Egolanza

The Hungarian pharmaceutical plant OJSC Egis is supplied to the modern market with a neuroleptic of the new generation Egolansa, which has high antipsychotic characteristics.

Indications Egolanza

The drug was developed purposefully, therefore indications for the use of Egolans are authentic and narrow-minded, although they exert a systemic influence on the human body.

• Schizophrenia is a fairly common polymorphic mental disorder that affects about one percent of the world's population. The drug is used both in the period of exacerbation, in the role of maintenance therapy, and with prolonged anti-relapse treatment.
• Manic-depressive psychosis, as a monotherapy or as part of a complex treatment (in combination with valproic acid and chemical compounds, the basis of which are lithium ions). In acute phases of the disease, in the case of a rapid alternation of periods of excitement and apathy.
• Relief of bipolar disorder relapses.
• Prevention of recurrence of bipolar disorders, if there is a positive dynamics in the case of arresting the manic phase of the pathology.

[1]

Release form

The active active chemical compound making up the basis of Egolans is olanzapine dihydrochloride trihydrate. For convenience of use and maintenance of the required dosage level, the manufacturer presents several different forms of release to the pharmacological market.

This is a tablet that has a hard top coat of yellow color on top. The form of the unit has a round, slightly oblong outline, with slightly convex sides. On one plane of the tablet, a separation depression can be observed, and on the other hand, embossing, which differs depending on the concentration of olanzapine dihydrochloride trihydrate in a unit of the drug.

1. The engraving "E 402" is put on a unit of medicine in which the concentration of the active substance is 7.03 mg, which corresponds to 5 mg of olanzapinum.
2. Stamping "E 403" is placed on a unit of medicine in which the concentration of the active substance is 10.55 mg, which corresponds to 7.5 mg of olanzapinum.
3. Another form of release is a tablet with an embossed "E 404" placed on a dosage unit in which the concentration of the active substance is 14.06 mg, which corresponds to 10 mg of olanzapinum.
4. The engraving "E 405" is put on a unit of medicine in which the concentration of the active substance is 21.09 mg, which corresponds to 15 mg of olanzapinum.
5. Embossing "E 406" is placed on a unit of medicine in which the concentration of the active substance is 28.12 mg, which corresponds to 20 mg of olanzapinum.

Additional substances included in the medicinal product of the tablet form of release 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 layer covering the tablet consists of a quinine yellow dye, hypromellose, opadar.

Seven medicinal units are located on one blister. The manufacturer produces cardboard boxes, in which there are four or eight blisters.

[2]

Pharmacodynamics

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

Egolanza is effective in affecting muscarinic (M1-5), H1 - histamine, α1 - adrenergic receptors. In this case, olanzapine is a persistent antagonist of dopamine (D1, D2, D3, D4, D5), cholinergic and 5HT-serotonin nerves.

The action of the drug progressively reduces the level of excitation of A10-mesolimbic neurons related to dopaminergic receptors. There is no evidence of a significant effect on A9-striatnyh pathways of nerve impulses.

The drug Egolansa is active in the regulatory processes of the patient's motor skills. Under its influence, the defense reflexes are selectively reduced. Such a therapeutic picture can be obtained with low doses of the drug, which helps prevent the development of such a pathological violation as catalepsy, a symptom of motor disorders characterized by a patient's fading in one posture for a long time or a sudden loss of muscle tone, resulting in a person falling "like a sheaf."

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

[3], [4]

Pharmacokinetics

After oral administration, the drug is perfectly absorbed by the mucosa of the digestive tract. The intake of food does not have such a significant effect on the characteristics of absorption and distribution. Pharmacokinetics Egolansa shows the maximum concentration of the active substance Cmax in the blood serum after five to eight hours after administration. Changing the Cmax in the blood, at a dose of 1 to 20 mg, is carried out according to linear laws: the higher the amount of the drug in question, the greater the concentration to the plasma.

Olanzapine has a high percentage of binding to blood proteins (about 93%). Mostly it works with alpha-acid glycoprotein and albumin.

Through oxidation and conjugation, olanzapine undergoes biotransformation, which takes place in the liver. The result of the metabolism is the main chemical compound 10-N-glucuronide, later circulating through the systems of the patient's body. Glucuronide is deprived of opportunities 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 iso-enzymes.

The basic pharmacokinetics of Egolans is due to olanzapine, the severity 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 organism, the half-life of the drug is on the average 33 hours, but is capable of showing T1 / 2 from 21 to 54 hours. The average plasma clearance is from 12 to 47 l / h, the average number is 26 liters per hour.

The indicator of the half-life of T1 / 2 largely depends on the sex and age of the patient, as well as the status of the smoker:

• If the patient is female: the plasma clearance of olanzapine approximately indicates a figure of 18.9 l / h, the elimination half-life is 36.7 hours.
• If the patient is male: the plasma clearance of olanzapine is higher and may correspond to a figure of 27.3 l / h, the half-life on average is 32.3 hours.
• The patient smokes: the plasma clearance of olanzapine approximately shows a figure of 27.7 l / h, the elimination half-life is 30.4 hours.
• The patient does not smoke: the plasma clearance of olanzapine approximately indicates a figure of 18.6 l / h, the elimination half-life is 38.6 hours.
• If the patient "crossed" the rubicon at age 65: the plasma clearance of olanzapine approximately indicates a figure of 17.5 l / h, the half-life is 51.8 hours.
• If the patient is younger than 65 years: the plasma clearance of olanzapine approximately indicates a figure of 18.2 l / h, the half-life is 33.8 hours.

Significant differences in similar values in patients with severe renal dysfunction and in patients without pathological abnormalities in this area have not been established.

[5], [6]

Dosing and administration

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

Neuroleptic new generation Egolansa is introduced into the body orally, that is, through the mouth. The drug intake is not associated with the time of consumption of food. The drug is administered once a day.

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

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

If schizophrenia, weighed down by manic-depressive syndrome, is diagnosed, then the starting amount of the drug administered is taken at a rate of 10 mg per day. If the patient has already undergone Egolans therapy to stop the manic case, then with preventive measures of relapse, treatment with the same dosages is recommended. If 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 Egolans, so as not to get a failure syndrome. The maximum daily dosage of the drug in question should not exceed 20 mg.

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

Correction of dosage according to sex and smoker status is not carried out. If the patient has more than one factor that causes the inhibition of metabolism, it is necessary to consider the question of reducing the initial amount of the drug administered to 5 mg daily.

[10]

Use Egolanza during pregnancy

To date, strictly conducted studies and data on monitoring the clinical picture, as the results of the introduction of olanzapine in the period of gestation by a female baby, is not available. Therefore, the developers of the drug use Egolans during pregnancy and lactation is not recommended. An exception can only be the decision of the attending physician, who, after receiving 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 alleged harm to the fetus, the medication is prescribed.

Egolanza does not cross the blood-brain barrier, it does not enter the mother's milk, but, nevertheless, it should not be recommended for administration during lactation. If such a need arose, it is advisable for the period of therapeutic treatment, to stop breastfeeding the baby.

Contraindications

Any medicinal product shows how the expected positive dynamics of the impact, so it can negatively affect the organs, pathologically changed by other diseases, available in the patient's medical history. Proceeding from this, there are also contraindications to the use of Egolans.

• Individual intolerance to the constituent components of the drug.
• Closed-angle glaucoma is a kind of glaucoma, in which the pressure in the eye rises too fast.
• Psychoses of different genesis.
• Glucose-galactose malabsorption.
• Dementia is a slowly developing decline in mental abilities, in which disorders of thinking, memory, learning ability and concentration of attention occur.
• Pregnancy and the period of feeding a newborn baby with breast milk.
• With a lack of lactase in the patient's body.
• The age of patients under the age of 18 is due to a lack of clinical data.
• Hypersensitivity of the patient's body to lactose.

With special caution should be appointed olanzapine:

• Kidney and / or liver dysfunction.
• Hyperplasia (increase in the number of structural elements of tissues by their excess neoplasm) of the prostate.
• Propensity to epileptic seizures.
• Propensity to convulsions.
• Myelosuppression, including neutropenia and leukopenia, is a reduced content of the corresponding blood constituents.
• Paralytic ileus.
• Arterial hypotension, including its precursors: cardiovascular and cerebrovascular diseases.
• Myeloproliferative pathologies (in the bone marrow there is an increased production of platelets, leukocytes or erythrocytes).
• Congenital pathology of the heart.
• Congestive cardiac dysfunction.
• Hypereosinophilic syndrome.
• Immobilization - immobility of any part of the body with some damage to the body.
• The elderly.

[7], [8]

Side effects Egolanza

In the case of passing therapy with the drug in question, with a frequency of less or more, side effects of Egolans may occur.

Neuralgic reactions:

• Drowsiness and general apathy.
• The appearance of involuntary, uncontrolled movements.
• Dizziness.
• Symptoms of Parkinson's disease.
• Neuropsychiatric weakness.
• Convulsions.
• Extrapyramidal syndrome characterized by non-rhythmical forced rotational movements in various parts of the body.
• Single cases of the onset of malignant neuroleptic syndrome were observed.
• Increased body temperature.
• Instability of the vegetative system.
• Activation of the sweat glands.
• Failure of rhythm and heart rate.
• Tremor.
• Sleep disturbance.
• Emotional instability.

Reaction of the cardiovascular system:

• The growth of blood pressure.
• Bradycardia, which can be accompanied by acute vascular insufficiency.
• Single cases of ventricular tachycardia with chaotic electrical activity of the atria with a pulse frequency of 350-700 per minute were recorded. Such a picture can provoke a sudden death.
• Thromboembolism, both pulmonary and deep veins.

Reaction of the exchange system:

• Body weight gain of the patient.
• A constant feeling of hunger.
• Hypertriglyceridemia.
• In rare cases, you can observe hyperglycemia.
• Symptoms of diabetes may appear.
• Hypercholesterolemia.
• Accumulation of excess heat in the human body.
• A lethal outcome is possible.

The reaction of the gastrointestinal tract:

• Growth of ALT- and ACT-transaminases of the liver.
• Constipation.
• Hepatitis.
• Reducing the humidity of the oral mucosa.
• Less often, one can observe the defeat of liver tissue of a cholestatic and / or hepatological nature.
• Pancreatitis.

The reaction of other body systems:

• The release into the blood of myoglobin as a result of rapid damage to skeletal muscles.
• Retention of urine in the body.
• Painful urination.
• Allergic reaction.
• Sometimes photosensitivity is observed.
• Puffiness.
• Asthenia - the body works out of last effort.
• Urinary incontinence.

[9],

Overdose

Each person is individual, therefore it is possible to observe various symptoms of taking the same medication. If the amount of the prescribed drug has been incorrectly calculated, an overdose of the drug may occur, which manifests itself by a similar pathological symptomatology:

• Failure in heart rate.
• Overexcitation and aggression.
• Inhibition of breathing.
• Violation of the speech apparatus, manifested by a disorder of articulation.
• Blocking of consciousness, which is expressed in symptoms of varying severity from mild sedation to coma.
• Extrapyramidal failures.
• Convulsions.
• Psychological insanity.
• Problems with blood pressure: a rapid rise or fall in blood pressure indicators.
• Malignant neuroleptic syndrome.
• Stop breathing and / or heart.

It is quite difficult to designate dangerous doses for human life, since a lethal outcome was recorded after taking 450 mg of olanzapine. Then, as is known, when the patient entered 1500 mg of Egolanza, the patient remained alive.

When the first signs of an overdose appear, it is first necessary for the affected person to rinse the stomach and induce a vomiting reflex. After that, you should take any sorbent, for example, activated charcoal. Further treatment is symptomatic. In this period, careful medical control over the patient's condition is necessary.

[11], [12]

Interactions with other drugs

It is much easier to predict the response of the patient's body to monotherapy. But the introduction of a complex treatment schedule conceals a certain unpredictability, if the doctor is not able to predict the result of the mutual influence of the drugs present in the protocol of treatment, on each other. Therefore, in order to achieve the necessary therapeutic effectiveness, while avoiding pathological complications, one should know the consequences of Egolans interaction with other drugs.

Drugs that excite CYP1A2 iso-enzyme (inducers), are capable of influencing the metabolism of the active substance in the patient's body. In this case, the clearance of olanzapine increases its performance if the patient "indulges" with nicotine. A similar situation with the joint introduction of Egolans with a group of drugs, which includes carbamazepine. This combination of chemical compounds can provoke a decrease in the amount of olanzapine in the blood plasma of the patient. In such a case, it may be necessary to increase the dosage.

Drugs that inhibit the CYP1A2 iso-enzyme (inhibitors) can influence the metabolism of the active substance in the patient's body.

The same reaction is indicated by the tandem entry of the drug and fluvoxamine. This decreases the clearance of the active substance, while the maximum concentration in the serum increases: 55% for non-smokers of the weaker sex and for 77% for men who have a predilection for nicotine. Based on such indicators, the interaction of Egolans with other drugs, in particular fluvoxamine, or any other inhibitor of the isoenzyme CYP1A2 (for example, such as ciprofloxacin), it is necessary to reduce the starting dosage of olanzapine.

Significant influence on the physico-chemical properties of the drug in question is not rendered by joint injection with ethanol, only an increase in the sedative characteristics of the former can be observed.

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

With the simultaneous use of the drug in question with adsorption preparations, such as, for example, activated charcoal, the bioavailability of olanzapine is significantly reduced. The change in this indicator can range from fifty to sixty percent. To avoid such a situation, it is necessary to spread the introduction of two drugs in time. The interval between receptions should not be less than two hours.

Valproic acid can slightly reduce the ability of olanzapine to biotransform. While the active substance Egolansa inhibits the synthesis of valproic acid glucuronide. The therapeutically sensitive pharmacodynamic interaction between the two drugs is unlikely.

When diagnosing a patient with Parkinson's disease, administer olanzapine, when antiparkinsonian therapy is performed, is not desirable.

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

Do not simultaneously administer olanzapine with dopamine or levodopa. Since the first depresses the action of the second, being their antagonist.

There is no significant mutual influence in the case of co-administration of the drug in question with the isoenzymes CYP1A2 (theophyllines), CYP 2D6 (tricyclic antidepressants), CYP 2C9 (warfarins), and diazepam CYP 2S19 and CYP 3A4, biperidenom.

[13]

Storage conditions

The high pharmacological characteristics of the drug largely depend on the thoroughness of the Egolange storage condition.

• The drug should be stored in a room where temperature values do not cross the 30 ° C mark.
• The room must be dry.
• The storage location should not be accessible to the kids.

[14],

Shelf life

If all the requirements for the storage of the medicinal product are met, the shelf life is three years. After the expiration of this period, the use of Egolans is unacceptable. The timeframe for the effective and safe use of the drug is necessarily reflected on the carton and on each blister of the drug.