Risperidone, 1 mg/ml 30 ml

Pharmacotherapeutic group:antipsychotic drug (neuroleptic).

ATX code N05AX08

Pharmacological properties

Pharmacodynamics

Risperidone is a selective monoaminergic antagonist with high affinity for serotonergic 5-NT2 and dopaminergic D2 -receptors. Risperidone also binds to α1-adrenergic receptors and, somewhat weaker, to H1 -histaminergic and α2 -adrenergic receptors. Risperidone has no tropism to cholinergic receptors. Risperidone reduces the productive symptomatology of schizophrenia, causes less suppression of motor activity and is less likely to induce catalepsy than classical neuroleptics. Balanced central antagonism to serotonin and dopamine probably reduces the propensity for extrapyramidal side effects and extends the therapeutic effects of the drug to include negative and affective symptoms of schizophrenia.

Pharmacokinetics

Intake

Risperidone is completely absorbed after oral administration, reaching maximum plasma concentrations in 1-2 hours. The absolute bioavailability of risperidone after oral administration is 70%. The relative bioavailability after oral administration of risperidone in tablet form is 94 % compared to risperidone in solution form. Food has no effect on absorption of the drug, therefore risperidone may be prescribed regardless of meals. The equilibrium concentration of risperidone in the body in most patients is reached within 1 day. The equilibrium concentration of 9-hydroxirisperidone is reached within 4-5 days.

Distribution

Risperidone is rapidly distributed in the body. The volume of distribution is 1-2 l/kg. In plasma, risperidone binds to albumin and alpha1-acid glycoprotein. Risperidone is 90% bound by plasma proteins, 9-hydroxysperidone – by 77%.

Metabolism and excretion

Risperidone is metabolized by CYP 2D6 isoenzyme to 9-hydroxyrisperidone, which has similar pharmacological effects to risperidone. Risperidone and 9-hydroxysperidone constitute the active antipsychotic fraction. The CYP 2D6 isoenzyme is subject to genetic polymorphism. In patients with intensive metabolism by CYP 2D6 isoenzyme, risperidone is rapidly converted to 9-hydroxyrisperidone, while in patients with poor metabolism, this transformation is much slower. Although patients with intensive metabolism have lower risperidone concentrations and higher 9-hydroxysperidone concentrations than patients with poor metabolism, the total pharmacokinetics of risperidone and 9-hydroxysperidone (active antipsychotic fraction) after one or more doses are similar in patients with intensive and with poor CYP 2D6 metabolism.

The other pathway of risperidone metabolism is N-dealkylation. In vitro studies on human liver microsomes have shown that risperidone in clinically significant concentrations generally does not inhibit the metabolism of drugs undergoing biotransformation by P450 system isoenzymes, including CYP 1A2, CYP 2A6, CYP 2C8/9/10, CYP 2D6, CYP 2E1, CYP 3A4 and CYP 3A5. One week after the start of the drug, 70% of the dose is excreted in the urine, 14% – in the feces. In the urine, risperidone together with 9-hydroxyrisperidone make up 35-45% of the dose. The remaining amount consists of inactive metabolites. After oral administration in patients with psychosis, risperidone is eliminated from the body with a half-life (T1/2) of about 3 hours. The T1/2 of 9-hydroxysperidone and the active antipsychotic fraction is 24 hours.

Linearity

The plasma concentration of risperidone is directly proportional to the dose taken in the therapeutic dose range.

Elderly patients and patients with hepatic and renal impairment

After a single dose of risperidone, older patients had on average 43% higher plasma concentrations of the active antipsychotic fraction, a 38% longer half-life, and a 30% decrease in clearance. In patients with renal insufficiency, increased plasma concentrations and decreased clearance of the active antipsychotic fraction by 60% on average were observed. In patients with hepatic insufficiency, plasma concentrations of risperidone did not change, but the average concentration of the free fraction of risperidone increased by 35%.

Children

The pharmacokinetics of risperidone, 9-hydroxysperidone and the active antipsychotic fraction in children are comparable to those in adult patients.

The influence of sex, race, and smoking

Population pharmacokinetic analysis showed no apparent effect of sex, race, or smoking on the pharmacokinetics of risperidone and the active pharmacokinetic fraction.

Indications

• treatment of schizophrenia in adults and children from 13 years old;
• treatment of manic episodes associated with bipolar disorder of moderate to severe degree in adults and children from 10 years old;
• short-term (up to 6 weeks) symptomatic treatment of persistent aggression as part of a behavioral disorder in children 5 years and older with DSM-IV diagnosed intellectual disability in which the severity of aggression or other disruptive behavior requires pharmacotherapy. Pharmacotherapy should be part of a broader treatment program, including psychological and educational interventions. Risperidone should be prescribed by a specialist in child neurology and child psychiatry or by a physician familiar with the treatment of conduct disorder in children and adolescents.
  

Active ingredient

Risperidone

Composition

Active ingredient: risperidone – 1 mg.

Excipients: tartaric acid – 7.5 mg, benzoic acid – 2 mg, sodium hydroxide – to pH 3.0±0.1, purified water – to 1 ml.

How to take, the dosage

Schizophrenia

Adults

Rispoletto® may be administered once or twice daily. The initial dose of Rispolettes® is 2 mg per day. On day 2, the dose may be increased to 4 mg per day. From then on, the dose can either be maintained at the same level or adjusted individually if necessary. Usually the optimal dose is 4-6 mg per day. In some cases, slower dose increases and lower starting and maintenance doses may be warranted.
Doses above 10 mg per day have not been shown to be more effective than lower doses and may cause extrapyramidal symptoms. Because the safety of doses above 16 mg per day has not been studied, doses above this level are not recommended.

Elderly patients

The initial dose of 0.5 mg per dose twice daily is recommended. The dosage can be increased individually by 0.5 mg twice daily to 1-2 mg twice daily.

Children 13 years and older

The recommended starting 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 to 1 mg daily to the recommended dose of 3 mg daily if well tolerated. Although efficacy has been demonstrated in the treatment of schizophrenia in adolescents at doses of 1-6 mg daily, no additional efficacy has been observed at doses above 3 mg daily, and higher doses have caused more side effects. The use of doses higher than 6 mg daily has not been studied.

Patients who have persistent somnolence are advised to take half of the daily dose twice daily.

Manic episodes associated with bipolar disorder

Adults

The recommended starting dose of the drug is 2 mg daily in a single dose. If necessary, this dose may be increased after at least 24 hours by 1 mg per day. For most patients, the optimal dose is 1-6 mg daily. The use of doses higher than 6 mg daily in patients with manic episodes has not been studied.

As with any symptomatic therapy, the appropriateness of continuing treatment with Rispolettes® should be regularly evaluated and confirmed.

Elderly patients

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

Children over 10 years of age

The recommended starting 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 to 1 mg daily to the recommended dose of 1 to 2.5 mg daily if well tolerated. Although efficacy has been demonstrated in the treatment of manic episodes associated with bipolar disorder in children at doses of 0.5-6 mg daily, no additional efficacy has been observed at doses above 2.5 mg daily, and higher doses have caused more side effects.

The use of doses higher than 6 mg daily has not been studied.

Patients who have persistent somnolence are recommended to take half of the daily dose twice daily.

Intense aggression in patients with dementia due to Alzheimer’s disease

The initial dose of 0.25 mg per dose twice daily is recommended. The dosage may be increased individually to 0.25 mg twice daily if necessary, no more often than every other day. For most patients, the optimal dose is 0.5 mg twice a day. However, some patients can take 1 mg twice a day.

Rispolettes® should not be used for more than 6 weeks in patients with persistent aggression in patients with dementia due to Alzheimer’s disease.

Patients should be evaluated on a regular basis during treatment, as well as the need for continuation of therapy.

Incontinuous aggression in a behavioral disorder

Children 5 to 18 years of age

Patients weighing 50 kg or more have a recommended starting dose of 0.5 mg once daily. If necessary, this dose may be increased by 0.5 mg daily, no more often than every other day. For most patients, the optimal dose is 1 mg daily. However, some patients prefer to take 0.5 mg daily, while some need to increase the dose to 1.5 mg daily.

Patients weighing less than 50 kg have a recommended starting dose of 0.25 mg once daily. If necessary, this dose may be increased by 0.25 mg daily, no more often than every other day. For most patients, the optimal dose is 0.5 mg daily. However, some patients prefer to take 0.25 mg daily, while some require increasing the dose to 0.75 mg daily.

As with any symptomatic therapy, the appropriateness of continuing treatment with Rispolet® should be regularly evaluated and confirmed.

The use in children younger than 5 years of age is not recommended due to lack of data.

Hepatic and renal diseases.

Patients with renal disease have a reduced ability to excrete the active antipsychotic fraction compared to other patients. Patients with liver disease have increased plasma concentrations of the free fraction of risperidone.

The initial and maintenance dosage should be reduced by a factor of 2 as indicated, the dose increase in patients with liver and kidney disease should be carried out more slowly.

Risolept® should be administered with caution in this category of patients.

How to use

Ingestion. Food intake has no effect on the absorption of the drug.

The discontinuation of the drug is recommended to be done gradually. Acute “withdrawal” symptoms, including nausea, vomiting, sweating, and insomnia, have been observed very rarely after abrupt discontinuation of high doses of antipsychotic medication.

Transition from therapy with other antipsychotics.

At the beginning of treatment with Rispolettes®, it is recommended that prior therapy be gradually discontinued if clinically appropriate. At the same time, if patients are transferred from therapy with depot forms of antipsychotic drugs, it is recommended that therapy with Rispolettes® be started instead of the next scheduled injection. The need for continuation of current antiparkinsonian drug therapy should be evaluated periodically.

Interaction

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

The effects of Rispolettes® administration on other medications

Rispolettes® should be used with caution in combination with other drugs and centrally acting agents, especially alcohol, opiates, antihistamines, and benzodiazepines because of the increased risk of sedation.

Rispolept® may decrease the effectiveness of levodopa and other dopamine agonists. If this combination is necessary, especially in terminal Parkinson’s disease, the lowest effective dose of each drug should be administered.

When using risperidone in combination with antihypertensive drugs, clinically significant hypotension has been observed in the post-marketing period. Risperidone has no clinically significant effect on pharmacokinetics of lithium, valproate, digoxin or topiramate.

The effect of taking other drugs on Risperidone®

When using carbamazepine a decrease in plasma concentration of active antipsychotic fraction of risperidone was observed. Similar effects may be observed with other hepatic enzyme inducers and P-glycoprotein (e.g., rifampicin, phenytoin, phenobarbital). When prescribing and after withdrawal of carbamazepine or other hepatic enzyme inducers and P-glycoprotein the dose of Rispolet® should be adjusted.

Fluoxetine and paroxetine, which are inhibitors of CYP 2D6 isoenzyme, increase the concentration of risperidone in plasma, but less so the concentration of active antipsychotic fraction. It is assumed that other CYP 2D6 isoenzyme inhibitors (e.g., quinidine) affect the concentration of risperidone in the same way. When prescribing and after withdrawal of fluoxetine or paroxetine the dose of Rispolet® should be adjusted.
Verapamil, which is an inhibitor of CYP 3A4 isoenzyme and P-glycoprotein, increases the plasma concentration of risperidone.

Galantamine and donepezil have no clinically significant effect on the pharmacokinetics of risperidone and its active antipsychotic fractions.

Phenothiazines, tricyclic antidepressants and some β-adrenoblockers 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 minimal effect on the concentration of the active antipsychotic fraction. Erythromycin, an inhibitor of CYP 3A4 isoenzyme, has no effect on the pharmacokinetics of risperidone and the active antipsychotic fraction.

The co-administration of psychostimulants (e.g., methylphenidate) and Rispolettes® in children does not alter the pharmacokinetic parameters and efficacy of risperidone.

The use of risperidone together with paliperidone is not recommended due to the fact that paliperidone is the active metabolite of risperidone and the use of such a combination may lead to an increased concentration of the active antipsychotic fraction.

Special Instructions

Use in elderly patients with dementia.

Increased mortality in elderly patients with dementia

Elderly patients with dementia treated with atypical antipsychotics have an increased mortality rate compared to placebo in studies of atypical antipsychotics, including risperidone. For this population, the mortality rate for risperidone was 4.0% for patients taking risperidone compared to 3.1% for placebo. The mean age of patients who died was 86 years (range 67-100 years). Data collected from two extensive observational studies indicate that elderly patients with dementia treated with typical antipsychotics also have a slightly increased risk of death compared with untreated patients. At this time, insufficient data have been collected to estimate this risk accurately. Nor is the cause of the increased risk known. Also, the extent to which the increased mortality may be applicable to antipsychotic medications, rather than to the characteristics of this patient group, has not been determined.

Combined use with furosemide

. Elderly patients with dementia had an increased mortality with concomitant oral administration of furosemide and risperidone (7.3%, mean age 89 years, range 75-97 years) compared with the group taking risperidone alone (3.1%, mean age 84 years, range 70-96 years) and the group taking furosemide alone (4.1%, mean age 80 years, range 67-90 years). Increased mortality in patients taking risperidone together with furosemide was observed in 2 of the 4 clinical trials. Co-administration of risperidone with other diuretics (mainly low-dose thiazide diuretics) was not associated with increased mortality.

There are no established pathophysiological mechanisms to explain this observation. Nevertheless, special caution should be exercised when prescribing the drug in such cases. The risk/benefit ratio should be carefully evaluated before prescribing. No increase in mortality has been found in patients taking other diuretics concomitantly with risperidone. Regardless of treatment, dehydration is a common risk factor for mortality and should be closely monitored in elderly patients with dementia.

In elderly patients with dementia, increased cerebrovascular side effects (acute and transient cerebrovascular events), including fatalities in patients (mean age 85 years, range 73-97 years), have been observed with risperidone compared with placebo.

Cardiovascular effects.

In placebo-controlled clinical trials, patients with dementia taking certain atypical antipsychotics had an approximately 3-fold increased risk of cerebrovascular side effects. Combined data from 6 placebo-controlled studies including mostly elderly patients with dementia (age over 65 years) demonstrate that cerebrovascular side effects (serious and non-serious) occurred in 3.3% (33/1009) of patients taking risperidone and in 1.2% (8/712) of patients taking placebo. The risk ratio was 2.96 (1.34, 7.50) with a 95% confidence interval. The mechanism of increased risk is unknown. Increased risk has not been ruled out for other antipsychotics or for other patient populations. Risolept® 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 Rispolettes® in elderly patients with dementia, taking into account precursors to stroke risk individually in each patient. Patients and caregivers should be cautioned to immediately report signs and symptoms of cardiovascular events: such as sudden weakness or immobility/sensitivity in the face, legs, arms, as well as speech difficulties and vision problems. All treatment options, including discontinuation of risperidone, should be considered.
Risolept® may only be used for short-term treatment of persistent aggression in patients with moderate to severe dementia due to Alzheimer’s disease, as an adjunct to non-pharmacological interventions, when they are ineffective or of limited effectiveness, and when there is risk of patient harm to self or others.

The condition of patients and the need for continuation of therapy with risperidone should be continually evaluated.

Orthostatic hypotension.

Risperidone has alpha-blocking activity, and therefore may cause orthostatic hypotension in some patients, especially during initial dose adjustment. Clinically significant hypotension was observed in the post-marketing period when concomitant use with antihypertensive drugs. Risolept® should be used with caution in patients with known cardiovascular diseases (e.g., 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 reducing the dose in case of hypotension.

Late dyskinesia and extrapyramidal disorders.

The drugs with dopamine receptor antagonist properties may cause tardive dyskinesia, which is characterized by rhythmic involuntary movements, predominantly 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 presents with objective or subjective symptoms suggestive of tardive dyskinesia, all antipsychotic medications, including Rispolettes®, an oral solution, should be considered for withdrawal.

Malignant neuroleptic syndrome (MNS).

The antipsychotics, including risperidone, may cause malignant neuroleptic syndrome (MNS), which is characterized by hyperthermia, muscle rigidity, instability of autonomic nervous system function, depressed consciousness, and increased serum creatine phosphokinase concentrations. Myoglobinuria (rhabdomyolysis) and acute renal failure may also occur in patients with MNS. If a patient has objective or subjective symptoms of MNS it is necessary to immediately discontinue all antipsychotic drugs, including Risolept®.

Parkinson’s disease and dementia with Levi’s corpuscles.

Prescribing antipsychotic medications, including Rispolettes®, to patients with Parkinson’s disease or dementia with Levi’s corpuscles should be done with caution because both groups of patients have an increased risk of neuroleptic malignant syndrome and increased sensitivity to antipsychotic drugs (including blunting of pain sensitivity, confusion, postural instability with frequent falls and extrapyramidal symptoms). Risperidone may worsen the course of Parkinson’s disease.

Hyperglycemia and diabetes mellitus.

Hyperglycemia, diabetes mellitus, and exacerbation of preexisting diabetes mellitus have been observed during treatment with Rispolept®. It is likely that prior treatment weight gain is also a predisposing factor. Ketoacidosis may occur very rarely and diabetic coma is rare. All patients should be clinically monitored for symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia, and weakness).

In patients with diabetes mellitus, regular monitoring for worsening glucose control should be performed.

The increase in body weight.

A significant increase in body weight has been observed during treatment with Rispolettes®. Patients’ body weight should be monitored.

Hyperprolactinemia.

Based on the results of studies on tissue cultures, it has been suggested that growth of breast tumor cells may be stimulated by prolactin. Although clinical and epidemiologic studies have not shown a clear association of hyperprolactinemia with administration of antipsychotic medications, caution should be exercised when prescribing risperidone to patients with a severe medical history. Rispolept® should be used with caution in patients with existing hyperprolactinemia and in patients with possible prolactin-dependent tumors.

Longening of the QT interval.

Longening of the QT interval has very rarely been observed in the post-marketing follow-up period. As with other antipsychotics, caution should be exercised when prescribing Rispolettes® to patients with known cardiovascular disease, a family history of QT interval prolongation, bradycardia, electrolyte balance disorders (hypokalemia, hypomagnesemia), as this may increase the risk of arrhythmogenic effects; and when concomitant use with QT interval prolonging agents.

Convulsions.

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

Priapism.

Priorism can occur when taking risperidone because of its alpha-adrenoblocking effects.

The regulation of body temperature.

The undesirable effect attributed to antipsychotic drugs is impairment of the body’s ability to regulate temperature. Caution should be exercised when prescribing Rispolettes® to patients with conditions that may contribute to an increase in internal body temperature, which include intense physical exertion, dehydration of the body, exposure to high external temperatures or concomitant use of drugs with anticholinergic activity.

Venous thromboembolism.

In cases of venous thromboembolism have been reported with the use of antipsychotic drugs. Because patients taking antipsychotic medications are often at risk for venous thromboembolism, all possible risk factors should be identified before and during treatment with Rispolettes® and preventive measures should be taken.

Children and adolescents.

Before prescribing Rispolettes® to children or adolescents with mental retardation, they should be carefully evaluated for physical or social causes of aggressive behavior, such as pain or inadequate demands of the social environment.

The sedative effects of risperidone should be closely monitored in this population because of possible effects on learning ability. Changing the timing of risperidone administration may improve control of the effects of sedation on attention in adolescents and children.

The use of risperidone has been associated with mean increases in body weight and BMI. Growth changes in long-term studies were within expected age norms. The effects of long-term risperidone administration on sexual development and growth have not been fully investigated.
Due to the possible effects of prolonged hyperprolactinemia on growth and sexual development in children and adolescents, regular clinical evaluation of hormonal status, including measurement of height, weight, observation of sexual development, menstrual cycle and other possible prolactin-dependent effects should be performed regularly.

The presence of extrapyramidal symptoms and other movement disorders should be checked regularly during treatment with risperidone.

Impact on the ability to drive and operate vehicles

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

Contraindications

• individual hypersensitivity to risperidone or any other ingredient of this drug;
• phenylketonuria.

With caution

• cardiovascular disease (chronic heart failure, myocardial infarction, cardiac conduction disorders);
• disorders of cerebral circulation;
• Parkinson’s disease;
• convulsions (including in anamnesis);
• severe renal or hepatic insufficiency (see
• painful renal or hepatic impairment (see chapter Dosage and administration)
• painful drug abuse or drug dependence
• conditions predisposing to pirouette tachycardia (bradycardia, electrolyte imbalance, concomitant use of QT prolonging drugs)
• Risk factors for venous thromboembolism;
• Diffuse Levy disease;
• Elderly patients with cerebrovascular dementia;
• Pregnancy.

.

Side effects

The most frequently observed side effects (frequency of occurrence ≥10%) were: parkinsonism, headache and insomnia.
Side effects of Rispolettes® in therapeutic doses are given with frequency and organ system distributions. The frequency of side effects was classified as follows: very frequent (≥1/10 cases), frequent (≥1/100 and In each frequency group, side effects are presented in decreasing order of importance.

Disorders of laboratory and instrumental parameters:
frequent – increase in prolactin1 level, increase in body weight;
infrequent – prolongation of QT interval on electrocardiogram, ECG deviations, increase in transaminases, decrease in blood leukocyte count, increase in body temperature, increase in blood eosinophil count, decrease in hemoglobin level, increase in creatine phosphokinase level, increase in cholesterol concentration;
rarely – decrease of body temperature, increase of triglyceride concentration.

Cardiovascular system disorders:
often – tachycardia, arterial hypertension;
infrequently – atrioventricular block, Gis bundle block, atrial fibrillation, palpitation, cardiac conduction disorders;
rarely – sinus bradycardia, pulmonary embolism, deep vein thrombosis.

Hematological disorders and disorders of lymphatic system:
infrequent – anemia, thrombocytopenia;
rare – granulocytopenia, agranulocytosis.

Nervous system disorders:
very frequent – parkinsonism2, headache, somnolence, sedation;
frequent – akathisia2, dizziness2, tremor2, dystonia2, lethargy, dyskinesia2;
infrequent – no response to stimuli, loss of consciousness, fainting, impaired consciousness, stroke, transient ischemic attack, dysarthria, attention disorder, hypersomnia, postural dizziness, balance disorder, tardive dyskinesia, speech disorder, coordination disorder, hypoesthesia, taste disorders, distorted taste, convulsions, cerebral ischemia, movement disorders;
rarely – malignant neuroleptic syndrome, diabetic coma, cerebrovascular disorders, head tremor.

Ophthalmologic disorders:
often – blurred vision, conjunctivitis;
infrequent – red eyes, visual disturbances, ocular discharge, swelling of the area around the eyes, dry eyes, increased lacrimation, photophobia;
rarely – decreased visual acuity, involuntary rotation of the eyeballs, glaucoma, intraoperative flabby iris syndrome.

Ear and labyrinth:
infrequent – ear pain, tinnitus.

Respiratory, thoracic and mediastinal disorders:
often – shortness of breath, nasal bleeding, cough, nasal congestion, pain in the larynx and pharynx;
infrequently – wheezing, aspiration pneumonia, lung congestion, breathing disorders, moist wheezing, airway obstruction, dysphonia;
rarely – sleep apnea syndrome, hyperventilation.

Gastrointestinal tract disorders:
often – vomiting, diarrhea, constipation, nausea, abdominal pain, dyspepsia, dry mouth, stomach discomfort, hypersalivation;
infrequently – dysphagia, gastritis, fecal incontinence, fecaloma, gastroenteritis, flatulence;
rarely – bowel obstruction, pancreatitis, lip edema, heylitis.

With kidneys and urinary tract:
often – enuresis;
infrequently – urinary retention, dysuria, urinary incontinence, pollakiuria.

Skin and subcutaneous tissue disorders:
often – rash, erythema;
infrequently – skin lesions, skin disorders, itching, acne, acne, changes in skin color, alopecia, seborrheic dermatitis, dry skin, hyperkeratosis;
rarely – dandruff;
very rarely – Quincke’s edema.

With the musculoskeletal system and connective tissue:
often – arthralgia, back pain, limb pain;
infrequent – muscle weakness, myalgia, neck pain, swollen joints, bad posture, stiffness in the joints, muscle chest pain;
rarely – rhabdomyolysis.

Endocrine system disorders:
rarely – disruption of antidiuretic hormone production.

Metabolic and nutritional disorders:
often – increased appetite, decreased appetite;
infrequently – diabetes3, anorexia, polydipsia, hyperglycemia;
rarely – hypoglycemia, water intoxication;
very rarely – diabetic ketoacidosis.

Infections:
often – pneumonia, influenza, bronchitis, upper respiratory tract infections, urinary tract infections, sinusitis, ear infections;
infrequent – viral infections, tonsillitis, inflammation of subcutaneous fatty tissue, otitis media, eye infections, localized infections, acarodermatitis, respiratory tract infections, cystitis, onychomycosis;
rarely – chronic otitis media.

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

General disorders and phenomena due to the route of administration of the drug:
often – pyrexia, fatigue, peripheral edema, generalized edema, asthenia, chest pain;
infrequently – facial edema, gait disturbance, malaise, slowness, flu-like condition, thirst, chest discomfort, chills;
rarely – hypothermia, withdrawal syndrome, coldness of extremities.

The immune system:
infrequent hypersensitivity;
rarely – drug hypersensitivity, anaphylactic reaction.

Hepatobiliary disorders:
rarely – jaundice.

Reproductive system and mammary gland disorders:
infrequent – amenorrhea, sexual dysfunction, erectile dysfunction, ejaculation disorders, galactorrhea, gynecomastia, menstrual disorders, vaginal discharge;
rare – priapism.

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

Psychiatric disorders:
very often – insomnia;
often – anxiety, 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, salivation, cogwheel-like rigidity, bradykinesia, hypokinesia, mask-like face, muscle tightness, akinesia, neck muscle 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, hypertonia, torticollis, involuntary muscle contractions, muscle contractures, blepharospasm, eyeball movements, tongue paralysis, facial spasm, laryngospasm, myotonia, opisthotonus, oropharyngeal spasm, pleurotonus, tongue spasm and trismus. Tremors include tremor and parkinsonian resting tremor. It should also be noted that there is a broader range of symptoms that are not always of extrapyramidal origin.

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

The following are additional side effects observed in clinical trials of the prolonged injectable form of risperidone, Rispolette Consta®, but not seen with oral dosage forms of risperidone.

This list does not include adverse effects associated with the formulation or injectable route of administration of the drug:

Disorders of laboratory parameters: decrease in body weight, increase in gamma-glutamyltransferase levels, increase in liver enzymes.

• Cardiovascular system: bradycardia.
• Blood and lymphatic system: neutropenia.
• Nervous system: paresthesia, convulsions.
• Ocular system: blepharospasm, retinal artery occlusion.
• Ear and labyrinth: vertigo.
• Gastrointestinal tract: toothache, tongue spasm.
• Skin and subcutaneous tissue: eczema.
• Musculoskeletal and connective tissue: pain in the buttocks.
• Infections: lower respiratory tract infections, infections, gastroenteritis, subcutaneous abscess.
• Injuries and poisonings: fall.
• Vascular disorders: arterial hypertension.
• General disorders and phenomena due to the route of administration of the drug: pain.

Mental disorders: depression.

Class effects

As with other antipsychotic drugs, very rare cases of QT tooth prolongation have been noted in the post-marketing follow-up period. Other cardiovascular class effects observed with antipsychotic drugs that increase the QT tooth

The other class effects observed with antipsychotic drugs that increase the QT tooth include: ventricular arrhythmias, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac arrest, and bidirectional ventricular tachycardia.

Venous thromboembolism

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

Body 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 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 group taking Risoilept® (2.5%) and the group taking placebo (2.4%), and slightly higher in the active control group (3.5%).

In children with behavioral disorders in long-term clinical trials, body weight increased by an average of 7.3 kg after 12 months of therapy. The expected weight gain in children 5-12 years of age with normal development is 3-5 kg per year. From 12-16 years of age, the value of weight gain should be 3-5 kg per year for girls and about 5 kg per year for boys.

Further information on special patient populations

The side effects that have been 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 events were observed in elderly patients with dementia with an incidence of ≥5% and at least 2-fold that in other patient populations: urinary tract infections, peripheral edema, lethargy, and cough.

Children

The following adverse events were reported in children (5 to 17 years of age) with an incidence of ? 5% and at least 2 times the frequency in other patient populations in clinical trials: drowsiness/sedation, fatigue, headache, increased appetite, vomiting, upper respiratory infections, nasal congestion, abdominal pain, dizziness, cough, pyrexia, tremor, diarrhea, enuresis.

Overdose

Symptoms

In general, the observed symptoms of overdose were the already known pharmacological effects of risperidone in an enhanced form: drowsiness, sedation, tachycardia, arterial hypotension, extrapyramidal symptoms. QT interval prolongation and seizures have been observed. Bidirectional ventricular tachycardia has been observed in coadministration of an increased dose of risperidone and paroxetine. In cases of acute overdose, the possibility of overdose from taking more than one drug should be considered.

Treatment.

A clear airway should be achieved and maintained to ensure an adequate supply of oxygen and ventilation. Gastric lavage (after intubation if unconscious) and activated charcoal, along with a laxative, should be given only if the drug was taken no more than one hour ago. ECG monitoring should be started immediately to detect possible arrhythmias.

There is no specific antidote, appropriate symptomatic therapy should be given. Arterial 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. Continuous medical observation and monitoring should be continued until symptoms of intoxication disappear.

Pregnancy use

Pregnancy

No comprehensive studies on the use of risperidone in pregnant women have been conducted. According to post-marketing observations, when risperidone was used during the last trimester of pregnancy, reversible extrapyramidal symptoms occurred in the newborn, so newborns should be closely monitored. In animal studies, risperidone had no teratogenic effects; however, other reproductive toxicities have been observed. The potential risk in humans is unknown. Risolept® may be used during pregnancy only if the expected benefits of using the drug for the pregnant woman outweigh the potential risk to the fetus. If it is necessary to discontinue the drug during pregnancy, the drug should be withdrawn gradually.

Lactation

In studies in animals, risperidone and 9-hydroxyrisperidone have penetrated into breast milk. Risperidone and 9-hydroxyrisperidone have also been shown to penetrate into breast milk in humans in small amounts. There are no data on adverse effects in breastfed infants. Therefore, breastfeeding should be considered in light of the possible risk to the baby.

Breastfeeding should be considered.

Similarities

Risolept Consta, Torendo Ku-tab, Risperidone