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

Excipients: lactose monohydrate 40.00 mg / 80.00 mg / 120.00 mg / 160.00 mg; cellulose microcrystalline 44.75 mg / 89.50 mg / 134.25 mg / 179.00 mg; pregelatinized starch 7.50 mg / 15.00 mg / 22.50 mg / 30.00 mg; croscarmellose sodium 5.00 mg / 10.00 mg / 15.00 mg / 20.00 mg; sodium lauryl sulfate 1.00 mg / 2.00 mg / 3.00 mg / 4.00 mg; silicon dioxide colloidal anhydrous 0.50 mg / 1.00 mg / 1.50 mg / 2.00 mg; magnesium stearate 0.25 mg / 0.50 mg / 0.75 mg / 1.00 mg.

Shell

Tablets, film-coated, 1 mg

Drop off white Y-1.7000 2.50 mg (hypromellose 5 cps (62.50%), titanium dioxide E 171 (31.25%) macrogol (6.25%)).

Tablets, film-coated, 2 mg

Opaprai pink 03B 54942 5.00 mg (hypromellose 6 cps (63.65%), titanium dioxide E171 (29.477%), macrogol 400 (6.30%), iron (III) red oxide E172 (0.573%)).

Tablets, film-coated, 3 mg

Fade yellow 03B 52852 7.50 mg (hypromellose 5 cps (62.50%), titanium dioxide E 171 (28.75%), macrogol 400 (6.25%), quinoline yellow aluminum varnish (2.50%)) .

Tablets, film-coated, 4 mg

Opaprai pink 20A 54901 10.00 mg (giprolose (40.00%), hypromellose 6 cps (40.00%), titanium dioxide E171 (19.285%) iron (III) oxide red E 172 (0.645%), iron ( III) oxide black E172 (0.070%).

Description:

Tablets, film-coated, 1 mg: white biconvex, capsular tablets, film-coated, with a risk on one side.

Tablets, film-coated, 2 mg: pink, biconcave, capsular tablets, film-coated, with a risk on both sides.

Tablets, film-coated, 3 mg: yellow, biconvex, capsular tablets, film-coated, with a risk on one side.

Film-coated tablets, 4 mg: dark pink, biconvex, capsular tablets, film-coated, with a risk on both sides.

View of the break: white compressed mass coated with white (dosage 1 mg), pink (dosage 2 mg), yellow (dosage 3 mg) or dark pink color (dosage 4 mg).

Pharmacotherapeutic group:antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.X Other antipsychotics

N.05.A.X.08 Risperidone

Pharmacodynamics:

Risporux^® - antipsychotic agent (neuroleptic), a benzisoxazole derivative; also has a sedative, antiemetic and hypothermic effect.

It is a selective monoaminergic antagonist, has a high tropism for serotonergic 5-HT₂ and dopaminergic D₂receptors, also binds to alpha₁-adrenoceptors and somewhat weaker with H₁-gistaminergic and alpha₂-adrenergic receptors. Risperidone does not have tropism for cholinergic receptors.

Antipsychotic action is due to the blockade of dopamine D₂receptors of the mesolimbic and mesocortical system. Sedative action is caused by blockade of adrenoreceptors of the reticular formation of the brainstem; antiemetic action - blockade of dopamine D₂-receptors of the vomiting center's trigger zone; hypothermic action - blockade of dopamine receptors of the hypothalamus.

Risperidone is especially effective in the treatment of schizophrenia with productive symptoms (delirium, hallucinations, aggressiveness), also has a positive effect with negative symptoms.

A balanced central antagonism to serotonin and dopamine can reduce the propensity to extrapyramidal side effects and extend the therapeutic effect of the drug to cover the negative and affective symptoms of schizophrenia. It causes less inhibition of motor activity and to a lesser degree induces catalepsy than classical antipsychotic antipsychotics.

Pharmacokinetics:

Risperidone after oral administration is completely absorbed, reaching the maximum concentrations in the plasma after 1-2 hours. The maximum plasma concentration of 9-hydroxyrisperidone is reached after 3 hours, and after 17 hours in "slow" metabolizers. Eating does not affect the completeness and speed of absorption. The bioavailability of risperidone is 70-94%. The equilibrium concentration of risperidone in the blood in most patients is reached during the firstdays of treatment and after 5 days for "slow" metabolizers, 9-hydroxyrisperidone - on the 5th-6th day. The concentration of risperidone in plasma is proportional to the dose of the drug (within therapeutic doses).

Risperidone is rapidly distributed. The volume of distribution is 1-2 l / kg. Relationship with plasma proteins of risperidone (mainly with albumin and alpha₁-acid glycoprotein) is 90%, 5-hydroxyrisperidone - 77%.

Risperidone is metabolized in the liver. The main pathway of metabolism is carried out with cytochrome P450 isoenzyme CYP2D6 with the formation of 9-hydroxyrisperidone, the pharmacological activity of which is comparable with the activity of risperidone. Risperidone and 9-hydroxyrisperidone are the so-called neuroleptic fraction. Isozyme CYP2D6 depends on genetic polymorphism (about 6-8% of Caucasians, and very low percentage of Asians, practically have no activity and are called "slow" metabolizers).

Another way of metabolism of risperidone is N-dealkylation. In studies on microsomes of human liver in vitro it was shown that risperidone in a clinically significant concentration does not significantly inhibit the metabolism of drugs metabolized by the cytochrome P450 system, including isozymes CYP 1A2, CYP 2A6, CYP 2C8 / 9/10, CYP 2D6, CYP 2E1, CYP 3A4 and CYP 3A5.

One week after using risperidone, 70% of the dose is excreted by the kidneys (35-45% of the dose is represented by the neuroleptic fraction, the rest is inactive metabolites), 14% with feces. After oral administration, the half-life of risperidone is about 3 hours and 20 hours for "slow" metabolizers. The half-life of 9-hydroxyrisperidone and the active antipsychotic fraction is 20-24 hours. Plasma clearance for oral administration is 1.667 ml / s.

Application in elderly patients

Risperidone is excreted by the kidneys, and in elderly patients the decrease in renal function is most likely. Therefore, in order to avoid the development of unwanted effects in elderly patients, it is recommended that the initial dose be reduced and a more thorough titration of the dose of the drug is recommended.

Have patients with moderate and severe renal dysfunction (creatinine clearance of 59-15 ml / min) decreases the clearance of risperidone and its active fraction to 60%, therefore a dose adjustment is recommended.

Have patients with impaired liver function the pharmacokinetic properties of risperidone do not change, however, the mean plasma concentration of free risperidone rises by 35% due to a decrease in albumin and alpha₁-acid of the glycoprotein.

Have children the pharmacokinetics of risperidone, 9-hydroxyrisperidone and the active antipsychotic fraction are similar to adults.

Population pharmacokinetic analysis revealed no effect sex, race and smoking on the pharmacokinetics of risperidone and the active antipsychotic fraction.

Indications:

- Schizophrenia (relief of relapses, maintenance therapy) and other psychotic disorders with a predominance of productive and / or negative symptoms;

- Mania with bipolar disorders of moderate and severe severity;

- short-term (up to 6 weeks) treatment of persistent aggression in patients with dementia due to Alzheimer's disease, moderate to severe, not amenable to non-pharmacological correction methods and when there is a risk of harm to the patient and others;

- short-term (up to 6 weeks) symptomatic treatment of persistent aggression in the structure of behavioral disorders in children 13 years of age and older with mental retardation diagnosed in accordance with 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:

Hypersensitivity to risperidone or other components of the drug; rare hereditary forms of intolerance to galactose; deficiency of lactase or impaired absorption of glucose / galactose (because the composition contains lactose); lactation period; children under 13 years of age (or body weight less than 50 kg) in behavioral disorders in children; Children under 18 years of age (according to other indications).

Carefully:

- Severe renal or hepatic insufficiency;

- cardiovascular diseases (chronic heart failure, suffered myocardial infarction, atrioventricular blockade);

- hypovolaemia and dehydration;

- conditions predisposing to the development of tachycardia such as "pirouette" (bradycardia, electrolyte imbalance, concomitant use of drugs that extend the interval QT);

- Parkinson's disease;

- impaired cerebral circulation;

- Raynaud's syndrome;

- epilepsy, convulsions (including in the anamnesis);

- brain tumor;

acute drug overdose;

- intestinal obstruction; Reye syndrome (antiemetic effect of risperidone can mask the symptoms of these conditions);

- drug dependence or abuse of medicines;

- pregnancy and the period of breastfeeding.

Pregnancy and lactation:

Controlled studies of the use of risperidone during pregnancy have not been conducted. In animals risperidone did not have a direct toxic effect on the reproductive system, but caused some indirect effects, mediated by the effect on the central nervous system and the concentration of prolactin. None of the studies risperidone did not possess a teratogenic effect. According to post-marketing data, reversible extrapyramidal symptoms are observed in newborns whose mothers took risperidone during the third trimester of pregnancy. The potential risk to humans is unknown. Use of risperidone during pregnancy is only possible if the intended benefit to the mother exceeds the potential risk to the fetus.Stop use of the drug during pregnancy should be gradual.

The drug is excreted in breast milk in small amounts, but in spite of this, when it is necessary to take the drug by nursing mothers, it is necessary to resolve the issue of stopping breastfeeding.

Dosing and Administration:

Inside, regardless of food intake, washing down with water.

Schizophrenia

Adults

The initial dose of Risporux® for all patients (for acute manifestations of the disease and chronic course) is 2 mg / day (in one or two doses), on the second day the dose may be increased to 4 mg / day; further, if necessary, the dose may be increased or decreased by 1-2 mg at weekly intervals. Doses above 10 mg / day did not show higher efficacy compared with smaller doses and could cause extrapyramidal symptoms. The maximum daily dose is 16 mg.

If it is necessary to achieve a sedative effect simultaneously with Rispolux®, the use of benzodiazepines is possible.

Patients of the older age group

The recommended initial dose of Risperidone is 0.5 mg twice a day. This dose can be gradually (0.5 mg) increased to 1-2 mg per reception 2 times a day.

Mania in bipolar disorders

Adults

The initial dose of Rispolux® for all patients (for acute manifestations of the disease and chronic course) is 2-3 mg / day (in one or two doses). Correction of the dose should be carried out at 1 mg 1 time per day. Usually the optimal dose varies from 1-6 mg per day. Application of a daily dose of risperidone above 6 mg in the treatment of mania in bipolar disorders has not been studied. Prolonged symptomatic treatment with risperidone should be justified.

Patients of the older age group

The recommended initial dose of Risporux® is 0.5 mg twice a day. This dose can be gradually (0.5 mg) increased to 1-2 mg per reception 2 times a day.

Behavioral disorders

Adults

The recommended initial dose is 0.5 mg once a day. The optimal dose is 0.5 mg twice a day. If necessary, it is possible to increase the dose by 0.5 mg per day with an interval of at least 1 day. In some patients, however, the effective dose can be 1 mg twice daily (2 mg per day).

Rispolux® should not be used for more than 6 weeks in patients with persistent aggression with Alzheimer's dementia. During treatment with Rispolux®, frequent and regular assessment of the patient's condition is necessary to decide whether to continue treatment.

Adolescents over 13 years of age (or with a body weight of more than 50 kg) with a reduced intellectual level or mental retardation, including as a means of assistive therapy to stabilize the mood

The recommended initial dose is 0.5 mg once a day. If necessary, it is possible to increase the dose in steps of 0.5-1.0 mg once a day. The optimal dose is 1 mg once a day. The effective dose varies from 0.5 to 3.0 mg. During treatment with risperidone, frequent and regular assessment of the patient's condition is necessary to decide whether to continue treatment. Long-term use of Rispollux® in adolescents should be carried out under the constant supervision of a physician.

Application the patients with renal and / or liver failure

In patients with renal failure, the excretion of the active substance of risperidone is slowed.

With hepatic insufficiency, the concentrations of all three metabolites of risperidone in plasma increase.

Therefore, in patients with renal and / or liver failure, the initial and effective dose is recommended to be reduced by 50%.

With renal insufficiency (creatinine clearance less than 30 ml / min) or hepatic insufficiency (10-15 points on the scale Child Pugh System) the initial dose of risperidone should not exceed 0.5 mg twice daily. If necessary, the dose may be increased by 0.5 mg when applied 2 times a day. For doses of 1.5 mg or more twice a day, it is necessary to increase the interval to 1 week or more.

When switching to treatment with Risporux® it is recommended that the previously taken antipsychotic is phased out. If a neuroleptic-depot for parenteral administration has previously been used, the first dose of Rispholux® should be taken in place of injection in accordance with the mode of administration of the neuroleptic-depot.

With a sharp withdrawal of risperidone, there may be a "cancellation" syndrome (including nausea, vomiting, insomnia, excessive sweating), so it is recommended to stop the use of the drug gradually.

Side effects:

According to the World Health Organization (WHO), unwanted effects are classified according to their frequency of development as follows: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, < 1/100), rarely (> 1/10000, <1/1000) and very rarely (<1/10000), including individual messages, the frequency is unknown (can not be calculated from available data).

Infections

often: nasopharyngitis, infections upper respiratory tract, sinusitis, urinary tract infections, ear infections, influenza, pneumonia, bronchitis;

infrequently: viral infections, tonsillitis, eye infections, localized infections, cystitis, onychomycosis, acrodermatitis, bronchopneumonia, infections respiratory tract, tracheobronchitis, cellulitis, otitis media;

rarely: chronic otitis media.

On the part of the blood and lymphatic system

infrequently: anemia, decreased hematocrit, thrombocytopenia, neutropenia, leukopenia, eosinophilia;

rarely: granulocytopenia, agranulocytosis.

From the immune system

infrequently: hypersensitivity;

rarely: hypersensitivity to risperidone;

frequency is unknown: anaphylactic reaction.

From the endocrine system

often: hyperprolactinaemia;

rarely: impaired secretion antidiuretic hormone.

From the side of metabolism and nutrition

Hasto: decrease / increase in appetite, weight gain;

infrequently: diabetes mellitus, hyperglycemia, polydipsia, weight loss, anorexia, hypercholesterolemia;

rarely: Hypoglycemia, hyperinsulinemia, "water intoxication", glucosuria, diabetic coma, hypertriglyceridemia;

rarely: diabetic ketoacidosis.

From the nervous system

Often: parkinsonism (including extrapyramidal disorders as hypersecretion of saliva, stiff skeletal muscle, parkinsonism, drooling, rigidity of the type "gear", bradykinesia, hypokinesia, mask-like face, muscle tension, akinesia, stiff neck, muscle rigidity, parkinsonian gait, positive glabellar reflex, parkinsonian tremor), drowsiness, headaches, sedation, increased fatigue;

often: Non-systemic dizziness, postural dizziness, tremors, convulsions, dystonia (including dystonia, hypertension, torticollis, involuntary muscle contractions, muscle contracture, blepharospasm, oculogyric crisis, tongue paralysis, spasms of the facial muscles, laryngospasm, myotonia, opisthotonos, oropharyngeal spasm, plevrototonus, spasm language and lockjaw), akathisia (inability to sit still for a long time in one position or stay long without movement), lethargy (a condition similar to sleep and is characterized by immobility, lack of response to outside her anger and a sharp decrease in the intensity of all the external signs of life); dyskinesia (including muscle twitching, chorea and choreoathetosis), fainting;

infrequently: decreased ability to concentrate, apathy, stroke, transient ischemic attacks, dysarthria (impaired speech), speech impairment, coordination disorder, hyposthenia (decreased susceptibility of external stimuli), decreased level of consciousness, tardive dyskinesia;

rarely: malignant neuroleptic syndrome, cerebrovascular disease, cerebral ischemia, stammering, diabetic coma, tremor of the head.

Mental disorders

Often: insomnia (difficulty falling asleep and awakening during sleep);

often: sleep disturbance, agitation, depression, anxiety;

infrequently: mania, confusion, decreased libido, nervousness, night nightmares;

rarely: dulling of emotional reactions, anorgasmia.

From the side of the organ of vision

often: blurred vision, visual acuity; conjunctivitis;

infrequently: hyperemia of the eye, puffiness of the eyelids, dry eyes, lacrimation, photophobia, discharge from the eyes;

rarely: glaucoma, blepharitis, nystagmus, eye rolling, atonic iris syndrome (during the operation), retinal artery occlusion, crust formation on the edges of the eyelids.

From the side of the hearing organ and labyrinthine disorders

infrequently: pain in the ears, tinnitus (ringing in the ears), vertigo (systemic dizziness).

From the side of the cardiovascular system

often: tachycardia, increased blood pressure;

infrequently: atrial fibrillation, lengthening of the interval QT, atrioventricular blockade of the 1st degree, conduction disturbance, sinus bradycardia, orthostatic hypotension, lowering blood pressure, "tides" of blood to the face, palpitations;

rarely: pulmonary thromboembolism arteries, venous thrombosis, sinus tachycardia;

frequency is unknown: syncope, blockade of the right and left legs of the bundle of His.

From the respiratory system, organs of the chest and mediastinum

often: nasal congestion, shortness of breath, epistaxis, sinus congestion, cough, pain in the larynx and pharynx;

infrequently: wheezing, aspiration pneumonia, dysphonia, productive cough, airway obstruction, wet wheezing, breathing disorder, congestion in the lungs, swelling of the nasal mucosa;

rareabout: sleep apnea syndrome, hyperventilation;

From the gastrointestinal tract

hasto: dryness of the oral mucosa, nausea, vomiting, dyskinesia, dyspepsia, abdominal pain, abdominal discomfort, toothache, constipation, increased salivation, diarrhea;

infrequently: flatulence, gastritis, gastroenteritis, fecal calcification, fecal incontinence, dysphagia, hypo-salivation;

rarely: pancreatitis, intestinal obstruction, edema of the tongue, cheilitis, jaundice.

From the skin and subcutaneous tissues

often: skin rash, erythema;

infrequently: urticaria, skin itch, alopecia, skin discoloration, onychomycosis, papular rashes, generalized rash, maculopapular rash, dry skin, seborrheic dermatitis, hyperkeratosis, acne, eczema, skin disease, skin lesion, Quincke's edema;

rarely: dandruff, a drug rash.

From the musculoskeletal and connective tissue

often: wewspasm, arthralgia, back pain, musculoskeletal pain, pain in the limbs;

infrequently: violation of posture, gait disturbance, swelling of the joints, joint stiffness, muscle weakness, myalgia, neck pain;

rarely: rhabdomyolysis.

From the genitourinary system

often: urinary incontinence;

infrequently: pollakiuria, delay urination, dysuria, erectile dysfunction, ejaculation disorder, amenorrhea, menstrual disorder cycle, gynecomastia, galactorrhea, chest pain, discomfort in the mammary glands, vaginal discharge, vaginal bleeding, sexual dysfunction;

rarely: priapism, delay in menstruation, enlargement of the mammary glands, engorgement of the mammary glands, excrement from the mammary glands;

frequency unknown: enuresis, pain when urinating.

General disorders and disorders at the site of administration

Hasto: fatigue, swelling, asthenia, fever, pain in the chest area;

infrequently: thirst, poor health, swelling of the face, chills, gait disturbance, discomfort in the chest, malaise;

rarely: hypothermia, cold extremities, withdrawal syndrome, peripheral edema, compaction at the injection site.

Laboratory indicators

often: increase in concentration prolactin in the blood serum (in some cases can lead to gynecomastia, menstrual irregularities, amenorrhea and galactorrhea);

infrequently: increased activity of "liver" transaminases,increased activity of gamma-glutamyl transferase, increased activity creatinine phosphokinase.

Undesirable effects, associated with paliperidone

Paliperidone is an active metabolite of risperidone, therefore undesirable phenomena of these compounds complement each other. Additionally the following Undesirable effects were identified with the use of drugs with paliperidone.

From the side of the cardiovascular system: postural syndrome orthostatic tachycardia.

Class Effects

As with other antipsychotics, cases of lengthening of the interval are very rare QT, as well as ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac arrest and flutter-fibrillation of the ventricles tachycardia of the "pirouette" type.

Venous thromboembolism

Cases of venous thromboembolism, including pulmonary embolism and deep vein thrombosis, have been reported with the use of antipsychotics (incidence is unknown).

Weight gain

When assessing the criterion for an increase in body weight ≥ 7% in adult patients with schizophrenia, taking risperidone and placebo for 6-8 weeks, significantly higher body weight was found in patients taking risperidone (18%), compared to patients taking placebo (9%). In a population of adolescents with behavioral disorders in long-term studies, the body weight increased by an average of 7.3 kg after 12 months of treatment. The expected increase in body weight for healthy children aged 12-16 years is 3-5 kg per year for girls, 5 kg for boys.

Adverse events the special patient groups

Transient and acute disturbances of cerebral circulation were undesirable reactions, which in clinical studies were observed in elderly patients with dementia with a frequency of 1.4% and 1.5%, respectively. In addition, the following undesirable reactions were observed in elderly patients with dementia with a frequency of ≥ 5% and at least twice as often as in other populations of adult patients: urinary tract infections, peripheral edema, lethargy and cough.

Pediatric population

In general, it is assumed that the types of adverse reactions in children are the same as in adults. The following adverse reactions were recorded at a frequency of ≥5% and not less than twice as often in pediatric patients (aged 5 to 17 years) than in adults,participating clinical trials: somnolence / sedation, fatigue, headache, increased appetite, vomiting, upper respiratory tract infection, nasal congestion, abdominal pain, dizziness, cough, pyrexia, tremor, diarrhea, and enuresis, the syndrome of "lifting" the newborn.

The effect of long-term treatment with risperidone on puberty and growth has not been adequately studied.

In case of side effects not listed in this manual, you should consult your doctor.

Overdose:

Symptoms: drowsiness, sedation, tachycardia, arterial hypotension, extrapyramidal symptoms, rarely - lengthening of the interval QT, convulsions. With the simultaneous use of risperidone with paroxetine, cases of arrhythmia of the type "torsade de pointes".

Treatment. In acute overdosage should ensure a free airway to ensure an adequate oxygen supply and ventilation, ECG monitoring, gastric lavage, appointment of activated charcoal and laxatives, symptomatic therapy aimed to maintain vital body functions, the development of extrapyramidal symptoms assignment anticholinergic drugs ( eg, trihexyphenidyl).Continuous medical supervision should continue until the symptoms of intoxication disappear completely. There is no specific antidote.

Interaction:

Caution should be applied risperidone together with drugs that extend the interval QT, such as antiarrhythmics Ia class (eg, quinidine, procainamide, disopyramide), Class III, (eg, amiodarone, sotalol), tricyclic antidepressants (eg, amitriptyline), tetracyclic antidepressants (maprotiline and others), some antihistamines, others antipsychotics; some antimalarial drugs (eg, quinine, meflochisn), drugs that cause a violation of the electrolyte balance (hypokalemia, hypomagnesemia), drugs that inhibit the hepatic metabolism of risperidone.

Antacid preparations (eg, cimetidine, ranitidine) reduce the absorption of oral neuroleptics.

Risperidone reduces the effectiveness levodopa and other agonists of dopamine. If simultaneous application is required, it is recommended to use the minimum effective doses of drugs.

Hypotensive medicines increase the severity of lowering blood pressure on the background of taking risperidone.

Phenotiazine neuroleptics, tricyclic antidepressants and some beta-blockers with simultaneous application with risperidone can increase its concentration in blood plasma, without affecting the concentration of "neuroleptic fraction."

Carbamazepine and other inducers of "hepatic" enzymes (eg, rifampicin, phenytoin, phenobarbital) reduce the concentration of the active fraction of risperidone in the blood plasma.

At the beginning of the application / with the withdrawal of carbamazepine or other inducers of "liver" enzymes, the dosage of risperidone should be adjusted.

At simultaneous reception fluoxetine / paroxetine the concentration of risperidone in the blood plasma decreases, however the level of the "neuroleptic fraction" increases insignificantly. However, at the beginning of the application / with the abolition of fluoxetine / paroxetine, the dosage of risperidone should be adjusted.

It is expected that others inhibitors of CYP2D6, such as quinidine, may reduce the plasma concentration of risperidone.

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

Given that risperidone has an impact primarily on the central nervous system, it should be used with caution in combination with other drugs of central action (opiates, antihistamines, benzodiazepines) and with ethanol (alcohol) because of the increased risk of sedation.

With the simultaneous use of risperidone with furosemide In elderly patients with dementia, the risk of death increases. Simultaneous use of risperidone and paliperidone is not recommended, since the latter is an active metabolite of risperidone and possibly an increase in the antipsychotic effect.

There was no clinically significant interaction with the simultaneous use of risperidone with lithium preparations, sodium valproate, digoxin, topiramate, selective inhibitors of anticholinesterase (eg, galantamine, donepezil), amitriptyline, erythromycin, psychostimulating drugs (eg, methylphenidate).

Pediatric population

The interaction of risperidone with other drugs was evaluated only in adult patients.

Special instructions:

Results of a meta-analysis of 17 controlled trials atypical antipsychotics, including risperidone, showed an increase in mortality in elderly patients with dementia who received atypical antipsychotics compared with the placebo group.

In placebo-controlled studies of risperidone in this population, the death rate was 4.0% in the group of patients who received risperidone, compared with 3.1% in the group receiving placebo. The odds ratio (the exact confidence interval of 95%) was 1.21 (0.7-2.1). The average age of the deceased patients was 86 years (ranging from 67 to 100 years). Data from two large observational studies showed that elderly patients with dementia who received conventional antipsychotics also had a slight increase in the risk of death compared to patients who were not receiving active therapy. An accurate assessment of the increase in this risk is impossible due to insufficient data, and the cause of this phenomenon is unknown. It remains unclear to what extent the increase in mortality in observational studies may be due to the use of antipsychotics, given the impact on this indicator of certain characteristics of patients.

In placebo-controlled studies of risperidone, mortality was increased in elderly patients with dementia who received furosemide in combination with risperidone (7.3%, mean age 89 years, range from 75 to 97 years) compared with patients receiving only risperidone (3.1%, average age 84 years, ranging from 70 to 96 years) or only furosemide (4.1%, the average age is 80 years, ranging from 67 to 90 years). Increased mortality in patients who received furosemide in combination with risperidone, was observed in two of four clinical studies. The use of risperidone in combination with other diuretics (mainly low doses of thiazides) was not associated with an increase in the death rate of patients.

Regardless of the therapy, dehydration was a common factor in the increased risk of death of patients, so it is necessary to avoid the development of this condition in elderly patients with dementia.

Rispolux® follows use with caution in patients with risk factors for stroke. In randomized placebo-controlled studies in the population of patients with dementia who received atypical antipsychotics, an increased risk of cerebrovascular adverse reactions was approximately 3-fold.Combined data from six placebo-controlled trials in which elderly patients (> 65 years) with dementia mostly participated showed that cerebrovascular unwanted reactions (in total, serious and not serious) were observed in 3.3% (33/1009) of patients, who received risperidone, and in 1.2% (8/712) of the patients receiving the placebo. The odds ratio (the exact confidence interval of 95%) was 2.96 (1.34-7.50). The mechanism of this increase in risk is unknown. Increased risk can not be excluded if other neuroleptic drugs are used, or in other populations of patients. Rispolux® should be used with caution in patients with risk factors for developing acute cerebral circulation disorders.

Risk of cerebrovascular undesired reactions was significantly higher in patients with mixed or vascular dementia compared with dementia of the Alzheimer type. Therefore, Rispolux® should not be used in patients with other types of dementia other than Alzheimer's dementia.

Physicians are advised to evaluate the risks and benefits of using risperidone in elderly patients with dementia, taking into account the predictive signs of the risk of developing acute brain damage blood circulation in specific patients. Patients / caregivers should be alerted to immediately report potential signs and symptoms of cerebrovascular unwanted effects, such as sudden development of sensory or muscle weakness in the face, hands or feet, and speech or vision impairment. In these cases, consideration should be given to the possibility of using all appropriate therapies, including the discontinuation of risperidone.

Rispolux® should be used only briefly in patients with moderate to severe Alzheimer's disease in combination with persistent aggression in cases of insufficient effectiveness or complete ineffectiveness of non-pharmacological approaches and the potential risk of harm to yourself or others. The condition of patients should be regularly monitored and the need for further therapy to be reviewed. Rispolux® can block alpha-adrenergic receptors, so patients taking Rispolux®, especially at the beginning of therapy, may have a marked decrease in blood pressure (hypotension, including orthostatic).Caution should be used with Rispolux® in patients with cardiovascular disease, QT interval prolongation, bradycardia or electrolyte disorders (hypokalemia, hypomagnesemia), as this may increase the risk of arrhythmia. Also, due to the blocking effect of risperidone on alpha-adrenergic receptors, priapism may occur during treatment with the drug.

The use of drugs that can block dopamine receptors may be accompanied by induction of tardive dyskinesia (involuntary rhythmic movement, predominantly of the language and / or person). The occurrence of extrapyramidal symptoms is a risk factor for tardive dyskinesia. In the event of late discenezia or malignant neuroleptic syndrome characterized by hyperthermia, muscle rigidity, autonomic instability, altered consciousness and increased activity of creatine phosphokinase, and the development of myoglobinuria (due to rhabdomyolysis) and acute renal failure, the use of all antipsychotics, including risperidone, should be terminated.

With the use of neuroleptic drugs, a violation of the central regulation of body temperature is possible. It is recommended that patients be observed when using risperidone, especially when conditions arise that increase body temperature (for example, intensive exercise, visiting a bath / sauna), while using drugs with anticholinergic action or in patients with dehydration.

With the use of antipsychotics, cases of venous thromboembolism have been described, so before starting treatment with Risporux® it is necessary to identify all risk factors for thromboembolism and to carry out a number of preventive measures.

When using neuroleptics, including risperidone, in patients with Parkinson's disease or with dementia with Levy bodies, doctors should evaluate the benefit / risk ratio. The course of Parkinson's disease with risperidone may worsen. Both groups of patients have an increased risk of malignant neuroleptic syndrome, as well as increased sensitivity to neuroleptic medicines.Manifestations of hypersensitivity, in addition to extrapyramidal symptoms, may include confusion, dull sensitivity, postural instability with frequent falls.

In patients with low seizure threshold, Risporux® should be used with caution, since the risk of seizures increases.

When treating Risporux®, hyperglycaemia or exacerbation of already existing diabetes mellitus is possible. Therefore, it is advisable to regularly monitor the concentration of glucose in the blood plasma in patients with diabetes mellitus and with risk factors for the development of diabetes mellitus.

Studies on cells have shown that the growth of cells in human breast tumors can be stimulated by prolactin. Despite the lack of a clear link between tumor growth and the use of neuroleptics, Risporux® should be used with caution in patients with pre-existing hyperprolactinemia and in patients with the possible presence of prolactin-dependent tumors.

Before Rispholux® is administered to a child or adolescent with a behavioral disorder, fully assess the causes of aggressive behavior, eliminate pain, social problems. The sedative effect of risperidone should be closely monitored in children and adolescents because of a possible decrease in learning ability. The change in the time of application of risperidone can increase sedation and reduce attention in children and adolescents.

Because of the possible consequences of prolonged hyperprolactinemia on the growth and puberty of children and adolescents, a regular clinical and laboratory evaluation of the endocrinological status is necessary: height, weight, puberty, control of the menstrual cycle, and other potential effects of prolactin.

During treatment with Rispolux®, it is recommended that regular examination of the central nervous system function for extrapyramidal and other movement disorders.

Class Effect

When using antipsychotic drugs, incl. risperidone, possibly the occurrence of leukopenia / neutropenia, as well as agranulocytosis. Therefore, before using Rispollux ®, especially in patients with risk factors for developing leukopenia / neutropenia, a clinical blood test should be performed to count the leukocyte formula.If a patient exhibits severe neutropenia, the increase in body temperature or other symptoms of infection should be carefully monitored. Patients with severe neutropenia (absolute number of neutrophils less than 1000 / mm³), in the absence of other reasons, treatment with Risksolux® should be stopped until the number of white blood cells is fully restored. Drowsiness is the most common side effect when using risperidone and its expression is dose dependent.

When using antipsychotic drugs, incl. risperidone, reported violation of esophageal motility and aspiration. Aspiration pneumonia is the most common cause of morbidity and mortality in patients with dementia due to Alzheimer's disease. Risporux®should be used with caution in patients at risk of developing aspiration pneumonia.

Due to the fact that the use of Risporux® can lead to an increase in body weight, the patient should be advised on the diet regime.

When orthostatic hypotension occurs, especially at the beginning of treatment, the question of reducing the dose of the drug should be considered.

In patients with diseases of the cardiovascular system, as well as during dehydration, hypovolemia or cerebrovascular disorders, the dose of the drug should be increased gradually.

With the withdrawal of carbamazepine and other inducers of "liver" enzymes, the dose of Risporux® should be reduced.

Risperidone has antiemetic effect that can mask signs and symptoms of drug overdose or symptoms of intestinal obstruction, Reye's syndrome, and brain tumors.

With the use of alpha-1a-adrenoreceptor antagonists, including risperidone, atonic iris syndrome was noted during cataract surgery, which may increase the risk of complications during and after eye surgery. No potential the benefits of discontinuing therapy with alpha-1-adrenergic antagonists before surgery for cataracts, so it is necessary to cancel the drug after assessing the benefit / risk relationship of stopping antipsychotic therapy.

It is recommended that Risporux® be gradually phased out, after a sharp cessation of treatment high doses of neuroleptics may develop the syndrome of "withdrawal."

Special precautions when destroying an unused preparation

There is no need for special precautions when destroying an unused preparation.

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

During the period of treatment with Rispolux®, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:Film-coated tablets, 1 mg, 2 mg, 3 mg and 4 mg.

Packaging:

Tablets, film-coated, 1 mg or 2 mg: 10 tablets in a PVC / PE / PVDC / aluminum blister, 2, 5, 6 or 10 blisters each in a cardboard box together with instructions for medical use.

Tablets, film-coated, 3 mg or 4 mg: 10 tablets in a blister, 2, 5 or 6 blisters in a cardboard box, along with instructions for medical use.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-007905/08

Date of registration:07.10.2008 / 21.08.2013

Expiration Date:Unlimited

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

NOVARTIS (Bangladesh), Ltd. Bangladesh

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp26.12.2016

Illustrated instructions

Instructions

Rispolux® (Rispolux®)