Risperidone-SZ, 4 mg 30 pcs

Antipsychotic agent (neuroleptic)

ATX code: [N05AX08]

Pharmacodynamics

Risperidone is an antipsychotic agent, a benzisoxazole derivative, also has sedative, antiemetic and hypothermic effects.

Risperidone is a selective monoaminergic antagonist and has high affinity for serotonergic 5-HT2 and dopaminergic B2 receptors. Risperidone also binds to a,-adrenergic receptors and, somewhat weaker, to Hg receptors and a2-adrenergic receptors. Risperidone has no tropism to cholinergic receptors. Antipsychotic action is caused by blockade of 02-dopa-minergic receptors of mesolimbic and mesocortical system.

Risperidone reduces productive symptomatology of schizophrenia (delirium, hallucinations), aggressiveness, automatism, and induces catalepsy to a lesser extent than typical neuroleptics. Balanced central antagonism to serotonin and dopamine may reduce the propensity for extrapyramidal side effects and extend the therapeutic effects of the drug to include negative and affective symptoms of schizophrenia.

Clinical Data Schizophrenia

The efficacy of risperidone in the short-term treatment of schizophrenia has been demonstrated in four studies of 4 to 8 weeks in which 2500 patients meeting DSM-IV criteria for schizophrenia were included. In the 6-week placebo-controlled study, when titrated to a dose of 10 mg/d twice daily, risperidone outperformed placebo on the Brief Psychiatric Rating Scale (BPRS).

In a 6-week placebo-controlled study using risperidone at four fixed doses (2, 6, 10, and 16 mg/day, twice daily), group 4 risperidone was more effective than placebo on the positive and negative syndrome assessment scale (PANSS). In an 8-week comparison study of five fixed-dose risperidone (1,4,8,12, and 16 mg/day, 2 times daily), risperidone in the 4,8, and 16 mg/day groups was more effective than risperidone 1 mg/day on the PANSS scale. In a 4-week placebo-controlled comparative study of two fixed-dose risperidone (4 and 8 mg/d, once daily), risperidone in both groups was more effective than placebo on several PANSS scale items.

Manic episodes in bipolar disorder

The efficacy of risperidone in the monotherapy of acute manic episodes in bipolar disorder type I has been demonstrated in three double-blind, placebo-controlled studies involving approximately 820 patients with bipolar disorder

The DSM-IV Scale Type 1. In these three studies, risperidone at doses of 1-6 mg/day (a starting dose of 3 mg in two studies and 2 mg in one study) was statistically superior to placebo for the primary endpoint, that is, the change in Yang Mania Rating Scale (YMRS) score after 3 weeks compared to baseline. The results for the secondary efficacy endpoints were generally consistent with those for the primary endpoint. The percentage of patients with a reduction of > 50% of the YMRS score after 3 weeks compared to baseline was significantly higher for risperidone than in the placebo group.

The efficacy of risperidone in combination with mood regulators in treating mania has been demonstrated in two 3-week double-blind studies on approximately 300 patients meeting DSM-IV criteria for bipolar disorder type 1. In the 3-week study, risperidone at doses ranging from 1 to 6 mg/day, the starting dose

2 mg/day, in combination with lithium or valproate was more effective than lithium or valproate only at the end of the study on the primary criterion set, that is, on the change in the YMRS score sum compared with baseline at week 3.

Long-term aggression in dementia

The effectiveness of risperidone in treating psycho-behavioral symptoms of dementia, including behavioral problems such as aggression, agitation, psychosis, activity and affective disorders has been demonstrated in three double-blind, placebo-controlled studies on 1,150 patients with moderate to severe dementia. One study was conducted at fixed doses of 0.5,1 and 2 mg/day. Two studies examined unfixed doses, including groups with risperidone doses of 0.5 to 4 mg/d and 0.5 to 2 mg/d, respectively. Risperidone has shown clinically and statistically high efficacy in treating aggression and, to a lesser extent, agitation and psychosis in older patients with dementia (as measured by the Behavioral Abnormality in Alzheimer’s Disease scale (BEHAVE-AD) and the Cogen Mansfield Questionnaire for Agitation (CMAI)).

The efficacy of risperidone in the short-term treatment of aggressive behavior has been demonstrated in placebo-controlled studies in approximately 240 patients aged 5 to 12 years with DSM-IV disruptive behavior disorders and intellectual functioning below average or with mild mental retardation or moderate learning disabilities. In both studies, risperidone at doses of 0.02 to 0.06 mg/kg/day was significantly more effective than placebo on the prespecified primary efficacy endpoint.

Pharmacokinetics

Risperidone is completely absorbed after oral administration, reaching maximum plasma concentrations in 1-2 hours. The absolute oral bioavailability of risperidone is 70%.

Food has no effect on the absorption of risperidone, therefore it can be prescribed regardless of meals.

Risperidone is rapidly distributed in the body. The volume of distribution is 1-2 l/kg. In plasma, risperidone is bound to albumin and alpha-acid glycoprotein. Risperidone is 90% bound to plasma proteins, 9-hydroxysperidone – 77%. The equilibrium concentration of risperidone in the body in most patients is reached within 1 day. The equilibrium concentration of 9-hydroxysperidone is reached in 4-5 days. Plasma concentrations of risperidone are proportional to the dose of the drug (within therapeutic doses).

Risperidone is metabolized by the CYP2D6 isoenzyme to 9-hydroxy-risperidone, which has similar pharmacological effects to risperidone. Risperidone and 9-hydroxyrisperidone constitute the active antipsychotic fraction. Metabolism depends on the genetic polymorphism of the CYP2D6 isoenzyme.

The other route of metabolism of risperidone is N-dealkylation.

After oral administration in patients with psychosis, risperidone is excreted with a half-life (T1/2) of about 3 hours. The T1/2 of 9-hydroxysperidone and the active antipsychotic fraction is 24 hours.

After a week of taking the drug, 70% of the dose is excreted in the urine, 14% in the feces. In the urine, risperidone plus 9-hydroxyrisperidone make up 3545% of the dose. The remaining amount consists of inactive metabolites.

Particular patient groups

A single-dose study of the drug found higher plasma concentrations and slower excretion in the elderly and in patients with renal impairment. Plasma concentrations of risperidone in patients with hepatic impairment were normal.

The pharmacokinetics of risperidone and 9-hydroxirisperidone in pediatric patients are similar to those in adult patients.

There is no effect of sex, ethnicity or smoking on the pharmacokinetics of risperidone.

Indications

The treatment of schizophrenia.

The treatment of manic episodes in the structure of moderate to severe bipolar disorder.

The short-term (up to 6 weeks) treatment of persistent aggression in patients with moderate to severe dementia due to Alzheimer’s disease – when non-pharmacological methods of correction are ineffective and threatening to cause harm to the patient or others. Short-term (up to 6 weeks) symptomatic treatment of persistent aggression in behavioral disorders in children 5-16 years old with moderate to severe mental retardation, due to the severity of which pharmacological methods of correction are required (as part of complex therapy).

Active ingredient

Composition

Excipients (core): lactose monohydrate (milk sugar) – 114.0 mg; microcrystalline cellulose – 19.7 mg; corn starch pregelatinized (Starch 1500) – 3.0 mg; magnesium stearate – 1.0 mg; potato starch – 11.0 mg; povidone (polyvinylpyrrolidone medium molecular) – 7.3 mg.

The composition of the shell:

Opadray II, 5 mg (polyvinyl alcohol, partially hydrolyzed, 2.2000 mg; talc, 1.0000 mg; macrogol (polyethylene glycol 3350), 0.6175 mg; titanium dioxide E 171, 0.6545 mg; Soybean lecithin E 322 – 0.1750 mg; quinoline yellow aluminum varnish – 0.1010 mg; indigo carmine aluminum varnish – 0.2520 mg).

How to take, the dosage

Orally, regardless of meals

1. Schizophrenia

Adults. Risperidone may be prescribed once or twice daily.

The initial dose of Risperidone-SZ is 2 mg per day. On the second day, the dose should 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 to 6 mg per day. In some cases, slower dose increases and lower starting and maintenance doses may be warranted.

Doses above 10 mg daily 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 should not be used. Elderly patients. A starting dose of 0.5 mg per dose twice daily is recommended.

The dose can be increased individually at 0.5 mg twice daily to a dose of 1 to 2 mg twice daily.

Children

There is no information about the use of the drug for treatment of schizophrenia in children under 18 years of age.

2 Manic episodes in the structure of moderate to severe bipolar disorder

Adults. The recommended starting dose of the drug is 2 mg per day at 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.

Elderly patients. A starting dose of 0.5 mg per dose twice daily is recommended. If necessary, the dose may be individually increased by 0.5 mg twice daily to a dose of 1 to 2 mg twice daily. Caution should be exercised when prescribing the drug in elderly patients.

Children

There are no data on the use of the drug for the treatment of manic episodes in the structure of moderate to severe bipolar disorder in children under 18 years of age.

3. Discontinuous aggression in patients with moderate to severe dementia due to Alzheimer’s disease

The initial dose of 0.25 mg per dose twice daily is recommended. The dose can be individually increased 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 are indicated to take 1 mg twice a day. Risperidone should not be used longer than 6 weeks in the treatment of persistent aggression in patients with dementia due to moderate to severe Alzheimer’s disease.

4. Persistent aggression in conduct disorder in children 5-16 years old with moderate to severe mental retardation

Patients with a body weight of 50 kg or more – the recommended starting dose of the drug is 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.

Long-term administration of Risperidone-SZ in adolescents should be done under the constant supervision of a physician.

The drug Risperidone-SZ is not recommended for children under 5 years of age because there are no data on such disorders in children under 5 years of age.

Hepatic and renal impairment

Patients with renal impairment have a reduced ability to excrete 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 plasma. The initial and maintenance dose according to the indication should be reduced by a factor of 2, the dose increase in patients with liver and kidney disease should be carried out more slowly.

Interaction

In view of the fact that Risperidone-SZ primarily affects the central nervous system, it should be used with caution with alcohol, opiates, antihistamines and benzodiazepines because of the increased risk of sedation.

Risperidone decreases the effectiveness of levodopa and other dopamine receptor agonists. However, if concomitant use is necessary, especially in terminal Parkinson’s disease, the minimum effective dose of each treatment should be prescribed.

. Caution should be exercised when co-administering Risperidone-SZ with drugs that prolong the QT interval, such as class 1a antiarrhythmic drugs (e.g., quinidine, disopyramide, procainamide), class III antiarrhythmic drugs (e.g., amiodarone, sotalol), tricyclic antidepressants (amitriptyline) tetracyclic antidepressants (maprotiline), some antihistamines, other antipsychotics, some antimalarials (quinine and mefloquine), and some drugs that cause electrolyte disturbances (hypokalemia, hypomagnesemia), bradycardia, or that inhibit hepatic metabolism of risperidone.

Clozapine decreases the clearance of risperidone.

Carbamazepine has been observed to decrease the plasma concentration of the active antipsychotic fraction of risperidone. Similar effects may be observed with other CYP3A4 and P-glycoprotein isoenzyme inducers. The dose of Risperidone-SZ should be adjusted when prescribing and after withdrawal of carbamazepine or other inducers of CYP3A4/P-glycoprotein isoenzyme.

Fluoxetine and paroxetine, CYP2D6 isoenzyme inhibitors, increase the plasma concentration of risperidone, but less so the concentration of the active antipsychotic fraction. The dose of Risperidone-SZ should be adjusted when prescribed and after withdrawal of fluoxetine or paroxetine. Other CYP2D6 isoenzyme inhibitors, such as quinidine, may alter the plasma concentration of risperidone in the same manner.

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

Topiramate moderately decreases the bioavailability of risperidone, but not of the active antipsychotic fraction. This interaction is not considered clinically significant. Phenothiazine derivatives, tricyclic antidepressants and some p-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 CYP3A4 isoenzyme, has no effect on the pharmacokinetics of risperidone and the active antipsychotic fraction. Cholinesterase inhibitors (galantamine and donepezil), have no clinically significant effect on the pharmacokinetics of risperidone and the active antipsychotic fraction.

When Risperidone-SZ is used together with other drugs that are highly bound to plasma proteins, no clinically significant displacement of any drug from the plasma protein fraction is observed.

Hypotensive drugs increase the degree of reduction of blood pressure against risperidone.

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

Eating does not affect the absorption of risperidone.

Special Instructions

Transition from therapy with other antipsychotic drugs. In schizophrenia, at the beginning of treatment with Risperidone-SZ it is recommended to gradually withdraw the previous therapy if it is clinically justified. At the same time, if patients are transferred from depot forms of antipsychotic therapy, it is recommended to start therapy with Risperidone-SZ instead of the next scheduled injection. The need for continuation of current antiparkinsonian drug therapy should be evaluated periodically.

The use in elderly patients with dementia. Elderly patients with dementia have an increased mortality rate when treated with atypical antipsychotics compared with placebo in studies of atypical antipsychotics, including risperidone. For this population, the mortality rate for risperidone 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).

. For older patients with dementia taking oral forms of risperidone, there was an increased mortality in patients taking both 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). No pathophysiological mechanisms have been identified to explain this observation. Nevertheless, special caution should be exercised when prescribing the drug in such cases. 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.

Cerebrovascular disorders

The risk of adverse cerebrovascular reactions is significantly higher in patients with mixed or vascular dementia than in patients with Alzheimer’s dementia. Therefore, it is not recommended to prescribe risperidone to patients with mixed or vascular dementia.

The risks and therapeutic benefits of risperidone in elderly patients with dementia should be evaluated, considering the prognostic risk factors for stroke in the individual patient. The patient and the patient’s environment should be alerted to the need for urgent reporting of signs and symptoms of potential cerebrovascular adverse reactions, particularly sudden weakness or numbness of the face, upper and lower extremities, impaired speech or vision. In this case, all therapeutic options are urgently considered, including discontinuation of risperidone.

In persistent aggression in patients with Alzheimer’s dementia, risperidone is intended only for short-term use as an adjunct to non-pharmacological interventions when they are ineffective or limited in the absence of potential danger to the patient or his environment. Continuous monitoring and evaluation of the patient’s condition is necessary, as well as justification of the need for further treatment.

Orthostatic hypotension. Due to the a-blocking effect of risperidone, orthostatic hypotension may occur, especially during initial dose adjustment. A clinically significant decrease in blood pressure is observed when prescribing risperidone together with antihypertensive drugs. If blood pressure decreases, dose reduction should be considered. In patients with cardiovascular disease, as well as in dehydration, hypovolemia or cerebrovascular disorders, the dose should be increased gradually, according to recommendations.

Leukopenia, neutropenia, agranulocytosis

Leukopenia, neutropenia and agranulocytosis have been reported with antipsychotic agents, including with the use of Risperidone-SZ. Agranulocytosis was very rarely observed during post-marketing observations. In patients with a history of clinically significant decrease in leukocyte counts or drug-dependent leukopenia/neutropenia, a complete blood count during the first months of therapy is recommended; discontinuation of Risperidone-SZ treatment should be considered at the first clinically significant decrease in leukocyte counts in the absence of other possible causes. Patients with clinically significant neutropenia are advised to monitor for fever or symptoms of infection and initiate treatment immediately if such symptoms occur. Patients with severe neutropenia (absolute neutrophil count less than 1 x 109/l) should discontinue Risperidone-SZ until the leukocyte count normalizes.

Venous thromboembolism

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

Late dyskinesia and extrapyramidal disorders

Drugs with dopamine receptor antagonist properties may cause late dyskinesia, which is characterized by rhythmic involuntary movements, predominantly of the tongue and/or facial musculature. There are reports that the occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. Risperidone is less likely to cause extrapyramidal symptoms than classical neuroleptics. If signs and symptoms of tardive dyskinesia occur, discontinuation of all antipsychotic medications should be considered.

Malignant neuroleptic syndrome

. If malignant neuroleptic syndrome develops, characterized by hyperthermia, muscle rigidity, instability of autonomic functions, impaired consciousness and increased creatine phosphokinase activity (myoglobinuria (rhabdomyolysis) and acute renal failure may also be observed) all antipsychotic drugs, including Risperidone-SZ should be withdrawn.

Parkinson’s disease and dementia with Levi’s corpuscles

Prescribing antipsychotic drugs, including Risperidone-SZ, to patients with Parkinson’s disease or dementia with Levi’s corpuscles should be performed with caution, because Both groups of patients have an increased risk of malignant neuroleptic syndrome and increased sensitivity to antipsychotic medications (including blunting of pain sensitivity, confusion, postural instability with frequent falls and extrapyramidal symptoms).

Hyperglycemia and diabetes mellitus

diabetes, (see section “Side effects”),

Hyperprolactinemia

Tissue culture studies have shown that cell growth in breast tumors may be stimulated by prolactin. Risperidone should be used with caution in patients with hyperprolactinemia and in patients with potentially prolactin-dependent tumors.

Body weight gain

A significant increase in body weight has been observed during treatment with Risperidone-SZ. It is necessary to monitor the patients’ body weight during the therapy with Risperidone-SZ. prolongation of QT interval

As for other antipsychotic drugs, caution should be exercised when administering Risperidone-SZ in patients with a history of cardiac arrhythmias, patients with congenital prolongation of the QT interval and when concomitant use with drugs that prolong the QT interval.

Priapism

The drugs with alpha-adrenoblocking effects may cause priapism. In post-marketing studies of Risperidone-SZ, the development of priapism has been reported.

The regulation of body temperature

Antipsychotic medications have been ascribed such undesirable effects as impairment of the body’s ability to regulate body temperature. Caution should be exercised when prescribing Risperidone-SZ to patients with conditions that may contribute to an increase in internal body temperature, which include intense physical activity, dehydration of the body, exposure to high external temperatures or concomitant use of drugs with anticholinergic activity.

The antiemetic effect

The antiemetic effect of risperidone has been identified in preclinical studies. This effect, if produced in humans, may mask the objective and subjective symptoms of overdose of certain drugs, as well as diseases such as intestinal obstruction, Reye’s syndrome and brain tumors.

The seizure threshold

The ability of typical neuroleptics to lower the seizure threshold is known. Risperidone-SZ should be used with caution in patients with epilepsy.

Withdrawal syndrome

A gradual dose reduction is recommended when treatment is discontinued. Withdrawal symptoms: nausea, vomiting, sweating, and insomnia have very rarely been described with abrupt discontinuation of high doses of antipsychotic drugs.

Children and adolescents

The sedative effects of risperidone should be closely monitored and the timing of Risperidone-SZ administration may be altered.

Body weight should be monitored. Regular evaluation of endocrine function, extrapyramidal symptoms, and movement disorders is required.

Contraindications

– individual hypersensitivity to risperidone or any other ingredient of this medication;

Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;

– in the treatment of persistent aggression in conduct disorder in children with moderate to severe mental retardation, childhood under 5 years of age (insufficient experience of use);

In other indications, childhood under 18 years of age.

WARNING

To use with caution for the following conditions:

– diseases of the cardiovascular system (chronic heart failure, myocardial infarction, disorders of cardiac muscle conduction);

– dehydration and hypovolemia;

– cerebral circulatory disorders;

– Parkinson’s disease,

– seizures and epilepsy (including history);

– severe renal or hepatic impairment (see “Dosage and administration”),

– drug abuse or drug dependence (see “Dosage and administration”).

– abuse of or addiction to medicinal products (see section “Dosage and administration”);

– conditions predisposing to the development of pirouette tachycardia (bradycardia, electrolyte imbalance, concomitant use of QT interval prolonging drugs):

– brain tumor, intestinal obstruction, cases of acute drug overdose, Reyes syndrome (the antiemetic effect of risperidone may mask the symptoms of these conditions):

Pregnancy and lactation.

Side effects

The side effects of Risperidone-SZ in therapeutic doses are given with a frequency distribution and systemic organ classes. The frequency of side effects was classified as follows: very frequent (*1/10 cases), frequent (>1/100 and <1/10 cases), infrequent (>1/1000 and <1/100 cases), rare (>1/10000 and <1/1000 cases) and very rare (<1/10000 cases).

InLekii:

very common in elderly patients with dementia – urinary tract infections; frequent – nasopharyngitis, upper respiratory tract infections, bronchitis, sinusitis, urinary tract infections, rhinitis, flu-like illness: In elderly patients with dementia, pneumonia, phlegmon;

infrequently, ear infections, viral infections, tonsillitis, eye infections, localized infections, cystitis, onychomycosis, acrodermatitis, respiratory infections.

Hematological disorders and disorders of the lymphatic system

infrequent – thrombocytopenia, anemia, neutropenia, leukopenia, decreased hematocrit;

rarely – granulocytopenia, agranulocytosis

The immune system:

infrequent – hypersensitivity;

very rare – anaphylactic reactions, anaphylactic shock.

Endocrine system: frequently – hyperprolactinemia;

rarely – disorders of antidiuretic hormone secretion, diabetic coma.

Disorders of metabolism and nutrition:

often – increased appetite, in elderly patients with dementia – decreased appetite; infrequent – polydipsia, anorexia, diabetes mellitus: rarely – hypoglycemia, water intoxication; very rarely – diabetic ketoacidosis.

Mental disorders: very often – insomnia;

often – anxiety, sleep disturbances, nervousness, lethargy, in elderly patients with dementia – confusion;

infrequently – flattening of affect, mania, impaired libido, depression, nightmares; very rarely – anorgasmia.

Nervous system disorders:

very common – parkinsonism (hypersalivation, cogwheel syndrome, akinesia, brakinesia, hypokinesia, skeletal muscle rigidity, mask-like face), drowsiness, headaches, sedation, dizziness;

often – akathisia (incl. restlessness), tremor, dystonia (including muscle spasms, involuntary muscle contractions, muscle contracture, involuntary eyeball movements, tongue paralysis), lethargy, postural vertigo, dyskinesia (including muscle twitching, chorea and choreoathetosis), dysarthria, salivation, attention deficit, gait disturbance, increased sleepiness; in elderly patients with dementia – depressed state, salivation, cerebrovascular disorders; infrequent – lack of response to stimuli, impaired coordination of movements, loss of consciousness, fainting, speech impairment, hypoesthesia, paresthesia, psychomotor hyperactivity, tardive dyskinesia, cerebrovascular disorders;

Rarely, malignant neuroleptic syndrome, extrapyramidal symptoms (tremor, rigidity, hypersalivation, bradykinesia, akathisia, acute dystonia), rhythmic head nodding.

Ophthalmologic disorders:

often – decreased visual acuity, in elderly patients with dementia – conjunctivitis; infrequent – conjunctival hyperemia, involuntary rotation of the eyeballs, crust formation on the edges of the eyelids, dry eyes, increased lacrimation, photophobia, increased intraocular pressure.

Ear and labyrinth disorders:

Infrequent – ear noise, ear pain, vertigo, chronic otitis media.

Cardiovascular system disorders

often – tachycardia, orthostatic hypotension, decreased blood pressure, palpitations, in elderly patients with dementia – transient ischemic attack; infrequent – bradycardia, sinus arrhythmia, atrial fibrillation, atrioventricular block, “flushes” of blood, disorders of cardiac conduction; very rare – deep vein thrombosis, pulmonary embolism, venous thromboembolism. Respiratory, thoracic and mediastinal disorders: Frequent – nasal congestion, shortness of breath, nasal bleeding, sinus congestion, cough, rhinorrhea, pain in the larynx and pharynx, pulmonary congestion, in elderly patients with dementia – cough, rhinorrhea;

infrequent – wheezing, aspiration pneumonia, dysphonia, airway obstruction, wet rales, breathing disorders; rarely – sleep apnea syndrome, hyperventilation.

Gastrointestinal tract disorders:

often – nausea, constipation, dyspepsia, vomiting, diarrhea, salivation, dry mouth, stomach discomfort, abdominal pain, in elderly patients with dementia – dysphagia, fecaloma; infrequent – fecal incontinence, flatulence, gastroenteritis, toothache, tongue edema, heylitis. dysgeusia; very rare – bowel obstruction, pancreatitis.

Hepatobiliary disorders: rarely – jaundice.

Skin and subcutaneous tissue disorders:

often – rash, itching, acne, in elderly patients with dementia – erythema;

infrequently – eczema, dry skin, seborrheic dermatitis, hyperkeratosis, pigmentation disorders

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dermatitis, skin inflammation, skin damage, Quincke’s edema, alopecia;

rarely – dandruff.

Musculoskeletal and connective tissue disorders:

often – musculoskeletal pain, back pain, arthralgia, pain in the extremities, myalgia, pain

in the neck, in elderly patients with dementia – gait disturbances, swollen joints;

infrequent – stiffness in the joints, muscle weakness;

rarely – rhabdomyolysis.

Renal and urinary tract disorders: frequently – urinary incontinence, enuresis, semilakiuria; infrequently – urinary retention, dysuria.

Reproductive system and mammary gland disorders: frequent – absence of ejaculation, galactorrhea;

infrequent – menstrual disorders, amenorrhea, gynecomastia, vaginal discharge, erectile dysfunction, ejaculation disorders, breast enlargement, sexual dysfunction, breast discharge; very rare – priapism.

Impact on the course of pregnancy, postpartum and perinatal conditions: very rare – withdrawal syndrome in newborns.

General disorders:

often – fatigue, asthenia, fever, chest pain, weight gain, slowness, in elderly patients with dementia – peripheral edema, gait disturbance, mild edema;

infrequent – thirst, decreased temperature, malaise, facial edema, chills; rarely – hypothermia, withdrawal syndrome, cold extremities.

Disorders of laboratory and instrumental parameters: frequent – increased heart rate, in elderly patients with dementia – increased body temperature;

infrequent – increased eosinophil count in blood, increased creatine phokinase activity, decreased white blood cell count, increased liver enzyme activity, increased gamma-glutamyltransferase activity, decreased hematocrit, increased transaminase activity, increased blood cholesterol concentration, increased blood triglyceride concentration, granulocytopenia, hyperglycemia, weight loss, prolonged QT interval on electrocardiogram, change on cardiogram. Class effects

In post-marketing studies of risperidone, very rare cases of QT interval prolongation have been reported. In addition, effects such as ventricular arrhythmias, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac arrest, flutter and fibrillation have been reported.

Venous thromboembolism

In cases of venous thromboembolism, including pulmonary embolism, and deep vein thrombosis have been reported with neuroleptics (frequency unknown).

Body weight gain

In a 6- to 8-week placebo-controlled study in adult patients with schizophrenia using risperidone and placebo, a clinically significant increase in body weight of 7% or more was observed in the risperidone group (18%), higher than in the placebo group (9%). In a 3-week placebo-controlled study in adult patients with acute mania, an increase in body weight of 7% or more by the end of the study was adequate in the risperidone group (2.5%) and placebo group (2.4%) and was slightly greater in the control group (3.5%).

In children and adolescents with antisocial manifestations and other behavioral disorders in long-term studies, on average, body weight increased by 7.3 kg after 12 months of treatment. The expected weight gain in healthy children aged 5-12 years is 3 to 5 kg per year. Girls 12-16 years old gain 3 to 5 kg per year and boys about 5 kg per year.

Elderly patients with dementia

Side effects in older patients with dementia in clinical trials were: transient ischemic attack, stroke; urinary tract infections, peripheral edema, drowsiness, cough.

Children

The types of adverse reactions in children are similar to those seen in adult patients. The following adverse reactions have been reported with a frequency of 5% in children (5 to 17 years) and at least twice the frequency seen in adult clinical trials:

Sleepiness, sedation, fatigue, headache, increased appetite, vomiting, upper respiratory infections, stuffy nose, abdominal pain, dizziness, cough, fever, tremor, diarrhea and enuresis.

In long-term treatment with risperidone, the effects on puberty have not been studied.

Overdose

Symptoms: somnolence, sedation, tachycardia, decreased blood pressure, extrapyramidal symptoms. QT interval prolongation and seizures have been observed. Bidirectional ventricular tachycardia has been noted in coadministration of an increased dose of risperidone and paroxetine.

In case of overdose, the possibility of overdose from taking more than one drug should be considered.

Treatment. A clear airway should be established and maintained to allow adequate oxygen intake and ventilation, gastric lavage (after intubation if unconscious), and activated charcoal given along with a laxative. ECG monitoring should be initiated immediately to detect possible arrhythmias.

There is no specific antidote, and appropriate symptomatic therapy should be given. Decreased blood pressure and collapse should be treated with intravenous fluid infusions and/or sympathomimetic drugs. If acute extrapyramidal symptoms develop, m-cholinoblockers (e.g., trihexyphenidyl) should be prescribed. Continuous medical observation and monitoring should be continued until the symptoms of intoxication disappear.

Pregnancy use

In animal experiments, risperidone had no direct toxic effects on the reproductive system, but caused some indirect effects mediated through prolactin and the CNS. In none of the studies risperidone had teratogenic effects, If a woman took antipsychotic drugs (including Risperidone-SZ) in the third trimester of pregnancy, the newborn has a risk of extrapyramidal disorders and/or withdrawal syndrome of varying severity. These symptoms may include agitation, hypertension, hypotension, tremor, somnolence, respiratory disturbances, and feeding disorders.

The drug Risperidone-SZ may be used during pregnancy only when the potential benefit to the woman outweighs the possible risk to the fetus.

Because risperidone and 9-hydroxyrisperidone penetrate into breast milk, women using Risperidone-SZ should not breastfeed.

Similarities