Clozapine is a strong neuroleptic drug with a sedative effect.
Release form and composition
Clozapine is available in the following dosage forms:
- Tablets 25 and 100 mg;
- Solution for injection 2.5%.
The active ingredient of the drug is clozapine.
Indications for use
- Affective insanity;
- Manic states;
- Psychomotor agitation in psychopathy;
- Severe sleep disorders;
- Behavioral and emotional disorders, incl. in children.
- Diseases of the hematopoietic system (including in history);
- Myasthenia gravis;
- Alcoholic and intoxication psychosis;
- Lactation period (or should stop breastfeeding);
- Children's age up to 5 years;
- Hypersensitivity to the drug.
Outpatient (out-of-hospital) treatment is contraindicated for drivers of vehicles.
During pregnancy, the drug is prescribed only in extreme cases, if the expected benefit for the expectant mother outweighs the potential risks to the fetus.
With particular caution, Clozapine is used in the following cases: severe hepatic / renal failure, decompensated cardiovascular diseases, prostatic hyperplasia, epilepsy, increased tendency to seizures, intestinal atony, angle-closure glaucoma, intercurrent diseases with fever syndrome.
Dosing and Administration
Clozapine solution is injected intramuscularly with 1-2 ml at bedtime.
In the form of tablets, the drug is taken orally, regardless of the meal. Treatment begins with a dose of 50-100 mg 2-3 times a day, then it is increased to 200-400-600 mg per day. To maintain the therapeutic effect, as well as in patients with hepatic / renal / chronic heart failure and cerebrovascular disorders, 25–200 mg once a day is prescribed, before going to bed.
Single / daily doses for children:
- 6–8 years old - 5-10 / 15-30 mg;
- 8–15 years old - 10–20 / 30–60 mg,
Reception frequency - 2-3 times a day.
The maximum daily dose for children is 100 mg.
- Nervous system and sensory organs: increased body temperature of central genesis, drowsiness, dizziness, headache, agitation, fainting, akathisia, accommodation disturbance, confusion; rarely, sleep disturbances (including insomnia), extrapyramidal disorders (hypokinesia or akinesia, tremor, muscle stiffness), depression, seizures, late dyskinesia, neuroleptic malignant syndrome (tachycardia or arrhythmia, unstable blood pressure, neuroleptic malignant syndrome (tachycardia or arrhythmia, unstable blood pressure, neuroleptic malignant syndrome (tachycardia or arrhythmia, unstable blood pressure, neuroleptic malignant syndrome (tachycardia or arrhythmia, unstable blood pressure, neuroleptic malignant syndrome (tachycardia or arrhythmia, unstable blood pressure, neuroleptic malignant syndrome (tachycardia or arrhythmia, unstable blood pressure, arrhythmia, unstable blood pressure, neuroleptic malignancy), unhealthy arterial pressure, unstable blood pressure, inaccurate arterial pressure, unstable blood pressure, inadequate arterial pressure) , convulsions, increased body temperature of central genesis, increased sweating, pale skin, excessive fatigue or weakness, marked muscle stiffness, involuntary urination);
- Gastrointestinal tract: heartburn, nausea, vomiting, hypersalivation, dryness of the oral mucosa;
- Cardiovascular system: lower blood pressure (including orthostatic hypotension); less often - increased blood pressure, tachycardia, flattening of the T wave on the ECG;
- Hematopoiesis and hemostasis: leukopenia, thrombocytopenia, granulocytopenia, up to agranulocytosis (its first signs resemble flu symptoms: fever, chills, inflammation of the gums and oral mucosa, sore throat; further tonsillitis, pyoderma, periostitis, furuncture, oral sore throat;
- The urinary system: urinary retention, reduced potency;
- Other: weight gain, increased sweating, myasthenia gravis.
When taking clozapine, there is a significant risk of developing such potentially life-threatening complications as agranulocytosis. For this reason, in schizophrenia, the drug is prescribed only in cases where resistance or intolerance to classical neuroleptics is noted. In this case, a prerequisite are normal indicators of white blood. Periodically, during therapy, the number of leukocytes is determined and, if possible, the absolute number of neutrophils: 1 time per week for the first 18 weeks, afterwards - once a month for the entire period of treatment and 1 month after its termination. If granulocytopenia develops, clozapine is discontinued.
The drug in a dose-dependent manner reduces the threshold of convulsive readiness and can cause generalized convulsive seizures or myoclonic muscle contractions. The likelihood of developing these symptoms in patients with epilepsy increases with a rapid increase in dose. In this case, it is necessary to reduce the dose of clozapine and, if necessary, adjust anticonvulsant therapy.
Analysis of post-marketing messages suggests that Clozapine can lead to fatal myocarditis, especially in the first month of its administration. If you suspect the development of this disease, the drug should be immediately canceled.
One of the side effects of clozapine is orthostatic hypotension (sometimes with syncope). In some cases, the collapse may be accompanied by cessation of breathing and / or heart. It is important to keep in mind that usually orthostatic hypotension occurs during the initial titration of the dose due to its rapid increase. Particular care must be taken when prescribing the drug to patients who have received benzodiazepines or other psychotropic drugs, since they may have a collapse, cardiac arrest / respiration at the beginning of treatment.
In elderly patients with dementia-related psychosis, the risk of death increases with neuroleptic treatment. The causes of death are varied, but most deaths are associated with infectious (pneumonia) or cardiovascular (heart failure, sudden death) complications. How much the increase in mortality can be attributed to the action of antipsychotic drugs, and how much to the state of the patients themselves is not fully known, but Clozapine is not the drug of choice for treating psychosis in patients with dementia.
During treatment, it is necessary to refrain from driving and performing types of work that require speed of mental and / or motor reactions and increased attention.
Clozapine enhances the effects of alcohol, sleeping pills, analgesics, sedatives and narcotic drugs, weakens levodopa and other dopaminomimetics.
Clozapine is incompatible with drugs that cause agranulocytosis, such as co-trimoxazole, carbamazepine, chloramphenicol, penicillamine, pyrazolone analgesics, sulfonamides.
Possible undesirable reactions when combined with clozapine:
- Drugs that cause arterial hypotension - additive hypotensive effect;
- Caffeine - an increase in clozapine concentration in the blood and the frequency of side effects;
- Anticholinergics - enhancing their action;
- Rifampicin - increase the metabolic rate of clozapine;
- Drugs that cause myelodepression - increased inhibitory effect on bone marrow hematopoiesis;
- Lithium drugs - the development of myoclonus, seizures, psychosis, delirium, neuroleptic malignant syndrome.
The following drugs may increase clozapine plasma levels (sometimes accompanied by manifestations of toxicity): paroxetine, fluoxetine, sertraline, fluvoxamine, risperidone, and ciprofloxacin.
With simultaneous use of digoxin or drugs characterized by high binding to proteins (warfarin, heparin, phenytoin), their concentration in plasma may be increased and clozapine may be expelled from protein-binding sites.
Valproic acid affects the change in clozapine concentration, and there are practically no clinical manifestations of this interaction.
With the rapid replacement of clozapine risperidone may develop dystonia.
Terms and conditions of storage
Store at a temperature of 15-25 ºС in a place protected from moisture and sunlight.
Shelf life - 5 years.