Parnasan

Parnasan has neuroleptic and antipsychotic properties.

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Indications Parnasana

It is used to treat the following conditions:

• schizophrenia (during exacerbations, and also for long-term and maintenance treatment to prevent relapses). It is also prescribed for psychotic disorders that arise against the background of schizophrenia and are accompanied by productive (this includes 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 in combination with valproic acid or lithium drugs) - for acute manic attacks or mixed episodes, accompanied (or not) by psychotic symptoms, with rapid change of stages (or without);
• prevention of the development of relapses of mania in individuals with bipolar disorder (if the drug demonstrates effectiveness in the treatment of the manic stage).

Release form

The drug is released in tablets of 2.5, 5, as well as 7.5, 10, 15 and 20 mg. There are 10 tablets in a blister pack. There are 3 such packs in a pack.

Pharmacodynamics

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

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

The sedative effect occurs after blocking the adrenergic receptors of the brainstem formation.

The antiemetic effect is achieved by blocking the D2 endings of the trigger area of the vomiting center.

The hypothermic properties of the drug are a consequence of blocking dopamine endings in the hypothalamus.

In addition, the drug has an effect on adrenergic, muscarinic, H1-histamine and individual subclasses of serotonin endings.

Olanzapine is known to reduce the productive (hallucinations with delusions) and negative (feelings of suspicion and hostility, as well as autism of a social and emotional nature) signs of psychosis. Rarely leads to the appearance of extrapyramidal disorders.

Pharmacokinetics

Olanzapine absorption is quite high; its degree does not depend on food intake. Tmax values for oral administration are 5-8 hours. After taking doses within 1-20 mg, plasma values of the drug change linearly, in accordance with the portion size. With plasma values of 7-1000 ng/ml, protein synthesis is 93% (most of the substance binds to α1-acid glycoprotein, as well as albumin). The drug passes through histohematic barriers, including the BBB.

Metabolic processes occur in the liver via oxidation with conjugation; no active metabolic products are formed, the main therapeutic effect of the drug is provided by olanzapine. The main circulating metabolic product is glucuronide; the substance does not pass through the BBB. Isoenzymes of the CYP1A2 type, as well as CYP2D6 of the cytochrome P450 system are involved in the formation of N-desmethyl and 2-hydroxymethyl metabolic products of olanzapine.

Gender, age, and smoking influence the plasma clearance values of a substance and its half-life:

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

Plasma clearance values in people with liver failure, non-smokers and women are lower than in the corresponding categories of patients.

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

Dosing and administration

The tablets are taken orally, without regard to food intake, with plain water.

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

For manic episodes caused by bipolar disorder, take 15 mg of the substance per day (monotherapy) or 10 mg (in combination with valproic acid or lithium drugs). Maintenance therapy is also prescribed in this dosage.

To prevent relapses of manic attacks in bipolar disorder, you should first take 10 mg per day during remission. People who previously used Parnasan to treat manic episodes are prescribed the same dosages during maintenance treatment. When using the drug for a new depressive, manic or mixed episode, you need to increase the dose if necessary, additionally conducting treatment for mood disorders (taking into account the clinical symptoms).

The daily dose of the medication for the treatment of episodes of mania, schizophrenia and for the prevention of relapses of bipolar disorder may be within 5-20 mg per day (taking into account the clinical condition of the patient). Increasing the dose to values above the recommended initial size is allowed only after an adequately conducted repeated clinical examination of the patient and is usually performed at minimum 24-hour intervals.

Treatment of elderly people.

Reducing the initial dose (to 5 mg per day) is often not recommended, although it is allowed for people over 65 years of age if there are risk factors.

People with kidney or liver disease.

It is necessary to reduce the initial dosage to 5 mg per day. In case of moderate liver failure, it is the 5 mg per day portion that becomes the initial one. Later it can be increased, but with extreme caution.

If the patient has more than 1 factor that can affect the absorption of the drug (elderly people, women, non-smokers), it may be necessary to reduce its initial dose. If necessary, the dose can be increased later, but very carefully.

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Use Parnasana during pregnancy

Since there is very little information regarding the use of the drug during pregnancy, it is recommended to use it only in cases where the benefit to the woman is more likely than the harm to the fetus. The woman should notify the doctor about a planned or already existing pregnancy during treatment with Parnasan. There have been isolated reports of drowsiness, tremor, lethargy, and increased blood pressure in infants born to women who used olanzapine in the 3rd trimester.

Tests have shown that the drug passes into breast milk. The average dose (mg/kg) that the infant receives after reaching the woman's Css values is 1.8% of the maternal dose of the drug. Breastfeeding is prohibited during treatment.

Contraindications

Main contraindications:

• the presence of intolerance to the active element of the drug and its other components;
• hypolactasia or lactase deficiency, and also glucose-galactose malabsorption.

Caution is required when using the medication in the following cases:

• renal or hepatic insufficiency;
• benign prostatic hyperplasia;
• closed-angle glaucoma;
• intestinal obstruction of a paralytic nature;
• epileptic seizures;
• history of seizure disorder;
• leuko- or neutropenia of various origins;
• myelosuppression of various natures (this includes myeloproliferative pathologies);
• hypereosinophilic syndrome;
• cerebrovascular or cardiovascular diseases or other conditions that increase the likelihood of decreased blood pressure values;
• phenylketonuria;
• a congenital increase in the QT interval in 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 medications that prolong the QT interval);
• hypomagnesemia or -kalemia;
• CHF;
• elderly people;
• combination with drugs that have a central type of action;
• motionless state.

Side effects Parnasana

The use of the medication may cause some side effects:

• disorders affecting the nervous system: a feeling of drowsiness often occurs. Akathisia, dyskinesia, dizziness and asthenia with parkinsonism also often occur. Convulsive syndrome is observed occasionally (mainly in those who have this disorder in their anamnesis). Dystonia (including oculogyric crisis), NMS and dyskinesia in the late stage occur occasionally. Abrupt cessation of drug intake occasionally leads to the development of such manifestations as vomiting, hyperhidrosis, tremor, insomnia, nausea and a feeling of anxiety;
• dysfunction of the cardiovascular system: a decrease in blood pressure is often observed (this includes orthostatic collapse). Sometimes bradycardia appears (it may or may not be accompanied by collapse). Prolongation of the QTc interval in ECG readings, ventricular fibrillation or tachycardia and sudden death occur sporadically, as well as thromboembolism (this includes DVT and PE);
• problems with digestive activity: transient anticholinergic symptoms often develop, including dry mouth and constipation, as well as asymptomatic transient increase in liver transaminase activity (AST with ALT, especially at the initial stage of treatment). Hepatitis occasionally appears (this includes liver damage of cholestatic, hepatocellular or mixed form). Pancreatitis occurs sporadically;
• metabolic disorders: weight gain often occurs. Hypertriglyceridemia or increased appetite often develops. Hyperglycemia or decompensation of diabetes mellitus are occasionally noted, which sometimes manifests itself in the form of ketoacidosis or coma (can lead to death), as well as hypothermia and hypercholesterolemia;
• disorders of hematopoietic function: eosinophilia is often observed. Leukopenia appears occasionally. Thrombocyto- or neutropenia develops occasionally;
• lesions of the musculoskeletal system: rhabdomyolysis is observed sporadically;
• disorders in the functioning of the urogenital system: priapism or urinary retention may occasionally occur;
• Symptoms from the epidermis: rashes occasionally appear. Sometimes signs of photosensitivity occur. Alopecia develops sporadically;
• manifestations of allergy: rash is occasionally observed. Isolated cases – Quincke's edema, urticaria, anaphylactoid symptoms or itching;
• others: peripheral edema or asthenia often occur. Withdrawal syndrome occurs occasionally;
• Laboratory test data: hyperprolactinemia often occurs, although its clinical signs (including galactorrhea with gynecomastia and enlarged breasts) are rare. In many patients, prolactin levels stabilized on their own, without stopping treatment. Rarely, asymptomatic transient increases in AST and ALT activity are observed. Sometimes, CPK activity increases. Single increases in bilirubin or alkaline phosphatase levels and increased plasma sugar levels (to levels above 200 mg/dL, which is a factor in the possible presence of diabetes mellitus; or to levels of 160-200 mg/dL, which is considered a possible symptom of hyperglycemia) in individuals with initial glucose levels below 140 mg/dL. There were also cases of increased triglyceride levels (+20 mg/dL to baseline values) or cholesterol (+0.4 mg/dL) and the development of asymptomatic eosinophilia.

Elderly patients with dementia showed a higher incidence of death and cerebrovascular accidents (TIA or stroke) in tests. Falls and gait disturbances were very common in this group of patients. 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) against the background of shaking palsy, the appearance of hallucinations and worsening of Parkinsonian manifestations were often recorded.

There is information about the occurrence of neutropenia (4.1%) in case of combined use of the drug with valproic acid in people with bipolar mania. Combination with lithium or valproic acid leads to an increase in the frequency (over 10%) of cases of dry mouth, tremor, weight gain and increased appetite. In addition, speech disorders were 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 inhibition and reaching a comatose state) and various extrapyramidal disorders. Rarely, convulsions, NMS, delirium, aspiration, comatose state, decrease or increase in blood pressure, suppression of respiratory work and arrhythmia may be observed. Insufficiency of cardiopulmonary function develops sporadically.

In case of acute intoxication with a fatal outcome, the minimum dose of Parnasan is 0.45 g. The maximum dosage for poisoning with subsequent patient survival is 1.5 g.

The drug has no antidote. Inducing vomiting is prohibited. Gastric lavage, activated carbon (reduces the bioavailability of the drug by 60%) and symptomatic procedures with simultaneous monitoring of vital systems (this includes maintaining respiratory activity, treating orthostatic collapse and increasing low blood pressure) are required.

It is prohibited to use dopamine, epinephrine and other sympathomimetics with β-adrenomimetic properties, because the latter can increase the decrease in blood pressure. To determine the presence of arrhythmia, it is necessary to monitor the work of the cardiovascular system. The victim must be under constant medical supervision until complete recovery occurs.

Interactions with other drugs

Since olanzapine is metabolized by the CYP1A2 isoenzyme, substances that induce or inhibit the activity of cytochrome P450 isoenzymes, as well as those that have a specific effect on the function of CYP1A2, can alter the pharmacokinetics of the drug.

Drugs that induce CYP1A2 activity.

Values of drug clearance may increase in smokers when combined with carbamazepine, resulting in decreased plasma olanzapine values. Clinical monitoring is required, because in some cases an increase in the dosage of Parnasan may be necessary.

Agents that inhibit CYP1A2 activity.

Fluvoxamine is a specific inhibitor of the CYP1A2 element and significantly reduces the clearance rate 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 AUC values of the drug in these groups of patients is 52 and 108%, respectively.

For individuals taking fluvoxamine or another inhibitor of CYP1A2 isoenzyme activity (e.g. ciprofloxacin), treatment with Parnasan should be started with reduced doses. A reduction in the olanzapine dosage may also be necessary when adding substances that inhibit CYP1A2 isoenzyme activity to the treatment.

Other interactions.

Activated charcoal reduces the absorption of olanzapine by 50-60% after oral use, which is why it can be taken at least 2 hours before or after taking the drug.

Fluoxetine slows down the action of the CYP1A2 isoenzyme (1-time dose of 60 mg or similar multiple doses over 8 days) - increases the Cmax level by 16% and decreases the clearance of olanzapine by the same 16%. These changes are not clinically significant, so there is no need to adjust the dosage of the drug.

The drug is capable of reducing the effectiveness of dopamine agonists (direct or indirect type).

In vitro tests show that the active substance of the drug does not inhibit the main cytochrome P450 isoenzymes (including 1A2 and 2D6, as well as 2C9 with 2C19 and 3A4). In vivo studies have not shown any suppression of metabolic processes of the following active elements: theophylline (CYP1A2), tricyclics (CYP2D6) with warfarin (CYP2C9), and diazepam (CYP3A4 and 2C19 components).

It is necessary to combine the drug with other drugs with a central type of influence very carefully. Although a single serving of alcoholic beverages (45 mg/70 kg) does not have a pharmacokinetic effect, when alcohol is consumed simultaneously with the drug, a potentiation of the sedative effect on the central nervous system may be observed.

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Storage conditions

Parnasan must be kept in a place out of reach of small children. Temperature level – within 25°C.

Shelf life

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

Application for children

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

Analogues

Analogues of the drug are Egolanza, Olanzapine and Zalasta.