Description of the active substance :.
This information is a reference and it is not enough that the drug was prescribed by a doctor. .
PHARMACHOLOGIC EFFECT
An antipsychotic agent (neuroleptic), a derivative of dibenzodiazepine. Has a pronounced antipsychotic and sedative effect. Practically does not cause extrapyramidal disorders; in connection with this, clozapine is referred to the group of so-called "atypical" antipsychotics.
The antipsychotic effect is due to the blockade of dopamine D 2 receptors in the mesolimbic and mesocortical structures of the brain.
Sedative action is due to blockade of ОІ-adrenoreceptors of the reticular formation of the brainstem; antiemetic effect - blockade of dopamine D 2 receptors in the trigger zone of the vomiting center; hypothermic action - blockade of dopamine receptors of the hypothalamus. Has a peripheral and central m-holinoblokiruyuschee,? -adrenoblokiruyuschee action. Does not affect the concentration of prolactin in the blood.
Antipsychotic action is close to that of aliphatic phenothiazines, but without a "sub-melancholic shade" and unpleasant subjective sensations, does not have a cataleptogenic effect, reduces the threshold of convulsive readiness.
Does not affect the higher intellectual functions.
The development of the therapeutic effect is characterized by the gradualness: a rapid onset of hypnotic and sedative action; relief of anxiety, psychomotor agitation and aggressiveness (after 3-6 days); antipsychotic effect (after 1-2 weeks); effect on the symptoms of negativity (after 20-40 days).
PHARMACOKINETICS
When taken orally absorbed from the gastrointestinal tract quickly and almost completely. C max in plasma is achieved on average for 2.5 hours. C ss is achieved after 8-10 days of admission. It is subjected to intensive metabolism at the "first passage" through the liver with the formation of metabolites of low activity or inactive. Metabolized with the participation of the isoenzyme CYP1A2. The distribution is intense and rapid, it penetrates the GEB. Binding to proteins - 95%.
T 1/2 is characterized by variability and after taking a single dose of 75 mg is 8 hours (4-12 hours), after taking 100 mg 2 times / day - 12 hours (4-66 hours).
It is excreted by the kidneys - 50% and through the intestines - 30%.
INDICATIONS
Acute and chronic forms of schizophrenia, manic states, manic-depressive psychosis, psychomotor agitation in psychopathy, emotional and behavioral disorders (including in children), sleep disorders.
DOSING MODE
Install individually. For oral administration, a single dose of 50-200 mg, daily - 200-400 mg. Treatment usually begins with a dose of 25-50 mg, then gradually increased by 25-50 mg per day to 200-300 mg / day for 7-14 days. The daily dose can be applied once before bedtime or 2-3 times / day after eating. If you cancel treatment, you should gradually reduce the dose within 1-2 weeks. After reaching a therapeutic effect, they switch to a supportive course.
If necessary, clozapine can be administered in / m.
The maximum dose for ingestion is 600 mg / day.
For mild forms of the disease, for maintenance therapy, as well as in patients with hepatic and / or renal insufficiency, chronic heart failure, cerebrovascular disorders are prescribed at lower daily doses (25-200 mg).
SIDE EFFECT
From the side of the central nervous system: drowsiness, headache, rarely - agitation, akathisia, confusion, extrapyramidal disorders (akinesia, hypokinesia, rigidity of muscles, tremor), insomnia, restless sleep, depression, ZNS, epileptic seizures, tardive dyskinesia, .
From the cardiovascular system: tachycardia, arterial hypotension, orthostatic hypotension, accompanied by dizziness; rarely - flattening of the T wave on the ECG, hypertension.
On the part of the digestive system: hypersalivation, nausea, vomiting, dry mouth, heartburn.
From the side of metabolism: weight gain, increased sweating.
From the hemopoietic system: rarely - eosinophilia, granulocytopenia up to agranulocytosis, leukopenia, thrombocytopenia.
Effects due to anticholinergic activity: dry mouth, discomfort, constipation, urination disorders.
Other: myasthenia gravis, decreased potency, disruption of accommodation.
CONTRAINDICATIONS
Granulocytopenia or agranulocytosis in history (with the exception of the development of granulocytopenia or agranulocytosis due to previously used chemotherapy), oppression of bone marrow hematopoiesis, myasthenia gravis, coma, toxicosis (including alcohol), pregnancy, lactation, children under 5 years old, increased sensitivity to clozapine.
PREGNANCY AND LACTATION
Clozapine is contraindicated in pregnancy and lactation (breastfeeding).
APPLICATION FOR FUNCTIONS OF THE LIVER
Use with caution in severe renal failure. In patients with renal insufficiency, the drug is prescribed at a lower daily dose (25-200 mg).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Use with caution in severe hepatic insufficiency. In patients with hepatic insufficiency, the drug is prescribed at a lower daily dose (25-200 mg).
APPLICATION FOR CHILDREN
Contraindicated in children under 5 years. The safety and efficacy of clozapine in children and adolescents under the age of 16 years is not established.
SPECIAL INSTRUCTIONS
With caution apply for serious diseases of the cardiovascular system, severe renal and / or hepatic insufficiency, closed-angle glaucoma, with prostatic hyperplasia, intestinal atony, epilepsy, intercurrent diseases with febrile syndrome.
During the treatment period, a systematic control of the peripheral blood pattern is necessary.
When using clozapine, alcohol should be avoided.
The safety and efficacy of clozapine in children and adolescents under the age of 16 years is not established.
Impact on the ability to drive vehicles and manage mechanisms
Patients taking clozapine should refrain from potentially dangerous activities associated with the need for concentration and increased speed of psychomotor reactions.
DRUG INTERACTION
With simultaneous use with drugs that exert a depressing effect on the central nervous system (including benzodiazepine derivatives), ethanol-containing drugs, ethanol, the severity and frequency of manifestations of the oppressive effect on the central nervous system increases, and the respiratory center is depressed.
At simultaneous application with the means causing arterial hypotension, additive hypotensive effect is possible.
When used simultaneously with agents that cause myelodepression, it is possible to intensify the oppressive effect on bone marrow hematopoiesis; with anticholinergics - it is possible to strengthen the anticholinergic effect.
When used simultaneously with digoxin or with drugs characterized by high binding to proteins (including with heparin, warfarin, phenytoin), it is possible to increase their concentrations in the blood plasma, it is also possible to dislodge clozapine by these means from the sites of its binding to proteins.
With simultaneous application with valproic acid, a change in the concentration of clozapine in the blood plasma is possible, with no clinical manifestations of interaction.
With simultaneous use with carbamazepine, the concentration of clozapine in the blood plasma decreases. Cases of severe pancytopenia and malignant neuroleptic syndrome are described.
With simultaneous use with caffeine, clozapine concentration in the blood plasma increases and it is possible to increase the incidence of side effects.
With simultaneous application of lithium carbonate, myoclonus, convulsions, malignant neuroleptic syndrome, delirium, psychosis are possible.
With simultaneous application with risperidone, an increase in the concentration of clozapine in the blood plasma is possible, which is apparently due to a competitive effect on the isoenzyme CYP2D6, which leads to inhibition of clozapine metabolism. With rapid replacement of clozapine with risperidone, dystonia may develop.
Rifampicin can increase the rate of clozapine metabolism by inducing the isoenzymes CYP1A2 and CYP3A.
With simultaneous use with phenytoin, a decrease in the concentration of clozapine in the blood plasma is possible; with fluoxetine, paroxetine, sertraline, fluvoxamine, an increase in the concentration of clozapine in the blood plasma is possible, which in some patients is accompanied by manifestations of toxicity. This effect is particularly pronounced with the simultaneous use of clozapine with fluvoxamine.
With simultaneous use with ciprofloxacin, an increase in the concentration of clozapine in the blood plasma is possible.
