Atypical neuroleptic. Synonyms for clozapine: azaleptin, leponex, alemoxan, clazaril, iprox. In our country it is sold in two forms: azaleptin and leponex.
Clozapine
- one of the most powerful antipsychotics available today. It is included in the list of potent psychotropic drugs and therefore its circulation is especially controlled by the state (illegal trafficking may result in criminal liability).
In hospitals it is subject to special control and recording. It is prescribed to patients on special forms of strict accounting on numbered prescriptions of a special form: 148-1/u-88. Of all the antipsychotics, only two drugs have such enhanced control over their distribution and use: clozapine and levomepromazine (tisercin).
It was synthesized back in the 60s of the 20th century, the first experience of its use was in 1971, but it became widely used only in 1990. He is considered the founder of the second generation of antipsychotic drugs - atypical antipsychotics.
Unlike first-generation drugs, clozapine is able to influence negative symptoms (apathy, passivity, decreased emotions, withdrawal) and is noticeably less likely to cause extrapyramidal disorders.
Later, new antipsychotic drugs appeared and continue to appear, some of them are falling out of use, but clozapine is still widely used throughout the world as one of the most powerful antipsychotic drugs.
The mechanism of action is complex: it blocks dopamine (especially D-4) receptors in the brain. In addition, it has a similar effect on acetylcholine, adrenaline, histamine, GABA and serotonin receptors. Due to this, a strong sedative effect is achieved, excitement, impulsivity, and fear are relieved, and productive symptoms of psychosis (delusions, hallucinations) are reduced.
One of the intermediate products of clozapine metabolism is benzodiazepine, the active ingredient of many tranquilizers, which determines the anti-anxiety and hypnotic effects. In some cases, an antidepressant effect may also be observed.
How to take Azaleptin
To minimize the risk of low blood pressure, seizures and drowsiness, your doctor should gradually increase the dose of the drug. You should always take Azaleptin exactly as prescribed by your doctor. If you have any doubts, you should consult your doctor or pharmacist.
First of all, it is important not to change the dosage or stop taking Azaleptin without notifying your doctor. Continue taking the drug for as long as your doctor directs. If you are 60 years of age or older, your doctor may start treatment at a lower dosage and increase it gradually because patients in this age group are more likely to develop some unwanted side effects (See "What You Need to Know Before You Use Azaleptin").
If the dosage that you have been prescribed cannot be achieved with this dose, there are other doses of this drug that can be used to achieve the desired dosage of the drug.
Azaleptin tablets can be divided into equal doses.
Treatment of schizophrenia
The recommended starting dose is 12.5 mg (half a 25 mg tablet) once or twice on the first day, then 25 mg once or twice on the second day. Swallow the tablet with water. If this dose is well tolerated, your doctor may gradually increase the dose in increments of 25 to 50 mg over the next 2 to 3 weeks until the dose reaches 300 mg per day. After this, if necessary, the daily dose can be increased further in steps of 50 to 100 mg per half week or, preferably, at weekly intervals.
The recommended daily dose is 200 to 450 mg, divided into several single doses per day. Some people may need a higher dose. The permissible daily dose can be up to 900 mg. Frequent side effects (in particular, seizures) are possible with daily doses of more than 450 mg. Always take the individually determined minimum effective dose of the drug for you. Most people take part of the dose in the morning and another part in the evening. Your doctor will advise you on how to divide the daily dose correctly. If your daily dose is only 200 mg, then you can take it once in the evening. Over a period of time, while you are taking Azaleptin and experiencing positive results, your doctor may lower your dose. It is necessary to take Azaleptin for at least 6 months.
Treatment of severe thinking disorders in patients with Parkinson's disease
The recommended starting dose is 12.5 mg (half a 25 mg tablet) in the evening. Swallow the tablet with water. Your doctor may then gradually increase your dose in 12.5 mg increments, no faster than two steps per week, to a maximum dose of 50 mg by the end of the second week. Dosage increases should be stopped or delayed if you feel weak, dizzy or confused. To avoid these symptoms, blood pressure should be measured during the first weeks of treatment.
The recommended daily dose is 25 to 37.5 mg, taken once in the evening. The dose of 50 mg per day should only be exceeded in exceptional cases. The maximum daily dose is 100 mg. Always take the minimum effective dose of the drug individually selected for you.
If you take more Azaleptin than recommended
If you think you have taken a large number of Azaleptin tablets, or if someone has taken your tablets, you should immediately contact your doctor or seek emergency medical help.
Overdose symptoms include:
Drowsiness, fatigue, loss of energy, loss of consciousness, coma, confusion, hallucinations, agitation, incoherent speech, stiff limbs, tremors, seizures, increased salivation, dilated pupils, blurred vision, low blood pressure, collapse, fast or irregular heartbeat, shallow or difficult breathing.
If you forget to take Azaleptin
If you forget to take your next dose, take it as soon as you remember. If it is time for your next dose, skip the missed dose and take the next dose at the usual recommended time. Do not take a double dose to make up for a missed dose. Contact your doctor as soon as possible if you have not taken Azaleptin for more than 48 hours.
If you stop taking Azaleptin
Do not stop taking Azaleptin without the advice of your doctor, as you may experience withdrawal symptoms. It includes sweating, headache, nausea, vomiting and diarrhea.
If you experience any of the above symptoms, tell your doctor immediately. These symptoms may be followed by more serious side effects if not treated immediately.
Symptoms of the underlying disease may reappear. A gradual dose reduction in 12.5 mg increments over one to two weeks is recommended if treatment needs to be discontinued. Your doctor will tell you how to reduce the daily dose of the drug. If you have to suddenly stop treatment with Azaleptin, you will need to consult your doctor.
If your doctor decides to restart treatment with Azaleptin and the last dose of Azaleptin was taken more than two days ago, the recommended starting dose should be 12.5 mg.
If you have other additional questions related to the use of this drug, consult your doctor or pharmacist.
Description of the drug AZALEPTIN
When used simultaneously with drugs that have a depressant effect on the central nervous system (including benzodiazepine derivatives), ethanol-containing drugs, ethanol, the severity and frequency of manifestations of the inhibitory effect on the central nervous system and increased depression of the respiratory center increase.
When used simultaneously with drugs that cause arterial hypotension, additive hypotensive effects are possible.
When used simultaneously with drugs that cause myelosuppression, the inhibitory effect on bone marrow hematopoiesis may be enhanced; with anticholinergic drugs - the anticholinergic effect may be enhanced.
When used simultaneously with digoxin or with drugs characterized by high protein binding (including heparin, warfarin, phenytoin), their concentrations in the blood plasma may increase, and clozapine may also be displaced by these drugs from the sites of its protein binding.
When used simultaneously with valproic acid, a change in the concentration of clozapine in the blood plasma is possible, while clinical manifestations of the interaction were practically absent.
When used simultaneously with carbamazepine, the concentration of clozapine in the blood plasma decreases. Cases of severe pancytopenia and neuroleptic malignant syndrome have been described.
When used simultaneously with caffeine, the concentration of clozapine in the blood plasma increases and the incidence of side effects may increase.
When used simultaneously with lithium carbonate, myoclonus, convulsions, neuroleptic malignant syndrome, delirium, and psychosis are possible.
When used simultaneously with risperidone, an increase in the concentration of clozapine in the blood plasma is possible, apparently due to a competitive effect on the CYP2D6 isoenzyme, which leads to inhibition of the metabolism of clozapine. When quickly replacing clozapine with risperidone, dystonia may develop.
Rifampicin may increase the rate of metabolism of clozapine by inducing the isoenzymes CYP1A2 and CYP3A.
When used simultaneously with phenytoin, a decrease in the concentration of clozapine in the blood plasma is possible; with fluoxetine, paroxetine, sertraline, fluvoxamine, it is possible to increase the concentration of clozapine in the blood plasma, which in some patients is accompanied by toxicity. This effect is especially pronounced when clozapine is used concomitantly with fluvoxamine.
When used simultaneously with ciprofloxacin, it is possible to increase the concentration of clozapine in the blood plasma.
Indications for taking clozapine
- Psychosis with no effect from taking other antipsychotics.
- Schizophrenia
- Organic schizophrenia-like disorder
- Manic psychosis.
- Psychomotor agitation.
- Aggressiveness.
- Severe forms of insomnia.
- Personality disorders (psychopathy), decompensation.
- Derealization and depersonalization in depression.
- Suicidal behavior
The therapeutic effect develops gradually. Relief from agitation, aggressiveness and insomnia occurs within the first 24 hours. Antidelusional, antimanic and antipsychotic effect - within a month.
In a healthy person, taking clozapine can cause a state of indifference and apathy.
Azaleptin and its side effects
Clozapine, sold in Russia most often under the brand name Azaleptin, is an atypical antipsychotic. In fact, azaleptin may cause side effects, some of which are serious and potentially fatal. Common side effects of azaleptine include: constipation, night sweats, drooling, muscle rigidity, sedation, tremor, orthostatic hypotension, hyperglycemia, weight gain. The risk of extrapyramidal symptoms, such as tardive dyskinesia, is lower than with classical antipsychotics (typical antipsychotics); this may be due to the anticholinergic effects of clozapine. Extrapyramidal symptoms may be somewhat less severe after the patient switches from another antipsychotic to clozapine.
Azaleptin is rare, but still dangerous in relation to the development of agranulocytosis while taking it. Agranulocytosis occurs in about 1% of people who take clozapine during the first few months of treatment, and the risk of developing it is highest in about the first three months of treatment and decreases significantly thereafter, to less than 0.01% after a year. In the context of the trials, potentially dangerous low white blood cell counts appear to be more common in children and adolescents and in older adults than in young or middle-aged adults.)
Myocarditis is a sometimes fatal side effect of clozapine that usually develops within the first month of treatment. The first manifestations of the disease are fever, which may be accompanied by symptoms associated with an infection of the upper respiratory tract, gastrointestinal tract, or urinary tract. Monitoring guidelines recommend testing CRP (c-reactive protein) and troponin at baseline and every other week and every week for the first four weeks after starting azaleptin (clozapine) treatment and monitoring patients. Signs of heart failure are less common and may develop in parallel with the rise in troponin.
Another grossly underappreciated and potentially life-threatening side effect is decreased gastrointestinal contractions, which may manifest as severe constipation, intestinal obstruction, acute megacolon, ischemia, or necrosis. Colonic hypomotility has been shown to occur in up to 80% of people taking azaleptin when gastrointestinal function is objectively measured with radiopaque markers. The gastrointestinal wasting expected from clozapine now carries the risk of a higher mortality rate than the more well-known side effect of agranulocytosis. Monitoring bowel function and preferential use of laxatives in all patients treated with clozapine have been shown to improve colonic transit time and reduce the serious effects of azaleptine therapy.
Although clozapine is a muscarinic antagonist of the M1, M2, M3, and M5 receptors, azaleptin is also a full agonist of the M4 receptor. Because M4 is highly expressed in the salivary gland, its M4 agonist activity is thought to be responsible for hypersalivation.
Side effects of azaleptin on the central nervous system are varied and include: drowsiness, dizziness, headache, tremor, fainting, sleep disturbance, depression, anxiety, seizures, fatigue. There are also nightmares here. Like other antipsychotics, clozapine is rarely associated with neuroleptic malignant syndrome.
While taking azaleptin, leukopenia, neutropenia, suppression of bone marrow activity, dementia, and hypotension may occur.
. Treatment with azaleptin should begin with a small dose and slowly, ideally, once a week increasing it, under the control of determining the concentration of azaleptin (clozapine) in the blood. In our practice, we quite often encountered very high concentrations of clozapine in the blood at seemingly fairly low doses of azaleptin.
Many male patients complain of cessation of ejaculation as a side effect of clozapine, although this side effect is rarely described in official medication guides.
Abrupt cessation of taking azaleptin can lead to cholinergic effects (rebound effect), impaired motor activity, and decompensation with signs of psychosis. It is recommended that patients, family members and caregivers be aware of the symptoms and risks of abruptly stopping clozapine. When discontinuing clozapine, a gradual dose reduction is recommended to reduce the intensity of withdrawal effects.
