Zolafren

Zolafren is a psycholeptic from the antipsychotic drug category.

Indications Zolafrena

It is used for the treatment of schizophrenia in people who have previously been shown to respond to medication during the active phase of treatment.

It is used to treat various exacerbations, as well as in long-term maintenance therapy to prevent relapses in people with schizophrenia and other psychotic disorders that have intense productive (the appearance of automatisms and hallucinations) or negative symptoms (weakening of emotionality, deterioration of social activity, poverty of speech), and in addition to this, with concomitant disorders of an affective nature.

It is also prescribed for bipolar disorder – for the treatment of mixed or manic (acute) attacks (may be accompanied/not accompanied by psychotic symptoms and rapid change of stages).

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Release form

The drug is released in tablets, which are packaged in 30 pieces inside a blister pack. There is 1 pack of tablets in a pack.

Pharmacodynamics

Olanzapine is an atypical antipsychotic (neuroleptic), which is a selective antagonist of monoaminergic elements and has affinity for the following endings: serotonin (5HT2a/2c, as well as 5HT3 and 5HT6), dopamine (D1 and D2, as well as D3, D4 and D5), cholinergic muscarine (M1-5), histamine (H1), and also α1-adrenergic. Olanzapine selectively affects the mesolimbic system, without having a noticeable effect on the extrapyramidal system.

The exact pattern of development of the therapeutic effect of olanzapine, as well as other drugs used in schizophrenia, remains unknown. It was concluded that the effect of the drug in schizophrenia is provided by a combination of a dopamine antagonist and serotonin of the 5HT2 category.

Olanzapine demonstrates a stronger connection with 5HT2 endings (compared to synthesis with D2 endings). The drug binds to the latter ending worse than simple neuroleptics. This therapeutic profile explains the positive effect of the drug on pathological symptoms, and also has a single effect on the occurrence of extrapyramidal disorders and late-type dyskinesia associated with therapy in which olanzapine is used.

Antagonistic effects on other than dopamine and 5HT2 endings explain other individual drug effects and the negative impact of olanzapine. Antagonistic effects on M1-5 muscarine endings may explain its anticholinergic properties. Antagonism of the substance on H1 histamine endings may provoke a feeling of drowsiness, and antagonism on α1-adrenergic endings explains the development of orthostatic collapse.

Pharmacokinetics

Orally administered olanzapine is well absorbed from the gastrointestinal tract, reaching peak blood levels after 5-8 hours. Food intake does not affect absorption.

The drug is metabolized in the liver – by synthesis with oxidation (40% of the portion). The main decay product is the element 10-N-glucuronide, which does not have the ability to pass through the BBB. For the most part, the therapeutic effect of Zolafren depends on the activity of olanzapine, which has not undergone biotransformation.

The half-life is within 21-54 hours (average value is 30 hours), and the plasma clearance rate is 12-47 l/hour (average value is 25 l/hour).

Olanzapine is excreted largely in the form of breakdown products - about 57% in urine, and another 30% in feces.

The drug indicators in the blood plasma have a linear dependence on the size of the used dosage of the drug. With a single use of the drug per day for 7 days, a stable indicator is created in the blood plasma, corresponding to the double value after a single dose.

Plasma parameters, half-life and clearance rate of the substance may vary depending on the age and sex of the patients, as well as smoking. Plasma values of drug clearance are lower in women, the elderly and non-smokers. However, it should be noted that all these factors are not of particular importance in treatment.

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Dosing and administration

The medicine is taken once a day, without reference to food intake. At first, the daily dosage of the drug should be 10 mg, and later it can fluctuate within 5-20 mg. The optimal dose for the patient is selected taking into account his condition, and its increase by more than 10 mg/day should be justified by clinical indications. If necessary, the dose should be increased or decreased by 5 mg.

It is allowed to consume no more than 20 mg of the drug per day (increasing the dose to more than 15 mg/day is allowed after at least 4 days of therapy).

Elderly or low-weight individuals are advised to initially take 5 mg of the medication per day, but only if this dosage is sufficient to improve the condition. A similar dosage should also be taken by people with renal or hepatic insufficiency.

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Use Zolafrena during pregnancy

Zolafren should not be used during pregnancy or lactation.

Contraindications

Among the contraindications:

• the presence of strong sensitivity to medicinal elements;
• closed-angle glaucoma.

Side effects Zolafrena

Most often, the use of drugs leads to the appearance of the following symptoms: weight gain, drowsiness, asthenia (feeling of weakness), orthostatic collapse, dizziness. In addition, there is an increase in appetite, dry mouth, constipation, fluid retention (the appearance of peripheral edema), personality disorder, anxiety and akathisia (inability to lie or sit in one place).

The following manifestations are occasionally encountered: parkinsonism, visual disturbances, vomiting, dyskinesia (problems with precise movements; especially affects the fingers and hands), headaches and dystonia (impaired muscle tone).

At the initial stage of therapy, an increase in prolactin levels in the blood plasma may be observed, but in most patients they return to the initial level without interruption of the treatment course.

With a prolonged therapeutic cycle, galactorrhea, disappearance of menstruation or cycle disruption, as well as gynecomastia and enlargement of the mammary glands may be recorded. No noticeable effect of olanzapine on the duration of the QT interval on the ECG was revealed. A transient treatable increase in liver transaminase activity (ALT with AST) was noted.

Increases in CPK levels have also been reported sporadically. As with other neuroleptics, changes in blood values have been recorded. Severe photophobia has been reported rarely.

NMS may also develop, the symptoms of which include vegetative (tachycardia, hyperhidrosis, diarrhea, heart rhythm disorder and blood pressure change) and motor disorders (convulsions and muscle rigidity), as well as impaired consciousness, increased CPK levels, development of myoglobinaria (myoglobin appears in the urine) or acute renal failure. In case of NMS, no specific therapy is prescribed, it is necessary to immediately discontinue the use of the antipsychotic, as well as monitor the patient's condition and carry out intensive symptomatic measures.

Late-stage dyskinesias are a potentially incurable complex of abnormal movements of the trunk and limbs that cannot be controlled. The risk of such symptoms is high in older people (especially women). There is no specific therapy for late-stage dyskinesias, but there is a possibility that the syndrome will regress completely or partially after stopping the antipsychotic.

Overdose

Signs of poisoning include speech disorder, drowsiness, visual impairment, dilated pupils, breathing problems, extrapyramidal symptoms and decreased blood pressure.

In the acute stage of intoxication, it is necessary to ensure free passage of the respiratory tract and oxygen supply, and also monitor the patient's breathing processes. It is also necessary to determine whether he needs activated carbon and gastric lavage.

If collapse with hypotension develops, intravenous injection of fluid or norepinephrine should be administered. After poisoning with the drug, the victim should be under constant supervision of specialists until complete recovery occurs.

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Interactions with other drugs

Because olanzapine primarily affects the central nervous system, the medication should be combined with caution with other drugs that have an effect on the central nervous system.

Since Zolafren can lead to a decrease in blood pressure, it can potentiate the effect of certain antihypertensive drugs.

The drug has an antagonistic effect relative to the therapeutic effect of dopamine antagonists and levodopa.

Combination with fluoxetine reduces the clearance level of the drug; carbamazepine has the opposite effect - it increases the clearance values of Zolafren, as do rifampicin and omeprazole.

Single doses of cimetidine, as well as oral magnesium- or aluminum-containing antacids, do not affect the level of bioavailability of the drug taken orally.

Clinical data and in vitro tests suggest that the drug does not affect the metabolic processes of most therapeutic drugs.

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Storage conditions

Zolafren should be kept in a dry and dark place, out of the reach of small children. Temperature values are within the range of 15-25°C.

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Shelf life

Zolafren can be used within 36 months from the date of manufacture of the drug.

Application for children

It is prohibited to prescribe the medicine to people under 18 years of age.

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Analogues

Analogues of the drug are the drugs Adagio, Azapin with Zyprexa, Azaleptin and Ketilept, and in addition to this Azaleptol with Gedonin, Clozapine with Zyprexa adera and Quetiron. Also on the list are Olan, Leponex, Seroquel and Nantarid, and in addition Skizoril, Olanzapine, Egolanza and Parnasan.