Parnasan

Parnasan has antipsychotic and antipsychotic properties.

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Indications Parnasana

It is used to treat the following conditions:

• schizophrenia (with exacerbations, and also for long-term and supportive treatment to prevent relapse). It is also prescribed for psychotic disorders that occur on the background of schizophrenia and are accompanied by productive (including symptoms such as hallucinations, delusions and automatisms) or negative (deterioration of social activity, emotional flattening, and impoverishment of speech) manifestations and various affective disorders;
• BAR (for monotherapy or combination with valproic acid or lithium drugs) - with manic attacks of acute nature or mixed episodes, accompanied (or not) with psychotic symptoms, with a rapid change of stages (or without it);
• preventing the development of recurrence of mania in individuals with bipolar disorder (if the drug demonstrates efficacy in the treatment of the manic stage).

Release form

The release of the drug is made in tablets with a volume of 2.5, 5, as well as 7.5, 10, 15 and 20 mg. Inside the blister pack - 10 tablets. In a pack - 3 such packages.

Pharmacodynamics

The element olanzapine is an antipsychotic from the group of neuroleptics and has a large range of drug activity.

The antipsychotic effect develops by blocking the D2-terminations of the mesocortical and mesolimbic systems.

Sedative effect occurs after the blockade of the adrenoreceptors of the formation of the cerebral trunk.

Antiemetic effects are provided by blocking the D2-terminations of the trigger region of the emetic center.

Hypothermic properties of drugs - a consequence of blocking the endings of dopamine in the hypothalamus.

Along with this, the drug has an effect on adrenergic, muscarinic, H1-histamine and certain subclasses of serotonin endings.

It is known that olanzapine weakens the productive (hallucinations with delusions) and negative (a sense of suspicion and hostility, as well as autism of a social and emotional nature) signs of psychosis. Occasionally leads to the appearance of extrapyramidal disorders.

Pharmacokinetics

Olanzapine absorption is quite high; its degree does not depend on the use of food. Tmax in oral administration is 5-8 hours. After taking dosages in the range of 1–20 mg, plasma drug values change linearly, in accordance with the size of the portion. With plasma indices of 7-1000 ng / ml, protein synthesis is 93% (most of the substance is bound to α1-acid glycoprotein, as well as albumin). The drug passes through histohematogenous barriers, among which is the BBB.

Metabolic processes take place in the liver by means of oxidation with conjugation; however, the formation of active metabolic products is not observed, the main therapeutic effect of drugs is provided by olanzapine. The main circulating metabolic product is glucuronide; the substance does not pass through the BBB. CYP1A2 type isoenzymes, as well as CYP2D6 cytochrome P450 systems, are involved in the formation of N-desmethyl and 2-hydroxymethyl olanzapine metabolic products.

Sex, age, and smoking affect the values of the clearance of the substance inside the plasma and its half-life:

• the category of non-smokers - the half-life is 38.6 hours, and the level of clearance is 18.6 l / h;
• smoking category - half-life - 30.4 hours, clearance figures - 27.7 l / hour;
• women - T1 / 2 - 36.7 hours, clearance level - 18.9 l / h;
• men - clearance values - 27.3 l / h, half-life - 32.3 hours;
• people over the age of 65 - clearance is 17.5 l / h, and the half-life is 51.8 hours;
• persons younger than 65 years old - clearance values are 18.2 l / h, and half-life is 33.8 hours.

Values of clearance inside the plasma in people with liver failure, non-smoking people and women are lower compared with the corresponding categories of patients.

The excretion of the element mainly occurs through the kidneys (60%) in the form of metabolic products.

Dosing and administration

Tablets are taken orally, without reference to food intake, washed down with plain water.

For the treatment of schizophrenia - the size of the initial dosage is 10 mg per day.

For manic episodes caused by bipolar disorder, take 15 mg of the substance (monotherapy) or 10 mg per day (when combined with valproic acid or lithium drugs). In the same dosage prescribed and maintenance treatment.

To prevent recurrences of manic attacks with BAR, you must first take 10 mg per day during remission. People who have previously used Parnasan for the treatment of manic episodes, with maintenance treatment prescribed the same dosage. When using drugs for a new depressive, manic, or mixed episode, it is necessary to increase the dose when needed, additionally performing treatment for mood disorders (taking into account clinical symptoms).

The size of the daily portion of the drug in the treatment of episodes of mania, schizophrenia and to prevent recurrence of BAR can be in the range of 5-20 mg per day (taking into account the clinical condition of the patient). An increase in the portion to the values above the recommended initial size is allowed only after an adequately carried out repeated clinical examination of the patient and is usually performed at least 24-hour intervals.

Treatment of the elderly.

It is often not recommended to lower the initial portion (up to 5 mg per day), although it is allowed for people from 65 years old if there are risk factors.

People with kidney or liver disease.

It is required to reduce the initial dosage to 5 mg per day. In the case of a moderate form of impaired hepatic function, a portion of 5 mg per day becomes the initial. Later it can be increased, but with extreme caution.

If the patient has more than the 1st factor that may affect the absorption of the drug (elderly, women, non-smokers), it may be necessary to lower its initial portion. With the need, the dose may further increase, but very carefully.

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Use Parnasana during pregnancy

Since there is very little information about the use of the drug during pregnancy, it is recommended to apply it only in cases where the benefit to the woman is more likely than harm to the fetus. A woman should notify the doctor of a planned or already occurring pregnancy during treatment with Parnasan. A single report was reported on the appearance of drowsiness, tremors, the development of a lethargic state and an increase in blood pressure in infants who were born to women who had taken olanzapine during the 3rd trimester.

Tests have demonstrated that the drug passes into breast milk. The average portion size (mg / kg) that an infant receives after reaching Css values in a woman is 1.8% of the maternal dosage of drugs. It is forbidden to breastfeed during treatment.

Contraindications

Main contraindications:

• the presence of intolerance in relation to the active drug element and its other components;
• hypolactasia or lack of lactase, and besides this malabsorption of glucose-galactose.

Caution is necessary when using the drug in such cases:

• lack of kidney or liver function;
• prostate hyperplasia, having a benign character;
• glaucoma of a closed angle;
• intestinal obstruction, having a paralytic form;
• epileptic seizures;
• history of seizure syndrome;
• leuco-or neutropenia, having a different origin;
• myelosuppression of different nature (this includes myeloproliferative pathologies);
• hypereosinophilic syndrome;
• cerebral or cardiovascular diseases or other conditions that increase the likelihood of lower blood pressure values;
• phenylketonuria;
• an innate nature of an increase in the QT-interval in the ECG readings (prolongation of the corrected QT-interval (QTc)) or the presence of factors that in theory can lead to an increase in the QT-interval (for example, combination with drugs that prolong the level of the QT-interval);
• hypomagnesemia or Kalikaliemia;
• CHF;
• elderly people;
• combination with medications that have a central type of exposure;
• fixed state.

Side effects Parnasana

Using the medication may cause some side effects:

• disorders affecting the work of the National Assembly: often there is a feeling of drowsiness. Often, akathisia, dyskinesia, dizziness and asthenia with parkinsonism also appear. Occasionally, convulsive syndrome is observed (mainly in those who have this violation in history). Dystonia is singularly occurring (this includes the ocular curvature), ZNS and dyskinesia in the late stage. Abrupt cessation of drug intake alone leads to the development of such manifestations as vomiting, hyperhidrosis, tremor, insomnia, nausea and anxiety;
• Dysfunction of the cardiovascular system: a decrease in the level of blood pressure is often observed (this includes orthostatic collapse) Sometimes bradycardia appears (may be accompanied by collapse or not). A single QTc-interval prolongation occurs in ECG indications, fibrillation or tachycardia of the ventricles and sudden death, and also thromboembolism (this includes DVT and PEH);
• problems with digestive activity: transient anticholinergic symptoms often develop, including dryness of the oral mucosa and constipation, as well as an asymptomatic transient increase in liver transaminase activity (AST with ALT, especially at the initial stage of treatment). Occasionally, hepatitis appears (this includes hepatic lesions with cholestatic, hepatocellular, or mixed forms). Pancreatitis occurs alone;
• metabolic disorders: often increase in weight. Hypertriglyceridemia often develops or appetite increases. Hyperglycemia or decompensation of diabetes mellitus, which sometimes manifests itself in the form of ketoacidosis or a comatose state (which can lead to death), and in addition hypothermia and hypercholesterolemia are singled out individually;
• hematopoietic dysfunction: eosinophilia is often marked. Occasionally leukopenia appears. Thrombocyto- or neutropenia develops individually;
• ODA structure lesions: rhabdomyolysis is rarely observed;
• disorders in the urogenital system: a single priapism occurs or delayed urination processes;
• symptoms of the epidermis: occasionally rashes. Sometimes there are signs of photosensitivity. Alopecia develops individually;
• manifestations of allergies: rash is occasionally observed. Unity - angioedema, urticaria, anaphylactoid symptoms or itching;
• others: peripheral puffiness or asthenia often occur. The withdrawal syndrome is singularly manifested;
• data from laboratory tests: hyperprolactinemia often occurs, although its clinical signs (among them galactorrhea with gynecomastia, as well as an increase in the size of the mammary glands), occur only rarely. In many patients, prolactin levels stabilized independently, without discontinuing treatment. Asymptomatic transient increase in AST activity with ALT is rarely observed. Sometimes an increase in CPK activity develops. The values of bilirubin or alkaline phosphate increase individually, and the plasma sugar level rises (to indicators above 200 mg / dl, which is a factor in the possible presence of diabetes mellitus, or to values of 160-200 mg / dl, which is considered a possible symptom of the development of hyperglycemia) in people with baseline glucose values less than 140 mg / dl. There were also cases of an increase in triglycerides (+20 mg / dL to baseline values) or cholesterol (+0.4 mg / dL) and the development of asymptomatic eosinophilia.

In elderly people suffering from dementia, a higher incidence of death and cerebrovascular disorders (TIA or stroke) was recorded during the tests. It is extremely common for this group of patients to experience falls and gait disorders. Pneumonia, erythema, urinary incontinence, lethargy, fever and visual hallucinations were also frequently reported.

In people with drug-induced psychosis (due to the use of dopamine agonists), on the background of trembling paralysis, hallucinations and worsening of parkinsonian manifestations have often been recorded.

There is information about the occurrence of neutropenia (4.1%) in the case of the combined use of drugs with valproic acid in people with bipolar mania. The combination with lithium or valproic acid leads to an increase in the frequency (over 10%) of cases of dryness of the oral mucosa, tremor, weight gain and increased appetite. In addition, speech disorders were also noted (1-10%).

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Overdose

Signs of poisoning: often there is a feeling of aggression or excitement, tachycardia, dysarthria, deterioration of the level of consciousness (starting with a feeling of lethargy and reaching a comatose state) and various extrapyramidal disorders. Occasionally, convulsions, SNS, delirium, aspiration, coma, decrease or increase in blood pressure values, suppression of respiratory work and arrhythmias can occur. Failure of cardiopulmonary function develops individually.

In the case of acute fatal intoxication, the size of the minimum portion of Parnasan is 0.45 g. The maximum dosage for poisoning followed by patient survival was 1.5 g.

The medication does not have an antidote. It is forbidden to induce vomiting. Gastric irrigation, the use of activated carbon (reduces the bioavailability of drugs by 60%) and the implementation of symptomatic procedures while simultaneously monitoring the work of vital systems (this includes maintaining respiratory activity, treating orthostatic collapse and increasing reduced blood pressure) are required.

It is forbidden to use dopamine, epinephrine and other sympathomimetics with β-adrenomimetic properties, because the latter can enhance the decrease in blood pressure values. To determine the presence of arrhythmias, you need to track the work of the CAS. The victim must remain under constant medical supervision until full recovery occurs.

Interactions with other drugs

Since olanzapine is metabolized using CYP1A2 isoenzyme, substances that induce or slow down the activity of cytochrome P450 isoenzymes, as well as exhibit a specific effect on the function of CYP1A2, can change the pharmacokinetics of the drug.

Medicines inducing the activity of CYP1A2.

Drug clearance values may increase in smokers when combined with carbamazepine, resulting in lower plasma olanzapine levels. Clinical control is required, because in some cases it may be necessary to increase the dosage of Parnasan.

Means that slow down the activity of CYP1A2.

Fluvoxamine is a specific inhibitor of the element CYP1A2 and significantly reduces the level of clearance of olanzapine. In non-smoking women, the average increase in Cmax values of the drug after using fluvoxamine was 54%, and in men who smoke, 77%. At the same time, the average increase in the AUC values of drugs in these groups of patients is 52 and 108%, respectively.

Persons using fluvoxamine or another inhibitor of the activity of CYP1A2 isoenzyme (for example, ciprofloxacin), treatment with Parnasan is required to start with reduced portions. Reducing the dosage of olanzapine may be needed when adding to the treatment of substances that slow down the activity of isoenzyme CYP1A2.

Other interactions.

Activated carbon reduces the absorption of olanzapine by 50–60% after oral use, which can be taken at least 2 hours before or after taking the medicine.

Fluoxetine slows down the action of CYP1A2 isoenzyme (a single dose of 60 mg or a similar multiple dosage for 8 days) increases the level of Cmax by 16% and reduces the clearance of olanzapine by the same 16%. These changes do not have clinical value, therefore, it is not necessary to adjust the dosage of the drug.

The drug is able to reduce the effectiveness of dopamine agonists (direct or indirect type).

In in vitro tests, the active substance of drugs does not inhibit the main cytochrome P450 isoenzymes (among them 1A2 and 2D6, as well as 2C9 from 2C19 and 3A4). In in vivo studies, no suppression of the metabolic processes of such active elements was recorded: theophylline (CYP1A2), tricyclics (CYP2D6) with warfarin (CYP2C9), and diazepam (components of CYP3A4 and 2C19).

It is necessary to very carefully combine the medicine with other medicines with a central type of influence. Although a single dose of alcoholic beverages (45 mg / 70 kg) does not have a pharmacokinetic effect, if you drink alcohol at the same time as the drug, potentiation of the sedative effect on the central nervous system may be noted.

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Storage conditions

Parnasan is required to be kept in a place closed from access for young children. The temperature level is within 25 ° C.

Shelf life

Parnasan can be used within 36 months of the release of the therapeutic agent.

Application for children

The use of Parnasan in pediatrics (up to 18 years of age) is prohibited, because there are no data on the safety and therapeutic efficacy of the drug.

Analogs

Analogues of the drug are Egolanza, Olanzapine and Zalasta.