Zyprxa

Zyprexa is a psycholeptic, contains in its composition an active component of oxazepine.

Indications of the ziprex

It is used to quickly prevent the development of the agitation reaction, as well as behavioral disorders in people with schizophrenia or manic attacks (in situations where oral treatment is not appropriate).

If there is a possibility of switching to oral use of the substance, olanzapine is required to stop treatment with a drug in the form of an injection solution.

[1]

Release form

Release in the form of lyophilizate for the preparation of injections inside the flasks with a volume of 10 mg. In a pack - 1 bottle of powder.

Zyprexa Adera is an antipsychotic medicine in the form of a powder from which injection suspensions are made. It is available in vials of 210, 300 or 405 mg. A powder with a solvent (3 mg), 3 needles, and a syringe are attached to the powder.

Ziprexa Zidis is available in dispersible tablets with a volume of 5 or 10 mg, in blister packs - for 28 pieces.

[2], [3]

Pharmacodynamics

Olanzapine is an antipsychotic with an anti-manic effect. This substance helps to stabilize the mood and has a large range of activity, affecting various receptors. Tests conducted in the preclinical period found that the component is synthesized with serotonin receptors (5HT2A / 2C types, as well as 5HT3 with 5HT6), dopamine (types D1 with D2, and with it D3 with D4 and D5), acetylcholine (muscarinic M1 -M5), and together with them with α1-adrenoreceptors and H1-receptor of histamine.

When observing the behavior of animals to whom olanzapine was previously administered, it was found that this element has antagonism against the 5HT serotonin receptor, and in addition to the acetylcholine and dopamine receptors.

The olanzapine element has a good synthesis with serotonin 5HT2-type endings (better than dopamine type D2 endings) in in vitro and in vivo tests. In addition, electrophysiological tests demonstrated a selective decrease in the excitability of dopaminergic neurons of the mesolimbic type (A10) under the influence of the drug. But at the same time, a weak influence on the pathways of influence, related to motility - striatal (type A9) was noted.

The drug slows down avoidance (conditioned reflex), which is a confirmation of its antipsychotic properties after use in lower portions than those that provoke the appearance of catalepsy (this is a manifestation of a negative motor reaction). Olanzapine is able to potentiate a response to stimuli during the execution of anxiolytic testing, which can not be done by individual antipsychotics.

After a single dose of 10 mg of medication during the PET procedure (with the participation of volunteers), it was found that the active ingredient Ziprexes had a higher synthesis rate with 5HT2A endings than with dopamine type D2 endings. In addition, after analyzing the images obtained, using the SPECT technique, it was found that people with hypersensitivity to olanzapine showed a lower synthesis rate with D2 striatal-type endings than other persons with sensitivity to respiratory and other antipsychotics (compared to people with sensitivity to clozapine).

[4], [5], [6]

Pharmacokinetics

The component is well absorbed as a result of oral administration, reaching a plasma peak after 5-8 hours. Food does not affect the degree of absorption. The level of bioavailability of drugs in oral form in comparison with intravenous injections was not established.

The protein synthesis of olanzapine within the plasma is about 93% when dosages are used in the range of 7-1000 ng / ml. In the main, the component is synthesized with albumin, and in addition to the α1-acid glycoprotein.

The medicine passes the process of hepatic metabolism, where its oxidation and conjugation is carried out. The main circulating decay product is the element 10-N-glucuronide, which does not pass through the BBB. Hemoprotein types P450-CYP1A2, and in addition P450-CYP2D6 help form the decomposition products of N-desmethyl with 2-hydroxymethyl (these elements in comparison with olanzapine have significantly lower in vivo drug activity in animal tests). The predominant drug effect is due to olanzapine of the primary type.

When administered orally, the term of its half-life in volunteers varied according to the age and sex of the individual.

Older volunteers (from 65 years old) have a longer half life (compared with 51.8 and 33.8 hours, respectively), and the level of plasma clearance has been lower (17.5 and 18.2 l / h, respectively ). Pharmacokinetic variation in elderly volunteers is distributed within the same range as in the younger ones.

The female half-life of the drug in comparison with the male is longer (36.7 and 32.3 hours, respectively), and the plasma clearance value is lower (18.9 and 27.3 l / h, respectively). But in this case, the drug in a dose of 5-20 mg shows a comparable level of the safety profile - N = 467 (female) and N = 869 (male).

[7], [8]

Dosing and administration

The medicine must be injected with a / m method. Injection n / k or IV in the method is prohibited.

The size of the initial adult dosage for the IM injection is 10 mg (it is administered 1 time). Taking into account the patient's condition, 2 more hours after the procedure, another injection (also not more than 10 mg) can be administered. The third dose (maximum 10 mg) is allowed to enter a minimum after 4 hours after the second injection. During the clinical tests, the daily dose safety parameters were not studied, the total size of which exceeds 30 mg.

Provided that there are indications for prolongation of the treatment course, it is necessary to abandon the / m injections of the drug and use the oral form of olanzapine (in the amount of 5-20 mg) as quickly as possible after making a decision about the advisability of using this form of treatment.

Elderly patients.

Persons over 60 years of age should be prescribed an initial dosage of 2.5-5 mg. Taking into account all clinical indications, the 2nd injection (its size is also within 2.5-5 mg) can be introduced after 2 hours after the 1st procedure. The number of injections in the period of 24 hours - no more than 3; for a day is allowed to enter no more than 20 mg of the drug.

People with liver / kidney problems.

It is recommended to use reduced initial dosages (5 mg). If a patient has moderate liver failure, the initial dose may increase, but you need to do it carefully.

Reduced initial dosages can be administered to people with a combination of individual factors (elderly people, women, non-smokers) who are able to reduce the metabolism of the drug. If you need to increase the dose, you should do it with caution.

A method of manufacturing a medicinal solution for injection in the / m way.

The powder must be dissolved exclusively in a sterile injectable liquid using standard aseptic materials necessary for the dissolution of parenteral substances. Do not use any other solvents.

It is required to fill the syringe with a sterile liquid (2.1 ml), and then insert it into the vial containing the lyophilizate.

After this, you need to shake the contents of the container until the lyophilizate completely dissolves, transforming into a yellow liquid. In the flacon - 11 mg of active substance in the form of a solution of 5 mg / ml (1 mg of the drug remains inside the syringe and flacon, so the patient is administered a dose of 10 mg).

The following are the injection volumes from which the required dosages of the drug are obtained:

• injection of 2 ml - 10 mg of the drug;
• injection in the amount of 1.5 ml - 7.5 mg of the drug;
• dose of the drug in the amount of 1 ml - 5 mg of the drug;
• injection of 0.5 ml - 2.5 mg of the drug.

[12]

Use of the ziprex during pregnancy

There were no carefully controlled and adequate tests of the effect of the active component Ziprexa on pregnant women. During the period of olanzapine use, the patient should inform the attending doctor about the onset of pregnancy or about her planning. Because at the moment the experience of using the drug in pregnant women is limited, it is only permitted to apply it during this period in case of acute necessity.

If a pregnant woman in the trimester used antipsychotics (this includes olanzapine), the newborn may develop some negative manifestations, among which extrapyramidal disorders or withdrawal syndrome (after the birth signs of these disorders can vary in duration and strength). There was also information about hypotension, sensation of drowsiness or excitation, increased pressure, tremor, eating problems or hyaline membrane disease. Because of this, you need to carefully monitor the condition of the baby.

In olanzapine (during the study) healthy women during lactation, the substance was observed in milk. The average dosage, which does not have a negative impact on the child, is 1.8% of the dose taken by the mother (estimated in mg / kg). But in any case it is not recommended to use the drug when lactating.

Contraindications

The main contraindications: intolerance of the active component and any additional elements of the drug, and also the diagnosed probability of developing a glaucoma of a closed-angle type. There is also no information on the use of drugs in children. Zypresu in the form of lyophilizate for injection solutions is forbidden to adolescents and children (under 18 years of age), because there is only limited information on the effectiveness and safety of the effects of drugs in this category of patients.

[9], [10]

Side effects of the ziprex

Use of the medicine may cause some side effects:

• manifestations in the field of general blood flow and lymph: often there is leuko- or neutropenia or eosinophilia. Thrombocytopenia is observed occasionally;
• immune disorders: sometimes there is increased sensitivity;
• problems with nutrition and metabolic processes: mainly weight gain, less frequent appetite, sugar, cholesterol, triglycerides, and glucosuria. Sometimes there is a development of diabetes or its aggravation (occasionally this leads to ketoacidosis or coma, as well as death). Occasionally hypothermia develops;
• Disorders in the NA area: the sensation of drowsiness develops mainly. Often, there may be parkinsonism, akathisia, dizziness or dyskinesia. Sometimes, if there was an anamnesis or because of the presence of risk factors, epileptic seizures developed; In addition, there may sometimes develop a late degree of dyskinesia, dysarthria, dystonia (this includes the ocular symptom), as well as amnesia. Occasionally there is a withdrawal syndrome or ZNS;
• cardiac disorders: sometimes there is an extension of the QT-interval, as well as a bradycardia. Occasionally there is tachycardia / fibrillation of the ventricles or sudden death may occur;
• disorders in the work of the CCC: mainly marked by orthostatic collapse. Sometimes there is thromboembolism (this includes also PE or TGV);
• violations of the respiratory system, mediastinum and sternum: sometimes there is nasal bleeding;
• disorders of the function of the gastrointestinal tract: often there are short-term anticholinergic manifestations in mild form (among them dryness of the oral mucosa and constipation). Sometimes there is flatulence. Occasionally pancreatitis develops;
• problems in the hepatobiliary system: often there is a temporary increase in liver transaminase (AST and ALT), especially at the initial stage of the course (without symptoms), and peripheral puffiness is also observed. Occasionally, hepatitis (also in hepatocellular form) and hepatic disorder of cholestatic or mixed type develops;
• cutaneous and subcutaneous lesions: often there are rashes. Sometimes there is alopecia or photosensitivity;
• disturbances in the work of connective tissues, as well as the structure of muscles and bones: arthralgia often arises. Occasionally, rhabdomyolysis is observed;
• manifestations in the field of the organs of urination and kidneys: sometimes there are problems with urination, as well as urinary retention / incontinence;
• disorders in the area of mammary glands with reproductive organs: often men develop impotence, and in addition, in men and women, libido is weakened. Sometimes men develop breasts, there is a galactorrhea or amenorrhea in women. Occasionally, priapism occurs;
• systemic disorders: often there is a feeling of fatigue, there are swelling, developing asthenia or pyrexia;
• results of tests and analyzes: the plasma index of prolactin is mainly increased. Often, the values of CK, uric acid, alkaline phosphatase and GGT increase. Sometimes the overall level of bilirubin increases.

[11],

Overdose

Signs of intoxication: basically there is a feeling of excitement / aggressiveness, tachycardia, dysarthria, and in addition there is a weakening of the level of consciousness and the development of extrapyramidal manifestations. There may be a coma.

Among other significant complications are the development of the NSA, cardiopulmonary shock, cardiac arrhythmia, and coma. In addition, convulsions may occur, the blood pressure level may decrease / increase, the respiratory process may be suppressed. The death rate was observed in the case of acute poisoning - the use of 450 mg LS, although there is information about survival in the case of acute intoxication using 2 g of medication.

The medicine does not have a special antidote. In accordance with clinical symptoms, it is required to monitor vital body indications (among other things, support of the respiratory process, elimination of circulatory insufficiency, as well as hypotension) and eliminate the resulting disorders. It is necessary to abandon the use of dopamine and epinephrine, as well as other sympathomimetics, which possess properties characteristic of ß-agonists - due to the fact that ß-stimulation is able to strengthen hypotension.

To detect possible arrhythmia, you should monitor the performance of the CCC function. To monitor the condition of the victim and keep him under medical supervision is necessary until he completely recover.

[13], [14]

Interactions with other drugs

People who use drugs that can increase blood pressure or suppress the respiratory process or work of the National Assembly should be carefully appointed Ziprexu.

Probable interactions due to olanzapine injection.

When combined with / m administration of a drug with lorazepam, a feeling of drowsiness is enhanced (in comparison with the use of these two drugs alone).

The introduction of olanzapine in the / m method together with the parenteral injection of benzodiazepine is prohibited.

Probable interactions that can affect the effectiveness of olanzapine.

Since the metabolism of the active substance Ziprex is carried out with the participation of the element CYP1A2, the components depressing / activating this isoenzyme are able to influence the pharmacokinetics of oral olanzapine.

Induction of the activity of the element CYP1A2.

When combined with carbamazepine, and as a result of smoking, the level of clearance of olanzapine increased - from low to medium. It probably will not have a significant effect on the medical process, but it is still recommended to monitor the medication to increase its dose, if necessary.

Slowing down the activity of the CYP1A2 element.

Fluoxamine, which is an inhibitor of the CYP1A2 component, decreases the drug clearance. Because of this, there is an average increase in its peak values after the use of fluoxamine: in non-smokers, women by 54%, and by 77% among smokers. The corresponding rates of average increase in AUC level of olanzapine are 52% and 108%. People who use fluoxamine or some other inhibitor of the CYP1A2 element (eg, ciprofloxacin) need to adjust the reduced initial dosages of Ziprexa with it. If there is a need for the use of an inhibitor of the CYP1A2 element, consider the option of reducing the portion of olanzapine.

Medications that slow down the activity of the element CYP2D6.

When using fluoxetine (a single dose of 60 mg or a multiple dose of a similar dose for 8 days), an average increase in the peak values of olanzapine (by 16%) is observed, as well as a decrease in the average indicators of its clearance (by 16%). These factors are insignificant in comparison with the individual differences of different patients, which is why it is often not necessary to change the size of doses.

Decreased bioavailability.

In the case of activated charcoal, there is a decrease in the bioavailability of oral olanzapine (by approximately 50-60%), so it is recommended to take it either 2 hours before using Ziprex, or after 2 hours after using the drug.

Potential possibilities of drug interaction with other drugs.

The drug can act as an antagonist with respect to the properties of indirect and immediate dopamine agonists.

Combination of a drug with anti-Parkinsonics in people with dementia and trembling paralysis is prohibited.

Olanzapine has an antagonistic effect on α-1-adrenergic receptors. Persons using drugs that are able to lower blood pressure (and have a different mechanism of antagonism against α-1-adrenergic mechanism of exposure) should carefully use them in combination with olanzapine.

Since the drug can help reduce pressure, it must be taken into account that in combination with individual antihypertensive drugs it will potentiate their effect.

The drug is able to demonstrate an antagonistic effect on the properties of dopamine agonists, as well as levodopa.

The drug does not change the pharmacokinetic characteristics of diazepam with its active decay product N-desmethyldiazepam, but combined use of these agents potentiates orthostatic hypotension (compared to using each of these drugs separately).

Effect on the length of the QT-interval.

Prescribe Ziprexu with drugs that can prolong the length of the QT-interval, it is necessary with great care.

Storage conditions

Zyprexum should be kept out of the reach of children at a temperature value of not more than 25 ° C.

[15], [16],

Special instructions

Reviews

Zypreksa receives a large number of positive reviews - almost all the treating people say that the medicine shows a very good result, provided that it is used for a long time in supporting portions for outpatient treatment.

Among negative reviews about the drug most often there are censures for a large number and a high risk of side effects. People complain mostly about disorders of metabolic processes and a high probability of diabetes mellitus.

Men report an increase in the mammary glands, but this violation occurs even without the cessation of treatment. Individual patients suffered from dizziness, constipation, and also dryness of the oral mucosa. There are also reviews that mark the high price of the medication.

[17]

Shelf life

Zypresks in the form of lyophilizate can be used for 3 years from the date of manufacture of the drug. In this case, the shelf life of the already prepared solution is only 1 hour.