Azaleptol

Azaleptol has sedative and antipsychotic properties. Almost does not provoke the development of extrapyramidal disorders, because of what it is included in the category of "atypical" neuroleptic drugs.

Indications Azaleptol

Indications for prescribing drugs is schizophrenia (in the absence of results from therapy with standard neuroleptics or a patient's hypersensitivity to them).

Release form

Produced in the form of tablets in a volume of 25 or 100 mg. One blister contains 10 tablets, one package contains 5 blister plates. Also can be produced in containers of 50 tablets (1 container in a package). 

Pharmacodynamics

While it was not possible to establish definitively the mechanism of antipsychotic action of active substance LS. It is most active in relation to the dopamine receptors located in the limbic cephalic region. Here clozapine prevents the synthesis of dopamine with its receptors (such as D1 and D2). This property is not as pronounced as in standard neuroleptics - this substance is synthesized mainly on the nedophaminergic areas (where the receptors of histamine and serotonin are located, holinoretseptory, as well as α-adrenoreceptors).

Clozapine has little or no effect on the prolactin concentration inside the plasma, since it does not bind to the dopamine receptors inside the tuberoinfundibular tract.

Among the characteristic pharmacological properties of the active component is the suppression of the activation response due to electrical stimulation of the mid-cerebral reticular formation, and in addition, a pronounced cholinolytic central as well as peripheral action and a peripheral adrenolytic effect. The drug has no cataleptogenic properties. There is evidence that it can slow down the release of dopamine from the presynaptic nerve roots.

Clinical properties - a powerful antipsychotic effect, which is combined with soothing properties. Moreover, the drug does not have extrapyramidal side-reactions inherent in other neuroleptic drugs (it is possible that this property is due to the presence of a central anticholinergic effect in the medicine). Does not have a strong general inhibitory effect on the central nervous system, in contrast to the aminazine and other aliphatic phenothiazines.

Pharmacokinetics

The absorption index of Azaleptol after ingestion is 90-95%. The degree of absorption and its speed are not dependent on the intake of food. During the first pass, the medicine is moderately metabolized. Figures of bioavailability level - 50-60%.

In a steady state after a 2-time use of drugs, the peak of blood concentration occurs on average 2.1 hours later (within 0.4-4.2 hours). The distribution volume is 1.6 l / kg. Synthesis of the active component with a plasma protein is approximately 95%.

Before the process of excretion of the active component, it is almost completely metabolized. At the same time only one of the main decay products of the substance, desmethyl clozapine, is pharmacologically active. The properties of this metabolite are similar to those of clozapine, but they are mild and their effect is less prolonged.

The elimination of the active component is carried out in 2 stages (the average half-life is 12 hours (6-26 hours)). When using a single dose (75 mg), the elimination half-life is 7.9 hours. This indicator rises to 14.2 hours if the drug reaches a steady state due to taking a single dose daily for at least 1 week. A small part of the unchanged medication is determined in feces with urine. About 50% of the dosage is excreted under the guise of decay products along with urine, and another 30% - together with feces.

It is noted that at an equilibrium period of concentration in the case of an increase in the dosage of drugs from 37.5 to 75/150 mg 2 times a day - there is a linear (dose-dependent) increase in the level of AUC, and in addition to this minimum and maximum values within the blood plasma.

Dosing and administration

Use should be taken orally after meals, 2-3 times a day. A single dose to an adult patient is 50-200 mg. Within a day it is allowed to consume 200-400 mg of the drug. The treatment process usually begins with a dosage of 25-50 mg, and then it is gradually increased (every day for 25-50 mg) to a daily rate of 200-300 mg for 1-2 weeks.

With maintenance treatment, as well as outpatient patients should take 25-200 mg per day (a single dose is allowed in the evening).

In case of cancellation of the drug, you need to gradually reduce the dosage for 1-2 weeks. A day is allowed to take no more than 600 mg.

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Use Azaleptol during pregnancy

During pregnancy, you should take care with medicine. Assign it only in cases when the benefits of using drugs are higher than the development of negative effects from it for the fetus.

The neonatal effect of antipsychotics (including clozapine) during the third trimester of gestation may increase the risk of adverse reactions (among them extrapyramidal disorders or withdrawal syndrome) that develop after childbirth and can vary in duration and severity. There were symptoms of increased blood pressure, excitation, drowsiness, respiratory distress or nutrition. Therefore, the condition of the newborn requires careful monitoring.

Contraindications

Among the contraindications:

• when there are changes in blood levels (development of agranulocytosis or granulocytopenia);
• Alcohol and other psychoses caused by toxins;
• children's tetany;
• epilepsy;
• severe forms of diseases of the cardiovascular system, and in addition to this kidney or liver;
• pathology of the hematopoiesis system;
• closed-angle type of glaucoma;
• hypertrophy of the prostate;
• intestinal atony;
• state of coma;
• vascular collapse or suppression of the function of the central nervous system of any origin;
• paralytic form of intestinal obstruction.

Side effects Azaleptol

The possibility of developing or increasing adverse reactions increases when the drug is administered at a dosage greater than 450 mg (per day). Among them:

• agranulocytosis or granulocytopenia, which mainly appear during the first 18 weeks of the treatment course;
• may develop leukocytosis or eosinophilia of unknown origin (especially during the first treatment weeks);
• often develop severe fatigue or a feeling of drowsiness. There may be headaches, dizziness, seizures of epilepsy, and, in addition, convulsive twitching. It is rare that extrapyramidal disorder develops, usually in mild form. There are also data on the appearance of tremors, rigidity, and besides this akathisia. Malignant form of neuroleptic syndrome develops;
• dryness in the oral cavity, violation of sweating, accommodation or thermoregulation. Also the development of hyperthermia or ptimalism;
• can develop tachycardia or orthostatic collapse. In more rare cases, fainting (especially during the first weeks of therapy). Increased blood pressure is not often observed. Occasionally there is a collapse, which is accompanied by the inhibition of the respiratory process or its stop. Changes occur in the ECG indications, myocarditis, arrhythmia, thromboembolism or pericarditis develops;
• may develop constipation or vomiting along with nausea. Single activity of liver enzymes increases. Rarely there is pancreatitis, intrahepatic cholestasis or common cholestasis, as well as dysphagia;
• there is information about the development of urinary incontinence, or vice versa, its delay. Priapism, tubulointerstitial nephritis can be observed, as well as the level of creatine phosphokinase;
• weight gain. There is an allergy on the skin.

There is information about sudden deaths of patients, which occur equally often with patients suffering from mental disorders and treating antipsychotics, as well as with patients who have not been treated.

Among other reactions:

• the development of diabetes and a decrease in glucose tolerance;
• the development of delirium or the appearance of confusion;
• cardiomyopathy, anemia or thrombocytopenia;
• tardive dyskinesia;
• rapidly progressive necrosis of the liver;
• development of ketoacidosis, acute form of hyperglycemia, and in addition to hypertriglyceridemia or hypercholesterolemia, as well as the state of non-ketone coma;
• oppression of the respiratory process or its arrest.

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Overdose

Among the manifestations of an overdose:

• a feeling of drowsiness, agitation, or confusion;
• the appearance of hallucinations, seizures, or dyspnea;
• the development of tachycardia, mydriasis, arrhythmia, extrapyramidal disorders, collapse, aspiration form of pneumonia, and besides this birdism;
• a state of delirium, lethargy or coma;
• areflexion or vice versa hyperreflexia;
• loss of visual acuity;
• lowering blood pressure;
• changes in body temperature;
• problems with conduction inside the myocardium;
• inhibition of respiratory function or its arrest.

To eliminate such manifestations, gastric lavage should be performed, and if necessary, give the patient activated charcoal. Symptomatic therapy with control of the respiratory and cardiovascular systems is also performed; In addition, it is necessary to control the water-electrolyte, as well as the acid-base balance.

If the level of blood pressure is lowered, adrenaline and its derivatives can not be prescribed to the patient.

For a minimum of 4 days, you should see a doctor to rule out the risk of late reactions.

Hemodialysis with peritoneal dialysis does not give the desired effect.

Interactions with other drugs

Clozapine is able to enhance the central effect of ethyl alcohol, drugs, suppressing the central nervous system (such as benzodiazepine derivatives, antihistamines, and opiates), and also MAO inhibitors. In the case of drug combination with benzodiazepines, and in addition, when Azaleptol is used soon after the therapy with benzodiazepines, the possibility of hypotension reactions may appear, and in addition, the development of collapse and inhibition of respiration or its stopping.

When combined, the effect of Azaleptol and drugs with antihypertensive and cholinolytic effects, as well as drugs that suppress the respiratory function, can be mutually reinforced.

Coupling clozapine with drugs effectively synthesized with a plasma protein (eg, warfarin), the free fraction of any of the active components may increase in the blood, which can lead to side reactions.

It is forbidden to combine Azaleptol with drugs that suppress the medullar function.

Due to the combined administration of large doses of Azaleptol and erythromycin or cimetidine, the plasma concentration of clozapine increases, and side effects also develop.

There is some information about the increase in clozapine in the blood serum as a result of a compound with fluvoxamine or other selective inhibitors of reverse serotonin capture (this is sertraline or fluoxetine, as well as paroxetine or citalopram).

Drugs that increase the activity of the enzymes of the hemoprotein system P450, can lower the plasma concentration of the active component of Azaleptol. Due to the cancellation of the carbamazepine used simultaneously, the plasma index of clozapine increased. The compound with phenytoin lowers the plasma indices of clozapine, and the effectiveness of the drug is weakened.

The combination with lithium drugs, as well as drugs that affect the operation of the central nervous system, may increase the possibility of manifesting a malignant form of neuroleptic syndrome.

Since Azaleptol has adrenolytic properties, it is able to reduce the hypertensive effect of norepinephrine and, in addition, other drugs that have predominant α-adrenergic properties. It can also eliminate the pressor effect of adrenaline.

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Storage conditions

It is required to keep the drug in the usual conditions for medicines - outside of the sun, children, and moisture. The temperature is a maximum of 25 degrees.

Shelf life

Azaleptol is suitable for use within 3 years from the date of manufacture of this medicine.