Ridonal - instructions for use, doses, side effects, contraindications

Tablets 1 mg: silicon dioxide colloidal, anhydrous 0.30 mg; croscarmellose sodium 1.60 mg; lactose monohydrate 40.00 mg; magnesium stearate 0.80 mg; cellulose microcrystalline 41.30 mg.

Shell: giprolose 1.20 mg; titanium dioxide (E 171) 0.80 mg.

Tablets 2 mg: silicon dioxide colloidal, anhydrous 1.00 mg; croscarmellose sodium 4,0 mg; lactose monohydrate 100.00 mg; magnesium stearate 2.00 mg; cellulose microcrystalline 91.00 mg.

Sheath: giprolose 2,476 mg; titanium dioxide (E 171) 2.419 mg; dye sunset sunset yellow (E 110) 0.105 mg.

Tablets 3 mg: silicon dioxide colloidal, anhydrous 1.00 mg; croscarmellose sodium 4,0 mg; lactose monohydrate 100.00 mg; magnesium stearate 2.00 mg; cellulose microcrystalline 89.80 mg; dye quinoline yellow (E 104) 0.200 mg.

Sheath: giprolose 2,476 mg, titanium dioxide (E171) 2.419 mg, dye quinoline yellow (E104) 0.105 mg.

Description:

Tablets 1 mg: round, biconcave tablets, covered with a film shell of white color. The core is white.

Tablets 2 mg: round, biconcave tablets, covered with a film coating of a yellowish-orange color, with a risk on one side. The core is white.

Tablets 3 mg: round, biconcave tablets, covered with a film coat of yellow color, with a risk on one side. The core is yellow.

Pharmacotherapeutic group:antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.X Other antipsychotics

N.05.A.X.08 Risperidone

Pharmacodynamics:

Risperidone is an antipsychotic agent, it also has a sedative, antiemetic and hypothermic effect. Risperidone - selective antagonist of 5-HT₂-serotonin and D₂-dophamine receptors, is also associated with α₁-adrenoceptors with slightly less affinity with H₁-histamine and α₂-adrenoceptors. Has no affinity for cholinergic receptors.

The antipsychotic effect is due to the blockade of dopamine D₂receptors of the mesolimbic and mesocortical system.

Sedative action is due to blockade of adrenoreceptors of the reticular formation of the brainstem; antiemetic effect - blockade of dopamine D₂receptors of the trigger zone of the vomiting center; hypothermic action - blockade of dopamine receptors of the hypothalamus.

Reduces productive symptoms in schizophrenia (delirium, hallucinations), automatism. It causes less motor and depressive disorders and less potentiates catalepsy than classical neuroleptics.

Thanks to the simultaneous blockade of 5-HT₂-serotonin and D₂dopamine receptors reduces the likelihood of developing extrapyramidal disorders and increases the therapeutic breadth of the drug with respect to the effect on the negative and productive symptoms of schizophrenia.

Risperidone can cause a dose-dependent increase in prolactin concentration in the plasma.

Pharmacokinetics:

Suction. Risperidone completely absorbed after ingestion, the maximum concentration in the blood plasma is achieved after 1-2 hours. Absorption is not dependent on food intake, so the drug can be taken regardless of food intake.

Distribution. Risperidone is rapidly distributed in the body. The volume of distribution is 1-2 l / kg. In plasma, 88% of risperidone binds to plasma proteins (albumins and alpha₁glycoproteins), 77% of this amount is represented by its main metabolite 9-hydroxyrisperidone. In most patients, the equilibrium concentration of risperidone is reached one day after the start of treatment. The equilibrium state of 9-hydroxyrisperidone in most cases is achieved after 4-5 days.

Metabolism. Risperidone metabolized in the liver with the participation of isoenzyme CYP2D6 with the formation of 9-hydroxyrisperidone, which has a pharmacological action analogous to risperidone. Risperidone and 9-hydroxyrisperidone constitute the active antipsychotic fraction. Isozyme CYP2D6 has genetic polymorphism. High isoenzyme activity CYP2D6 quickly turns risperidone in 9-hydroxyrisperidone, and the low activity of the isoenzyme CYP2D6 makes this process slower. Although high isoenzyme activity CYP2D6 provides low concentrations of risperidone and higher concentrations of 9-hydroxyrisperidone than low isoenzyme activity CYP2D6, the general pharmacokinetics of risperidone and 9-hydroxyrisperidone (i.e., the active antipsychotic fraction) after a single and repeated administration is similar to high and low isoenzyme activity CYP2D6.

The concentration of risperidone in the blood plasma is proportional to the dose of the drug (within therapeutic doses) and has a wide therapeutic range.

Another, less significant, way of metabolizing risperidone is N-dealkylation.

Excretion. When administered orally risperidone is output with a half-life (T_1/2) for about 3 hours. It was established that the half-life of 9-hydroxyrisperidone and the active antipsychotic fraction is 24 hours. A week after the application of the preparation 70% dose is excreted by the kidneys, 14% - with bile, through the intestine. In the urine risperidone plus 9-hydroxyrisperidone constitute 35-45% of the dose. The rest is made up of inactive metabolites.

A study with a single application of risperidone showed that in the elderly and patients with renal insufficiency a higher concentration of the drug in the blood plasma is reached and its elimination is slowed down.

In patients with severe renal failure, the total clearance of risperidone and its metabolites is reduced by 60% compared to healthy volunteers.

Concentration of risperidone in blood plasma in patients with liver failure does not differ from that of volunteers.

Sex, race and tobacco. Population pharmacokinetic analysis did not reveal a distinct effect of sex, race or tobacco on the pharmacokinetics of risperidone and its active antipsychotic fraction. About 6-8% of Europeans have a low isoenzyme activity CYP2D6.

Indications:

- Treatment of schizophrenia;

- Treatment of manic episodes of moderate to severe severity due to bipolar disorder;

- Short-term (up to 6 weeks) treatment of persistent aggression in patients with dementia due to moderate to severe Alzheimer's disease,with ineffectiveness of non-pharmacological methods of treatment and in the presence of the risk of causing harm to the patient himself or third parties;

- Short-term (up to 6 weeks) symptomatic treatment of persistent aggression in behavioral disorders in children aged 5 years with mental retardation diagnosed according to DSM-IV, in which due to the severity of aggression or other destructive behavior, drug treatment is required. Pharmacotherapy should be part of a wider treatment program, including psychological and educational activities. Risperidone should be appointed by a specialist in the field of pediatric neurology and child psychiatry or a physician familiar with the treatment of behavioral disorders in children and adolescents.

Contraindications:

If you have any of the listed diseases, before taking the drug, be sure to consult a doctor:

- hypersensitivity to the components of the drug;

- the period of breastfeeding;

- treatment of schizophrenia in children under the age of 18;

- mania in bipolar affective disorders in children under the age of 18;

- with behavioral disorder in children under the age of 5 with mental retardation;

- deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome.

Carefully:

If you have any of the listed diseases, before taking the drug, be sure to consult a doctor:

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

- dehydration and hypovolemia;

- disorders of cerebral circulation;

- Parkinson's disease;

- convulsions (including in the anamnesis);

- severe renal and / or hepatic insufficiency (see recommendations for dosing);

- drug abuse or drug dependence (see recommendations for dosing);

- conditions predisposing to the development of tachycardia such as "pirouette" (bradycardia, electrolyte imbalance, concomitant medication prolonging the interval QT);

- advanced age with dementia;

- application in combination with furosemide;

- thrombophlebitis;

- hyperglycemia;

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

- pregnancy and lactation.

Pregnancy and lactation:

The safety of the use of risperidone in pregnant women has not been studied. The use of the drug Ridonal® during pregnancy is possible only if the expected benefit for the mother exceeds the potential risk to the fetus.

With the use of risperidone drugs in the third trimester of pregnancy, there is a risk of development in newborns of extrapyramidal disorders and (or) withdrawal syndrome. Infants may exhibit agitation, anxiety, hypertension, hypotension, tremor, muscle tone disorder, drowsiness, respiratory depression, respiratory distress syndrome, eating disorders. These symptoms are usually reversible, but sometimes require prolonged therapy. Continuous monitoring of the state of newborns is necessary.

Because the risperidone and 9-hydroxyrisperidone penetrate into breast milk, women using Risdonal® should not breast-feed.

Dosing and Administration:

Inside.

Schizophrenia

Adults. Ridonal® can be given once or twice a day.

The initial dose is 2 mg per day. On the second day, the dose should be increased to 4 mg per day. From this moment 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 increase and lower initial and maintenance doses may be justified.

Doses above 10 mg per day did not show a higher efficacy compared with smaller doses and may cause extrapyramidal symptoms. Due to the fact that safety of doses above 16 mg per day has not been studied, doses above this level can not be used.

For the treatment of Risdonal ®, benzodiazepines can be added if an additional sedative effect is required.

Children. The use of risperidone for the treatment of schizophrenia in children younger than 18 years is not recommended because of the lack of sufficient safety data.

Elderly patients. Recommended initial dose of 0.5 mg * per reception twice a day. The dose can be individually increased from 0.5 mg * twice a day to 1-2 mg twice a day.

Behavioral disorders in patients with dementia

The initial dose of 0.25 mg * per dose is recommended twice a day.If necessary, the dose can be individually increased by 0.25 mg * 2 times a day, not more often than every other day. For most patients, the optimal dose is 0.5 mg * twice daily. However, some patients receive 1 mg twice daily.

When the optimal dose is reached, it may be recommended to take the drug at a dose of 1 mg once a day.

Mania in bipolar disorders

Adults. The recommended initial dose of the drug is 2 mg once a day at a time. If necessary, this dose can be increased by 2 mg per day, not more often than every other day. For most patients, the optimal dose is 2-6 mg per day.

Children. Treatment of mania in bipolar disorders in children under 18 years of risperidone is not recommended, since there is no safety data.

Behavioral disorders in patients with mental retardation or with dominance in the clinical picture of destructive tendencies

Patients with a body weight of 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, not more often than every other day. For most patients, the optimal dose is a dose of 1 mg per day.However, for some patients it is preferable to take 0.5 mg * per day, while some require an increase in the dose 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, not more often than every other day. For most patients, the optimal dose is 0.5 mg * per day. However, for some patients it is preferable to take 0.25 mg per day, while some require an increase in the dose to 0.75 mg per day. Long-term use of Risdonal® in adolescents should be performed under the constant supervision of a physician.

Application in children under 5 years of age Not recommended.

It is recommended that the initial dose be reduced twofold, as well as subsequent dose increases in elderly patients and in patients with renal or hepatic insufficiency *.

Patients with liver and kidney disease

In comparison with patients with normal renal function, in patients with renal failure, the ability to excrete the active antipsychotic fraction of the drug has been reduced. In patients with weakened liver function, plasma concentrations of the free fraction of risperidone increase.

Regardless of the indications, for patients with renal or hepatic insufficiency it is necessary to halve the initial and subsequent corrective doses, and also to titrate the dose more slowly.

The use of Risdonal® in these patient groups requires caution.

An initial dose of 0.5 mg * is recommended for taking 2 times a day. This dose can be gradually increased to 1-2 mg per reception twice a day.

Drug Abuse or Drug Dependence - The recommended daily dose of the drug is 2-4 mg.

* For conditions requiring the use of the drug in a dose of less than 1 mg, it is recommended to use another preparation containing risperidone in a suitable dose.

Features of the drug at the first reception:

In connection with the α-adrenoblocking action of risperidone, orthostatic hypotension may occur, especially during the initial dose selection.

Features of the drug during its cancellation:

Do not stop taking the drug without consulting a doctor, as it is possible to return the symptoms. If the drug should be discontinued, the dose should be reduced gradually to a complete withdrawal.

Features of the actions of a doctor (paramedic), a patient with a missed intake of one or more doses of the drug:

It is necessary to take the missed dose as soon as an omission is discovered. If it is time to take the next dose, you need to skip the missed and continue to receive the prescribed schedule. Do not take a double dose to compensate for the missed dose.

Side effects:

More often the following adverse events were reported (frequency ≥10%): Parkinsonism, headache and insomnia.

On the frequency of occurrence of adverse reactions are divided into the following groups: very often (≥1/10), often (≥1/100 <1/10), infrequently (≥1/1000 <1/100), rarely (≥1/10 000 <1/1000), very rarely (<1/10 000) and unknown (it is impossible to estimate from the available data).

Violations of the blood and lymphatic system:

infrequently: anemia, thrombocytopenia;

rarely: neutropenia;

very rarely: eosinophilia;

unknown: agranulocytosis.

Immune system disorders:

infrequently: angioedema;

unknown: anaphylactic reaction, photosensitization.

Disorders from the endocrine system:

infrequently: hyperprolactinemia, diabetic coma.

rarely: syndrome of inadequate secretion of antidiuretic hormone (SNSSADG).

Disorders from the metabolism and nutrition:

often: in elderly patients with dementia - decreased appetite, in children - increased appetite;

infrequently: anorexia, polydipsia, hyperglycemia;

rarely: hypoglycemia;

very rarely: diabetic ketoacidosis;

unknown: hypervolemia, water intoxication, increase or decrease in body weight, hypo- or hypersalivation, exacerbation of pre-existing diabetes.

Disorders of the psyche:

very often: insomnia;

often: anxiety, agitation, agitation, sleep disorders, in elderly patients with dementia - confusion, in children - lethargy;

infrequently: confused consciousness, mania or hypomania, indifference, nervousness, increased fatigue;

rarely: emotional dullness.

Disturbances from the nervous system:

very often: Parkinsonism (hypersalivation, musculoskeletal rigidity, drooling, rigidity of the "cogwheel" type, bradykinesia, hypokinesia, masculine face, muscle tension, rigidity of the occipital muscles, gait parkinsonic and abnormal glabellar reflex), in children - drowsiness, headaches pain, sedation;

often: akathisia, dizziness, tremor, acute dystonia, drowsiness, sedation, lethargy, dyskinesia; in elderly patients with dementia - depressed condition; in children - dysarthria, attention disturbance, gait disturbance;

infrequent: impaired consciousness, fainting, impaired concentration, late dyskinesia (involuntary rhythmic movements predominantly of the tongue and / or face), speech impairment, improper coordination, hypoesthesia;

rarely: malignant neuroleptic syndrome *, extrapyramidal symptoms **, diabetic coma;

very rarely: convulsions, a violation of thermoregulation, is unknown: epileptic seizures.

Disturbances on the part of the organ of sight:

often: blurred vision, in elderly patients with dementia - conjunctivitis; infrequent: hyperemia of the eyes, dry eyes, increased lacrimation, photophobia; rarely: decreased visual acuity, circular movements of the eyeballs, glaucoma, conjunctivitis, edema of the eyes.

Hearing disorders and labyrinthine disorders:

infrequently: pain in the ear, ringing in the ears.

Heart Disease:

often: tachycardia (including reflex tachycardia), in elderly patients with dementia - transient ischemic attack, myocardial infarction, in children - palpitation;

infrequently: atrioventricular block, bundle bundle blockage, atrial fibrillation, sinus bradycardia, palpitation.

Vascular disorders:

infrequently: arterial hypotension, orthostatic hypotension, face redness, stroke (in elderly patients with dementia), transient ischemic attack;

unknown: increased blood pressure; cases of venous thromboembolism (VTE), including cases of pulmonary embolism and deep vein thrombosis.

Disturbances from the respiratory system, chest and mediastinal organs:

often: shortness of breath, nosebleeds, cough, rhinitis; in elderly patients with dementia - cough, rhinorrhea; children - cough, rhinorrhea, pain in the larynx and pharynx, stagnation in the lungs;

infrequently: wheezing, wheezing, congestion of the respiratory tract, dysphonia;

rarely: sleep apnea syndrome, hyperventilation, nasal congestion, sensation of sore throat, aspiration pneumonia, sinusitis, otitis media, tonsillitis.

Disorders from the gastrointestinal tract:

often: vomiting, constipation, nausea, abdominal pain, indigestion, dry mouth, abdominal discomfort;

infrequently: dysphagia, fecal incontinence, fecal calculus, anorexia, hypo- and hypersalivation;

rarely: intestinal obstruction, pancreatitis.

Disturbances from the liver and bile ducts:

rarely: jaundice.

Disturbances from the skin and subcutaneous tissues:

often: rash, erythema;

infrequently: itching, skin discoloration, alopecia, seborrhea, dry skin, hyperkeratosis;

rarely: seborrhea;

unknown: hyperpigmentation.

Disturbances from musculoskeletal and connective tissue:

often: arthralgia;

infrequent: muscle weakness, muscle pain, swelling and joint stiffness, atypical body position, back pain, pain in the limbs;

rarely: rhabdomyolysis.

Disorders from the kidneys and urinary tract:

often: enuresis;

infrequently: dysuria, urinary incontinence, pollakiuria;

rarely: cystitis.

Violations of the genitals and mammary gland:

infrequently: amenorrhea, erectile dysfunction, ejaculation disorders, decreased libido, anorgasmia, galactorrhea, gynecomastia, menstrual cycle disorder;

unknown: priapism.

General disorders and disorders at the site of administration:

often: hyperthermia, fatigue, peripheral edema, asthenia, chest pain;

infrequently: swelling of the face, gait disturbance, sensation of soreness, influenza-like illness, thirst, chest discomfort, chilliness;

rarely: generalized edema, hypothermia, withdrawal syndrome, sensation of coldness in the extremities.

Laboratory and instrumental data:

often: hyperprolactinemia ***, weight gain;

infrequent: interval lengthening QT, changes in the electrocardiogram, increased activity of "liver" transaminases, a decrease in the level of leukocytes in the blood, increased body temperature, an increase in the number of eosinophils in the blood, a decrease in hematocrit, an increase in activity of creatine phosphokinase;

rarely: a decrease in body temperature.

Pregnancy, postpartum and perinatal conditions:

unknown: neonatal narcotic withdrawal syndrome.

* Malignant neuroleptic syndrome (CNS): a rare, potentially dangerous condition associated with the use of antidepressants, including risperidone. Symptoms of ZNS: increased body temperature (hyperpyrexia), muscle rigidity, changes in mental status and instability of autonomic nervous system functions (arrhythmia, fluctuations in blood pressure, tachycardia, profuse sweating, heart rhythm disturbance, increased activity of creatine phosphokinase (CK), impaired consciousness).During the application of risperidone, some cerebrovascular symptoms have been reported; they developed mainly among elderly patients with existing risk factors.

** Extrapyramidal symptoms: risperidone has a lower ability to cause extrapyramidal disorders than classical antipsychotics. However, in some cases, the following extrapyramidal symptoms may develop: tremor, stiffness, hypersalivation, bradykinesia, akathisia, acute dystonia. These symptoms are usually mild and reversible after lowering the dose and / or administering antiparkinsonian drugs (if necessary).

*** Hyperprolactinemia: risperidone depending on the dose may cause an increase in the level of prolactin in the blood with the following possible manifestations: galactorrhea, gynecomastia, menstrual cycle disorders and amenorrhea.

Class Effects

In post-marketing observations very rare cases of lengthening of the interval were noted QT when taking risperidone, as well as during therapy with other antipsychotic drugs. Other class effects associated with the heart, marked with antipsychotic drugs, extending the interval QT, include: ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac arrest and polymor- phic ventricular pirouette tachycardia.

Venous thromboembolism

There have been cases of development of venous thromboembolism, including cases of pulmonary embolism and deep vein thrombosis during therapy with antipsychotics (the frequency is unknown).

Weight gain

In a 6-8-week, placebo-controlled study in adults with schizophrenia with 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 at the end of the study was adequate in the risperidone group (2.5%) and placebo (2.4%) and was slightly larger in the control group (3.5%).

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

Additional information for specific patient groups

Side effects reported more often in elderly patients with dementia and in pediatric patients than in adult patients:

Elderly patients with dementia

Transient ischemic attack and stroke were adverse reactions reported in clinical trials with a frequency of 1.4% and 1.5%, respectively, in elderly patients with dementia. In addition, the following adverse reactions have been reported with a frequency> 5% in elderly patients with dementia and at least among the rest of the adult population observed frequency is twice as large: urinary tract infections, peripheral edema, drowsiness, cough.

Patients of childhood

Typically, the types of adverse reactions in children were similar to those observed in adult patients.

The following adverse reactions were recorded at a frequency of 5% in children (5 to 17 years of age) and at least twice the frequency observed in adult clinical trials: drowsiness / sedation, fatigue, headache,increased appetite, vomiting, upper respiratory tract infection, nasal congestion, abdominal pain, dizziness, cough, fever, tremor, diarrhea, and urinary incontinence.

The long-term effects of risperidone on puberty and growth have not been studied properly (see "Precautions for use ", subsection "Children and adolescents").

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

Symptoms: drowsiness, sedation, depression, tachycardia, lowering blood pressure, extrapyramidal disorders, in rare cases, prolongation of the QT interval and convulsions. Fever / ventricular fibrillation was noted with a combined overdose of risperidone with paroxetine. In the case of acute overdose, it is necessary to exclude the possibility of taking several drugs.

Giving help: it is necessary to ensure free airway patency for adequate oxygenation and ventilation, gastric lavage (after intubation if the patient is unconscious) and the appointment of activated carbon in combination with laxatives (only if taken less than 1 hour ago).Symptomatic therapy aimed at maintaining vital body functions. With arterial hypotension or vascular collapse, appropriate measures are taken, in particular intravenous fluids or sympathomimetics. In the case of acute extrapyramidal symptoms, the patient is prescribed anticholinergic drugs. For timely diagnosis of possible cardiac arrhythmias, ECG monitoring should be started as soon as possible. Careful medical observation and ECG monitoring is performed until the symptoms of intoxication disappear completely. There is no specific antidote.

Interaction:

As with other antipsychotics, caution should be exercised when using risperidone with drugs that extend the interval QT, for example, with antiarrhythmic drugs IA class (for example, quinidine, disopyramide, procainamide), antiarrhythmic drugs of III class (for example, amiodarone, sotalol), tricyclic antidepressants (i.e. amitriptyline), tetracyclic antidepressants (i.e. maprotiline), some blockers H₁-histamine receptors, with other antipsychotic drugs; with some antimalarial drugs (for example, mefloquine), and with drugs that cause electrolyte imbalance (hypokalemia, hypomagnesemia), bradycardia, or those that inhibit the hepatic metabolism of risperidone. This list is indicative only and is not exhaustive.

Given that risperidone has an effect primarily on the central nervous system, it should be used with caution in combination with other drugs of central action, especially with narcotic analgesics, blockers H₁-gistaminovyh receptors, benzodiazepines and with alcohol.

Risperidone reduces the effectiveness of levodopa and other dopamine receptor agonists.

Hypotensive drugs increase the severity of lowering blood pressure when using risperidone.

Clozapine reduces the clearance of risperidone.

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

When carbamazepine was used, a decrease in the concentration of the active antipsychotic fraction of risperidone in plasma was noted. Similar effects can be observed with the use of other inducers of microsomal enzymes of the liver, rifampicin, phenytoin and phenobarbital, together with stimulation of the hepatic enzyme system CYP3A4 and P-glycoprotein. With the appointment or withdrawal of carbamazepine and other stimulants of hepatic enzymes CYP 3A4 / P-glycoprotein (P-gp) it is necessary to adjust the dose of risperidone.

Phenothiazine derivatives, tricyclic antidepressants and some β-adrenoblockers can 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 its active antipsychotic fraction.

Cimetidine and ranitidine enhance the bioavailability of risperidone only with a borderline effect on the active antipsychotic fraction.

Inhibitor CYP3A4 erythromycin does not affect the pharmacokinetics of risperidone and its active antipsychotic fraction.

Fluoxetine and paroxetine may increase the concentration of risperidone in plasma, but to a lesser extent the concentration of the active antipsychotic fraction. It is expected that other inhibitors CYP2D6, for example, quinidine, are also capable of similarly affecting plasma concentrations of risperidone. When appointing or discontinuing the concomitant administration of fluoxetine or paroxetine, the dosage of risperidone should be adjusted.

Verapamil increases the concentration of risperidone in the blood plasma (inhibitor CYP 3A4/P-gp).

With the use of risperidone, along with other drugs that bind highly to plasma proteins, there is no clinically significant displacement of any drug from the plasma protein fraction.

Hypotensive drugs increase the severity of lowering blood pressure when using risperidone.

With the simultaneous treatment of risperidone and furosemide in elderly people with dementia, there is a risk of increased mortality.

The simultaneous use of risperidone with paliperidone is not recommended, since paliperidone is an active metabolite of risperidone and their simultaneous application can lead to an additive exposureactive antipsychotic fraction.

Special instructions:

Transition from therapy with other antipsychotic drugs

In schizophrenia, at the beginning of the use of the Risdonal drug, it is recommended to gradually cancel the previous therapy, if it is clinically justified. If the patient is transferred from the therapy of depot forms of antipsychotics, then the use of the Risdonal® drug should be started instead of the next scheduled injection. Periodically, the need to continue therapy with antiparkinsonian drugs should be evaluated.

Risk of development mania and / or hypomania can be significantly reduced by applying low dosages or gradually increasing them.

In connection with α-adrenoblocking action of risperidone may occur orthostatic hypotension, especially during the initial dose selection. Clinically significant reduction in blood pressure is observed with the joint appointment of risperidone with antihypertensive drugs. With a decrease in blood pressure should consider reducing the dose. Patients with diseases of the cardiovascular system (heart failure, myocardial infarction,violation of cardiac conduction), as well as during dehydration, hypovolemia or cerebrovascular disorders, the dose should be increased gradually.

Interval lengthening QT

Cases of lengthening the interval QT very rarely reported in post-marketing studies. As with other antipsychotics, caution should be exercised when prescribing Risdonal® to patients with cardiovascular disease, history of cardiac arrhythmias, patients with lengthening of the interval QT in a family history, bradycardia, or a violation of the electrolyte balance (hypokalemia, hypomagnesemia), since it is possible to increase the risk of arrhythmogenic effects and also when combined with drugs that increase the interval QT.

The use of drugs with antagonistic properties with respect to dopamine receptors was accompanied by the appearance of tardive dyskinesia, which is characterized by rhythmic involuntary movements, predominantly of the tongue and / or face.

The occurrence of extrapyramidal symptoms is a risk factor for development tardive dyskinesia. In case of signs and symptoms of tardive dyskinesia, consideration should be given to the abolition of all antipsychotics.

When malignant neuroleptic syndrome (NSA), characterized by hyperthermia, muscle rigidity, instability of autonomic functions, impaired consciousness and increased activity of creatine phosphokinase, it is necessary to immediately stop the use of the drug Ridonal®. Additional signs may include myoglobinuria (rhabdomyolysis) and acute renal failure.

If you cancel carbamazepine and other inducers of liver enzymes The dose of risperidone should be reduced.

When treating the drug, a significant increase in body mass is possible. It is necessary to monitor the body weight of patients using the Risdonal® drug. Patients should be advised to refrain from overeating due to with the possibility of increasing body weight.

The ingestion of food does not affect the absorption of the drug Ridonal®.

Care should be taken when treating patients with Parkinson's diseaseBecause Risdonal® can aggravate the course of this disease.

The administration of antipsychotics, including Ridonal®, to patients with Parkinson's disease or dementia with Levy bodies should be done with caution, since in both groups of patients, the risk of malignant neuroleptic syndrome increased and sensitivity to antipsychotic drugs increased (including blunting of pain sensitivity, confusion, postural instability with frequent falls and extrapyramidal symptoms).

It is known that classical antipsychotics reduce the threshold of convulsive readiness. When treating patients from epilepsy care must be taken.

In elderly patients with dementia when treated with atypical antipsychotics, including risperidone, there is a risk of increased mortality. When using risperidone for a given population, the incidence of fatalities was 4.0% for patients taking risperidone, compared with 3.1% for placebo. The average age of the deceased patients is 86 years (range 67-100).

For elderly patients with dementia who take oral forms of risperidone, there was an increased mortality in patients taking furosemide and risperidone (7.3%, mean age 89 years, range 75-97 years) compared with the group taking only risperidone (3.1%, average age 84 years, range 70-96 years) and a group that only took furosemide (4.1%, average age 80 years, range 67-90 years). There are no pathophysiological mechanisms that explain this observation. Nevertheless, special care should be taken when prescribing the drug in such cases. Increased mortality in patients taking both furosemide and risperidone, was observed in two of four clinical trials. There was no increase in mortality in patients taking other diuretics simultaneously (mainly thiazide diuretics used in low doses) together with risperidone. Regardless of treatment, dehydration is a common risk factor for mortality and should be carefully monitored in elderly patients with dementia.

In elderly patients with dementia, there was an increase in cerebral circulation, including deaths in patients (mean age 85 years, range 73-97 years) with risperidone compared with placebo.

In elderly patients with dementia, the use of risperidone leads to an increased risk of stroke and transient ischemic attack. Special care should be taken when prescribing the drug in such cases.

In patients with dementia in the treatment of atypical antipsychotics, there is an approximately 3-fold increased risk cerebrovascular adverse reactions in randomized, placebo-controlled clinical trials. A generalized analysis of the results of six placebo-controlled studies of risperidone, mainly in elderly patients (> 65 years) with dementia, showed that cerebrovascular unwanted reactions (serious and non-serious, combined) appeared in 3.3% (33/1009) of patients who received risperidone and in 1.2% (8/712) of the patients receiving the placebo. The mechanism of this increase in risk has not been studied. Increased risk can not be ruled out for other antipsychotics and other groups of patients. Risperidone should be used with caution in patients with risk factors for stroke.

The risk of developing unwanted cerebrovascular reactions is significantly higher in patients with mixed or vascular dementia than in patients with Alzheimer's dementia.Therefore, patients with mixed or vascular dementia should not be prescribed risperidone.

It is necessary to assess the risks and therapeutic benefits of using risperidone in elderly patients with dementia, taking into account the prognostic risk factors for stroke in a particular patient. The patient and his environment should be warned about the urgent need to report symptoms and signs of potential cerebrovascular unwanted reactions, in particular about sudden weakness or numbness of the face, upper and lower extremities, speech or vision impairment. In this case, all therapeutic options are urgently considered, including the discontinuation of risperidone.

With persistent aggression in patients with Alzheimer's dementia risperidone is intended only for short-term use as an adjunct to non-pharmacological interventions if they are ineffective or limited in the absence of potential danger to the patient or his environment. Need constant monitoring and evaluation of patients, as well as the rationale for the need for further treatment.

Caution should be exercised when using risperidone in patients from hyperprolactinaemia and in patients with prolactin-dependent tumors.

In the treatment with risperidone, priapism in connection with α-adrenoblocking action of risperidone.

With the use of antipsychotic drugs bind thermoregulation disorders organism. Caution is advised when prescribing risperidone to patients whose lifestyle is associated with exposures that increase internal body temperature, for example, intense physical activity, exposure to high temperatures, concomitant medication with anticholinergic activity, and a state of dehydration.

When using antipsychotics, cases have been reported venous thromboembolism (VTE). Since patients taking antipsychotics often have VTE risk factors, all possible risk factors for VTE should be determined before and during treatment with risperidone and preventive measures are taken.

Children and teenagers with behavioral disorders are prescribed risperidone only after a careful study of the physical and social causes of aggressive behavior, for example, pain or inconsistency with the requirements of the environment.

Due to the possible impact on the ability to learn in this category of patients, careful monitoring of the sedative effect of the drug is necessary. The time to take risperidone should be chosen in such a way as to optimize the effect of sedation on the ability to focus attention in children and adolescents. Due to the potential effects of prolonged hyperprolactinemia on the physical and sexual development of children and adolescents, a regular clinical evaluation of the endocrinological condition is needed, including data on growth, body weight, sexual development, monitoring of the menstrual cycle and other potential prolactin effects.

When treating risperidone, regular examinations are needed to identify extrapyramidal symptoms and other motor disorders.

Late dyskinesia is a side effect of prolonged use of antipsychotics. Rarely, dysphagia may be the only manifestation of tardive dyskinesia in some patients.

During treatment, it is necessary to refrain from engaging in potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions, as well as on the intake of alcohol.

In the treatment with risperidone have been registered hyperglycemia, diabetes mellitus and exacerbation of pre-existing diabetes. In some cases, a previous increase in body weight was noted, which could become a predisposing factor. Very rarely reported on the association with ketoacidosis and rarely with diabetic coma. In accordance with the principles of the application of antipsychotic recommendations, appropriate clinical monitoring is recommended. Patients taking atypical antipsychotics, including risperidone, should be monitored for the detection of symptoms of hyperglycemia (eg, polydipsia, polyuria, polyphagia and weakness). Patients with diabetes are encouraged to regularly check their glucose levels.

Have elderly patients with impaired hepatic and / or renal function a careful dose selection and special supervision are necessary.

Special information on excipients

The preparation Risdonal® contains lactose, therefore, it should not be used in patients with galactosemia, lactase deficiency or glucose-galactose malabsorption syndrome. Tablets of 2 mg contain a dye sunset yellow E110, which can cause allergic reactions.

Effect on the ability to drive transp. cf. and fur:

During treatment with Ridonal®, it is necessary to refrain from engaging in potentially dangerous activities requiring increased concentration of attention and speed of psychomotor reactions, as well as from taking alcohol.

Form release / dosage:

Film-coated tablets, 1 mg, 2 mg and 3 mg.

Packaging:

10 tablets per blister are perforated from aluminum foil and PVC film.

2 blister (20 tablets) together with instructions for use are placed in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 of the year.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000780

Date of registration:03.08.2010 / 27.03.2013

Expiration Date:Unlimited

The owner of the registration certificate:Alkaloid, JSCAlkaloid, JSC Macedonia

Manufacturer: & nbsp

MAKIZ-PHARMA, LLC Russia

SKOPINSKY FARM ZAVOD, ZAO Russia

ALKALOID, AD Macedonia

Representation: & nbspALKALOID, AOALKALOID, AO

Information update date: & nbsp18.12.2016

Illustrated instructions

Instructions

Ridonal® (Risdonal®)