Azaleptin

Azaleptin is an antipsychotic drug whose active ingredient is clozapine.

[1], [2], [3], [4]

Indications Azaleptin

Indications for the use of Azaleptin is the treatment of chronic, and in addition acute forms of schizophrenic syndrome, manic syndromes, and psychoses of manic-depressive type.

In addition, the drug can be used in the event of a psychomotor agitation, or in psychotic states that develop as a result of overexcitation.

In some cases, it may be prescribed to patients who have resistance to other neuroleptics.

Release form

Produced in the form of tablets. In one glass or polymer bottle with a lid contains 50 tablets. One package contains 1 such bottle.

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Pharmacodynamics

Azaleptin has differences from standard antipsychotics. After using clozapine, there was no development of catalepsy symptoms, and suppression of standard behavior, provoked by the introduction of apomorphine or amphetamine into the body.

Azaleptin acts as a weak blocker of D1-3, as well as D5-receptors, and in addition, it largely affects the receptors of type D4. The active substance of the drug has potent adrenolytic, anticholinergic, and antihistamine properties, and also suppresses the activation reaction and has moderate antiserotonergic properties.

In conditions of clinical trials, Azaleptin has a rapid and pronounced sedative effect, and besides it has a powerful antipsychotic effect. The last property of the drug is also observed in patients with schizophrenic syndrome, which are resistant to treatment with other drugs. In such cases, the drug acts effectively both in the presence of productive schizophrenic symptoms, and in the presence of prolapses.

After using drugs, positive dynamics is described in patients with cognitive disorders. Also, in people suffering from schizophrenia and treated with Azaleptin, the frequency of attempts to commit suicide and suicide is markedly reduced (in comparison with patients who do not take the medicine). Epidemiological data show that the frequency of such attempts with clozapine decreased by> 7 times relative to patients who were not treated with Azaleptin.

The drug has almost no effect on the indices of prolactin and, in general, is well tolerated. The use of clozapine only occasionally led to the development of severe adverse reactions in patients.

Pharmacokinetics

Azaleptin is rapidly absorbed from the intestine. The maximum active concentration reaches 2.5 hours later. Equilibrium indices of concentration in the blood plasma are established by the 8th-10th day of treatment. The bioavailability index of clozapine is approximately 27-60%. Its accumulation occurs within the parenchymal organs (in the lungs, and in addition to the kidneys with the liver). About 95% of the active ingredient is synthesized with the protein within the plasma.

The metabolism of clozapine is carried out in the liver. In the process, low-level or inactive decay products are formed.

Excretion is mainly carried out through the kidneys, about 35% is excreted together with bile. The half-life lasts 4-12 hours after a single dose of medicine (75 mg) or 4-66 hours in the case of a drug at a dosage of 100 mg 2 times a day.

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Dosing and administration

Azaleptin is used orally. Usually it is taken after a meal. The daily dosage is generally divided into 2-3 doses. For maintenance treatment in the amount of not more than 50 mg of medication, the daily dose is prescribed by a single dose (in the evening). The duration of the treatment course, as well as the dosage size, are determined exclusively by the doctor.

For adults, the drug is usually prescribed in a single dose of 50-200 mg. Selection of the dose occurs individually, and begins with 25-100 mg, with a gradual increase in size until the desired drug effect. Dosage is usually increased for 1-2 weeks (25-50 mg per day).

A day is allowed to take not more than 600 mg of the drug.

When the improvement in the patient's health is achieved, the support dosages should be switched. On average, the maintenance dose per day is 150-200 mg. Sometimes this figure can be less - for 25-100 mg of the drug.

Patients who have a mild form of pathology, but also elderly people or people with insufficient body weight, as well as in the presence of disorders in the work of the heart or kidneys and in cerebrovascular pathologies - can not be prescribed more than 200 mg per day.

It is necessary to cancel the medication by gradually reducing the dosage.

Use Azaleptin during pregnancy

Azaleptin is prohibited from prescribing during pregnancy. When treating with clozapine, women who are in reproductive age should use reliable contraceptives.

During the lactation period, it is not recommended to take the medicine. It can be appointed only after consultation with the attending physician, and also after the abolition of breastfeeding.

Contraindications

Among the main contraindications:

• the drug is prohibited for patients who are hypersensitive to the active substance or auxiliary elements of the drug;
• It is not possible to use in the treatment of patients who have a history of possible changes in blood counts (especially when they are associated with the use of neuroleptic drugs or tricyclics);
• It is forbidden to use patients with toxic psychoses (including alcoholic ones), pathologies of the cardiovascular system in severe form (as well as with symptoms of heart failure and circulatory disorders), myasthenia, and in addition liver or kidney pathologies with disturbances in the functioning of these organs ;
• it is contraindicated to take Azaleptin and in the presence of epilepsy, glaucoma, prostatic hypertrophy, and in addition to intestinal atony or infections;
• medicine is also prohibited for children.

During treatment with the use of Azaleptin it is forbidden to drive a car, and also to operate machinery that can pose a potential danger to life and health.

Side effects Azaleptin

Basically, patients tolerate Azaleptin well. But in the case of taking the drug in a daily dosage of more than 450 mg, the likelihood of side effects increases.

Among the possible side reactions:

• organs of the hematopoietic system: development of eosinophilia, granulocytopenia and leukocytosis of unknown origin. In addition, agranulocytosis can develop, which can be prevented by constant monitoring of blood counts (during the first 18 weeks of treatment - every day, and then at long intervals). If the patient has an agranulocytosis, it is necessary to cancel the drug taking and transfer it to intensive therapy;
• organs of the National Assembly: the appearance of headaches or dizziness, a feeling of drowsiness or severe fatigue, extrapyramidal disorders (mostly expressed weakly), or disorders of thermoregulation, accommodation, and sweating. In addition, birdism or hyperthermia. There is a single appearance of tremors of limbs, akathisia, rigidity, and besides this malignant form of neuroleptic syndrome;
• organs of the digestive system: the occurrence of vomiting or stool disorders, as well as the development of dryness of the mucous membranes inside the oral cavity. In addition, the development of cholestasis or an increase in the activity of liver transaminases;
• organs of the cardiovascular system: the development of tachycardia or orthostatic collapse, and in addition raising the level of blood pressure or loss of consciousness. Individuals in patients develop a collapse with a violation of the respiratory process, myocarditis, arrhythmia, as well as changes in ECG;
• Other: delay urination or vice versa, her incontinence, the development of allergies on the skin. Suddenly, the patient died suddenly. Prolonged use of drugs can cause weight gain.

[7], [8]

Overdose

In the case of the use of Azaleptin in large doses, patients may experience confusion, a state of excitement or drowsiness, the development of areflexia, or, conversely, an increase in reflexes. In addition, hallucinations or convulsions may occur, tachycardia, mydriasis develop, temperature change, blood pressure level decrease, conduction inside the myocardium or rhythm of the heartbeat. There may also be pentavalism and a deterioration in visual acuity. In the most severe cases, problems with respiratory processes developed, and in addition collapse with coma.

There is no specific antidote for the elimination of symptoms. In case of an overdose, it is necessary to quickly make a gastric lavage and give the patient enterosorbents. It is also required to monitor the functioning of the cardiovascular and respiratory systems. The doctor may prescribe symptomatic therapy.

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Interactions with other drugs

Azaleptin is prohibited from prescribing to patients treated with drugs that have a depressing effect on the bone marrow.

The drug can not be combined with NSAIDs, but in addition to derivatives of pyrazolone, thyreostatic and antimalarial drugs, and the means of gold.

Azaleptin must be taken with caution in conjunction with antipsychotics, antidepressants, antimicrobial drugs and anticonvulsants, and in addition to derivatives of sulfonylurea and antidiabetic agents.

When the active ingredient is combined with MAO inhibitors, benzodiazepines, narcosis preparations, ethanol, antihistamine drugs, and in addition other CNS-suppressing substances, the central effect of these drugs is enhanced. With extreme caution, you need to apply Azaleptin to people who take (or have recently taken) benzodiazepines or other psychotropic drugs, because in this case the possibility of developing a collapse increases (with the depressing of the respiratory process and the stopping of the heart).

Antihypertensives and anticholinergic drugs, as well as drugs that suppress respiratory function, should be combined with caution with clozapine.

As a result of the combination of Azaleptin with drugs that significantly bind to plasma proteins, the risk of side effects may increase (due to the displacement of elements from the connection with the plasma protein, as well as an increase in the plasma concentration of the unbound component).

In conjunction with drugs that are metabolized mainly through the hemoproteins P450 1A2, and also P450 2D6, the plasma concentration of the active component of Azaleptin can increase. The tests did not show an increase in the medicinal effect of clozapine due to the combination with tricyclics, phenothiazines, as well as antiarrhythmic drugs of the IC category (metabolized with the help of hemoprotein P450 2D6). It is possible that the concentration of these drugs in plasma increases under the influence of clozapine, therefore, when they are connected, it is necessary to monitor the patient's condition and regulate the dosage of phenothiazines and other drugs that pass through the hemoprotein P450 2D6, if necessary.

Azaleptin weakens the medicinal effect of levodopa, as well as other dopaminimulants.

Cimetidine with erythromycin, as well as drugs that suppress the processes of reverse serotonin capture (such as paroxetine and fluvoxamine), in the case of compound with Azaleptin, increase the active substance of the latter in plasma.

In conjunction with inducers of the hemoprotein P450 (eg, carbamazepine), the concentration of clozapine in the plasma decreases, and its medicinal action is also weakened.

As a result of the combination of Azaleptin with lithium drugs, the risk of developing a malignant form of neuroleptic syndrome increases.

Active substance Azaleptin reduces the severity of the hypertensive effect of norepinephrine, as well as other drugs that have predominantly adrenergic properties, and in addition significantly reduces the pressor effect of adrenaline.

Absorption of the drug from the intestine slows down when combined with antacids gel-like form, as well as cholestyramine.

[10], [11]

Storage conditions

Azaleptin must be kept in conditions that are acceptable for most drugs - a dry place, closed from the sun, inaccessible to children. The temperature should remain within 15-30 degrees.

[12]

Shelf life

Azaleptin can be used for a maximum of 3 years after the release of the drug.

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