Azaleptinum

General characteristics. Structure:

Active ingredient: 25,0 mg or 100,0 mg of clozapine.

Excipients: lactoses monohydrate (sugar milk); potato starch; calcium stearate.

Drug of group of antipsychotic means. Treats neuroleptics, has sedative properties. Promotes muscular relaxation, strengthens effect of anesthetics and somnolent drugs. Has peripheral and central cholinolytic effect.

Pharmacological properties:

Pharmacodynamics. Antipsychotic means (neuroleptic) derivative of dibenzodiazepine. Has the expressed antipsychotic and sedative effect. Practically does not cause extrapyramidal disturbances; in this regard clozapine is carried to group of so-called "atypical" neuroleptics.

Antipsychotic action is caused by blockade dopamine D2 receptors in mesolimbic and mesocortical structures of a brain.

Sedative action is caused by blockade of α-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. Renders peripheral and central m-holinoblokiruyushchee, α-adrenoceptor blocking action. Does not influence concentration of prolactin in blood.

Antipsychotic action is close to that of aliphatic fenotiazin, but without "a submelancholic shade" and unpleasant subjective feelings, has no kataleptogenny effect, reduces a threshold of convulsive readiness.

Does not influence the highest intellectual functions.

Development of therapeutic effect is characterized by staging: bystry approach of somnolent and sedative action; stopping of concern, psychomotor excitement and aggression (in 3-6 days); antipsychotic action (in 1-2 weeks); action on negativism symptoms (in 20-40 days).

Pharmacokinetics. At intake it is absorbed from a GIT quickly and almost completely. Cmax in plasma is reached on average during 2.5 h Css reached in 8-10 days of reception. Is exposed to intensive metabolism at "the first passing" through a liver with formation of metabolites of low activity or inactive. It is metabolized with the participation of CYP1A2 isoenzyme. Distribution intensive and bystry, gets through GEB. Linkng with proteins - 95%.

T1/2 is characterized by variability and after reception of a single dose of 75 mg makes 8 h (4-12 h), after reception on 100 mg of 2 times/days - 12 h (4-66 h).

It is removed by kidneys - 50% and through intestines - 30%.

Indications to use:

Schizophrenia (including resistant to therapy by other neuroleptics and/or at their intolerance), maniacal states, maniac-depressive psychosis, psychomotor excitement at psychopathies, emotional and behavioural frustration (including at children), frustration of a dream.

Route of administration and doses:

Establish individually. For intake the single dose makes 50-200 mg, daily - 200-400 mg. Treatment usually begin 25-50 mg with a dose, then gradually increase by 25-50 mg a day to 200-300 mg/days within 7-14 days. The daily dose can be applied once before going to bed or 2-3 times/days after food. At cancellation of treatment it is necessary to reduce gradually a dose within 1-2 weeks. After achievement of therapeutic effect pass to the supporting course.

In case of need clozapine it is possible to enter in oil.

The maximum dose at intake makes 600 mg/days.

At easy forms of a disease, for a maintenance therapy, and also at patients with a liver and/or renal failure, chronic heart failure, cerebrovascular frustration appoint in lower daily doses (25-200 mg).

Features of use:

With care apply at a serious illness of cardiovascular system, a heavy renal and/or liver failure, closed-angle glaucoma, at a hyperplasia of a prostate, atony of intestines, epilepsy, intercurrent diseases with a feverish syndrome.

During treatment systematic control of a picture of peripheral blood is necessary.

At use of clozapine it is necessary to exclude alcohol intake.

Safety and efficiency of effect of clozapine at children and teenagers aged up to 16 years is not established.

The patients accepting clozapine should abstain from potentially dangerous types of activity connected with need of concentration of attention and the increased speed of psychomotor reactions.

With care apply at a heavy renal failure. At patients with a renal failure drug is appointed in lower daily dose (25-200 mg).

With care apply at a heavy liver failure. At patients with a liver failure drug is appointed in lower daily dose (25-200 mg).

It is contraindicated at children's age up to 5 years. Safety and efficiency of effect of clozapine at children and teenagers aged up to 16 years is not established.

Clozapine is contraindicated at pregnancy and in the period of a lactation (breastfeeding).

Side effects:

From TsNS: drowsiness, a headache, it is rare - agitation, an akathisia, confusion of consciousness, extrapyramidal disturbances (an akineziya, a hypokinesia, muscle tension, a tremor), sleeplessness, an uneasy dream, a depression, ZNS, epileptic seizures, late dyskinesia, temperature increase of the central genesis.

From cardiovascular system: tachycardia, arterial hypotension, the orthostatic hypotension which is followed by dizziness; seldom - flattening of a tooth of T on an ECG, arterial hypertension.

From the alimentary system: hypersalivation, nausea, vomiting, dryness in a mouth, heartburn.

From a metabolism: increase in body weight, the increased sweating.

From system of a hemopoiesis: seldom - an eosinophilia, a granulocytopenia up to an agranulocytosis, a leukopenia, thrombocytopenia.

The effects caused by anticholinergic activity: dryness in a mouth, accommodation disturbances, locks, disturbances of an urination.

Others: myasthenia, decrease in a potentiality, accommodation disturbance.

Interaction with other medicines:

At simultaneous use with the medicines exerting the oppressing impact on TsNS (including with benzodiazepine derivatives), etanolsoderzhashchy drugs, ethanol weight and frequency of manifestations of the oppressing action on TsNS, strengthening of oppression of a respiratory center increases.

At simultaneous use with the means causing arterial hypotension, the perhaps additive hypotensive action.

At simultaneous use with the means causing a miyelodepressiya strengthening of the oppressing action on a marrowy hemopoiesis is possible; with anticholinergics - strengthening of anticholinergic action is possible.

At simultaneous use with digoxin or with the medicines which are characterized by high linkng with proteins (including with heparin, warfarin, Phenytoinum), increase in their concentration in a blood plasma is possible, also clozapine replacement by these means from sites of its linkng with proteins is possible.

At simultaneous use with valproic acid change of concentration of clozapine in a blood plasma is possible, at the same time clinical manifestations of interaction were practically absent.

At simultaneous use with carbamazepine concentration of clozapine in a blood plasma decreases. Cases of a heavy pancytopenia and a malignant antipsychotic syndrome are described.

At simultaneous use with caffeine concentration of clozapine in a blood plasma increases and increase in frequency of development of side effects is possible.

At simultaneous use from lithium a carbonate the myoclonus, spasms, a malignant antipsychotic syndrome, a delirium, psychoses are possible.

At simultaneous use with risperidony the increase in concentration of clozapine in a blood plasma caused, apparently, by competitive influence on CYP2D6 isoenzyme that leads to clozapine metabolism oppression is possible. At bystry replacement of clozapine on рисперидон development of dystonia is possible.

Rifampicin can increase the speed of metabolism of clozapine by induction of isoenzymes of CYP1A2 and CYP3A.

At simultaneous use with Phenytoinum reduction of concentration of clozapine in a blood plasma is possible; with fluoxetine, paroksetiny, sertraline, fluvoksaminy increase in concentration of clozapine in a blood plasma is possible that at some patients is followed by toxicity manifestations. This action is especially expressed at simultaneous use of clozapine with fluvoksaminy.

At simultaneous use with ciprofloxacin increase in concentration of clozapine in a blood plasma is possible.

Contraindications:

Granulocytopenia or agranulocytosis in the anamnesis (except for development of a granulocytopenia or an agranulocytosis owing to earlier applied chemotherapy), oppression of a marrowy hemopoiesis, a myasthenia, comas, toxic psychosis (including alcoholic), pregnancy, the lactation period, children's age up to 5 years, hypersensitivity to clozapine.

Overdose:

At reception of the overestimated drug Azaleptinum doses at patients development of drowsiness, confusion of consciousness, excitement, an areflexia, increase in reflexes, spasms, hallucinations, a mydriasis, tachycardia, changes of body temperature, arterial hypotension, disturbances of a cordial rhythm, disturbances of conductivity of a myocardium, decrease in visual acuity and increase in salivation is noted. In hard cases development of respiratory depression, a collapse and a coma was noted.

The specific antidote is not known. At overdose it is necessary to wash out as soon as possible a stomach and to appoint to the patient enterosorbentny means. At overdose of clozapine control of functions of respiratory and cardiovascular systems is necessary. On doctor's orders carry out a symptomatic treatment.

Storage conditions:

List of strong substances. To store in the place protected from light at a temperature not above 30 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

10 pieces - planimetric strip packagings (5) - packs cardboard.
50 pieces - banks polymeric (1) - packs cardboard.
50 pieces - banks of dark glass (1) - a pack cardboard.