes: difficulty falling asleep, intrasomnia disorder. Seizures include: grand mal seizure. Menstrual disorders include: irregular menstruation, oligomenorrhea. Edema includes: generalized edema, peripheral edema, and punctate edema.

Adverse reactions of paliperidone

Paliperidone is an active metabolite of risperidone, so the adverse reaction profiles of these substances (including oral and injectable formulations) are similar. In addition to the above-mentioned adverse reactions, postural orthostatic tachycardia syndrome has been reported with paliperidone, which is likely to occur with rispolept®.

Adverse reactions characteristic of antipsychotic drugs

QT prolongation

As with other antipsychotics, QT prolongation has been reported with risperidone in post-marketing experience. Other cardiac adverse reactions that prolong the QT interval, such as ventricular arrhythmia, atrial fibrillation, ventricular tachycardia, sudden death, cardiac arrest, and torsades de pointes, have also been reported with the use of antipsychotic drugs.

venous thromboembolism

When using antipsychotic drugs, cases of venous thromboembolism, including pulmonary embolism and deep vein thrombosis, have been reported.

Weight gain

A comparison of the number of patients receiving Rispolept ® and patients receiving placebo who had a 7% increase in body weight in placebo-controlled studies lasting 6 to 8 weeks showed a statistically significant difference in the incidence of weight gain in the group of patients taking Rispolept ® (18%) compared with that of patients taking placebo (9%). In 3-week placebo studies in adult patients with acute mania, the incidence of weight gain ≥7% was comparable to that in the Rispolept ® group (2.5%) and placebo group (2.4%). and was slightly higher in the active control group (3.5%).

In a long-term study population of children with behavioral disorders, patients' body weight increased by an average of 7.3 kg after 12 months of treatment. The expected weight gain for children with normal body weight aged 5-12 years is from 3 to 5 kg per year. Starting from the age of 12, the increase in body weight for girls remains from 3 to 5 kg per year, while boys gain an average of 5 kg per year.

Additional information on special categories of patients

Adverse reactions in elderly patients with dementia or in children, which were reported at a higher frequency than in adult patients, are described below.

Elderly patients with dementia

Transient ischemic attack and cerebrovascular disorders are adverse reactions reported during clinical trials with an incidence of 1.4% and 1.5%, respectively, in elderly patients with dementia. In addition, these adverse reactions were reported at a frequency of ≥ 5% in elderly patients with dementia and at least twice as high as in other adult patients: urinary tract infections, peripheral edema, lethargy and cough.

);

drug abuse or dependence;

conditions predisposing to the development of tachycardia of the “pirouette” type (bradycardia, electrolyte imbalance, concomitant use of medications that prolong the QT interval);

brain tumor, intestinal obstruction, cases of acute drug overdose, Reye's syndrome (the antiemetic effect of risperidone may mask the symptoms of these conditions);

risk factors for the development of venous thromboembolism;

diffuse Lewy body disease;

elderly patients with cerebrovascular dementia;

pregnancy.

Use during pregnancy and lactation

Pregnancy
There have been no comprehensive studies on the use of risperidone in pregnant women. According to post-marketing observations, reversible extrapyramidal symptoms occurred in the newborn when risperidone was used during the last trimester of pregnancy, so newborns should be closely monitored. In animal studies, risperidone was not teratogenic, however, other types of toxic effects on the reproductive system were observed. The potential risk to humans is unknown. Rispolept ® can be used during pregnancy only if the expected benefit of the drug for the pregnant woman outweighs the potential risk to the fetus. If it is necessary to stop taking the drug during pregnancy, the drug should be withdrawn gradually.

Lactation
In animal studies, risperidone and 9-hydroxyrisperidone were excreted into breast milk. Risperidone and 9-hydroxyrisperidone have also been demonstrated to pass into breast milk in small amounts in humans. There are no data on side effects in breastfed infants. Therefore, the issue of breastfeeding should be decided taking into account the possible risk to the child.

Directions for use and doses

Schizophrenia

Adults
Rispolept ® can be prescribed once or twice a day. The initial dose of Rispolept ® is 2 mg per day. On the second day, the dose can be increased to 4 mg per day. From this point on, the dose can either be kept at the same level or individually adjusted if necessary. Usually the optimal dose is 4-6 mg per day. In some cases, a slower dose escalation and lower initial and maintenance doses may be justified.
Doses higher than 10 mg per day have not been shown to be more effective than lower doses and may cause extrapyramidal symptoms. Due to the fact that the safety of doses above 16 mg per day has not been studied, doses above this level are not recommended.

Children from 13 years old
The recommended initial dose is 0.5 mg once daily in the morning or evening. If necessary, the dosage can be increased after at least 24 hours by 0.5 - 1 mg per day to the recommended dose of 3 mg per day if well tolerated. Despite the effectiveness demonstrated in the treatment of schizophrenia in adolescents with doses of 1-6 mg per day, no additional effectiveness was observed at doses above 3 mg per day, and higher doses caused more side effects. Doses higher than 6 mg per day have not been studied.

Manic episodes associated with bipolar disorder

Adults
The recommended initial dose of the drug is 2 mg per day at a time. If necessary, this dose can be increased after at least 24 hours by 1 mg per day. For most patients, the optimal dose is 1-6 mg per day. Doses higher than 6 mg per day have not been studied in patients with manic episodes.

Elderly patients
An initial dose of 0.5 mg twice daily is recommended. The dosage can be individually increased by 0.5 mg twice daily to 1-2 mg twice daily. Caution must be exercised due to limited experience with the drug in elderly patients.

Children from 10 years old
The recommended initial dose is 0.5 mg once daily in the morning or evening. If necessary, the dosage can be increased after at least 24 hours by 0.5 - 1 mg per day to the recommended dose of 1-2.5 mg per day if well tolerated. Despite the effectiveness demonstrated in the treatment of manic episodes associated with bipolar disorder in children with doses of 0.5-6 mg per day, no additional effectiveness was observed at doses above 2.5 mg per day, and higher doses caused more side effects.
Doses higher than 6 mg per day have not been studied.
For patients who experience persistent drowsiness, it is recommended to take half the daily dose 2 times a day.

Persistent aggression in patients with Alzheimer's dementia
A starting dose of 0.25 mg twice daily is recommended. If necessary, the dosage can be increased individually by 0.25 mg 2 times a day, no more than every other day. For most patients, the optimal dose is 0.5 mg twice daily. However, some patients are advised to take 1 mg 2 times a day.
Rispolept ® should not be used for more than 6 weeks in patients with persistent aggression in patients with dementia due to Alzheimer's disease. During treatment, patients' condition should be assessed on a regular basis, as well as the need for continued therapy.

Persistent aggression in the structure of conduct disorder

Children from 5 to 18 years old
Patients weighing 50 kg or more - the recommended initial dose of the drug is 0.5 mg once a day. If necessary, this dose can be increased by 0.5 mg per day, no more than every other day. For most patients, the optimal dose is 1 mg per day. However, for some patients, 0.5 mg per day is preferable, while some require an increase to 1.5 mg per day.
Patients weighing less than 50 kg - the recommended initial dose of the drug is 0.25 mg once a day. If necessary, this dose can be increased by 0.25 mg per day, no more than every other day. For most patients, the optimal dose is 0.5 mg per day. However, for some patients, 0.25 mg per day is preferable, while some require an increase in dose to 0.75 mg per day.
As with any other symptomatic therapy, the advisability of continuing treatment with Rispolept ® should be regularly assessed and confirmed.
Use in children under 5 years of age is not recommended due to lack of data.

Liver and kidney diseases.
Patients with kidney disease have a reduced ability to eliminate the active antipsychotic fraction compared to other patients. In patients with liver disease, there is an increased concentration of the free fraction of risperidone in the blood plasma.
The initial and maintenance dose, in accordance with the indications, should be reduced by 2 times; the dose increase in patients with liver and kidney diseases should be carried out more slowly.
Rispolept ® should be prescribed with caution in this category of patients.

Mode of application
Inside. Eating does not affect the absorption of the drug.
It is recommended to discontinue taking the drug gradually. Acute withdrawal symptoms, including nausea, vomiting, sweating and insomnia, have been observed very rarely after abrupt cessation of high-dose antipsychotic medications.

Transition from therapy with other antipsychotic drugs.
At the beginning of treatment with Rispolept ® it is recommended to gradually withdraw previous therapy if clinically justified. Moreover, if patients are transferred from therapy with depot forms of antipsychotic drugs, then it is recommended to start therapy with Rispolept ® instead of the next scheduled injection. The need to continue current antiparkinsonian drug therapy should be periodically assessed.

Side effect

The most commonly observed side effects (incidence ≥ 10%) were parkinsonism, headache and insomnia.
Side effects of the drug Rispolept ® in therapeutic doses are given with a distribution by frequency and organ system. The frequency of side effects was classified as follows: very common (≥1/10 cases), common (≥1/100 and In each frequency group, side effects are presented in decreasing order of their importance.

Violations of laboratory and instrumental indicators:
often – increase in prolactin level 1, increase in body weight;
uncommon – prolongation of the QT interval on the electrocardiogram, ECG abnormalities, increased transaminase levels, decreased number of leukocytes in the blood, increased body temperature, increased number of eosinophils in the blood, decreased hemoglobin level, increased level of creatine phosphokinase, increased cholesterol concentration;
rarely – a decrease in body temperature, an increase in the concentration of triglycerides.

often – tachycardia, arterial hypertension;
uncommon – atrioventricular block, His bundle block, atrial fibrillation, palpitations, cardiac conduction disturbances;
rarely - sinus bradycardia, pulmonary embolism, deep vein thrombosis.

Hematological and lymphatic system disorders:
uncommon – anemia, thrombocytopenia;
rarely – granulocytopenia, agranulocytosis.

From the nervous system:
very often – parkinsonism 2, headache, drowsiness, sedation;
often – akathisia 2, dizziness 2, tremor 2, dystonia 2, lethargy, dyskinesia 2;
uncommon – lack of response to stimuli, loss of consciousness, fainting, impaired consciousness, stroke, transient ischemic attack, dysarthria, impaired attention, hypersomnia, postural dizziness, imbalance, tardive dyskinesia, speech impairment, impaired coordination, hypoesthesia, taste disorders, perversion taste, convulsions, cerebral ischemia, movement disorders;
rarely - neuroleptic malignant syndrome, diabetic coma, cerebrovascular disorders, head tremor.

Ophthalmological disorders:
often – blurred vision, conctivitis;
uncommon – redness of the eyes, blurred vision, discharge from the eyes, swelling of the area around the eyes, dry eyes, increased lacrimation, photophobia;
rarely - decreased visual acuity, involuntary rotation of the eyeballs, glaucoma, intraoperative floppy iris syndrome.

From the ear and labyrinth:
uncommon – ear pain, tinnitus.

Respiratory, thoracic and mediastinal disorders:
often – shortness of breath, nosebleeds, cough, nasal congestion, pain in the larynx and pharynx;
uncommon – wheezing, aspiration pneumonia, pulmonary congestion, respiratory distress, moist rales, airway obstruction, dysphonia;
rarely – sleep apnea syndrome, hyperventilation.

often – vomiting, diarrhea, constipation, nausea, abdominal pain, dyspepsia, dry mouth, stomach discomfort, hypersalivation;
uncommon – dysphagia, gastritis, fecal incontinence, fecaloma, gastroenteritis, flatulence;
rarely – intestinal obstruction, pancreatitis, swelling of the lips, cheilitis.

From the kidneys and urinary tract:
often – enuresis;
uncommon – urinary retention, dysuria, urinary incontinence, pollakiuria.

often – rash, erythema;
uncommon – skin lesions, skin disorders, itching, acne, acne, skin discoloration, alopecia, seborrheic dermatitis, dry skin, hyperkeratosis;
rarely – dandruff;
very rarely - Quincke's edema.

often – arthralgia, back pain, pain in the limbs;
uncommon – muscle weakness, myalgia, neck pain, swollen joints, poor posture, stiffness in the joints, muscle pain in the chest;
rarely – rhabdomyolysis.

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

Metabolic and nutritional disorders:
often – increased appetite, decreased appetite;
uncommon – diabetes mellitus 3, anorexia, polydipsia, hyperglycemia;
rarely – hypoglycemia, water intoxication;
very rarely - diabetic ketoacidosis.

Infections:
often – pneumonia, flu, bronchitis, upper respiratory tract infections, urinary tract infections, sinusitis, ear infections;
uncommon – viral infections, tonsillitis, inflammation of subcutaneous fat, otitis media, eye infections, localized infections, akarodermatitis, respiratory tract infections, cystitis, onychomycosis;
rarely – chronic otitis media.

Vascular disorders:
uncommon – hypotension, orthostatic hypotension, hot flashes.

often - pyrexia, fatigue, peripheral edema, generalized edema, asthenia, chest pain;
uncommon – facial swelling, gait disturbance, poor health, sluggishness, flu-like condition, thirst, chest discomfort, chills;
rarely – hypothermia, withdrawal syndrome, cold extremities.

From the immune system:
uncommon – hypersensitivity;
rarely – drug hypersensitivity, anaphylactic reaction.

Hepatobiliary disorders:
rarely – jaundice.

From the reproductive system and mammary glands:
uncommon – amenorrhea, sexual dysfunction, erectile dysfunction, ejaculation disorder, galactorrhea, gynecomastia, menstrual disorder, vaginal discharge;
rarely – priapism.

Pregnancy, postpartum and neonatal periods:
rarely – withdrawal syndrome in newborns.

Mental disorders:
very often – insomnia;
often - restlessness, agitation, sleep disturbances, anxiety;
infrequently - confusion, mania, decreased libido, lethargy, nervousness;
rarely – anorgasmia, flattening of affect.

1 – hyperprolactinemia in some cases can lead to gynecomastia, menstrual irregularities, amenorrhea and galactorrhea.

2 – extrapyramidal disorders may manifest as: parkinsonism (hypersalivation, musculoskeletal stiffness, parkinsonism, drooling, cogwheel rigidity, bradykinesia, hypokinesia, mask-like face, muscle tension, akinesia, nuchal rigidity, muscle rigidity, parkinsonian gait , glabellar reflex disorders), akathisia (akathisia, restlessness, hyperkinesia and restless legs syndrome), tremor, dyskinesia (dyskinesia, muscle twitching, choreoathetosis, athetosis and myoclonus), dystonia.
The term dystonia includes dystonia, muscle spasms, hypertension, torticollis, involuntary muscle contractions, muscle contracture, blepharospasm, eye movements, tongue paralysis, facial spasm, laryngospasm, myotonia, opisthotonus, oropharyngeal spasm, pleurototonus, tongue spasm, and trismus. Tremors include tremor and parkinsonian resting tremor. It should also be noted that there is a wider range of symptoms that are not always of extrapyramidal origin.

3 - In placebo-controlled studies, diabetes mellitus occurred in 0.18% of patients taking risperidone compared with 0.11% of patients in the placebo group. The overall incidence of diabetes mellitus across all clinical trials was 0.43% of all patients treated with risperidone.

Below are additionally listed side effects observed during clinical studies of the long-acting injection form of risperidone - Rispolept Consta ®, but which did not appear when using oral dosage forms of risperidone.
This list does not include side effects associated with the composition or injection route of administration of the drug:
Laboratory abnormalities: decrease in body weight, increase in gamma-glutamyltransferase levels, increase in liver enzymes.
From the cardiovascular system: bradycardia.
From the blood and lymphatic system: neutropenia.
From the nervous system: paresthesia, convulsions.
From the eyes: blepharospasm, retinal artery occlusion.
From the ear and labyrinth: vertigo.
From the gastrointestinal tract: toothache, tongue spasm.
For the skin and subcutaneous tissues: eczema.
From the musculoskeletal system and connective tissue: pain in the buttocks.
Infections: lower respiratory tract infections, infections, gastroenteritis, subcutaneous abscess.
Injuries and poisonings: a fall.
Vascular disorders: arterial hypertension.
General disorders and phenomena caused by administration of the drug: pain.
Mental disorders: depression.

Class effects
As with other antipsychotic drugs, very rare cases of QT wave prolongation have been reported during post-marketing surveillance. Other cardiovascular class effects observed with antipsychotic drugs that prolong the QT wave include: ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac arrest, and torsade de pointes.

Venous thromboembolism
Cases of venous thromboembolism, including pulmonary embolism and cases of deep vein thrombosis, have been observed with the use of antipsychotic drugs (frequency unknown).

Weight gain
In placebo-controlled studies in patients with schizophrenia, an increase in body weight of at least 7% after 6-8 weeks was observed in 18% of patients taking Rispolept ® and in 9% of patients taking placebo. In placebo-controlled clinical trials in patients with manic episodes, the incidence of weight gain of 7% or more after 3 weeks of treatment was comparable in the Rispolept ® group (2.5%) and in the placebo group (2 .4%), and in the active control group it was slightly higher (3.5%).
In long-term clinical studies, children with conduct disorders increased body weight by an average of 7.3 kg after 12 months of therapy. The expected increase in body weight in children 5-12 years of age with normal development is 3-5 kg ​​per year. From 12-16 years of age, the increase in body weight should be 3-5 kg ​​per year for girls and about 5 kg per year for boys.

Additional information on special patient populations

Side effects that were reported with greater frequency in older patients with dementia and in children than in adult patients are described below:

Elderly patients with dementia
Transient ischemic attack and stroke were observed in clinical trials with an incidence of 1.4% and 1.5%, respectively, in elderly patients with dementia. In addition, the following adverse effects have been reported in elderly patients with dementia with an incidence of ≥ 5% and an incidence at least 2 times higher than in other patient populations: urinary tract infections, peripheral edema, lethargy and cough.

Children
The following side effects were observed in children (from 5 to 17 years old) with frequency? 5% and with an incidence at least 2 times higher than in other patient populations during clinical trials: somnolence/sedation, fatigue, headache, increased appetite, vomiting, upper respiratory tract infection, nasal congestion, abdominal pain , dizziness, cough, pyrexia, tremor, diarrhea, enuresis.

Overdose

Symptoms
In general, the observed symptoms of overdose were already known pharmacological effects of risperidone in an enhanced form: drowsiness, sedation, tachycardia, arterial hypotension, extrapyramidal symptoms. QT prolongation and seizures have been observed. Bidirectional ventricular tachycardia has been observed during co-administration of increased doses of risperidone and paroxetine. In case of acute overdose, the possibility of overdose from multiple drugs should be considered.

Treatment.
An open airway should be achieved and maintained to ensure adequate oxygen supply and ventilation. Gastric lavage (after intubation, if the patient is unconscious) and taking activated charcoal along with a laxative should be carried out only if the drug was taken no more than one hour ago. ECG monitoring should be started immediately to identify possible arrhythmias.
There is no specific antidote; appropriate symptomatic therapy must be carried out. Hypotension and vascular collapse should be treated with intravenous fluid infusions and/or sympathomimetic drugs. If severe extrapyramidal symptoms develop, anticholinergic drugs should be prescribed. Constant medical observation and monitoring should be continued until symptoms of intoxication disappear.

Interaction with other drugs

As with other antipsychotic drugs, caution should be exercised when co-prescribing Rispolept ® with drugs that increase the QT interval, for example, with class Ia antiarrhythmic drugs (quinidine, disopyramide, procainamide, etc.), class III (amiodarone, sotalol and etc.), tricyclic antidepressants (amitriptyline, etc.), tetracyclic antidepressants (maprotiline, etc.), some antihistamines, other antipsychotics, some antimalarials (quinine, mefloquine, etc.), drugs that cause electrolyte imbalance (hypokalemia, hypomagnesemia), bradycardia or inhibit the hepatic metabolism of risperidone. This list is not exhaustive.

The effect of taking the drug Rispolept ® on other drugs
Rispolept ® should be used with caution in combination with other centrally acting drugs and substances, especially alcohol, opiates, antihistamines and benzodiazepines due to the increased risk of sedation.
Rispolept ® may reduce the effectiveness of levodopa and other dopamine agonists. If this combination is necessary, especially in end-stage Parkinson's disease, the lowest effective dose of each drug should be prescribed.
When risperidone was used in conjunction with antihypertensive drugs, clinically significant hypotension was observed in the post-marketing period. Risperidone does not have a clinically significant effect on the pharmacokinetics of lithium, valproate, digoxin or topiramate.

The influence of taking other medications on the drug Rispolept ®
When using carbamazepine, a decrease in the concentration of the active antipsychotic fraction of risperidone in plasma was observed. Similar effects may be observed with other hepatic enzyme and P-glycoprotein inducers (eg, rifampicin, phenytoin, phenobarbital). When prescribing and after discontinuation of carbamazepine or other inducers of liver enzymes and P-glycoprotein, the dose of Rispolept ® should be adjusted.
Fluoxetine and paroxetine, which are inhibitors of the CYP 2D6 isoenzyme, increase the concentration of risperidone in plasma, but to a lesser extent the concentration of the active antipsychotic fraction. It is assumed that other inhibitors of the CYP2D6 isoenzyme (for example, quinidine) affect the concentration of risperidone in the same way. When prescribing and after discontinuation of fluoxetine or paroxetine, the dose of Rispolept ® should be adjusted.
Verapamil, which is an inhibitor of the CYP 3A4 isoenzyme and P-glycoprotein, increases the concentration of risperidone in plasma.
Galantamine and donepezil do not have a clinically significant effect on the pharmacokinetics of risperidone and its active antipsychotic fractions.
Phenothiazines, tricyclic antidepressants and some beta-blockers may increase plasma concentrations of risperidone, but this does not affect the concentration of the active antipsychotic fraction. Amitriptyline does not affect the pharmacokinetics of risperidone and 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 the CYP 3A4 isoenzyme, does not affect the pharmacokinetics of risperidone and the active antipsychotic fraction.
The combined use of psychostimulants (for example, methylphenidate) and the drug Rispolept ® in children does not change the pharmacokinetic parameters and effectiveness of risperidone.
It is not recommended to use risperidone in combination with paliperidone due to the fact that paliperidone is an active metabolite of risperidone, and the use of such a combination may lead to an increase in the concentration of the active antipsychotic fraction.

special instructions

Use in elderly patients with dementia.

Increased mortality in older patients with dementia
Elderly patients with dementia treated with atypical antipsychotics experienced increased mortality compared with placebo in studies of atypical antipsychotics, including risperidone. When using risperidone in this population, the incidence of death was 4.0% for patients taking risperidone compared with 3.1% for placebo. The mean age of patients who died was 86 years (range, 67–100 years). Data collected from two large observational studies show that older patients with dementia treated with typical antipsychotic medications also have a slightly increased risk of death compared with patients not treated. At present, insufficient data have been collected to accurately assess this risk. The reason for the increase in this risk is also unknown. Also unknown is the extent to which the increased mortality may be attributable to antipsychotic drugs rather than to the characteristics of this patient population.

Combined use with furosemide
In elderly patients with dementia, there was an increased mortality rate when taking furosemide and oral risperidone concomitantly (7.3%, mean age 89 years, range 75-97 years) compared with the risperidone alone 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 with furosemide was observed in 2 of 4 clinical studies. Concomitant use of risperidone with other diuretics (mainly low-dose thiazide diuretics) was not associated with 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, the risk/benefit ratio must be carefully assessed. 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 older patients with dementia.
In elderly patients with dementia, an increase in cerebrovascular adverse events (acute and transient cerebrovascular accidents), including patient deaths (mean age 85 years, range 73-97 years) was observed with risperidone compared with placebo.

Cardiovascular effects.
In placebo-controlled clinical trials, an approximately 3-fold increased risk of cerebrovascular side effects was observed in patients with dementia taking certain atypical antipsychotic drugs. Pooled data from 6 placebo-controlled studies involving primarily elderly patients with dementia (age >65 years) demonstrate that cerebrovascular adverse events (serious and non-serious) occurred in 3.3% (33/1009) of patients taking risperidone. and in 1.2% (8/712) of patients receiving placebo. The risk ratio was 2.96 (1.34, 7.50) with a 95% confidence interval. The mechanism by which this risk increases is unknown. An increased risk cannot be excluded for other antipsychotic drugs, as well as for other patient populations. Rispolept ® should be used with caution in patients with risk factors for stroke.
The risk of cerebrovascular side effects is much higher in patients with mixed or vascular dementia compared to patients with Alzheimer's dementia. Therefore, patients with any type of dementia other than Alzheimer's should not take risperidone.
Physicians should evaluate the risk/benefit ratio of using Rispolept ® in elderly patients with dementia, taking into account the precursors of stroke risk individually for each patient. Patients and caregivers should be cautioned to immediately report signs and symptoms of cardiovascular events, such as sudden weakness or stiffness/numbness in the face, legs, arms, as well as difficulty speaking and vision problems. All possible treatment options should be considered, including discontinuation of risperidone.
Rispolept ® can only be used for the short-term treatment of persistent aggression in patients with moderate to severe Alzheimer's dementia, as an adjunct to non-pharmacological treatment methods when they are ineffective or of limited effectiveness, and when there is a risk of harm to the patient himself or herself to other persons.
Patients' condition and the need for continued risperidone therapy should be continually assessed.

Orthostatic hypotension.
Risperidone has alpha-blocking activity and may therefore cause orthostatic hypotension in some patients, especially during initial dose titration. Clinically significant hypotension has been observed in the post-marketing period when used concomitantly with antihypertensive drugs. Rispolept ® should be used with caution in patients with known cardiovascular disease (eg, heart failure, myocardial infarction, cardiac conduction disorders, dehydration, hypovolemia or cerebrovascular disease). Appropriate dose adjustment is also necessary. It is recommended to evaluate the possibility of dose reduction if hypotension occurs.

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 experiences objective or subjective symptoms indicating tardive dyskinesia, the advisability of discontinuing all antipsychotic drugs, including Rispolept ®, oral solution, should be considered.

Neuroleptic malignant syndrome (NMS).
Antipsychotics, including risperidone, may cause neuroleptic malignant syndrome (NMS), which is characterized by hyperthermia, muscle rigidity, instability of autonomic nervous system function, depression of consciousness, and increased serum concentrations of creatine phosphokinase. Myoglobinuria (rhabdomyolysis) and acute renal failure may also occur in patients with NMS. If a patient experiences objective or subjective symptoms of NMS, all antipsychotic drugs, including Rispolept ® , must be immediately discontinued.

Parkinson's disease and dementia with Lewy bodies.
Antipsychotic medications, including Rispolept ® , should be prescribed with caution to patients with Parkinson's disease or dementia with Lewy bodies. Both groups of patients have an increased risk of developing neuroleptic malignant syndrome and increased sensitivity to antipsychotic drugs (including dullness of pain sensitivity, confusion, postural instability with frequent falls and extrapyramidal symptoms). Parkinson's disease may worsen when taking risperidone.

Hyperglycemia and diabetes mellitus.
Hyperglycemia, diabetes mellitus and exacerbation of existing diabetes mellitus were observed during treatment with Rispolept ®. It is likely that weight gain prior to treatment is also a predisposing factor. Very rarely, ketoacidosis and rarely, diabetic coma can occur. All patients should be clinically monitored for symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia and weakness).
Patients with diabetes mellitus should be regularly monitored for worsening glucose control.

Increase in body weight.
When treated with Rispolept ®, a significant increase in body weight was observed. It is necessary to monitor patients' body weight.

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

Prolongation of the QT interval.
QT prolongation has been observed very rarely during post-marketing surveillance. As with other antipsychotics, caution should be exercised when prescribing Rispolept ® to patients with known cardiovascular diseases, a family history of QT interval prolongation, bradycardia, electrolyte imbalance (hypokalemia, hypomagnesemia), as this may increase the risk of an arrhythmogenic effect; and when used together with drugs that prolong the QT interval.

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

Priapism.
Priapism may occur with risperidone due to alpha-blocking effects.

Regulation of body temperature.
Antipsychotic drugs are associated with such undesirable effects as disruption of the body's ability to regulate temperature. Caution should be exercised when prescribing Rispolept ® to patients with conditions that may contribute to an increase in core body temperature, such as intense physical activity, dehydration, exposure to high external temperatures, or concomitant 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 are often at risk of developing venous thromboembolism, all possible risk factors should be identified before and during treatment with Rispolept ® and preventive measures should be taken.

Children and teenagers.
Before prescribing the drug Rispolept ® to children or adolescents with mental retardation, it is necessary to carefully assess their condition for the presence of physical or social causes of aggressive behavior, such as pain or inadequate demands of the social environment.
The sedative effect of risperidone should be carefully monitored in this population due to the possible effect on learning ability. Changing the timing of risperidone administration may improve control of the effects of sedation on attention in adolescents and children.
Risperidone use was associated with mean increases in body weight and body mass index. Height changes in longitudinal studies were within expected age-related norms. The effects of long-term use of risperidone on sexual development and growth have not been fully studied.
Due to the possible impact of prolonged hyperprolactinemia on growth and sexual development in children and adolescents, regular clinical assessment of hormonal status should be carried out, including measurement of height, weight, monitoring of sexual development, menstrual cycle and other possible prolactin-dependent effects.
During treatment with risperidone, regular monitoring for the presence of extrapyramidal symptoms and other movement disorders should be carried out.

Impact on the ability to drive vehicles and machinery
Rispolept ®, oral solution, may have a small to moderate effect on the ability to drive vehicles and operate machinery. Patients should be advised to refrain from driving a car and operating machinery until their individual sensitivity to the drug is determined.

Release forms

Oral solution 1 mg/ml.
30 or 100 ml of the drug in a dark glass bottle with a screw cap. The bottle, graduated pipette and instructions for use are placed in a cardboard box.

Storage conditions

At temperatures from 15 °C to 30 °C. Do not freeze.
Keep out of the reach of children.

Best before date

3 years. Do not use after expiration date.

Conditions for dispensing from pharmacies.

On prescription.

Manufacturer
Production of finished dosage form, packaging and release control –
Janssen Pharmaceuticals N.V., Belgium, Beerse, 2340, Turnhoutseweg, 30.

Marketing authorization holder, organization receiving claims:
Johnson & Johnson LLC, Russia, 121614, Moscow, st. Krylatskaya, 17/2

**** JANSSEN PHARMACEUTICA JANSSEN-CILAG Janssen-Cilag Spa Alkermes Inc./Cilag AG Alkermes Controlled Therapeutics II. Alkermes Controlled Therapeutics II/Silag AG Janssen -Silag S. p. A. Janssen Pharmaceuticals N.V. Janssen Pharmaceuticals NV, prod. Janssen Silag S.p.A. Janssen-Ortho LLC/Janssen-Cilag S.p.A. Janssen-Cilag AG/Alkermes Controlled Therapeutics II Janssen-Cilag S.p.A./packed by ZAO MFPDC Biotek Janssen-Cilag S.p.A./Janssen Pharmaceuticals N.V.

Country of origin

Belgium Italy Italy/Russia Puerto Rico/Italy UNITED STATES USA/Switzerland Switzerland

Product group

Nervous system

Antipsychotic drug (neuroleptic)

Release forms

• 10 - blisters (2) - cardboard packs. 10 - blisters (6) - cardboard packs. 30 ml - dark glass bottles (1) complete with a graduated pipette - cardboard packs. 4 - contour cell packaging (7) - cardboard packs. 4 - contour cell packaging (14) - cardboard packs. 4 - contour cell packaging (7) - cardboard packs. 4 - contour cell packaging (14) - cardboard packs. 4 things. - contour cellular packaging (14) - cardboard packs. Three-needle system. Bottles (1) complete with a syringe filled with solvent (2 ml), Hypoint™ needles for preparing a suspension (2), Needle-Pro needle (with safety device) for intramuscular injection Bottles (1) complete with a syringe, filled with solvent (2 ml), Hypoint™ needles for preparing a suspension (2), Needle-Pro needle (with a protective device) for intramuscular injection (1) - packing cellular Vials (1) complete with a syringe filled with solvent ( 2 ml), Hypoint™ needles for preparing a suspension (2), Needle-Pro needle with a protective device for intramuscular injection (1) - blister packs

Description of the dosage form

• The powder for the preparation of a suspension for intramuscular administration of prolonged action is white or almost white, free from visible inclusions; the enclosed solvent is a clear, colorless aqueous solution, free of visible inclusions. The powder for the preparation of a suspension for intramuscular administration of prolonged action is white or almost white, free from visible inclusions; the enclosed solvent is a clear, colorless aqueous solution, free of visible inclusions. The powder for the preparation of a suspension for intramuscular administration of prolonged action is white or almost white, free from visible inclusions; The enclosed solvent is a clear, colorless, aqueous solution free of visible inclusions. The solution for oral administration is transparent, colorless. Lozenges, light pink, lyophilized, round, biconvex, engraved"R2" с одной стороны. Таблетки для рассасывания светло-розового цвета, лиофилизированные, круглые, двояковыпуклые, с выгравированной надписью "R2" с одной стороны. Таблетки для рассасывания светло-розового цвета, лиофилизированные, круглые, двояковыпуклые, с выгравированной надписью "R2" с одной стороны. Таблетки, покрытые оболочкой зеленого цвета, продолговатые, двояковыпуклые, с риской, с надписью "Ris" и "4" на одной стороне; на изломе - белого цвета. Таблетки, покрытые оболочкой светло-оранжевого цвета, продолговатые, двояковыпуклые, с риской, с надписью "Ris" и "2" на одной стороне; на изломе - белого цвета.!}

pharmachologic effect

After oral administration, it is completely absorbed, reaching Cmax in plasma after 1–2 hours. Food does not affect the absorption of the drug, so risperidone can be prescribed regardless of food intake. Quickly distributed in the body. The volume of distribution is 1–2 l/kg. In plasma, risperidone binds to albumin and α1-glycoprotein. Risperidone is 88% bound to plasma proteins, 9-hydroxy-risperidone is 77% bound. The equilibrium concentration of risperidone in the body is achieved within 1 day in most patients; 9-hydroxy-risperidone - after 4–5 days. Plasma concentrations of risperidone are proportional to the dose of the drug (within therapeutic doses). Metabolized by the enzyme cytochrome P450 CYP2D6 to 9-hydroxy-risperidone, which has a pharmacological effect similar to risperidone. Risperidone and 9-hydroxy-risperidone constitute the active antipsychotic fraction. Another route of metabolism of Rispolept Quicklet is N-dealkylation. After oral administration in patients with psychosis, risperidone is released with T1/2 for about 3 hours; 9-hydroxy-risperidone and active antipsychotic fraction - 24 hours. After a week of taking the drug, 70% of the dose is excreted in the urine, 14% in feces. In urine, risperidone and 9-hydroxy-risperidone account for 35–45% of the dose. The remaining amount consists of inactive metabolites. A single-dose study showed higher plasma concentrations and slower elimination in the elderly and in patients with renal impairment. Plasma concentrations of risperidone were normal in patients with hepatic impairment. Rispolept Quiclet tablets are bioequivalent to regular Rispolept tablets.

Pharmacokinetics

Absorption Risperidone is completely absorbed from the Rispolept Konsta suspension. After intramuscular injections of Rispolept Konsta in doses of 25 mg or 50 mg once every 2 weeks, the average values ​​of Cmin and Cmax of the active fraction are 9.9-19.2 ng/ml and 17.9-45.5 ng/ml, respectively. With this dosing regimen, the pharmacokinetics of risperidone is linear. In a long-term (12 months) study in patients who were administered Rispolept Consta in doses of 25 mg or 50 mg once every 2 weeks, no accumulation of risperidone was observed. Due to the peculiarities of the dosage form, after a single intramuscular administration of the drug Rispolept Consta, the release profile of risperidone consists of a small initial phase (

Special conditions

Use with caution in patients with diseases of the cardiovascular system (including heart failure, myocardial infarction, cardiac muscle conduction disorders), as well as in cases of dehydration, hypovolemia or cerebrovascular disorders. In this category of patients, the dose should be increased gradually. The risk of developing orthostatic hypotension is especially increased in the initial period of dose selection. If hypotension occurs, dose reduction should be considered. When using drugs that have the properties of dopamine receptor antagonists, the occurrence of tardive dyskinesia, characterized by involuntary rhythmic movements (mainly of the tongue and/or face), was noted. There are reports that the occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. Risperidone causes extrapyramidal symptoms to a lesser extent than classical antipsychotics. If symptoms of tardive dyskinesia occur, discontinuation of all antipsychotic medications should be considered. If NMS develops, all antipsychotics, including risperidone, should be discontinued. Risperidone should be used with caution in patients with Parkinson's disease, as it is theoretically possible that the disease may worsen. Classical antipsychotics are known to lower the seizure threshold. Given this, risperidone is recommended to be used with caution in patients with epilepsy. Risperidone should be used with caution in combination with other centrally acting drugs. When discontinuing carbamazepine and other hepatic enzyme inducers, the dose of risperidone should be reconsidered and, if necessary, reduced. During the treatment period, patients should be advised to refrain from overeating due to the possibility of weight gain. There are no data on the safety of risperidone in children under 15 years of age. Effect on the ability to drive vehicles and operate machinery During the treatment period, until individual sensitivity to risperidone is determined, patients should avoid driving vehicles and other activities that require high concentration and speed of psychomotor reactions.

Compound

• 1 ml risperidone 1 mg Excipients: tartaric acid, benzoic acid, sodium hydroxide, purified water. 1 tab. risperidone 2 mg Excipients: lactose, corn starch, microcrystalline cellulose, hypromellose, magnesium stearate, colloidal anhydrous silicon dioxide, sodium lauryl sulfate, propylene glycol, talc, titanium dioxide, orange-yellow S (E110). 1 tab. risperidone 4 mg Excipients: lactose, corn starch, microcrystalline cellulose, hypromellose, magnesium stearate, colloidal anhydrous silicon dioxide, sodium lauryl sulfate, propylene glycol, talc, titanium dioxide, choline yellow, indigotin disulfonate. 1 g microgranules 1 fl. risperidone (in the form of extended-release microgranules) 381 mg 50 mg Excipients: polymer 7525 DLJN (poly-D,L-lactide-coglycolide) - 619 mg per 1 g of microgranules; possible presence of trace amounts of ethyl acetate, benzyl alcohol, anhydrous ethanol, and water. Solvent: polysorbate 20, sodium carmellose (with a viscosity of 40 mPa.s), sodium hydrogen phosphate dihydrate, anhydrous citric acid, sodium chloride, sodium hydroxide, water for injection. 1 tab. risperidone 2 mg Excipients: polyacrylex resin, gelatin type A, mannitol, glycine, simethicone, carbomer 34,000, sodium hydroxide, aspartame, red iron oxide, peppermint oil. 1 tab. risperidone 2 mg Excipients: polyacrylex resin, gelatin type A, mannitol, glycine, simethicone, carbomer 34,000, sodium hydroxide, aspartame, red iron oxide, peppermint oil. risperidone (in the form of extended-release microgranules) 381 mg 37.5 mg Excipients: polymer 7525 DLJN (poly-D,L-lactide-coglycolide); possible presence of trace amounts of ethyl acetate, benzyl alcohol, anhydrous ethanol, and water. Solvent: polysorbate 20, sodium carmellose (with a viscosity of 40 mPa.s), sodium hydrogen orthophosphate dihydrate, anhydrous citric acid, sodium chloride, sodium hydroxide, water for injection. risperidone (in the form of extended-release microgranules) 381 mg/g Excipients: polymer 7525 DLJN (poly-D,L-lactide-coglycolide); possible presence of trace amounts of ethyl acetate, benzyl alcohol, anhydrous ethanol, and water. Solvent: polysorbate 20, sodium carmellose (with a viscosity of 40 mPa.s), sodium hydrogen orthophosphate dihydrate, anhydrous citric acid, sodium chloride, sodium hydroxide, water for risperidone 2 mg Excipients: polyacrylex resin, type A gelatin, mannitol, glycine, simethicone, carbomer 34,000, sodium hydroxide, aspartame, red iron oxide, peppermint oil.

Rispolept indications for use

• Treatment of schizophrenia (including new-onset acute psychosis, acute attack of schizophrenia, chronic schizophrenia); psychotic states with pronounced productive (hallucinations, delusions, thought disorders, hostility, suspicion) and/or negative (blunted affect, emotional and social detachment, poverty of speech) symptoms; to reduce affective symptoms (depression, guilt, anxiety) in patients with schizophrenia; prevention of relapses (acute psychotic states) in chronic schizophrenia; treatment of behavioral disorders in patients with dementia with symptoms of aggressiveness (outbursts of anger, physical violence), mental disturbances (agitation, delusions) or psychotic symptoms; treatment of mania in bipolar disorders (as a mood stabilizer as an adjuvant therapy).

Rispolept contraindications

• - lactation period; - hypersensitivity to the components of the drug. Use with caution in diseases of the cardiovascular system (chronic heart failure, previous myocardial infarction, conduction disorders of the heart muscle), dehydration and hypovolemia, cerebrovascular accident, Parkinson's disease, seizures (including a history), severe renal or liver failure, drug abuse 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 tumors, intestinal obstruction, in case of acute drug overdose , with Reye's syndrome (the antiemetic effect of risperidone may mask the symptoms of these conditions), during pregnancy, in children under 15 years of age (efficacy and safety have not been established).

Rispolept dosage

• 1 mg, 2 mg 1 mg/ml 1, 2, 3, 4 mg 2 mg 25 mg 25 mg, 37.5 mg, 50 mg 37.5 mg 4 mg 50 mg

Rispolept side effects

• From the nervous system: insomnia, agitation, anxiety, headache; sometimes - drowsiness, fatigue, dizziness, impaired concentration, blurred vision; rarely - extrapyramidal symptoms: tremor, rigidity, hypersalivation, bradykinesia, akathisia, acute dystonia. In patients with schizophrenia: hypervolemia (either due to polydipsia or the syndrome of inappropriate ADH secretion), tardive dyskinesia (involuntary rhythmic movements mainly of the tongue and/or face), neuroleptic malignant syndrome (hyperthermia, muscle rigidity, instability of autonomic functions, impaired consciousness and increased levels of creatine phosphokinase), thermoregulation disorders and epileptic seizures. From the digestive system: constipation, dyspepsia, nausea or vomiting, abdominal pain, increased activity of liver enzymes, dry mouth, hypo- or hypersalivation, anorexia, increased appetite, increased or decreased body weight. From the cardiovascular system: orthostatic hypotension, reflex tachycardia, increased blood pressure. During treatment with Rispolept, the development of strokes has been described, mainly in elderly patients with predisposing factors. From the hematopoietic organs: neutropenia, thrombocytopenia. From the endocrine system: galactorrhea, gynecomastia, menstrual irregularities and amenorrhea; In very rare cases, hyperglycemia and exacerbation of pre-existing diabetes mellitus in patients have been reported.

Drug interactions

Rispolept Konsta increases the severity of the inhibitory effect on the central nervous system of opioid analgesics, hypnotics, anxiolytics, tricyclic antidepressants, general anesthesia, ethanol. Rispolept Konsta may weaken the effect of levodopa and other dopamine agonists. It has been established that carbamazepine reduces the plasma content of the active antipsychotic fraction of risperidone. Other hepatic enzyme inducers may cause similar effects. After discontinuation of carbamazepine or other hepatic enzyme inducers, the dose of Rispolept Consta should be reconsidered and, if necessary, reduced. Phenothiazines, tricyclic antidepressants and some beta-blockers may decrease plasma concentrations of risperidone. With simultaneous use, fluoxetine may increase the plasma concentration of risperidone, but to a lesser extent - the concentration of the active antipsychotic fraction. Pharmaceutical interactions

Overdose

When using parenteral forms of risperidone, overdose is less likely than when using oral forms. When using oral forms, the following symptoms are possible: severe drowsiness, tachycardia, arterial hypotension, extrapyramidal symptoms; rarely - increase in QT interval.

Storage conditions

• store in a dry place
• keep away from children
• store in a place protected from light

Information provided by the State Register of Medicines.

Synonyms

• Ingredients: powder d/susp prolong. with solvent + alaris needle-free device for preparation of suspension + needle / 1 pc. /

Mental behavior disorders are common among patients. The causes of their appearance are dementia, severe stress, and inhibition of mental development. Antipsychotic drugs are used to prevent the development of schizophrenia, aggression and behavioral disorders. A popular one is Rispolept. Read its instructions for use.

Instructions for use of Rispolept

The antipsychotic drug Rispolept is an antipsychotic. In domestic pharmacies you can find a drug produced by the Belgian and Italian pharmacological companies Janssen. The active substance of the drug is risperidone, which normalizes human behavior, eliminates outbursts of anger, impulsiveness and aggression.

Composition and release form

There are three known forms of release of the drug Rispolept - tablets, oral solution and powder for the preparation of intramuscular suspension. Their differences in composition:

	Pills		Powder Konsta
Description	White, orange, green or yellow film coated	Transparent colorless liquid	Fine powder in the form of microgranules
Risperidone concentration, mg	1, 2, 3 or 4 per piece.		25, 37.5 or 50 per bottle
Auxiliary components	Propylene glycol, lactose monohydrate, hypromellose, corn starch, colloidal silicon dioxide, sodium lauryl sulfate, magnesium stearate, microcrystalline cellulose, titanium dioxide, talc, sunset yellow, indigo carmine or quinoline yellow	Water, tartaric acid, sodium hydroxide, benzoic acid	Copolymer of glycolic and lactic acids. Solvent: water, polysorbate, sodium chloride, carmellose, sodium hydroxide, sodium hydrogen phosphate dihydrate, anhydrous citric acid.
Package	Blisters of 10 pcs., 2 or 6 blisters per pack	Bottles with graduated pipette, 30 or 100 ml	Dark glass bottles with 2 ml syringe with solvent, safety needle and needle-free dissolution device

Pharmacodynamics and pharmacokinetics

The active substance of the composition, risperidone, is a selective monoaminergic antagonist with a high affinity for serotonin and dopamine receptors. It binds to alpha-adrenergic receptors, histamine receptors, and is not bound to cholinergic receptors. Risperidone induces catalepsy (decreased sensitivity to stimuli) less than classical antipsychotics, and is a central antagonist to serotonin and dopamine.

After entering the body, risperidone is absorbed, reaching maximum concentration after 1-2 hours with 70% bioavailability, which is independent of food intake. In plasma, the active substance binds to albumin and alpha glycoprotein by 90%, its metabolite 9-hydroxyrisperidone – by 77%. Metabolism of the component occurs in the liver using isoenzymes. This results in an active antipsychotic fraction. A week after the start of therapy, 70% of the drug dose is excreted in the urine, the rest in feces. The withdrawal period is 6-48 hours.

Indications for use

The drug is used to treat psychotic disorders in adolescents and adults. Indications for use:

• schizophrenia in children over 13 years of age and adults;
• manic episodes associated with moderate to severe bipolar disorder starting at age 10;
• short-term treatment (up to 1.5 months) of persistent aggression in patients with dementia due to Alzheimer's disease;
• symptomatic treatment of persistent aggression in children from five years of age against the background of mental retardation.

Directions for use and dosage

Tablets and solution are taken orally. The powder for preparing a suspension is used intramuscularly after dissolution. The dosage of each drug depends on the type of disease, the degree of its severity, the age of the patient and the additional therapy used with other medications. There are instructions for each form.

The medication in tablets is taken orally, regardless of food intake. For manic episodes associated with bipolar disorder, adults are prescribed 2 mg/day at a time, increasing by 1 mg every 24 hours. Children are prescribed 0.5 mg once a day, elderly – 0.5 twice a day. For persistent aggression associated with Alzheimer's disease, it is recommended to take 0.25 mg twice a day for a course of no more than 6 weeks.

For schizophrenia, the initial dose is 2 mg 1-2 times a day, on the second day it is increased to 4 mg. You can leave it as is or increase it to 6 mg/day. Doses above 10 mg do not show higher effectiveness. If persistent drowsiness is observed, it is recommended to reduce the dose by half. For elderly patients, the initial dosage is 0.5 mg twice a day with a gradual increase to 1-2 mg. Children over 13 years of age with schizophrenia are prescribed 0.5 mg once a day, in the morning or evening, with an increase of 0.5-1 mg every 24 hours or up to 3 mg/day.

With ongoing aggression in the structure of behavior, children 5-18 years old are prescribed 0.5 mg once a day, increasing by 0.5 mg every day to 1 mg. For body weight less than 50 kg, the dose is 0.25 mg once a day. For liver diseases, the dose is halved. The drug is discontinued gradually to eliminate nausea, vomiting, sweating, and insomnia. If other antipsychotic drugs were taken before taking Rispolept, then therapy with them is canceled gradually. If injections were used, the planned one is replaced by taking pills.

Rispolept Konsta

Intramuscular injections should be administered by medical personnel in a hospital setting. Storage of the suspension is not intended for longer than 6 hours at a temperature of 25 degrees. The solution is applied once every 14 days by inserting a needle deeply into the gluteal muscle, using different buttocks alternately. For adults and the elderly, the initial dose is 25 mg, the maximum dosage is 50 mg once every 14 days. After the first injection, the patient must take antipsychotic medications for 21 days. The dose of Konsta solution is increased no more than once a month.

Rispolept solution

The dosage of the oral solution is equal to the tablet dosage. Doctors recommend taking liquid instead of tablets when the dose is less than 1 mg - it’s more convenient to measure it. For schizophrenia, 2-4 mg 2-3 times a day is prescribed for adults, 0.5 mg twice a day for elderly patients and 0.5-1 mg once a day for children over 13 years of age. For manic episodes, adults receive 1-6 mg at a time, elderly 0.5 mg twice a day, children over 10 years old - 0.5-1 mg at a time.

For persistent aggression in elderly people with dementia, 0.25-0.5 mg twice a day is prescribed for a course of 1.5 months. For persistent aggression in children aged 5-18 years with a body weight over 50 kg, 0.5-1 mg once a day is prescribed, less than 50 kg - 0.25-0.5 mg. The solution is taken orally and can be washed down with a small amount of water. Its withdrawal occurs gradually, as does the transition from other antipsychotics.

special instructions

When using Rispolept preparations, you need to carefully study the special instructions in the instructions. Rules of use:

1. With dementia, older patients may experience increased mortality. Its level is partially affected by simultaneous administration of furosemide.
2. With dementia and treatment with risperidone, the risk of developing side effects from the cerebrovascular and cardiovascular systems (stroke, heart attack) increases.
3. Patients with dementia other than Alzheimer's should not be treated with the drug.
4. Risperidone can cause orthostatic hypotension, especially during the initial period of dose selection, and lead to tardive dyskinesia, characterized by rhythmic involuntary movements of the tongue or facial muscles.
5. An antipsychotic drug can cause neuroleptic malignant syndrome (NMS), manifested by hyperthermia, depression of consciousness, and muscle rigidity. The consequences of NMS are myoglobinuria and acute renal failure.
6. During treatment with the drug, hyperglycemia, diabetes mellitus or its exacerbation are observed. Rarely, this can result in ketoacidosis and diabetic coma.
7. Therapy with the drug may lead to weight gain. In case of hyperprolactinemia, the drug is used with caution due to the risk of prolactin-dependent tumors.
8. During treatment there is a risk of priapism, impaired thermoregulation, and venous thromboembolism.
9. The tablets contain lactose, so they should not be taken if you have galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.
10. The dyes included in the film shell of the tablets can cause allergic reactions.
11. During therapy, you should refrain from driving a car or operating dangerous machinery.

During pregnancy

According to observational data, the use of risperidone in the third trimester of pregnancy caused reversible extrapyramidal symptoms in the newborn. Animal studies have shown that the drug is not teratogenic to the fetus, but other types of toxic effects on the reproductive system have been observed. The medication can be used during pregnancy if the benefit to the mother exceeds the risk to the child. The issue of breastfeeding is resolved in the same way. It has been proven that the active substance and its metabolites pass into breast milk.

The use of the solution is permitted from the age of five, tablets from the age of 15, and powder for suspension from the age of 18. Before prescribing medications, children and adolescents with mental retardation are monitored for reasons for aggression. It is advisable to take the drug in the morning because it affects the child's level of sedation. The effect of long-term use of risperidone on the growth and development of the genital area has not been studied. During therapy, the hormonal status of children is regularly assessed.

Drug interactions

Like all antipsychotics, the drug is prescribed with caution with antiarrhythmic drugs and (Quinidine, Procainamide, Sotalol), tricyclic and tetracyclic antidepressants (Amitriptyline, Maprotiline), antihistamines, antimalarials (Quinine, Mefloquine), drugs that cause electrolyte imbalance. Other examples of combinations:

1. Ethanol, opiate, antihistamines and benzodiazepines increase their sedative effect when combined with medication.
2. The drug reduces the effectiveness of Levodopa, dopamine agonists, and increases arterial hypotension when combined with antihypertensive drugs.
3. Fluoxetine, Paroxetine, Quinidine, Verapamil, Phenothiazine increase the level of the active component in the body.
4. The combination of the drug with psychostimulants is allowed, but it is prohibited with Paliperidone.

Side effects of Rispolept

The most common side effects of the drug are headache, parkinsonism, and insomnia. Other negative reactions include:

• infections: pneumonia, otitis media, influenza, cystitis, bronchitis, onychomycosis, sinusitis, tonsillitis, eye infections, abscess, flu-like symptoms;
• hypersensitivity, anaphylactic reactions;
• tachycardia, arterial hypertension, arterial or orthostatic hypotension, atrial fibrillation, rapid heartbeat;
• anemia, agranulocytosis, granulocytopenia, thrombocytopenia;
• dizziness, dystonia, tremor, lethargy, loss of consciousness, dyskinesia, stroke, dysarthria, hypesthesia, imbalance, ischemia, convulsions, anxiety;
• disturbance of taste, movements, head tremors, agitation, anxiety, confusion, decreased libido, lethargy, mania;
• blurred vision, conjunctivitis, red eyes;
• ear pain, tinnitus;
• shortness of breath, nosebleeds, cough, nasal congestion, wheezing, pain in the larynx and pharynx, moist rales, apnea syndrome, nasopharyngitis, dry mouth;
• vomiting, constipation, diarrhea, nausea, dyspepsia, stomach discomfort or pain, gastritis, fecal incontinence, flatulence, pancreatitis, intestinal obstruction;
• jaundice, enuresis, kidney intoxication;
• rash, erythema, skin lesions, hyper- or hypopigmentation, Quincke's edema, dandruff, alopecia, seborrheic dermatitis;
• arthralgia, pain in the back and limbs, swelling of the joints, rhabdomyolysis, akinesia, bradykinesia, gait disturbances;
• increased or decreased appetite, anorexia, hypoglycemia;
• akathisia, pyrexia, fatigue, chest pain, slowness, thirst, hypokinesia, hypothermia;
• amenorrhea, impaired ejaculation, menstruation, urinary tract infections, swelling of the mammary glands.

Overdose

Symptoms of overdose are drowsiness, sedation, hypotension, tachycardia, extrapyramidal symptoms, convulsions. Treatment consists of clearing the airways, gastric lavage, taking activated charcoal and laxatives. An electrocardiogram is performed to detect arrhythmias. There is no specific antidote; symptomatic therapy is carried out. Hypotension and collapse are treated with intravenous infusions, and a range of extrapyramidal symptoms are treated with anticholinergic drugs.

Contraindications

The medication is contraindicated for use in case of phenylketonuria or hypersensitivity to the components of the composition. It should be used with caution when:

• diseases of the cardiovascular system;
• dehydration, hypovolemia;
• cerebrovascular accident;
• drug addiction;
• bradycardia, blockade;
• brain tumors;
• intestinal obstruction, Reye's syndrome, cases of acute drug overdose;
• risk factor for thromboembolism;
• diffuse Lewy body disease;
• pregnancy;
• cerebrovascular dementia.

Terms of sale and storage

You can buy the drug only with a prescription. Tablets and solution are stored at a temperature of 15-30 degrees, powder at 2-8 degrees, the shelf life for all forms is three years.

Analogues

Drugs containing antipsychotic components can replace the drug. These include:

• Invega is a paliperidone-based antipsychotic;
• Abilify - contains aripiprazole, available in tablet and injection format;
• Xeplion is an antipsychotic drug against schizophrenia based on paliperidol;
• Amdoal – contains aripiprazole, helps with bipolar disorder;
• Zilaxera is an aripiprazole-based antipsychotic;
• Aripiprazole is a direct analogue of the drug.

Rispolept price

The cost of the medicine depends on many factors: the price of raw materials, the concentration of the active substance, the number of tablets or the volume of bottles, and the trade margin. Approximate price for the product in Moscow:

Variety	Internet price tag, rubles	Pharmacy cost, rubles
Tablets 2 mg 50 pcs.
Powder 25 mg