Egolanza

The Hungarian pharmaceutical plant Egis OJSC supplies the new generation neuroleptic Egolanza, which has high antipsychotic properties, to the modern market.

Indications Egolanza

The drug was developed purposefully, therefore the indications for the use of Egolanza are authentic and narrowly targeted, although they have a systemic effect on the human body.

• Schizophrenia is a fairly common polymorphic mental disorder, which affects about one percent of the entire population of the Earth. The drug is used both during an exacerbation, as a maintenance therapy, and in long-term anti-relapse treatment.
• Manic-depressive psychosis, as monotherapy or as part of complex treatment (in combination with valproic acid and chemical compounds based on lithium ions). In acute phases of the disease, in the case of rapid alternation of periods of excitement and apathy.
• Stopping relapses of bipolar disorder.
• Prevention of relapses of bipolar disorders if positive dynamics are observed in the case of stopping the manic phase of the pathology.

[ 1 ]

Release form

The active chemical compound that makes up the basis of Egolanza is olanzapine dihydrochloride trihydrate. For ease of use and maintaining the required dosage level, the manufacturer presents several different forms of release to the pharmacological market.

This is a tablet with a hard yellow coating layer on top. The shape of the medicinal unit has a round, slightly oblong outline, with slightly convex sides. On one plane of the tablet, a dividing groove can be seen, and on the other, an embossing that differs depending on the concentration of olanzapine dihydrochloride trihydrate in the medicinal unit.

1. The engraving "E 402" is placed on the medicinal unit, in which the concentration of the active substance is 7.03 mg, which corresponds to 5 mg olanzapine (olanzapinum).
2. The embossing "E 403" is placed on the medicinal unit, in which the concentration of the active substance is 10.55 mg, which corresponds to 7.5 mg olanzapine (olanzapinum).
3. Another form of release is a tablet with the embossing "E 404" placed on a medicinal unit, in which the concentration of the active substance is 14.06 mg, which corresponds to 10 mg of olanzapine (olanzapinum).
4. The engraving "E 405" is placed on the medicinal unit, in which the concentration of the active substance is 21.09 mg, which corresponds to 15 mg olanzapine (olanzapinum).
5. The embossing "E 406" is placed on the medicinal unit, in which the concentration of the active substance is 28.12 mg, which corresponds to 20 mg olanzapine (olanzapinum).

Additional substances included in the composition of the medicinal product in tablet form are microscopic crystals of cellulose (from 40.99 mg to 163.94 mg), hydroxypropyl cellulose (from 5 mg to 20 mg), lactose monohydrate (from 40.98 mg to 163.94 mg), magnesium stearate (from 1 mg to 4 mg), crospovidone (from 5 mg to 20 mg).

The coating layer of the tablet consists of quinine yellow dye, hypromellose, and opadray.

One blister contains seven medicinal units. The manufacturer produces cardboard boxes containing four or eight blisters.

[ 2 ]

Pharmacodynamics

The drug was developed as a neuroleptic with an extended pharmacological spectrum of action. The pharmacodynamics of Egolanza is mainly based on the chemical and physical properties of olanzapine, a chemical compound that is the basis of the drug. Olanzapine is selective in its effect and selects only some receptors. Due to the similarity of pharmacodynamics, the active substance effectively inhibits or, conversely, activates the action of serotonin 5HT6, 5HT3, 5-HT2A/C nerve endings.

Egolanza is effective in influencing muscarinic (M1-5), H1-histamine, α1-adrenergic receptors. At the same time, olanzapine is a persistent antagonist of dopamine (D1, D2, D3, D4, D5), cholinergic and 5HT-serotonin nerve endings.

The action of the drug progressively reduces the level of excitation of A10-mesolimbic neurons related to dopaminergic receptors. No significant effect on A9-striatal pathways of nerve impulses has been confirmed.

The drug Egolanza is active in the regulatory processes of the patient's motor skills. Under its influence, there is a selective reduction in protective reflexes. Such a therapeutic picture can be obtained with low doses of the drug, which helps prevent the development of such a pathological disorder as catalepsy - a symptom of movement disorders characterized by the patient freezing in one position for a long time or a sudden loss of muscle tone, as a result of which the person falls "like a sheaf".

In the case of passing an anxiolytic test, which is carried out to assess emotional and behavioral reactions to stress and assess stress-protective effects, olanzapine enhances the anti-anxiety result. The drug is good at stopping both negative and productive symptoms, including hallucinations and delusional insinuations.

[ 3 ], [ 4 ]

Pharmacokinetics

After oral administration, the drug is perfectly absorbed by the mucous membrane of the digestive tract. Food intake does not have such a significant effect on the absorption and distribution characteristics. The pharmacokinetics of Egolanza shows the maximum concentration of the active substance Cmax in the blood serum after five to eight hours after administration. The change in Cmax in the blood, with a dose of 1 to 20 mg, occurs according to linear laws: the higher the administered amount of the drug in question, the higher the concentration in the plasma.

Olanzapine has a high protein binding rate (approximately 93%). It primarily binds to alpha1-acid glycoprotein and albumin.

Through oxidation and conjugation processes, olanzapine undergoes biotransformation, which occurs in the liver. The result of metabolism is the main chemical compound 10-N-glucuronide, which subsequently circulates through the patient's body systems. Glucuronide is unable to penetrate the blood-brain barrier.

Other metabolites of the drug, 2-hydroxymethyl and N-desmethyl, are biotransformed with the direct participation of CYP2D6 and CYP1A2 isoenzymes.

The main pharmacokinetics of Egolanza is due to olanzapine, the effect of its metabolites is less noticeable. The drug is excreted from the body mainly in the form of metabolites through the kidneys, together with urine.

Depending on the individual characteristics of the patient's body, the half-life of the drug is on average 33 hours, but can also show T1/2 from 21 to 54 hours. The average plasma clearance rate is from 12 to 47 l/h, the average number is 26 liters per hour.

The half-life T1/2 indicator largely depends on the patient's gender and age, as well as smoking status:

• If the patient is a woman: plasma clearance of olanzapine is approximately 18.9 L/h, half-life is 36.7 hours.
• If the patient is a man: the plasma clearance of olanzapine is higher and can correspond to a figure of 27.3 l/h, the half-life is on average 32.3 hours.
• The patient smokes: plasma clearance of olanzapine is approximately 27.7 l/h, half-life is 30.4 hours.
• The patient does not smoke: plasma clearance of olanzapine is approximately 18.6 l/h, the half-life is 38.6 hours.
• If the patient has crossed the Rubicon at 65 years of age: the plasma clearance of olanzapine is approximately 17.5 l/h, the half-life is 51.8 hours.
• If the patient is under 65 years old: plasma clearance of olanzapine is approximately 18.2 l/h, half-life is 33.8 hours.

No significant differences in similar values were found between patients with severe renal dysfunction and patients without pathological abnormalities in this area.

[ 5 ], [ 6 ]

Dosing and administration

Depending on the diagnosis, the patient's age and the severity of the disease, the attending physician selects the method of administration and the dose of the administered drug necessary to achieve the desired therapeutic effect.

The new generation neuroleptic Egolanza is administered orally, that is, through the mouth. Taking the medicine is not related to the time of food consumption. The drug is administered once a day.

The starting dosage is usually prescribed within the range of 5 to 20 mg. In case of schizophrenia diagnosis, 10 mg is initially prescribed.

If mania is diagnosed in the acute stage of the course and it is established that the underlying cause of pathological changes is bipolar mental disorders, the patient is prescribed olanzapine in a dosage of 15 mg (if monotherapy is planned) or 10 mg in combination with drugs, the basic element of which is lithium ion (Li+). In this situation, a combination with valproic acid is also practiced. In the case of maintenance therapy, tandem drugs are administered in similar dosages.

If schizophrenia aggravated by manic-depressive syndrome is diagnosed, the starting dose of the administered drug is taken at the rate of 10 mg per day. If the patient has already undergone Egolanza therapy to stop a manic case, then in case of preventive measures for relapses, treatment with the same dosages is recommended. If the therapy is primary, then a starting dose is prescribed, which is adjusted during the course of therapy.

It is not recommended to abruptly stop taking Egolanz, so as not to get withdrawal syndrome. The maximum daily dosage of the drug in question should not exceed 20 mg.

For patients who are already over 65 years old, if therapy is necessary, the starting dose should be lower (5 mg daily). For patients with impaired liver and/or kidney function, the amount of the drug is prescribed in smaller doses. If necessary, the dose should be increased very carefully.

Dosage adjustments based on gender and smoking status are not performed. If the patient has more than one factor that causes metabolic inhibition, it is necessary to consider reducing the initial dose of the drug to 5 mg daily.

[ 10 ]

Use Egolanza during pregnancy

To date, there are no strictly conducted studies and data on monitoring the clinical picture as a result of the introduction of olanzapine during the period of bearing a child by a woman. Therefore, the developers of the drug do not recommend the use of Egolanza during pregnancy and lactation. The only exception can be the decision of the attending physician, who, having received an objective picture of the disease, is able to assess the situation. And if the real help to the young mother in solving her health problems is more significant than the expected harm to the fetus, the drug is prescribed.

Egolanza does not cross the blood-brain barrier and does not enter breast milk, but nevertheless, it should not be recommended for introduction during lactation. If such a need arises, it is advisable to stop breastfeeding the baby for the duration of therapeutic treatment.

Contraindications

Any medicine shows both the expected positive dynamics of impact, and can also negatively affect organs pathologically changed by other diseases in the patient's medical history. Based on this, there are contraindications to the use of Egolanz.

• Individual intolerance to the components of the drug.
• Closed-angle glaucoma is a type of glaucoma in which the pressure in the eye rises too quickly.
• Psychoses of various origins.
• Glucose-galactose malabsorption.
• Dementia is a slowly developing decline in mental abilities that affects thinking, memory, learning, and concentration.
• Pregnancy and the period of breastfeeding a newborn.
• When there is a lack of lactase in the patient’s body.
• Patients under 18 years of age due to insufficient clinical data.
• Hypersensitivity of the patient's body to lactose.

Olanzapine should be used with extreme caution:

• Kidney and/or liver dysfunction.
• Hyperplasia (an increase in the number of structural elements of tissues due to their excessive neoplasm) of the prostate gland.
• Tendency to epileptic seizures.
• Tendency to convulsions.
• Myelosuppression, including neutropenia and leukopenia – decreased levels of the corresponding blood components.
• Paralytic ileus.
• Arterial hypotension, including its precursors: cardiovascular and cerebrovascular diseases.
• Myeloproliferative pathologies (increased production of platelets, leukocytes or erythrocytes is observed in the bone marrow).
• Congenital heart disease.
• Congestive cardiac dysfunction.
• Hypereosinophilic syndrome.
• Immobilization is the immobility of any part of the body due to certain injuries to the body.
• For elderly people.

[ 7 ], [ 8 ]

Side effects Egolanza

In case of undergoing therapy with the use of the drug in question, side effects of Egolanza may occur with a greater or lesser frequency.

Neuralgic reactions:

• Drowsiness and general apathy.
• The appearance of involuntary, uncontrolled movements.
• Dizziness.
• Symptoms of Parkinson's disease.
• Nervous and mental weakness.
• Cramps.
• An extrapyramidal syndrome characterized by arrhythmic forced rotational movements in various parts of the body.
• Isolated cases of the development of malignant neuroleptic syndrome have been observed.
• Elevated body temperature.
• Instability of the autonomic nervous system.
• Activation of sweat glands.
• Irregularities in heart rhythm and rate.
• Tremor.
• Sleep disturbance.
• Emotional instability.

Cardiovascular response:

• Increased blood pressure.
• Bradycardia, which may be accompanied by acute vascular insufficiency.
• There have been isolated cases of ventricular tachycardia, which occurs with chaotic electrical activity of the atria with a pulse rate of 350-700 per minute. Such a picture can provoke sudden death.
• Thromboembolism, both pulmonary and deep veins.

Reaction of the exchange system:

• Increase in patient body weight.
• Constant feeling of hunger.
• Hypertriglyceridemia.
• In rare cases, hyperglycemia may be observed.
• Symptoms of diabetes may appear.
• Hypercholesterolemia.
• Accumulation of excess heat in the human body.
• Fatal outcome is possible.

Gastrointestinal reaction:

• Increased ALT and AST liver transaminases.
• Constipation.
• Hepatitis.
• Decreased humidity of the oral mucosa.
• Less frequently, damage to liver tissue of a cholestatic and/or hepatological nature can be observed.
• Pancreatitis.

Reaction of other body systems:

• The release of myoglobin into the blood as a result of rapid damage to skeletal muscles.
• Retention of urine in the body.
• Painful urination.
• Allergic reaction.
• Photosensitivity is sometimes observed.
• Swelling.
• Asthenia - the body is working at its last strength.
• Urinary incontinence.

[ 9 ]

Overdose

Each person is individual, so different symptoms of taking the same medicine can be observed. If the amount of the prescribed drug was calculated incorrectly, an overdose of the drug can occur, which manifests itself in such pathological symptoms:

• Heart rhythm disturbance.
• Overexcitability and aggression.
• Respiratory depression.
• A disorder of the speech apparatus, manifested by an articulation disorder.
• Blocking of consciousness, which is expressed in symptoms of varying severity from mild sedation to a comatose state.
• Extrapyramidal disorders.
• Cramps.
• Psychological insanity.
• Problems with blood pressure: a rapid rise or fall in blood pressure readings.
• Neuroleptic malignant syndrome.
• Respiratory and/or cardiac arrest.

It is quite difficult to define doses that are dangerous for human life, since a fatal outcome was recorded after taking 450 mg of olanzapine. While there is a known case when after the introduction of 1500 mg of Egolanz the patient remained alive.

When the first signs of overdose appear, the victim must first wash out the stomach and induce a gag reflex. After that, any sorbent should be taken, for example, activated carbon. Further treatment is symptomatic. During this period, careful medical monitoring of the patient's condition is necessary.

[ 11 ], [ 12 ]

Interactions with other drugs

It is much easier to predict the patient's reaction to monotherapy. But the introduction of a complex treatment schedule is fraught with some unpredictability if the doctor is unable to predict the result of the mutual influence of the drugs present in the treatment protocol on each other. Therefore, in order to achieve the necessary therapeutic effectiveness, while preventing pathological complications, you should know the consequences of the interaction of Egolanz with other drugs.

Medicines that stimulate the CYP1A2 isoenzyme (inducers) can affect the processes of metabolism of the active substance in the patient's body. In this case, the clearance of olanzapine increases its indicators if the patient "indulges" in nicotine. A similar situation occurs with the combined administration of Egolanza with a group of drugs that include carbamazepine. Such a combination of chemical compounds can provoke a decrease in the amount of olanzapine in the patient's blood plasma. In this case, it may be necessary to increase the dosage.

Drugs that have an inhibitory effect on the CYP1A2 isoenzyme (inhibitors) are capable of influencing the processes of metabolism of the active substance in the patient's body.

The same reaction is shown by the tandem administration of the drug in question and fluvoxamine. In this case, a decrease in the clearance of the active substance is observed, while its maximum concentration in the serum increases: by 55% in non-smoking representatives of the weaker sex and by 77% in men who are addicted to nicotine. Based on these indicators, when Egolanza interacts with other drugs, in particular fluvoxamine, or any other inhibitor of the CYP1A2 isoenzyme (for example, such as ciprofloxacin), it is necessary to reduce the starting dosage of olanzapine.

The combined administration with ethanol does not have a significant effect on the physicochemical properties of the drug in question; only an increase in the sedative properties of the former may be observed.

Fluoxetine, a drug that inhibits the action of the CYP2D6 enzyme, antacid drugs based on magnesium and aluminum ions, as well as cimetidine do not significantly affect the pharmacodynamics and pharmacokinetics of Egolanza.

When the drug in question is used simultaneously with adsorption drugs, such as activated carbon, the bioavailability of olanzapine drops significantly. The change in this indicator can range from fifty to sixty percent. To avoid such a situation, it is necessary to separate the administration of the two drugs. The interval between doses should not be less than two hours.

Valproic acid may slightly reduce the biotransformation potential of olanzapine. Whereas the active substance of Egolanza inhibits the synthesis of valproic acid glucuronide. Therapeutic sensitive pharmacodynamic interactions between the two drugs are unlikely.

If a patient is diagnosed with Parkinson's disease, it is not advisable to administer olanzapine when antiparkinsonian therapy is being administered.

With special caution should be taken in parallel with such drugs as amitriptyline, sotalol, sulfamethoxazole, ketoconazole, trimethoprim, chlorpromazine, droperidol, terbutatin, erythromycin, thioridazine, fluconazole, pimozide, ephedrine, quinidine, adrenaline, procainamide and other drugs that can prolong the QTc interval. This fact disrupts the electrolyte balance in the patient's body, inhibits the biotransformation of olanzapine in the liver.

Olanzapine should not be administered simultaneously with dopamine or levodopa, since the former inhibits the action of the latter, being their antagonist.

No significant mutual influence is observed in case of combined administration of the drug in question with isoenzymes CYP1A2 (theophyllines), CYP 2D6 (tricyclic antidepressants), CYP 2C9 (warfarins), as well as diazepam CYP 2C19 and CYP 3A4, biperiden.

[ 13 ]

Storage conditions

The high pharmacological characteristics of the drug largely depend on the careful observance of the storage conditions of Egolanza.

• The drug must be stored in a room where the temperature does not exceed 30°C.
• The room must be dry.
• The storage location should not be accessible to children.

[ 14 ]

Shelf life

If all requirements for storage conditions of the drug are met, the shelf life is three years. After this period, the use of Egolanz is unacceptable. The time frame for the effective and safe use of the drug is necessarily reflected on the cardboard packaging and on each blister of the drug.