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

Excipients: tablet core: lactose monohydrate 33 mg, cellulose microcrystalline 14,121 mg, corn starch 8.621 mg, sodium carboxymethyl starch 2.5 mg, talc 0.379 mg, magnesium stearate 0.379 mg,

film-coated tablets: opadrai II 31F58914 white (hypromellose, lactose monohydrate, titanium dioxide (E171), macrogol-4000 and sodium citrate dihydrate) 2,500 mg.

Dosage 2 mg

Active substance: risperidone 2 mg;

Excipients: tablet core: lactose monohydrate 66 mg, cellulose microcrystalline 28,243 mg, corn starch 17,243 mg, sodium carboxymethyl starch 5.0 mg, talc 0.757 mg, magnesium stearate 0.757 mg,

film-coated tablets: opadrai II 31F58914 white (hypromellose, lactose monohydrate, titanium dioxide (E171), macrogol-4000 and sodium citrate dihydrate) 4.972 mg, dye solar sunset yellow (E110) 0.028 mg.

Dosage 3 mg

Active substance: risperidone 3 mg;

Excipients: tablet core: lactose monohydrate 99 mg, microcrystalline cellulose 42.364 mg, corn starch 25.864 mg, carboxymethyl starch sodium 7.5 mg, talc 1.136 mg, magnesium stearate 1.136 mg,

film sheath tablet: opadrai II 31F58914 white (hypromellose, lactose monohydrate, titanium dioxide (E171), macrogol-4000 and sodium citrate dihydrate) 7.479 mg, dye quinoline yellow (E104) 0.021 mg.

Dosage 4 mg

Active substance: risperidone 4 mg;

Excipients: tablet core: lactose monohydrate 132 mg, microcrystalline cellulose 56.486 mg, corn starch 34.486 mg, sodium carboxymethyl starch 10.0 mg, talc 1.514 mg, magnesium stearate 1.514 mg,

film sheath tablet: opadrai II 31F58914 white (hypromellose, lactose monohydrate, titanium dioxide (E171), macrogol 4000 and sodium citrate dihydrate) 9.910 mg, quinoline yellow (E104) dye 0.075 mg, indigocarmine (E132) 0.015 mg.

Description:

Dosage of 1 mg. Round, biconvex tablets, covered with a film shell of white color, with a risk on one side.

Dosage 2 mg. Round, biconvex tablets, covered with a film membrane from light orange to orange, with a risk on one side.

Dosage of 3 mg. Round, biconvex tablets, covered with a film coating from yellow to yellow with a greenish tint of color, with a risk on one side.

Dosage 4 mg. Round, biconvex tablets, covered with a film membrane of green color, with a risk on one side. The control is performed visually.

Pharmacotherapeutic group:antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.X Other antipsychotics

N.05.A.X.08 Risperidone

Pharmacodynamics:

Antipsychotic agent (antipsychotic), benzisoxazole derivative; also has a sedative, antiemetic and hypothermic effect. Selective monoaminergic antagonist, has a high tropism for serotonergic 5-NT₂ and dopaminergic D₂receptors, also binds to alF₁-adrenoceptors and with somewhat less affinity with H₁-gystaminergic and alphaa₂-adrenergic receptors. Has no tropism 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.

Suppresses productive symptoms (delirium, hallucinations, aggressiveness), automatism. Causes less inhibition of motor activity and to a lesser degree induces catalepsy than classical antipsychotics (antipsychotics) (APS). 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.

Can induce a dose-dependent increase in prolactin concentration in plasma.

Pharmacokinetics:

Absorption is fast and complete (food does not affect the completeness and absorption rate). Absolute bioavailability - 74%; relative (tablets in comparison with the solution) - 94%. Time to reach the maximum concentration in plasma risperidone - 1 hour; 9-hydroxyrisperidone - 3 hours (with high isoenzyme activity CYP2D6) and 17 hours (with low isoenzyme activity CYP2D6).

The equilibrium concentration of risperidone in the body in most patients is reached within 1 day, and 9-hydroxysperipidone - 4-5 days. Concentrations of risperidone and 9-hydroxyrisperidone in plasma are proportional to the dose of the drug (within 1-16 mg / day). Rapidly distributed throughout the body, penetrates into the central nervous system (CNS), breast milk. The volume of distribution is 1-2 l / kg. The connection with plasma proteins (with alpha-acidic glycoprotein and albumins) of risperidone - 90%, 9-hydroxyrisperidone - 77%. 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. The half-life (T_1/2) risperidone - 3 h (with high isoenzyme activity CYP2D6) and 20 hours (with low isoenzyme activity CYP2D6), T_1/29-hydroxyrisperidone - 21 hours (with high isoenzyme activity CYP2D6) and 30 hours (with low isoenzyme activity CYP2D6); active antipsychotic fraction - 20 h.

It is excreted by the kidneys 70% (35-45% in the form of a pharmacologically active antipsychotic fraction) and with bile (14%).

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

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

Indications:

Curbing acute attacks and prolonged maintenance therapy:

- acute and chronic schizophrenia and other psychotic disorders with productive and negative symptoms;

- affective disorders in schizophrenia;

- Behavioral disorders in patients with dementia with symptoms of aggressiveness (outbursts of anger, physical abuse), impairment (excitement, delirium) or psychotic symptoms;

- behavioral disorders in adolescents with 15 years of age and adult patients with a reduced intellectual level or mental retardation, in cases where destructive behavior (aggressiveness, impulsivity,autoaggression) is leading in the clinical picture of the disease.

To stabilize the mood in the treatment of mania in bipolar affective disorders (as a means of supportive therapy).

Contraindications:

Hypersensitivity to the components of the drug; lactation period; children under 15 years of age (effectiveness and safety not established); mania in bipolar affective disorders in children under the age of 18 (efficacy and safety not established); deficiency of lactase, lactose intolerance, glucose-galactose malabsorption.

Carefully:

Diseases of the cardiovascular system (chronic heart failure, suffered myocardial infarction, conduction disorders of the heart muscle); conditions predisposing to the development of tachycardia such as "pirouette" (bradycardia, electrolyte imbalance, concomitant medication prolonging the interval QT); risk factors for thromboembolism of venous vessels; dehydration and hypovolemia; impaired cerebral circulation; brain tumor; including prolactinoma of the pituitary gland; Parkinson's disease; disease of diffuse Levi bodies; convulsions (incl.in the anamnesis); severe renal insufficiency; severe hepatic impairment; drug abuse or drug dependence; intestinal obstruction; acute drug overdose; Reye syndrome (antiemetic effect of risperidone can mask the symptoms of these conditions); pregnancy; elderly patients with dementia.

Pregnancy and lactation:

The safety of risperidone during pregnancy has not been studied. The use of risperidone during pregnancy is only possible if the expected benefit to the mother exceeds the potential risk to the fetus.

Because the risperidone and 9-hydroxyrisperidone penetrate into breast milk, if necessary, the drug during lactation should stop breastfeeding.

Dosing and Administration:

Schizophrenia

Inside, 1 or 2 times a day. The initial dose is 2 mg / day. On the 2nd day the dose should be increased to 4 mg / 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 / day. In a number of cases, for example, in patients with a new episode of the disease, a slower dose increase and lower initial and maintenance doses may be justified.

When applied at doses of more than 10 mg / day, there was no increase in the therapeutic effect compared with smaller doses, with the appearance of extrapyramidal symptoms. The maximum daily dose is 16 mg / day.

For elderly patients an initial dose of 0.5 mg 2 times a day is recommended. If necessary, the dose can be increased to 1-2 mg 2 times a day.

With liver and kidney diseases an initial dose of 0.5 mg 2 times a day is recommended. This dose can be gradually increased to 1-2 mg 2 times a day.

Behavioral disorders the patients with dementia

For most patients, the optimal dose is 0.5 mg 2 times a day. The dose can be increased by no more than 0.5 mg, not more often than every other day. However, some patients receive 1 mg twice daily. When the optimal dose is reached, the administration may be recommended once a day.

Behavioral disorders in patients with mental retardation

The initial dose is 0.5 mg once a day. The dose can be increased by no more than 0.5 mg, not more often than every other day. The usual maintenance dose is 1 mg 1 time per day. Dosing interval 0.5-1.5 mg once a day.

Mania in bipolar affective disorders

Adults

The initial dose is 2 mg once a day.Then the dose is selected individually, increasing it by 1 mg / day, not more often than every other day. In most cases, the optimal dose is from 2 to 6 mg / day.

As with all symptomatic treatment, during treatment should assess the effectiveness and correct dosing regimen as needed.

For elderly patients an initial dose of 0.5 mg 2 times a day is recommended. If necessary, increase the dose to 1-2 mg 2 times a day.

With liver and kidney diseases an initial dose of 0.5 mg 2 times a day is recommended. The dose is gradually increased to 1-2 mg twice a day.

Side effects:

From the central and peripheral nervous system: insomnia, agitation, anxiety, headache; drowsiness, fatigue, dizziness, decreased ability to concentrate, blurred vision; mania, hypomania, extrapyramidal symptoms (tremor, rigidity, hypersalivation, bradykinesia, akathisia, acute dystonia).

Patients with schizophrenia - hypervolemia (either due to polydipsia or because the syndrome of inappropriate secretion of antidiuretic hormone), tardive dyskinesia (involuntary rhythmic movements mainly language and / or persons), neuroleptic malignant syndrome (hyperthermia,muscle rigidity, instability of autonomic functions, impaired consciousness and increased activity of creatinine phosphokinase), thermoregulatory disorders and epileptic seizures.

From the digestive system: constipation, dyspepsia, nausea or vomiting, abdominal pain, increased activity of "liver" transaminases, dryness of the oral mucosa, hypo- or hypersalivation, anorexia, increased appetite.

From the side of the cardiovascular system: Orthostatic hypotension, reflex tachycardia, increased blood pressure (BP), lengthening interval QT, pirouette ventricular arrhythmia, ventricular fibrillation, stroke and transient ischemic attacks (in elderly patients with dementia), thromboembolism of venous vessels, including thromboembolism of pulmonary vessels and deep veins.

On the part of the hematopoiesis system: neutropenia, thrombocytopenia.

From the endocrine system: galactorrhea, gynecomastia, menstrual irregularities, amenorrhea; increase or decrease in body weight, hyperglycemia and exacerbation of pre-existing diabetes.

On the part of the reproductive system: priapism, erectile dysfunction, ejaculation disorders, anorgasmia.

From the urinary system: urinary incontinence, urinary tract infection.

From the skin: dry skin, hyperpigmentation, itching, seborrhea.

Allergic reactions: rhinitis, rash, angioedema, photosensitivity.

Other: arthralgia.

Overdose:

Symptoms: increased pharmacological effects - drowsiness, sedation, tachycardia, lowering blood pressure, extrapyramidal symptoms. It was reported about taking the drug in a dose of 360 mg. The data obtained suggest a wide range of drug safety. In rare cases, an overdose marked lengthening interval QT.

In case of acute overdose with combined therapy, one should keep in mind the possibility of taking several drugs.

Treatment: should achieve and maintain free airway to ensure adequate oxygen supply and ventilation; gastric lavage (after intubation, if the patient is unconscious) and the use of activated charcoal together with laxatives. Immediately begin monitoring the ECG to identify possiblearrhythmias. There is no specific antidote. It is necessary to conduct appropriate symptomatic therapy. 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-holinoblockers should be used. Continuous medical surveillance and monitoring should continue until the symptoms of intoxication disappear.

Interaction:

Given that APS, including risperidone, have an impact primarily on the central nervous system, they should be used with caution in combination with other drugs of central action.

Risperidone enhances the effect of ethanol, narcotic analgesics, H1-histamine receptor blockers and benzodiazepines.

For the treatment with risperidone, benzodiazepines can be added if an additional sedative effect is required.

When therapy with a combination of risperidone with other APS, lithium, antidepressants, antiparkinsonics, drugs with a central anticholinergic effect increases the risk of developing tardive dyskinesia.

Risperidone has no effect on the clinical effect and pharmacokinetics of lithium, valproic acid, digoxin and topiramate, therefore, for such combinations, dose adjustment is not required.

Risperidone reduces the effectiveness of levodopa and other dopamine receptor agonists. A similar effect is possible with risperidone in combination with other inducers of microsomal liver enzymes such as barbiturates, rifampicin, phenytoin and St. John's wort. In this case, the dose of risperidone should be reviewed.

Do not prescribe the drug in conjunction with carbamazepine to patients with mania in bipolar affective disorder. When carbamazepine is used, the concentration of the active antipsychotic phase of risperidone in plasma is decreased.

Clozapine reduces the clearance of risperidone.

Phenothiazine derivatives, tricyclic antidepressants and some beta-blockers may increase the concentration of risperidone in plasma, but the concentration of the active antipsychotic phase does not change.

Quinidine, fluoxetine, paroxetine, terbinafine and other isoenzyme inhibitors CYP2D6 can increase the plasma concentration of risperidone and, to a lesser extent, the concentration of the active antipsychotic phase.

Cimetidine and ranitidine increase the concentration of risperidone in plasma, but the antipsychotic effect does not increase.

The simultaneous use of risperidone with furosemide in elderly patients with cerebrovascular dementia was associated with high mortality. The mechanism of such interaction has no clear explanation. It is necessary to evaluate the ratio of potential benefits and possible risks to these patients with simultaneous use of risperidone and diuretics, including furosemide.

Risperidone can increase blood pressure, reducing the effectiveness of phenoxybenzamine, labetalol and other alpha-blockers, reserpine, methyldopa and other antihypertensive agents of central action.

The lowering of AD effect of guanitidine is blocked by risperidone.

Attention and caution accompanying risperidone with medications that extend the interval QT, such as other APS, antiarrhythmic facilities IA and III classes, moxifloxacin, erythromycin, methadone, mefloquine, erythromycin, tricyclic antidepressants, lithium and cisapride.

It is necessary to be careful with the concomitant administration of risperidone with drugs that can cause disturbances in electrolyte metabolism, such as thiazide diuretics (hypokalemia). This combination increases the risk of developing a malignant arrhythmia.

Special instructions:

When schizophrenia, before treatment with risperidone, it is recommended to gradually cancel the previous therapy, if it is clinically justified. If patients are transferred from depot therapy to APS, it is advisable to start the treatment instead of the next scheduled injection. Periodically, the need to continue current therapy with anti-Parkinsonics should be assessed.

Risperidone for children can be prescribed only by a doctor with special training in child psychiatry.

Risperidone should be used with caution in elderly patients with dementia, including with furosemide and other diuretics.

Meta-analysis of the results of 17 controlled clinical trials showed an increased mortality of elderly patients with dementia (mean age 86 years) who received atypical APS, including risperidone, compared with placebo. Among patients who received risperidone and placebo, the death rate was 4% and 3.1%, respectively.

For elderly patients with dementia, taking risperidone, there was an increased mortality in patients taking furosemide and risperidone compared with the group that only risperidone and a group that only furosemide. There are no pathophysiological mechanisms that explain this observation. There was no increase in mortality in elderly patients concurrently taking other diuretics with risperidone. Regardless of treatment, dehydration is a common risk factor for mortality and should be carefully monitored in elderly patients with dementia.

In placebo-controlled studies, an increased incidence of cerebral circulatory disorders (stroke and / or transient ischemic attacks), including fatal cases, was found in elderly patients with dementia who received some atypical APS, including risperidone, compared with placebo.

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

When orthostatic hypotension occurs, especially in the initial period of dose selection, consideration should be given to reducing the dose.

APS, including risperidone, promote the development of thromboembolic complications in patients with a predisposition to the formation of thrombi.

Before starting risperidone therapy, all possible risk factors for venous thromboembolism should be identified and appropriate measures taken to prevent the development of thromboembolic complications.

The risk of developing mania or hypomania can be significantly reduced by applying low doses or gradually increasing them.

If there are signs and symptoms of tardive dyskinesia or a malignant neuroleptic syndrome it is necessary to cancel all APS, including risperidone, conduct symptomatic therapy and consider resumption of APS therapy. To prevent the development of malignant neuroleptic syndrome against the backdrop of treatment with APS, it is necessary to regularly adjust the dose taken.

It is necessary to carefully evaluate the ratio of potential benefits and possible risks to the use of risperidone in patients with diffuse Levy's disease and Parkinson's disease,because such patients may have an increased risk of developing a neuroleptic malignant syndrome and increased sensitivity to APS.

With the withdrawal of carbamazepine and other inducers of microsomal liver enzymes, the dose of risperidone should be reduced.

Patients should be advised to refrain from overeating due to the possibility of weight gain.

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

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Film-coated tablets, 1 mg, 2 mg, 3 mg and 4 mg.

Packaging:

10 tablets are placed in a blister of PVC / PVDC and aluminum foil.

For 2 or 6 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

In a place protected from moisture, at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-000978

Date of registration:17.05.2011

Expiration Date:Unlimited

The owner of the registration certificate:Pliva of Hrvatska dooPliva of Hrvatska doo Croatia

Manufacturer: & nbsp

PLIVA HRVATSKA, d.o.o. Croatia

Representation: & nbspTeva Teva Israel

Information update date: & nbsp27.12.2016

Illustrated instructions

Instructions

Risset® (Risset®)