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

Composition:Composition per one tablet
Active substance risperidone 1.0 mg; 2.0 mg; 3.0 mg; 4.0 mg.
Excipients: lactose monohydrate 35.0 mg; 70.0 mg; 105.0 mg; 140.0 mg; of HD50 (microcrystalline cellulose - 98%, colloidal silicon dioxide - 2%) - 10.0 mg; 20.0 mg; 30.0 mg; 40.0 mg; microcrystalline cellulose - 2.5 mg; 5.0 mg; 7.5 mg; 10.0 mg; carboxymethyl starch sodium (sodium starch glycolate) 2.0 mg; 4.0 mg; 6.0 mg; 8.0 mg; magnesium stearate - 0.5 mg; 1.0 mg; 1.5 mg; 2.0 mg;
shell: Opadrai II (white OY-L-28900) (lactose monohydrate 36%, hypromellose 28%, macrogol 4000-10%, titanium dioxide 26%) 2.0 mg; 4.0 mg; 6.0 mg; 8.0 mg.

Description:Tablets covered with a film coat of white or almost white color, round, biconvex (for a dosage of 1 mg) or planoclinic with a risk on one side (for dosages of 2 mg and 3 mg) or biconvex with a risk on one side (for a dosage of 4 mg).

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, a benzisoxazole derivative. It also has a sedative, antiemetic and hypothermic effect. Risperidone - selective antagonist cof 5-HT₂- and dopamine D₂receptors. It is also associated with α₁-adrenoceptors and, with a slightly less affinity, with H₁-histaminergic and α₂-adrenergic receptors. 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 alpha-adrenergic receptors of the reticular formation of the brain stem; antiemetic effect - blockade of dopamine D2- receptors of the trigger zone of the vomiting center; hypothermic action - blockade of dopamine receptors of the hypothalamus.

Reduces productive symptoms (delirium, hallucinations, aggressiveness), automatism. It causes less pronounced inhibition of motor activity and to a lesser degree induces catalepsy than classical antipsychotics.

Thanks to the simultaneous blockade of 5-HT₂ cof D₂dopamine receptors in the central nervous system (CNS) decreases the likelihood of developing extrapyramidal side effects and expands the therapeutic effect on the negative and affective symptoms of schizophrenia.

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

Pharmacokinetics:

After ingestion risperidone quickly and completely absorbed from the gastrointestinal tract, the maximum concentration in the blood is reached after 1-2 hours. Food does not affect the completeness and speed of absorption of the drug.

In most patients, the equilibrium concentration of risperidone is reached within 1 day, 9-hydroxyrisperidone - within 4-5 days after the start of treatment.The concentration of risperidone in plasma is proportional to the dose of the drug (within therapeutic doses). Rapidly distributed in the body, penetrates into the central nervous system, breast milk. The volume of distribution is 1-2 l / kg. In the plasma risperidone binds to albumin and α1- glycoprotein. The binding of risperidone to plasma proteins is 88%, 9-hydroxyrisperidone - 77%.

Risperidone is metabolized in the liver with the participation of isoenzyme CYP2D6 cytochrome P450 system to the active metabolite of 9-hydroxyrisperidone, which has a similar pharmacological effect. Risperidone and 9-hydroxyrisperidone are the active antipsychotic fraction. Another way of metabolizing risperidone is N-dealkylation.

It is excreted by the kidneys (70%, 35-45% of them in the form of pharmacologically active fraction) and bile (14%). The half-life of risperidone from the blood plasma is about 3 hours, the half-life of 9-hydroxyrisperidone and the active antipsychotic fraction is 20-24 hours.

In elderly patients and in patients with renal insufficiency, after a single dose, elevated plasma concentrations and delayed clearance of risperidone are noted. In chronic renal failure, the clearance of risperidone is reduced by 60%.

In liver failure, the content of risperidone in plasma is increased by 35%.

Indications:- Schizophrenia (acute, including the first acute acute psychosis, and chronic) and other psychotic states with pronounced productive (hallucinations, delusions, thinking disorders, hostility, suspicion) and / or negative (blunted affect, emotional and social detachment, lack of speech ) symptomatology.
- Affective disorders in various mental illnesses.
- Behavioral disorders in patients with dementia with symptoms of aggressiveness (outbursts of anger, physical abuse), with mental disorders (agitation, delirium) or psychotic symptoms.
- Mania in bipolar disorders - as an auxiliary therapy.
- As an auxiliary therapy (as a mood stabilizer), behavioral disorders in adolescents with 15 years of age and adults with reduced intellectual level or mental retardation, in cases where destructive behavior (aggressiveness, impulsivity, autoaggression) is leading in the clinical picture of the disease.

Contraindications:Hypersensitivity to the main and / or auxiliary components of the drug; lactation period; children's age till 15 years; deficiency of lactase, lactose intolerance, glucose-galactose malabsorption (the preparation contains lactose).
During treatment it is recommended to refrain from taking alcohol (ethanol).

Carefully:- Diseases of the cardiovascular system (coronary heart disease, recently transferred myocardial infarction, chronic heart failure, impaired conduction of the heart muscle).
- Disorders of cerebral circulation.
- Brain tumor.
- Dehydration (especially in elderly patients with dementia), hypovolemia.
- Parkinson's disease.
- Convulsions (including in the anamnesis).
- Severe renal or hepatic insufficiency.
- Drug abuse or drug dependence.
- Conditions predisposing to the development of tachycardia such as "pirouette" (bradycardia, electrolyte imbalance, concomitant medication prolonging the QT interval).
- Intestinal obstruction, acute drug overdose in a history, Reye's syndrome (antiemetic effect of risperidone can mask the symptoms of these conditions).
- Hyperprolactinemia, not associated with taking medications, prolactin-dependent tumors (breast cancer).

Pregnancy and lactation:Use in pregnancy is possible only if the expected positive effect for the mother exceeds the potential risk to the fetus.

Dosing and Administration:Inside, squeezed enough water, regardless of food intake, preferably at the same time.
To obtain the required dose, appropriate dosage forms should be used.
Schizophrenia
Adults and children over 15 years. Risperidone may 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 in the range of 4-6 mg per day. In some cases, a slower dose increase and lower initial and maintenance doses may be justified.
When using risperidone at a dose of more than 10 mg per day, there is no increase in efficacy compared with lower doses, but the risk of developing extrapyramidal symptoms increases.The maximum dose is 16 mg per day. Due to the fact that safety of doses more than 16 mg per day is not studied, doses above this level can not be applied. If additional sedation is necessary, another drug should be used, but do not increase the dose of risperidone.
Elderly patients. An initial dose of 0.5 mg 2 times a day is recommended. The dose can be individually increased by 0.5 mg twice a day to 1-2 mg 2 times a day. Use the drug with caution, because the clinical experience of use in the elderly is limited.
Diseases of the liver and kidneys. 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.
Behavioral disorders in patients with dementia
The initial dose is recommended - 0.25 mg per dose twice a day. If necessary, the dose can be individually increased by 0.25 mg twice a day, not more often than every other day. For most patients, the optimal dose is 0.5 mg twice daily, while some patients receive 1 mg twice daily. When the optimal dose is reached, the drug can be taken once a day.
It is recommended to evaluate the risks and appropriateness of using risperidone in elderly patients with dementia,taking into account risk factors for stroke or concomitant cardiovascular pathology in each patient.
Mania in bipolar disorders
The recommended initial dose of the drug is 2 mg per day at a time. If necessary, this dose can be increased by 1 mg per day, not more often than every other day. For most patients, the optimal dose is 1-6 mg per day.
Since patients with bipolar disorders have a low threshold for tardive dyskinesia, a regular assessment should be made of the need for continued treatment with risperidone.
Diseases of the liver and kidneys. In patients with impaired renal function, there is a decrease in the elimination of the active antipsychotic fraction compared to patients with normal renal function. In this regard, the initial and subsequent doses should be reduced by half, and titration of the dose in such patients should be carried out more slowly.
With a mild liver injury, dose adjustment is not required. Care should be taken in the treatment of patients with moderate to severe hepatic impairment-data on this group of patients is limited.
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 1 mg per day. For some patients, 0.5 mg per day is preferred, while others require an increase in the dose to 1.5 mg per day.
Patients weighing less than 50 kg: the recommended initial dose 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. For some patients, a dosage of 0.25 mg per day is preferred, while others require an increase in the dose to 0.75 mg per day.
Long-term use of risperidone in adolescents over 15 years of age should be carried out under the constant supervision of a physician.
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.

Side effects:From the nervous system: insomnia, agitation, anxiety, headache, sometimes drowsiness, increased fatigue, dizziness, impaired concentration, impaired vision, rarely - extrapyramidal symptoms (tremor, stiffness, hypersalivation, bradykinesia, akathisia, acute dystonia), manic disorders, stroke (in elderly patients with predisposing factors), late dyskinesia (involuntary rhythmic movements predominantly of the tongue and / or face), malignant neuroleptic syndrome (hyperthermia, yshechnaya rigidity, autonomic functions instability, impaired consciousness and elevated CPK), thermoregulation disorders and seizures.
From the digestive system: constipation, dyspepsia, nausea, vomiting, abdominal pain, dry mouth, hypo- or hypersalivation, dysphagia, anorexia or increased appetite, increased or decreased body weight, increased activity of "liver" transaminases.
From the cardiovascular system: sometimes - orthostatic hypotension, orthostatic collapse, reflex tachycardia; increase in blood pressure.
From the hematopoiesis: neutropenia and / or thrombocytopenia.
From the endocrine system: galactorrhea, gynecomastia, menstrual disorders, including amenorrhea, weight gain, hyperglycemia and exacerbation of pre-existing diabetes mellitus (very rarely), hypervolemia (due to polydipsia or due to the syndrome of inadequate secretion of antidiuretic hormone).
From the genitourinary system: erectile dysfunction, priapism, ejaculation disorders, anorgasmia, urinary incontinence.
Allergic reactions: rhinitis, rash, angioedema, photosensitivity.
From the skin: dry skin, hyperpigmentation, itching, seborrhea.
Other: arthralgia.

Overdose:Symptoms: drowsiness, sedation, oppression of consciousness, tachycardia, arterial hypotension, extrapyramidal disorders, in rare cases, prolongation of the QT interval.
Treatment: 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.For timely diagnosis of possible arrhythmias, ECG monitoring should be started as soon as possible. There is no specific antidote.
Symptomatic therapy should be aimed at maintaining vital body functions. Epinephrine use should not be, since stimulation of beta-adrenoreceptors can aggravate arterial hypotension in risperidone-induced blockade of alpha-adrenergic receptors.
Careful medical supervision and ECG monitoring are performed until the symptoms of intoxication disappear completely.

Interaction:With simultaneous administration with drugs that have a central effect, the effects can be summed up.
Risperidone can potentiate the effects of alcohol.
Reduces the effectiveness of levodopa and other dopamine receptor agonists.
With the simultaneous use of other antipsychotic drugs, lithium, antidepressants, anti-Parkinsonian drugs and funds with m-cholinoblocking activity, the risk of developing tardive dyskinesia increases.
The alpha-1-adrenoceptor effect of risperidone may potentiate the hypotensive effect of phenoxybenzamine,labetalol and other alpha-adrenoblockers, methyldopa, reserpine and other antihypertensive drugs with a central mechanism of action. On the contrary, the antihypertensive effect of guanethidine is blocked.
Carbamazepine causes a decrease in the concentration of risperidone and its active metabolite in plasma. Similar effects were observed when using other drugs that are inducers of microsomal liver enzymes.
Quinidine, fluoxetine, paroxetine, terbinafine and other potent inhibitors of the CYP2D6 isoenzyme may cause an increase in the concentration of the active antipsychotic fraction in the plasma. In this regard, the dose of risperidone should be reviewed before and after the withdrawal of these drugs.
Phenothiazines, tricyclic antidepressants, and beta-blockers can cause an increase in the concentration of risperidone in the plasma, and to a lesser extent - the concentration of the active antipsychotic fraction. In this regard, the overall effect does not change to the extent that it could be clinically significant.
Ranitidine and cimetidine (inhibitors of the isoenzyme CYP2D6) can cause an increase in the concentration of risperidone in the plasma,but the antipsychotic effect in this case is not always increased, since the concentration in the plasma of the active metabolite is reduced. Simultaneous reception of risperidone with other antipsychotics, antiarrhythmic drugs of classes IA and III, moxifloxacin, erythromycin, methadone, mefloquine, tricyclic antidepressants, lithium or cisapride may cause an increase in the QTc interval.
Simultaneous reception with other drugs that can cause electrolyte disorders, for example, with thiazide diuretics (hypokalemia), increases the risk of arrhythmia.
Risperidone does not have a clinically significant effect on the pharmacokinetics of valproic acid and topiramate.
When risperidone is used together with other drugs that bind highly to plasma proteins, no clinically significant displacement of any drug from the plasma protein is observed.

Special instructions:Transition from therapy with other antipsychotic drugs. When moving to risperidone with other antipsychotics, a gradual cancellation of the previous drug is necessary.When transferring patients from depot therapy to neuroleptics, risperidone treatment is started instead of the next planned injection.
Periodically, the need to continue therapy with antiparkinsonian drugs should be evaluated.
In connection with the alpha-adrenoblocking action of risperidone, orthostatic hypotension and tachycardia can occur, especially during the initial dose selection. With the development of hypotension, the possibility of reducing the dose of risperidone should be considered. The patient must be warned that it is not advisable to quickly move from a sitting or lying position to a vertical position.
In patients with diseases of the cardiovascular system, as well as in dehydration, hypovolemia or cerebrovascular disorders, the dose should be increased cautiously and gradually (see Dosage and Administration). Persistently avoid dehydration in elderly patients with dementia. Before deciding to consider the risks and benefits of a combination of risperidone and furosemide or the simultaneous use of risperidone with other powerful diuretics!
The occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. In case of signs and symptoms of tardive dyskinesia, consideration should be given to the abolition of all antipsychotics.
When a malignant neuroleptic syndrome characterized by hyperthermia, muscle rigidity, instability of autonomic functions, impaired consciousness, leukocytosis and increased activity of creatine phosphokinase, it is necessary to cancel all antipsychotic medicines, including risperidone.
Perhaps a paradoxical exacerbation of such symptoms as agitation, agitation and aggression. In such cases, it may be necessary to reduce the dose of risperidone or to cancel it.
The possibility of suicide or suicide attempts is inherent in psychosis and bipolar mania, therefore, drug therapy should be complemented by close monitoring and appropriate clinical management of high-risk patients.
Before taking carbamazepine or other inducers of microsomal liver enzymes, the dose of risperidone should be reviewed and, if necessary, increased.With the withdrawal of carbamazepine and other inducers of microsomal liver enzymes, the dose of risperidone should be reduced.
Patients with diabetes mellitus or having risk factors for diabetes mellitus should be under appropriate medical control in connection with the possibility of worsening of the course of previously developed diabetes mellitus or the development of hyperglycemia.
Patients should be advised to refrain from overeating due to the possibility of weight gain.
During treatment it is recommended to refrain from taking alcohol (ethanol).
In rare cases of abrupt discontinuation of treatment with high doses of risperidone, it is possible to develop acute withdrawal symptoms (nausea, vomiting, sweating, insomnia). Psychotic symptoms may resume, involuntary movements (akathisia, dystonia, dyskinesia) may appear. In this regard, it is recommended to cancel the drug gradually.
If a dose is missed, the next scheduled dose should be taken as usual (you can not double the dose).

Effect on the ability to drive transp. cf. and fur:In the period of treatment, until the individual sensitivity to risperidone is clarified,patients need to refrain from driving motor vehicles and other activities that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:Tablets, film-coated, 1.0 mg; 2.0 mg; 3.0 mg and 4.0 mg.

Packaging:10 tablets in a planar cell packaging made of a polyvinylchloride film and aluminum foil.
2 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:In a dry, protected from light place, at a temperature of no higher than 30 ° 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:LSR-005102/10

Date of registration:01.06.2012

The owner of the registration certificate:MAKIZ-PHARMA, LLC MAKIZ-PHARMA, LLC Russia

Manufacturer: & nbsp

FAMAR, S.A. Greece

MAKIZ-PHARMA, LLC Russia

SKOPINSKY FARM ZAVOD, LLC Russia

Representation: & nbspMAKIZ-PHARMA, LLCMAKIZ-PHARMA, LLCRussia

Information update date: & nbsp17.10.2015

Illustrated instructions

Instructions

Risperidone (Risperidone)