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

Excipients: microcrystalline cellulose 58 mg, lactose monohydrate 35 mg, povidone 2 mg, sodium carboxymethyl starch (sodium starch glycolate) 2 mg,silicon dioxide colloid 1 mg, magnesium stearate 1 mg.

Sheath: fall off II pale blue 4 mg, in t.ch. polyvinyl alcohol partially hydrolyzed 1.6 mg, macrogol (0.808 mg), talc 0.592 mg, titanium dioxide 0.974 mg, indigocarmine (aluminum lacquer) 0.024 mg, quinoline yellow (aluminum varnish) 0.002 mg.

For a dosage of 2 mg:

Active substance: one tablet contains active ingredient risperidone 2 mg.

Excipients: cellulose, microcrystalline 116 mg, lactose monohydrate 70 mg, povidone 4 mg, sodium carboxymethyl starch (sodium starch glycolate) 4 mg, silicon dioxide colloid 2 mg, magnesium stearate 2 mg.

Sheath: opadrai II pale blue 8 mg, incl. polyvinyl alcohol partially hydrolyzed 3.2 mg, macrogol (polyethylene glycol) 1.616 mg, talc 1.184 mg, titanium dioxide 1.948 mg, indigocarmine (aluminum varnish) 0.048 mg, quinoline yellow (aluminum lacquer) 0.004 mg.

For a dosage of 3 mg:

Active substance: one tablet contains active ingredient risperidone 3 mg.

Excipients: cellulose microcrystalline 174 mg, lactose monohydrate 105 mg, povidone 6 mg, sodium carboxymethyl starch (sodium starch glycolate) 6 mg, silicon dioxide colloid 3 mg, magnesium stearate 3 mg.

Sheath: opadraj II pale blue 12 mg, incl. polyvinyl alcohol partially hydrolyzed 4.8 mg, macrogol (polyethylene glycol) 2.424 mg, talc 1,776 mg, titanium dioxide 2,922 mg, indigocarmine (aluminum lacquer) 0.072 mg, quinoline yellow (aluminum lacquer) 0.006 mg.

For a dosage of 4 mg:

Active substance: one tablet contains active ingredient risperidone 4 mg.

Excipients: cellulose microcrystalline 232 mg, lactose monohydrate 140 mg, povidone 8 mg, sodium carboxymethyl starch (sodium starch glycolate) 8 mg, silicon dioxide colloid 4 mg, magnesium stearate 4 mg.

Sheath: opadrai II pale blue 16 mg, incl. polyvinyl alcohol partially hydrolyzed 6.4 mg, macrogol (polyethylene glycol) 3.232 mg, talc 2.368 mg, titanium dioxide 3.896 mg, indigocarmine (aluminum lacquer) 0.096 mg, quinoline yellow (aluminum lacquer) 0.008 mg.

Description:Tablets, covered with a film membrane, pale blue, round, biconvex.

Pharmacotherapeutic group:Antipsychotic agent (antipsychotic).

ATX: & nbsp

N.05.A.X Other antipsychotics

N.05.A.X.08 Risperidone

Pharmacodynamics:

Antipsychotic agent - (neuroleptic), a derivative of benzisoxazole; also has a sedative, antiemetic and hypothermic effect. Selective monoaminergic antagonist, possesses high tropicity to 5-HT₂serotonin and D₂dopamine receptors, is also associated with α₁-adrenoceptors and with slightly less affinity with H₁-histamine and α₂-adrenoceptors.Has no tropism for cholinergic receptors.

Antipsychotic action due to blockade D₂dopamine receptors of the mesolimbic and mesocortical system. Sedative action is due to blockade of adrenoreceptors of the reticular formation of the brainstem; antiemetic effect - blockade D₂-dophamine receptors of the trigger zone of the vomiting center; hypothermic action - blockade of dopamine receptors of the hypothalamus.

Suppresses productive symptoms (delirium, hallucinations, aggressiveness), automatism. Causes less inhibition of motor activity and less degree induces catalepsy than "typical" antipsychotics (neuroleptics). Blockade as 5-HT₂-serotonin, and D₂-dophamine receptors can reduce the propensity to extrapyramidal side effects. Can induce a dose-dependent increase in prolactin concentration in plasma.

Pharmacokinetics:

Suction and distribution

Absorption is fast and complete (food does not affect the completeness and absorption rate). The time to reach the maximum concentration (T_Cmax) in plasma - 1-2 hours. Equilibrium concentration (C_ss) risperidone in the body in most patients is achieved within 1 day, 9-hydroxyrisperidone - 4-5 days. The concentrations of risperidone in plasma are proportional to the dose of the drug (within therapeutic doses). Quickly distributed, penetrates into the central nervous system, breast milk. The volume of distribution is 1.1 l / kg. Connection with plasma proteins (with α₁glycoprotein and albumin) risperidone - 90%, 9-hydroxyrisperidone - 77 %.

Metabolism

Metabolized by isoenzyme CYP2D6 to the active metabolite of 9-hydroxyrisperidone (risperidone and 9-hydroxyrisperidone constitute the active antipsychotic fraction). Another way of metabolism is N-dealkylation.

Excretion

The half-life (T_1/2) risperidone -, 3 h, T_1/2- 9-hydroxyrisperidone and active antipsychotic fraction - 20-24 h.

It is excreted by the kidneys (70 %, of them -35-45% in the form of pharmacologically active fraction) and intestine (14%).

In chronic Renal insufficiency (CRF) clearance of risperidone is reduced by 60%. In liver failure, the content of risperidone in plasma is increased by 35%.

In elderly patients, clearance decreases and lengthens T_1/2.

Indications:

Curbing acute attacks and prolonged maintenance therapy:

- schizophrenia in adults;

Contraindications:

Hypersensitivity to the drug components, lactation period, children under 18 years of age, lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

Carefully:

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

- dehydration and hypovolemia;

- disorders of cerebral circulation;

- Parkinson's disease;

- convulsions and epilepsy (including in the anamnesis);

- severe renal or hepatic impairment (see section "Method of use and doses");

- abuse of medicines or drug dependence (see para.

section "Method of administration and dose");

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

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

Pregnancy and lactation:Pregnancy

Data on the safety of risperidone in pregnant women are not available. In animal experiments risperidone did not have a direct toxic effect on the reproductive system, but caused some indirect effects mediated through prolactin and the central nervous system. None of the studies risperidone did not possess a teratogenic effect. In the case of a woman taking antipsychotic drugs (including risperidone) in the third trimester of pregnancy, neonates have a risk of extrapyramidal disorders and / or syndrome "cancellation" of varying severity. These symptoms may include agitation, muscle hypertension and hypotension, tremor, drowsiness, respiratory disorders, and breast-feeding disorders. Risperidone can be used during pregnancy only in In cases where the potential benefit to the mother outweighs the possible risk to the fetus.

Lactation

Because the risperidone and 9-hydroxyrisperidone penetrate into breast milk, to women using risperidone, do not breast-feed.

Dosing and Administration:

Inside, regardless of food intake.

Schizophrenia

Adults. Risperidone may be given once or twice a day.

The initial dose of risperidone 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 stored, or if necessary, adjusted. Usually the optimal dose is 4-6 mg per day. In a number of cases, a slower dose increase and a lower initial and maintenance dose.

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

If an additional sedative effect is required, risperidone therapy can be supplemented with benzodiazepine derivatives.

Due to the impossibility of accurate dose selection in elderly patients with schizophrenia, the drug is not used.

Patients who have sustained drowsiness, it is recommended to take half the daily dose 2 times a day.

Bipolar disorders in mania

Adults. The recommended initial dose of the drug is 2 or 3 mg per day at a time. If necessary, this dose can be increased at least 24 hours per 1 mg per day. For most patients, the optimal dose is 1-6 mg per day.

Patients who have sustained drowsiness, it is recommended to take half the daily dose 2 times a day.

Diseases of the liver and kidneys

In comparison with other patients, the ability to excrete the active antipsychotic fraction has been reduced in patients with kidney diseases. In patients with liver disease, there is an increased concentration of free fraction of risperidone in the blood plasma.

The initial and maintenance dose in accordance with the indications should be reduced 2 times, increasing the dose in patients with liver and kidney disease should be slower.

In this category of patients risperidone should be administered with caution.

Side effects:Side effects of risperidone in therapeutic doses are given with a frequency distribution and system-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 (<1/10 000 cases).

Infections and invasions: very often - urinary tract infections in elderly patients with dementia; often - nasopharyngitis, upper respiratory tract infections, sinusitis, urinary tract infections,in elderly patients with dementia - pneumonia, phlegmon, in children - rhinitis, flu-like syndrome; infrequently - ear infections, viral infections, pharyngitis, tonsillitis, bronchitis, eye infections, local infections, cystitis, onychomycosis, acrodermatitis, bronchopneumonia, respiratory infections, tracheobronchitis.

On the part of the organs of hematopoiesis and lymphatic system: often - anemia; infrequently - granulocytopenia, neutropenia; very rarely - thrombocytopenia, agranulocytosis.

From the immune system: infrequently - hypersensitivity reactions; very rarely - anaphylactic shock.

From the endocrine system: infrequently - giperprolaktinemiya, diabetic coma; very rarely - a violation of the secretion of antidiuretic hormone.

From the side of metabolism and nutrition: often - decreased appetite (in elderly patients with dementia), increased appetite (in children); infrequently - polydipsia, anorexia; rarely - diabetic ketoacidosis, diabetes mellitus, hypoglycemia, water intoxication.

Mental disturbances: very often - insomnia; often - anxiety, nervousness, in elderly patients with dementia - confusion, in children - lethargy; infrequently - agitation, flattening of affect, sleep disturbances, weakening of libido, anorgasmia; very rarely - mania.

From the side of the nervous system: very often - Parkinsonism (including extrapyramidal disorders, "cogwheel" syndrome, akinesia, bradykinesia, hypokinesia, muscle rigidity), in children - drowsiness, headaches, sedation; often akathisia (including restlessness), drowsiness, dizziness, sedation, tremor, dystonia (including muscle spasms, involuntary muscle contractions, muscle contractions, involuntary eyeball movements, tongue paralysis), lethargy, postural dizziness, dyskinesia (including muscle twitching, chorea and choreoathetosis), fainting, in elderly patients with dementia - depressed condition, in children - dysarthria, attention disturbance, gait disturbance; infrequent - lack of response to stimuli, impaired coordination, loss of consciousness, speech impairment, hypoesthesia, impaired movement, tardive dyskinesia, cerebral ischemia, cerebrovascular disorders, malignant neuroleptic syndrome, rhythmic nodding.
From the side of the organ of vision: often - reduced visual acuity, in elderly patients with dementia - conjunctivitis; infrequently - congestion hyperemia, visual impairment,involuntary rotation of the eyeballs, edema of the eyelids, periorbital edema, crust formation at the edge of the eyelids, dry eyes, increased lacrimation, photophobia, increased intraocular pressure.

From the side of the organ of hearing and the labyrinth: often - pain in the ear; infrequently, noise in the ears. From the cardiovascular system: often - tachycardia, orthostatic hypotension, lowering of arterial pressure, in elderly patients with dementia - transient ischemic attack, myocardial infarction, stroke, in children - palpitation; infrequently - sinus bradycardia, sinus tachycardia, palpitations, atrioventricular blockade of the 1st degree, blockage of the right or left legs of the bundle of the Hisnia, atrioventricular blockade, "hot flashes" of blood; very rarely - atrial fibrillation.

On the part of the respiratory system, chest and mediastinum: often - nasal congestion, shortness of breath, epistaxis, sinus congestion, in elderly patients with dementia - cough, rhinorrhea, in children - cough, rhinorrhea, pain in the larynx and pharynx, stagnation in the lungs; infrequently - wheezing, aspiration pneumonia, dysphonia, productive cough, blockage of the respiratory tract, wet wheezing, respiratory failure, edema of the nose, hyperventilation; very rarely - sleep apnea syndrome.

Gastro-intestinal tract: often - nausea, constipation, dyspepsia, vomiting, diarrhea, drooling, dry mouth, stomach discomfort, abdominal pain, in elderly patients with dementia - dysphagia, fekaloma; infrequently - encopresis, gastritis, edema of lips, cheilitis, aptializm, dysgeusia; very rarely - intestinal obstruction, pancreatitis.

From the liver and biliary tract: very rarely - jaundice.

Skin and subcutaneous tissue disorders: often - a rash, dry skin, dandruff, seborrheic dermatitis, hyperkeratosis, elderly patients with dementia - Erythema in children - itching, acne; infrequently - a violation of skin pigmentation, rash erythematous, papular rash, generalized rash, maculopapular rash; very rarely - Quincke's edema, alopecia.

On the part of the musculoskeletal system and connective tissue disorders: often - back pain, arthralgia, pain in the limbs, in elderly patients with dementia - abnormal gait, swelling of the joints in children - myalgia, pain in the neck; rarely - muscle chest pain, stiffness in the joints, muscle weakness, rhabdomyolysis.

From the kidneys and urinary tract: often - incontinence, in children - enuresis, pollakiuria; infrequently - pain when urinating; very rarely - urinary retention.

From the reproductive system and mammary glands: often: - lack of ejaculation, in children - galactorrhea; infrequent - menstruation, amenorrhea, gynecomastia, vaginal discharge, erectile dysfunction, ejaculatory disturbance, breast enlargement, sexual dysfunction, retrograde ejaculation; very rarely - priapism.

Influence on the course of pregnancy, postpartum and perinatal conditions: very rarely - withdrawal syndrome in newborns.

Common violations: often - fatigue, asthenia, fever, pain in the chest, in elderly patients with dementia - peripheral edema, in children - sluggishness, discomfort in the chest area; infrequent - thirst, flu-like syndrome, general malaise, swelling (including facial edema, general edema), chills, cold extremities, withdrawal syndrome; very rarely - hypothermia. Violations of laboratory and instrumental indicators: often - increased activity of creatine phosphokinase, increased heart rate, in elderly patients with dementia - increased body temperature, in children - weight gain, hyperprolactinaemia; infrequently - increased activity of alanine aminotransferase, ECG disorder, eosinophilia,increase the activity of aspartate aminotransferase, leukocytosis, hyperglycemia, decreased hemoglobin, hematocrit decrease, lowering blood pressure, an increase in blood cholesterol concentration, an increase in the concentration of triglycerides in the blood; very rarely - an extension of the QT interval on the ECG.

Overdose:Symptoms: drowsiness, sedation, tachycardia, lowering of arterial pressure, extrapyramidal symptoms. There was an extension of the QT interval and convulsions. Bi-directional ventricular tachycardia was noted in a simultaneous application of an increased dose of risperidone and paroxetine.
In case of an overdose, the possibility of an overdose from taking several drugs should be considered.
Treatment. It is necessary to achieve and maintain a free airway to ensure adequate oxygen delivery and ventilation, gastric lavage (after intubation if the patient is unconscious) and appoint Activated carbon together with laxative / Immediately begin monitoring ECG to identify possible arrhythmias.
Specific antidote does not exist, appropriate symptomatic therapy should be conducted.Reduction of blood pressure and collapse should be eliminated by intravenous fluid infusions and / or adrenomimetics. In case of development of acute extrapyramidal symptoms, m-holinoblokatory (for example, trihexyphenidyl). Continuous medical supervision should continue until the symptoms of an overdose disappear.

Interaction:Risperidone enhances the effect of other drugs, depressing the central nervous system, including ethanol. Risperidone reduces the effectiveness of levodopa and other dopamine receptor agonists.
With the simultaneous use of risperidone with drugs that extend the QT interval, caution should be exercised.
Clozapine reduces the clearance of risperidone.
With simultaneous use with carbamazepine, 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 liver enzymes. When the appointment and after the withdrawal of carbamazepine or other inducers of microsomal liver enzymes, the dose of risperidone should be adjusted. Fluoxetine and paroxetine (inhibitors of microsomal liver enzymes) increase the concentration of risperidone in plasma, but to a lesser extent the concentration of the active antipsychotic fraction. When the appointment and after the abolition of fluoxetine or paroxetine, the dose of risperidone should be adjusted.
Topiramate moderately reduces the bioavailability of risperidone, but not the active antipsychotic fraction. This interaction is not considered clinically significant. 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 the active antipsychotic fraction.
Cimetidine and ranitidine increase the bioavailability of risperidone, but have a minimal effect on the concentration of the active antipsychotic fraction.
Erythromycin (an inhibitor of microsomal liver enzymes) does not affect the pharmacokinetics of risperidone and the active antipsychotic fraction.
Cholinesterase inhibitors (galantamine and donepezil), do not have a clinically significant effect on the pharmacokinetics of risperidone and the active antipsychotic fraction.
With the simultaneous use of risperidone with other drugs that bind well to plasma proteins, there is no clinically pronounced displacement of any drug from the plasma protein fraction.
Hypotensive drugs increase the degree of reduction in blood pressure in the background of risperidone.
Risperidone does not have a 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. At the beginning of risperidone treatment for schizophrenia, if clinically justified, it is recommended that the previous therapy be gradually phased out. In this case, if patients are transferred from the therapy of depot forms of antipsychotics, then risperidone therapy is recommended to begin, instead of the next scheduled injection. Periodically, the need to continue therapy with antiparkinsonian drugs should be evaluated.
Use in elderly patients with dementia. In clinical studies in elderly patients with dementia in the treatment of "atypical" antipsychotic agents, including risperidone, there was an increased mortality in comparison with placebo. When using risperidone in this population, the incidence of fatalities was 4% for patients taking risperidone, compared with 3.1% for placebo. The average age of the deceased patients is 86 years (range 67-100 years). For elderly patients with dementia who took 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 (4.1%, average age 84 years, range 75-96 years) and a group that only took furosemide (3.1%, the average age is 80 years, the range is 67-90 years). There are no pathophysiological mechanisms that explain this observation. However, you should observe, extra care when using the drug in such cases. There was no increase in mortality in patients taking other diuretics simultaneously with risperidone.Regardless of the treatment, in elderly patients with dementia, dehydration is a common risk factor for mortality and should be carefully monitored.
When risperidone was used in comparison with placebo, elderly patients with dementia experienced an increase in cerebrovascular accidents, including deaths (mean age 85 years, range 73-97 years).
Orthostatic hypotension. In connection with the α-adrenoblocking action of risperidone, orthostatic hypotension may occur, especially during the initial dose selection. Clinically significant reduction in blood pressure is observed with the simultaneous use of risperidone with antihypertensive drugs. With a decrease in blood pressure should consider reducing the dose of one or both drugs. In patients with diseases of the cardiovascular system, as well as in the dehydration of hypovolemia or cerebrovascular disorders, the dose should be increased gradually, according to the recommendations.
There are reports that the occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. Risperidone rarely causes the appearance of extrapyramidal symptoms than the "typical" neuroleptics. If signs and symptoms of tardive dyskinesia occur, you should consider withdrawing all antipsychotics.
In the case of malignant neuroleptic syndrome characterized by hyperthermia, muscle rigidity, instability of autonomic functions, impaired consciousness and increased activity of creatine phosphokinase in the blood (myoglobinuria (rhabdomyolysis) and acute renal failure may also occur), all antipsychotics, including risperidone. The use of antipsychotics, including risperidonePatients with Parkinson's disease or dementia with Levy bodies should be treated with caution, since in both groups of patients, the risk of malignant neuroleptic syndrome increased and sensitivity to antipsychotics was increased (including blunting of pain sensitivity, confusion, postural instability with frequent falls and extrapyramidal symptoms).
In the treatment with risperidone, hyperglycemia, diabetes mellitus, or exacerbation of already existing diabetes mellitus were observed. The establishment of the relationship between the use of "atypical" antipsychotics and impaired glucose metabolism is complicated by an increased risk of developing diabetes in patients with schizophrenia and the prevalence of diabetes in the general population. Given these factors, the relationship between the use of "atypical" antipsychotics and the development of side effects associated with hyperglycemia has not been fully established. In all patients, it is necessary to conduct clinical monitoring for the presence of symptoms of hyperglycemia and diabetes mellitus.
In the treatment with risperidone, a significant increase in body weight was observed. When treating risperidone, it is necessary to monitor the body weight of patients. Patients should be advised to refrain from overeating due to the possibility of weight gain.
As with other antipsychotics, caution should be exercised in prescribing risperidone to patients with a history of arrhythmias, patients with congenital QT interval elongation and with simultaneous use with drugs that increase the QT interval.
The ability of typical neuroleptics to reduce the threshold of convulsive readiness is known, so caution should be given risperidone patients with epilepsy.

Effect on the ability to drive transp. cf. and fur:Risperidone can have an impact on activities requiring increased attention and speed of psychomotor reactions: patients should be advised not to drive vehicles and not work with machinery until they find out their individual sensitivity to the drug.

Form release / dosage:Tablets, film-coated, 1 mg, 2 mg, 3 mg and 4 mg.

Packaging:10 tablets per contour cell package; 2 contour packagings along with instructions for use are placed in a pack.
For 20 or 100 tablets per can of polymer. Each bank along with the instruction for use is placed in a bundle.

Storage conditions:In a dry, protected from light place at a temperature of no higher than 25 ° C.
Keep out of the reach of children!

Shelf life:2 years.
Do not use the drug after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000943

Date of registration:18.10.2011

The owner of the registration certificate:Berezovsky Pharmaceutical Plant, ZAO Berezovsky Pharmaceutical Plant, ZAO Russia

Manufacturer: & nbsp

Berezovsky Pharmaceutical Plant, ZAO Russia

Information update date: & nbsp23.10.2015

Illustrated instructions

Instructions

Risperidone (Risperidone)