Klozasten - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate 42.0 mg or 67.5 mg, microcrystalline cellulose 30.0 mg or 75.0 mg, croscarmellose sodium 1.0 mg or 2.5 mg, silicon dioxide colloid (aerosil) 1.0 mg or 2.5 mg, magnesium stearate 1.0 mg or 2.5 mg.

Description:

Round planocylindrical tablets are greenish-yellow with a bevel for dosing 25 mg, with a facet and a risk on one side for a dosage of 100 mg.

Pharmacotherapeutic group:Antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.H.02 Clozapine

Pharmacodynamics:

An antipsychotic agent (neuroleptic), a derivative of dibenzodiazepine. Has a pronounced antipsychotic and sedative effect. Virtually does not cause extrapyramidal disorders due to this clozapine belong to the group of so-called "atypical" antipsychotics.

Antipsychotic effect due to blockade of dopamine D2 receptors in the mesolimbic and mesocortical structures of the brain.

Sedation is due to blockade α-adrenoreceptors of the reticular formation of the brainstem; antiemetic effect - blockade of dopamine D2-receptors of the trigger zone of the emetic center; hypothermic action - blockade of dopamine receptors of the hypothalamus. Has a peripheral and central m-cholinoblocking, α-adrenoblocking 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 action (after 1-2 weeks); effect on the symptoms of negativity (after 20-40 days).

Pharmacokinetics:

The drug is well absorbed in the gastrointestinal tract. Bioavailability - 27-60%.Level of maximum concentration (C_mOh) in the blood is determined after 2.5 hours (1-6 hours), stable equilibrium concentrations in the blood plasma (Css) after 8-10 days and averaged 319 ng / ml (102-771 ng / ml). The connection with plasma proteins is 95%. Clozapine quickly distributed in the body and accumulates in the parenchymal organs (lungs, liver, kidneys).

Metabolized in the liver by an enzyme system CYP1A2, metabolites are weakly active or inactive, excreted by the kidneys (50%) and bile (35%). The half-life (T_1/2) is subject to large fluctuations, after taking a single dose of 75 mg - 8 hours (4-12 hours); at reception of 100 mg 2 times a day -12 h (4-66 h).

Indications:

- Acute and chronic forms of schizophrenia (including those resistant to therapy with other neuroleptics and / or with their intolerance);

- manic states;

- affective insanity;

- psychomotor agitation in psychopathy;

- emotional and behavioral disorders (including in children);

- sleep disorders.

Contraindications:

- Granulocytopenia or agranulocytosis in the anamnesis (with the exception of the development of granulocytopenia or agranulocytosis due to previously used chemotherapy);

- oppression of bone marrow hematopoiesis;

- myasthenia gravis;

- comatose conditions;

- toxic psychosis (incl.alcoholic);

- pregnancy;

- lactation period;

- Children's age till 16 years;

- increased sensitivity to clozapine;

- lactose intolerance, lactase deficiency and glucose-galactose malabsorption.

Carefully:

Decompensated diseases of the cardiovascular system, severe hepatic and / or renal insufficiency, angle-closure glaucoma, prostatic hyperplasia, intestinal atony, epilepsy, intercurrent diseases with febrile syndrome.

Pregnancy and lactation:

Contraindicated in pregnancy.

For the duration of treatment, breastfeeding should be discontinued.

Dosing and Administration:

Inside, after eating, 2-3 times a day.

A single dose for adults and children over the age of 16 lies - 50-200 mg, the initial daily dose is 150-300 mg, the average daily dose is 200-400 mg. The highest daily dose is 600 mg.

Dose is selected individually, starting with the appointment of small doses (25 mg) and increasing them by 25-50 mg per day, until the therapeutic effect.

For mild forms of the disease for maintenance therapy, as well as in patients with hepatic and / or renal insufficiency, chronic heart failure (CHF), with cerebrovascular disorders are prescribed at lower daily doses (25-200 mg).

It is necessary to take into account the stage-by-stage manifestation of the therapeutic effect: the rapid onset of hypnotic and sedative action; relief of anxiety, psychomotor agitation and aggressiveness (after 3-6 days); antipsychopathic effect (after 1-2 weeks); effect on the symptoms of negativity (after 20-40 days). After reaching a therapeutic effect, they switch to a supportive course.

Side effects:

From the central nervous system: dizziness, drowsiness, headache, fever, fainting, agitation, akathisia, confusion; rare - extrapyramidal disorders (akinesia or hypokinesia, rigidity of muscles, tremor), insomnia, sleep disturbances, depression, malignant neuroleptic syndrome (convulsions, shortness of breath or tachypnea, tachycardia or arrhythmia, fever, unstable blood pressure, involuntary urination, severe stiffness muscle, paleness of the skin, excessive fatigue or weakness), epileptic seizures, late dyskinesia.

From the genitourinary and urinary system: retention of urine, decreased potency.

From the side of metabolism: weight gain.

From the side of the musculoskeletal system: myasthenia gravis.

From the digestive system: Salivation, nausea, vomiting, heartburn, dry mouth, constipation.

From the hematopoiesis: granulocytopenia, until agranulocytosis (first signs of agranulocytosis may be flu-like symptoms: chills, fever, sore throat, gingivitis and oral mucosa; inertly healing wounds, abrasions, exacerbation of chronic or latent infection foci - tonsillitis, periostitis, pyoderma ), leukopenia, thrombocytopenia.

From the sense organs: violation of accommodation.

From the side of the cardiovascular system: decrease in blood pressure (including orthostatic hypotension); less often - increased blood pressure, tachycardia, flattening of the T wave on the electrocardiogram.

Overdose:

Symptoms: Stupor, drowsiness, soporous condition, respiratory depression, coma, delirious disorders, the development of large seizures, anxiety, agitation, lability of fever, tachycardia, decreased blood pressure, heart rhythm disturbances, collapse, atony bowel.

Treatment: washing the stomach with the appointment of sorbents, maintaining the function of breathing to the cardiovascular system, monitoring electrolyte balance and acid-base state (CBS); symptomatic treatment.

For 4 days after the disappearance of the symptoms of poisoning, the patient is monitored because of possible late complications.

Peritoneal dialysis or hemodialysis are ineffective.

Interaction:

Increases the effect of sedative and hypnotic drugs, drugs for general anesthesia, narcotic analgesics, monoamine oxidase inhibitors, antihypertensive drugs, ethanol.

Weakens the effect of levodopa and other dopamine stimulants.

Absorption from the intestine worsens with the use of gel-like antacids and colestyramine.

In combination with benzodiazepines, excessive lowering of blood pressure, impaired consciousness, depression or respiratory arrest may occur.

Simultaneous reception of lithium drugs increases neurotoxicity (delirium, cramps, extrapyramidal disorders).

Pentetrazole increases the risk of seizures.

Do not use together with tricyclic antidepressants,antipsychotic drugs, drugs that damage blood cells (pyrazolone-containing non-steroidal anti-inflammatory drugs), antidepressants, carbamazepine, gold preparations, thyreostatics and antimalarial drugs.

Caution should be exercised when co-prescribing antiepileptic medicines, anticoagulants, antimicrobial and hypoglycemic drugs (sulfonylurea derivatives).

Myelotoxic drugs increase the manifestation of hematotoxicity of the drug.

Special instructions:

When the phenomena of granulocytopenia develop, treatment should be stopped immediately.

To eliminate arterial hypotension, which develops with the use of clozapine, you can use only angiotensin or norepinephrine derivatives.

When taking clozapine, you should refrain from using ethanol.

Initially, weekly, and then every 3-4 months, it is necessary to monitor the blood picture. When granulocytopenia appears, treatment is immediately stopped.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care must be taken when driving vehicles and engaging in other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 25 mg and 100 mg.

Packaging:

For 10 or 25 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

5 contour cell packs but 10 tablets or 2 contourcell packs of 25 tablets together with the instructions but applied to a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

The drug belongs to the list of potent substances for the purposes of Art. 234 and other articles of the Criminal Code of the Russian Federation.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002478/10

Date of registration:26.03.2010 / 01.12.2016

Expiration Date:Unlimited

The owner of the registration certificate:VALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Manufacturer: & nbsp

VALENTA PHARMACEUTICS, JSC Russia

Representation: & nbspVALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Information update date: & nbsp29.01.2018

Illustrated instructions

Instructions

Clozasten® (Clozasten®)