Risperidon

General characteristics. Structure:

Active agents: risperidona of 1 mg, 2 mg and 4 mg;

excipients: hydrophosphate calcium dihydrate, povidone (пласдон K 29/32 or коллидон 30), starch prezhelatinizirovanny (C*Pharm starch), magnesium stearate, cellulose microcrystallic;

structure of a film cover: селекоат AQ–02003 (gipromelloza of 2910 (hydroxypropyl-methyl cellulose 2910), macrogoal-6000 (polyethyleneglycol 6000), titanium dioxide).

Opisaniye:tabletki, film coated white or almost white color, round, biconvex. On cross section — almost white color.

Pharmacological properties:

Pharmacodynamics. Antipsychotic means (neuroleptic) derivative of a benzizoksazol. Renders also sedative, antiemetic and hypothermal action. The selection monoaminergichesky antagonist, possesses a high tropnost to serotonergic 5-HT2 and dofaminergichesky D2 receptors. Communicates also from an alfa1-adrenoceptor-mi at a little smaller affinity with H1-gistaminergichesky and alfa2-adrenergi-cheskimi receptors. Does not possess a tropnost to holinoretseptor.

Antipsychotic action is caused by blockade dopamine D2 receptors of mesolimbic and mesocortical system. Sedative action is caused by blockade of adrenoceptors of a reticular formation of a trunk of a brain; antiemetic action — blockade dopamine D2 receptors of a trigger zone of the emetic center; hypothermal action — blockade of dopamine receptors of a hypothalamus.

Suppresses productive symptomatology (nonsense, hallucinations, aggression), automatism. Causes smaller suppression of motor activity and to a lesser extent induces a katalepsy, than classical antipsychotic medicines (neuroleptics). The balanced central antagonism to serotonin and dopamine can reduce tendency to extrapyramidal side effects and expand therapeutic influence of drug with coverage of negative and affective symptoms of schizophrenia.

Can induce the increase in concentration of prolactin depending on a dose in plasma.

Pharmacokinetics. Absorption bystry and full. Food does not influence completeness and speed of absorption. There is 1 h TCmax of a risperidon, a 9-gidroksirisperidona — 3 h (at high activity of an isoenzyme of CYP2D6) and 17 h (at low activity of an isoenzyme of CYP2D6). Concentration of a risperidon in a blood plasma are proportional to a drug dose. Equilibrium concentration of a risperidon at most of patients is reached within 1 day, 9-hydroxy-risperidona — in 4–5 days.

Risperidon is quickly distributed in an organism. Gets into the central nervous system (CNS), breast milk. The volume of distribution is 1–2 l/kg. Linkng with proteins of plasma (with an alfa1-acid glycoprotein and albumine) a risperidona makes 90%,
9-gidroksirisperidona — 77%.

It is metabolized by CYP2D6 isoenzyme to an active metabolite — 9-hydroxy-risperidona (рисперидон and 9-gidroksirisperidon make active antipsychotic fraction). Some other way metabolism of a risperidon is
N-dealkylation.

The elimination half-life of a risperidon makes 3 h; a 9-gidroksirisperidon and active antipsychotic fraction — 20–24 h.

It is removed by kidneys (70%: from them 35–45% — in the form of pharmacological active fraction) and intestines (14%).

The research of a single dose of drug revealed higher concentration in a blood plasma and slower removal at patients of advanced age and at patients with a renal failure. Removal is slowed down at patients of advanced age and at patients with a renal failure.

At a liver failure the maintenance of a risperidon in plasma increases by 35%.

Indications to use:

- schizophrenia (acute and chronic) and other psychotic states with productive and/or negative symptomatology;

- affective frustration at various mental diseases;

- behavioural frustration at patients with dementia at manifestation of symptoms of aggression (fits of anger, physical abuse), at disturbances of mental activity (excitement, nonsense) or psychotic symptoms;

- as auxiliary therapy at treatment of manias at bipolar disorders;

- as auxiliary therapy of disorders of behavior at teenagers since 15 years and adult patients with the reduced intellectual level or a delay of intellectual development, in cases if the destructive behavior (aggression, impulsiveness, an autoaggression) is the leader in a clinical picture of a disease.

Route of administration and doses:

It is applied inside. To adults and children 15 years are more senior 1 or 2 times a day are appointed.

Schizophrenia: The initial dose makes 2 mg/days. For the 2nd day — to 4 mg/days. From this point if necessary the dose can or be kept at the previous level, or to correct individually in the range — 4–6 mg/days.

Doses higher than 10 mg/days did not show higher performance in comparison with smaller doses and can cause emergence of extrapyramidal symptoms. The maximum daily dose makes 16 mg.

Behavioural frustration at patients with dementia: An optimum dose — 1 mg once a day.

Bipolar disorders at manias: an initial dose — 2 mg/days on 1 reception. Increase in a dose (on 2 mg/days) — not more often than every other day. An optimum dose — 2–6 mg/days.

Behavioural frustration at patients with a delay of intellectual development or with domination in a clinical picture of destructive tendencies: Patients with the body weight of 50 kg and more. An optimum dose — 1 mg/days.

It is recommended to reduce twice both an initial dose, and the subsequent increases in a dose at elderly patients and at patients with a renal or liver failure (if necessary to use an adequate dosage form).

Features of use:

At schizophrenia, in an initiation of treatment risperidony, it is recommended to cancel gradually the previous therapy if it is clinically justified. If patients are transferred from therapy of depot forms of antipsychotic medicines, then reception is recommended to be begun instead of the following planned injection. Periodically it is necessary to estimate need of continuation of the current therapy by protivoparkinsoniche-sky medicines.

The risk of development of a mania or hypomania can be significantly reduced when using low doses of a risperidon or at their gradual increase.

When developing orthostatic hypotension, especially in an initial stage of selection of a dose, it is necessary to consider a question of a dose decline. At patients with diseases of cardiovascular system, and also at dehydration, a hypovolemia or cerebrovascular disturbances the dose of a risperidon should be increased gradually.

If there are signs and symptoms of late dyskinesia, it is necessary to consider a question of cancellation of all antipsychotic medicines. At a malignant antipsychotic syndrome — it is necessary to cancel all antipsychotic medicines, including рисперидон.

At cancellation of carbamazepine and other inductors of microsomal enzymes the dose of a risperidon has to be lowered.

Patients should recommend to refrain from an overeating in connection with a possibility of increase in body weight.

During treatment it is necessary to be careful during the driving of vehicles and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From the central nervous system: sleeplessness, agitation, uneasiness, a headache, drowsiness, increased fatigue, dizziness, decline in the ability to concentration of attention, a sight illegibility, extrapyramidal symptoms (a tremor, rigidity, hypersalivation, a bradykinesia, an akathisia, acute dystonia), a mania or a hypomania, a stroke (at elderly patients with the contributing factors).

At patients with schizophrenia — a hypervolemia (either because of a polydipsia, or because of a syndrome of inadequate secretion of antidiuretic hormone), late dyskinesia (the involuntary rhythmic movements, preferential language and/or the person), a malignant antipsychotic syndrome (a hyperthermia, muscular rigidity, instability of autonomous functions, disturbance of consciousness and increase in activity of a kreatinfosfokinaza), thermal control disturbances, epileptic seizures.

From the alimentary system: locks, dyspepsia, nausea or vomiting, an abdominal pain, increase in activity of "hepatic" transaminases, dryness in a mouth, a hypoptyalism or hypersalivation, anorexia.

From cardiovascular system: orthostatic hypotension, reflex tachycardia or increase in the arterial pressure (AP).

From bodies of a hemopoiesis: neutropenia, thrombocytopenia.

From endocrine system: a galactorrhoea, a gynecomastia, disturbances of a menstrual cycle, an amenorrhea, increase or decrease in body weight, a hyperglycemia or an aggravation of earlier existing diabetes mellitus.

From urinogenital system: priapism, disturbances of an erection, disturbance of an ejaculation, disturbance of an orgasm, including anorgazmiya, urine incontience.

Allergic reactions: itch, rash, Quincke's disease.

From integuments: xeroderma, hyperpegmentation, seborrhea, photosensitization.

Others: arthralgia, rhinitis.

Interaction with other medicines:

Risperidon reduces efficiency of a levodopa and agonists of dopamine.

Fenotiazina, tricyclic antidepressants and beta adrenoblockers increase concentration of a risperidon in plasma (do not influence concentration of active antipsychotic fraction).

At a concomitant use of carbamazepine and other inductors of microsomal enzymes decrease in concentration of active antipsychotic fraction of a risperidon in plasma is noted.

Clozapine reduces clearance of a risperidon.

At simultaneous use with risperidony the ethanol, medicines oppressing the central nervous system (CNS) lead to the additive oppression of the TsNS function.

Hypotensive medicines increase expressiveness of decrease in the ABP against the background of use of a risperidon.

Fluoxetine can increase concentration of a risperidon in plasma (to a lesser extent — its active antipsychotic fraction).

Contraindications:

- hypersensitivity;

- lactation period;

- children's age (up to 15 years) — efficiency and safety are not established.

With care it is applied at a tumor of a brain, intestinal impassability, overdose by medicines, a syndrome to Reja (the antiemetic effect of a risperidon can mask symptoms of these states), diseases of cardiovascular system (chronic heart failure, an atrioventricular block, a myocardial infarction), dehydration, disturbances of cerebral circulation, hypovolemia, Parkinson's disease, spasms (including in the anamnesis), abuse of medicines, medicinal dependence, a renal failure of heavy degree, a liver failure of heavy degree, states contributing to development of tachycardia like "pirouette" (bradycardia, disturbance of electrolytic balance, the accompanying reception of the medicines extending QT interval), pregnancy.

Overdose:

Symptoms: drowsiness, sedation, tachycardia, decrease in the ABP, extrapyramidal frustration, it is rare — lengthening of an interval of QT.

Treatment: to provide free passability of respiratory tracts for ensuring adequate supply with oxygen and ventilation, a gastric lavage (after an intubation if the unconscious patient) and reception of absorbent carbon together with laxative. To immediately begin monitoring of an ECG for detection of possible arrhythmias. There is no specific antidote. It is necessary to carry out the symptomatic therapy directed to maintenance of the vital functions of an organism. At decrease in the ABP and a vascular collapse — intravenously to enter infusion solutions and/or adrenostimulyator. In case of development of acute extrapyramidal symptoms — anticholinergic medicines. Constant medical observation and monitoring should be continued before disappearance of symptoms of intoxication.

Storage conditions:

List B. In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 2 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 1 mg, 2 mg and 4 mg.

On 10, 20 or 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.

On 1, 2, 3, 5, 6, 10 blister strip packagings on 10 tablets or on 1, 3, 5 blister strip packagings on 20 tablets, or on 1, 2, 3 blister strip packagings on
30 tablets together with the application instruction place in a pack from a cardboard.