Zyprexa
Zyprexa: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Zyprexa
ATX code: N05AH03
Active ingredient: olanzapine (olanzapine)
Manufacturer: Lilly del Caribe Inc. (Lilly del Caribe Inc.) (Puerto Rico); Lilly S. A. (Lilly, SA) (Spain); Eli Lilly & Company Limited (UK)
Description and photo update: 2019-20-08
Prices in pharmacies: from 2018 rubles.
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Zyprexa is an antipsychotic agent used in the treatment of schizophrenia and bipolar disorder.
Release form and composition
Dosage forms of Zyprexa:
- Film-coated tablets: round, white, one side has an identification inscription, depending on the content of the active substance: 2.5 mg - "LILLY 4112", 5 mg - "LILLY 4115", 7.5 mg - " LILLY 4116 ", 10 mg -" LILLY 4117 "(7 pcs. In blisters, 1, 2, 4, 8 blisters in a cardboard box);
- Lyophilisate for the preparation of a solution for intramuscular (i / m) administration: compacted mass or yellow powder (10 mg in vials, 1 vial in a cardboard box).
Composition of 1 tablet:
- Active ingredient: olanzapine - 2.5 mg, 5 mg, 7.5 mg or 10 mg;
- Auxiliary components: hydroxypropyl cellulose (hyprolose), crospovidone, lactose monohydrate, magnesium stearate, microcrystalline cellulose;
- Sheath: Methyl hydroxypropyl cellulose (hypromellose), white dye blend, carnauba wax (for polishing), food blue ink (for identification lettering).
Composition of 1 bottle of lyophilisate:
- Active ingredient: olanzapine - 10 mg;
- Auxiliary components: tartaric acid, lactose monohydrate.
Pharmacological properties
Pharmacodynamics
The active ingredient of Zyprexa is olanzapine, an antipsychotic substance (neuroleptic) with a wide pharmacological spectrum of influence on a number of receptor systems.
In the course of preclinical studies, it was found that olanzapine has an affinity for adrenergic α 1, dopamine D 1, D 2, D 3, D 4 and D 5, serotonin 5-HT 2A / C, 5HT 3 and 5HT 6, muscarinic M 1– -5 and histamine H 1 receptors. In experiments on animals, olanzapine was found to have antagonism towards dopamine, cholinergic and 5HT receptors.
In vitro and in vivo, olanzapine has a more pronounced activity and affinity for serotonin 5HT2 receptors compared to dopamine D2 receptors. According to the data of electrophysiological studies, olanzapine selectively reduces the excitability of mesolimbic (A10) dopaminergic neurons and at the same time has some effect on the striatal (A9) nerve pathways that are involved in the regulation of motor functions.
The conditioned defense reflex (a test characterizing antipsychotic activity) can be reduced by olanzapine at lower doses than doses that cause catalepsy (a disorder reflecting an undesirable effect on motor function). Unlike other antipsychotics, olanzapine enhances the anti-anxiety effect of an anxiolytic test. Zyprexa provides a statistically significant reduction in productive (hallucinations, delusions, etc.) and negative disorders.
Pharmacokinetics
After oral administration, olanzapine is well absorbed. Its maximum plasma concentration is reached within 5-8 hours. Food intake does not affect the degree of absorption.
After intramuscular administration, the maximum plasma concentration of the drug is observed in 15–45 minutes. With the intramuscular administration of a dose of 5 mg, the concentration of the substance in the plasma is 5 times higher than the concentration, which is determined when taking a similar dose orally.
The metabolic characteristics of oral and parenteral olanzapine are similar.
Olanzapine is metabolized in the liver by conjugation and oxidation. The main circulating metabolite is 10-N-glucuronide, which presumably does not cross the blood-brain barrier. Two more metabolites of olanzapine are 2-hydroxymethyl and N-desmethyl, in the formation of which isoenzymes CYP1A2 and CYP2D6 of cytochrome P450 are involved. In animal studies, it was found that both of these metabolites in vivo have significantly less pronounced pharmacological activity than olanzapine. Thus, the main pharmacological action of Zyprexa is due to the original active substance olanzapine.
The average plasma clearance is 26 l / h. The half-life (T ½) of olanzapine averages 33 hours. In studies with different doses in the range from 1 to 20 mg, it was found that the concentration of the drug in plasma is proportional to the dose and is linear.
The pharmacokinetic parameters of olanzapine differ depending on gender, age and smoking status. Plasma half-life / clearance rates:
- non-smokers - 38.6 h / 18.6 l / h;
- smokers - 30.4 h / 27.7 l / h;
- patients under the age of 65 years - 33.8 h / 18.2 l / h;
- elderly patients (over 65 years old) - 51.8 h / 17.5 l / h;
- men: 32.3 h / 27.3 l / h;
- women: 36.7 h / 18.9 l / h.
However, the degree of these changes in patients of different sex, age and smoking patients is significantly lower than the degree of differences in these data in individuals.
No significant differences were found between the mean values of T ½ and plasma clearance in patients with severe renal impairment and in patients with normal renal function. Approximately 57% of radioisotope-labeled olanzapine is excreted in the urine, mainly in the form of metabolites. The clearance of olanzapine in smokers with minor liver dysfunction is lower than in nonsmokers without hepatic dysfunction. When the concentration of the drug in plasma in the range of 7-1000 ng / ml, the connection with plasma proteins (mainly albumin and α 1 -acid glycoprotein) is approximately 93%. In studies involving representatives of the European, Japanese and Chinese races, there were no differences in the pharmacokinetics of olanzapine associated with race.
The activity of the isoenzyme CYP2D6 of cytochrome P450 does not affect the metabolism of olanzapine.
Indications for use
Film-coated tablets
- Bipolar disorder: Zyprexa, alone or in combination with valproate or lithium, is used to treat mixed or acute manic episodes in bipolar disorder with or without psychotic manifestations and rapid phase changes; in patients with bipolar disorder in whom olanzapine has been effective in treating the manic phase, it is also indicated for the prevention of relapse;
- Schizophrenia: exacerbation therapy; supportive and long-term anti-relapse treatment of both schizophrenia and other psychotic disorders with severe symptoms (negative (including emotional flattening, speech impoverishment, decreased social activity) and / or productive (including hallucinations, delusions, automatism)) and concomitant affective disorders.
Zyprexa in combination with fluoxetine is indicated for the treatment of depressive conditions associated with bipolar disorder.
Lyophilisate for preparation of solution for intramuscular injection
The injection of Zyprexa is recommended for the rapid relief of psychomotor agitation (agitation) in patients with bipolar disorder and schizophrenia.
Contraindications
Absolute:
- age up to 18 years;
- period of breastfeeding (lactation);
- galactose intolerance, lactase deficiency and glucose-galactose malabsorption (for tablets);
- diagnosed hypersensitivity to any of the components of Zyprexa.
A relative contraindication is the period of pregnancy - taking the drug is required under medical supervision.
Instructions for the use of Zyprexa: method and dosage
Film-coated tablets
Zyprex tablets are taken orally, regardless of food intake.
The daily dose is selected individually and depends on the clinical condition of the patient. The dose above the standard should be increased gradually (maintaining an interval of at least 24 hours), and only after an appropriate clinical examination.
Recommended dosage regimen of Zyprexa:
- Schizophrenia and similar psychotic disorders: the initial dose of the drug (it is also the standard) - 10 mg 1 time per day; therapeutic doses - from 5 to 20 mg per day;
- Acute mania in bipolar disorder: the initial dose of the drug (it is also the standard) - 15 mg once a day; therapeutic doses - from 5 to 20 mg per day.
For elderly people, patients with moderate hepatic insufficiency, with severe renal insufficiency, an initial dose of olanzapine is recommended - 5 mg per day.
Also, a decrease in the initial dose of Zyprexa is indicated with a combination of the following factors: female patients, nonsmokers, elderly patients - due to a possible slowdown in the metabolism of the active substance.
Lyophilisate for preparation of solution for intramuscular injection
A solution prepared from a lyophilisate is injected intramuscularly. Zyprex should not be administered subcutaneously or intravenously.
The use of olanzapine in the form of an injection is necessary for the rapid relief of agitation in patients with bipolar disorder and schizophrenia.
The recommended starting dose of Zyprexa is 10 mg (single intramuscular injection). Further, taking into account the clinical condition of the patient, no earlier than 2 hours later, it is allowed to make a second injection - up to 10 mg. After at least 4 hours after the second injection, it is allowed to make a third - up to 10 mg. The safety of doses greater than 30 mg per day has not been evaluated in clinical studies.
If there are indications for the continuation of therapy, intramuscular injections of Zyprexa should be canceled and, if clinically feasible, switch to oral administration of olanzapine at a dose of 5 to 20 mg.
A single intramuscular injection of Zyprexa at a dose of 2.5-5 mg is recommended for the elderly or patients with other clinical risk factors.
The lyophilisate is allowed to be dissolved exclusively with sterile water for injection.
Do not mix olanzapine in the same syringe with lorazepam, diazepam and haloperidol, as the dissolution time, precipitation and / or weakening of the effect of olanzapine are possible.
To prepare the solution, 2.1 ml of sterile water for injection should be added to the contents of the vial:
- The solution should be yellow, transparent;
- It is necessary to use the solution within 1 hour after preparation;
- The unused residue should be drained;
- Before the introduction, you need to control the solution for the presence of mechanical impurities (if the container and solution allow this).
Dose of olanzapine in mg, corresponding to the volume of the solution used for i / m injection:
- The entire contents of the bottle are 10 mg;
- 1.5 ml - 7.5 mg;
- 1 ml - 5 mg;
- 0.5 ml - 2.5 mg.
Side effects
Side effects associated with the use of olanzapine, according to clinical studies:
- Very often (> 1/10): drowsiness and weight gain, mild transient increase in plasma prolactin concentration (up to 34% of cases) *;
- Often (<1/10 to? 1/100): dizziness, asthenia, akathisia, increased appetite, peripheral edema, orthostatic hypotension, constipation, dry mouth;
- Rarely (1/10 000): transient asymptomatic increase in hepatic ALT (alanine aminotransferase) and AST (aspartate aminotransferase) levels in blood serum;
- In isolated cases (<1/10 000): an increase in plasma glucose concentration ≥200 mg / dL (suspected diabetes mellitus), an increase in plasma glucose concentration from ≥160 mg / dL to <200 mg / dL (suspected hyperglycemia) with a baseline glucose of ≤140 mg / dL.
Note:
* - The maximum values of prolactin concentration on average do not reach the upper limit of the norm and do not differ statistically significantly from placebo; clinical symptoms and signs of hyperprolactinemia such as gynecomastia, breast enlargement and galactorrhea are rare; in most cases, the normalization of prolactin levels occurs without canceling Zyprexa.
In clinical studies with the participation of 1185 patients (N = 1185), an increase in triglyceride levels by an average of 20 mg / dL from baseline was noted.
According to the results of placebo-controlled studies (N = 2528), cholesterol levels increased on average by 0.4 mg / dL from baseline.
There have been isolated cases of asymptomatic eosinophilia.
Summary data on the main side effects and the frequency of their manifestation (according to the results of clinical trials and / or data from the post-registration period in the treatment of various dosage forms of Zyprexa):
- The organism as a whole: very often - an increase in body weight 1; often - asthenia 2; infrequently - increased photosensitivity 2;
- Cardiovascular system: often - orthostatic hypotension 1; infrequently - bradycardia 2;
- Digestive system: often - constipation 2, dry mouth 2, increased appetite 2; very rarely - hepatitis 3;
- Metabolic disorders: often - peripheral edema 2; very rarely - diabetic coma 3, diabetic ketoacidosis 3.5, hyperglycemia 3, hypertriglyceridemia 3.6;
- Nervous system: very often - gait disturbance 4, drowsiness 2; often - akathisia 2, dizziness 2; rarely - seizures 3;
- Skin and appendages: rarely - rash 3;
- Genitourinary system: very rarely - priapism 3;
- Clinical biochemistry: very often - an increase in prolactin 1; often - an increase in ALT 1, an increase in AST 1, isolated cases of an increase in glucose concentration ≥160 mg / dl- <200 mg / dl (suspected hyperglycemia) 1, isolated cases of an increase in glucose concentration ≥200 mg / dl (suspected diabetes) 1;
- Hematology: often - eosinophilia 1; rarely - leukopenia 3; very rarely - thrombocytopenia 3.
Notes
1 - Assessment of indicators from the database of clinical trials.
2 - Side effects registered in the clinical trial database.
3 - Side effects reported spontaneously during post-marketing studies.
4 - Side effects found in clinical studies in patients with dementia of the Alzheimer's type.
5 - Diabetic acidosis as classified in the Coding Dictionary for Adverse Reactions (COSTART).
6 - Hyperlipidemia according to the COSTART classification.
Frequency gradation depending on the number of marked episodes: very often (> 1/10); often (1/100); infrequently (1/1000); rarely (1/10 000); very rare (<1/10 000).
Overdose
Most often (≥ 10%) with an overdose, the following symptoms occur: articulation disorder, agitation, aggressiveness, tachycardia, various extrapyramidal disorders, impaired consciousness of varying severity (from sedation to coma). Other signs of overdose: neuroleptic malignant syndrome, convulsions, delirium, aspiration, respiratory depression, arrhythmia, decrease or increase in blood pressure, respiratory and cardiac arrest.
The minimum fatal dosage was 450 mg olanzapine. The maximum dose that ended favorably (the patient survived) is 1500 mg.
There is no specific antidote for olanzapine. Inducing vomiting is not recommended. Standard procedures can be carried out, including gastric lavage and intake of activated charcoal (intake of an adsorbent reduces the bioavailability of olanzapine taken orally to about 50-60%). Further treatment of an overdose is symptomatic, aimed at maintaining the functions of vital organs and eliminating the complications that have developed, including lowering high blood pressure, restoring circulatory disorders and maintaining respiratory function. The use of dopamine, epinephrine and other sympathomimetics, which are beta-adrenergic receptor agonists, is contraindicated, since stimulation of these receptors can aggravate the decrease in blood pressure.
special instructions
Therapy with any neuroleptics, including olanzapine, can cause the development of neuroleptic malignant syndrome (NMS), a potentially fatal symptom complex. Clinical manifestations of NMS: significant increase in body temperature, changes in mental status, muscle stiffness, autonomic disorders (unstable blood pressure, pulse, cardiac arrhythmias, tachycardia, increased sweating). Additional confirmation of ZNS may be: an increase in the level of creatine phosphokinase, myoglobinuria (rhabdomyolysis), acute renal failure. Such clinical manifestations of NMS, or a significant increase in temperature without other symptoms, require the withdrawal of all antipsychotics, including olanzapine.
In comparative studies for more than 6 weeks, olanzapine therapy was significantly less likely to be accompanied by the development of dyskinesia requiring medical correction than treatment with haloperidol. In this case, it is necessary to take into account the risk of tardive dyskinesia in the case of prolonged therapy with antipsychotics. In case of development of signs of tardive dyskinesia, a dose reduction or withdrawal of olanzapine is recommended. After discontinuation, Zyprexa may increase or manifest symptoms of tardive dyskinesia.
In some cases, the use of Zyprexa, as a rule, at the beginning of therapy, was accompanied by an asymptomatic, transient increase in the levels of hepatic transaminases (ALT and AST). Particular care should be taken with such an increase in patients with hepatic insufficiency, with limited liver functional reserve, or in the case of therapy with potentially hepatotoxic drugs. An increase in ALT and / or AST levels during treatment requires close monitoring of the patient and, if necessary, dose reduction.
Zyprexa is used with caution in the presence of a history of epileptic seizures, or in patients exposed to factors that reduce the seizure threshold. Seizures in these patients were rare during olanzapine therapy.
You should also be careful with: a decreased number of neutrophils and / or leukocytes; signs of toxic disorders / suppression of bone marrow function under the influence of drugs in the anamnesis; depression of bone marrow function due to concomitant diseases; a history of radiotherapy or chemotherapy; hypereosinophilia; myeloproliferative diseases.
According to the results of clinical studies, there were no relapses of clozapine-dependent neutropenia or agranulocytosis when using Zyprexa in patients with a history of these disorders.
In the course of clinical trials, the use of Zyprexa with anticholinergic side effects was rarely accompanied. However, in the presence of concomitant diseases, clinical experience with olanzapine is limited, therefore, caution must be exercised in clinically significant prostatic hypertrophy, paralytic bowel obstruction, angle-closure glaucoma, and similar conditions.
In vitro, olanzapine acts as a dopamine antagonist and, like other antipsychotics, is theoretically able to suppress the action of dopamine and levodopa agonists.
Given the main effect on the central nervous system (CNS), care must be taken when using Zyprexa in combination with other centrally acting drugs and ethanol-containing substances.
The effect of olanzapine for i / m injections in the age group of patients under 18 has not been studied.
Influence on the ability to drive vehicles and complex mechanisms
According to the instructions, Zyprexa is capable of causing drowsiness, therefore, in the course of therapy, it is recommended to be extremely careful when driving mechanical means, including a car.
Application during pregnancy and lactation
The experience of using olanzapine during pregnancy is not enough to assess its safety, therefore Zyprexa can be used only if the expected benefit to the woman is higher than the potential risks to the fetus. Women of childbearing age should be warned that they should inform their doctor in case of pregnancy planning or its occurrence during drug treatment.
In newborns whose mothers took antipsychotics in the third trimester of pregnancy, there is a risk of developing undesirable effects, including withdrawal symptoms and extrapyramidal disorders of varying severity and duration. Cases of drowsiness, tremor, agitation, hypotension, respiratory distress syndrome, hypertension, and malnutrition have also been reported. Therefore, such newborns should be under constant medical supervision.
Olanzapine passes into breast milk, and therefore Zyprexa is contraindicated during lactation. If treatment is necessary, breastfeeding should be discontinued.
Pediatric use
The efficacy and safety of olanzapine in patients under the age of 18 has not been established, therefore, Zyprex is contraindicated in pediatric practice.
With impaired renal function
In severe renal failure, a decrease in the initial daily dose of Zyprexa is recommended.
For violations of liver function
In case of hepatic insufficiency of moderate severity, it is recommended to reduce the initial daily dose of Zyprexa.
Use in the elderly
Recommended initial daily doses of Zyprexa for the treatment of elderly patients, depending on the form of release of the drug:
- tablets - up to 5 mg;
- solution for intramuscular injection, prepared from lyophilisate - 2.5–5 mg once.
Drug interactions
With the simultaneous use of Zyprexa with certain drugs, the following effects may occur:
- Activated carbon: when administered orally, olanzapine reduces its bioavailability by up to 50-60%;
- Antacids: aluminum or magnesium-containing, cimetidine - use in a single dose does not violate the bioavailability of Zyprexa in tablet form;
- Valproic acid: unlikely to have a clinically relevant pharmacokinetic interaction with olanzapine;
- Substances / drugs metabolized with the participation of CYP1A2, such as theophylline: their pharmacokinetics are largely unchanged, since olanzapine is not a potential inhibitor of CYP1A2 activity;
- Known potential inhibitors of CYP1A2: May decrease the clearance of olanzapine;
- Cytochrome P 450 isozymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A): olanzapine is potentially unable to suppress their activity (according to in vitro studies using human liver microsomes);
- Imipramine or its metabolite desipramine (CYP2D6, CYP3A, CYP1A2), warfarin (CYP2C19), theophylline (CYP1A2) or diazepam (CYP3A4, CYP2C19): the metabolism of these substances is not inhibited (according to clinical studies, when they are administered with ol with zapratine)
- Inhibitors or inducers of cytochrome P 450 isoenzymes, exhibiting specific activity against CYP1A2: can alter olanzapine metabolism;
- Carbamazepine and the patient's smoking: increase the clearance of olanzapine (increasing the activity of CYP1A2);
- Lithium, biperiden: no signs of drug interactions were found;
- Lorazepam: with the i / m administration of lorazepam at a dose of 2 mg 1 hour after the i / m injection of olanzapine at a dose of 5 mg, there was no significant effect on the pharmacokinetics of olanzapine and total or unconjugated lorazepam, but this combination of injections increases the drowsiness observed with the use of each drugs separately;
- Drugs capable of lowering blood pressure by mechanisms other than adrenergic antagonism of α-1: it is possible to decrease blood pressure and / or bradycardia with intramuscular administration of olanzapine, due to its activity as an adrenergic antagonist of α-1;
- Fluvoxamine (an inhibitor of CYP1A2): reduces the clearance of olanzapine, increasing the average value of its C max: in non-smoking women by 54%, in smoking men by 77%; mean AUC: by 52% and 108%, respectively. Olanzapine in low doses should be taken by patients receiving fluvoxamine treatment;
- Fluoxetine (with a single dose of 60 mg or 60 mg daily for 8 days): causes an increase in the maximum concentration of olanzapine by an average of 16% and also an average of 16% - a decrease in its clearance. It is not recommended to change the dose of olanzapine when administered in combination with fluoxetine;
- Ethanol: there were no changes in the pharmacokinetics of ethanol against the background of a stable concentration of olanzapine, but this combination may increase the pharmacological effect of olanzapine, for example, a sedative.
Analogs
Analogs of Zyprexa are: Zalasta, Zyprexa Zidis, Q-tab, Olanzapine, Olanzapine Canon, Normiton, Olanex, Olanzapine-Teva, Parnasan, Safris, Egolanza.
Terms and conditions of storage
Store in a dark, dry place out of the reach of children at a temperature of 15-30 ° C. Do not freeze the lyophilisate.
The shelf life is 3 years.
The prepared solution should be used within an hour.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Zyprex
Reviews of Zyprex as an antipsychotic agent are mostly positive. Patients note the high efficacy of the drug when used according to indications.
Negative reviews describe side effects, the most common of which are a significant increase in appetite, weight gain, metabolic disorders, and the development of a withdrawal syndrome after stopping therapy. There are complaints of dizziness, dry mouth, constipation. In some men, the mammary glands become enlarged, but this phenomenon disappears as treatment continues. Many patients express dissatisfaction with the high cost of Zyprexa.
Zyprexa price in pharmacies
Approximate prices for Zyprexa (film-coated tablets, 28 pcs. Per package): 5 mg each - 2220-2650 rubles; 10 mg each - 4200–4860 rubles.
Zyprexa: prices in online pharmacies
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Drug name Price Pharmacy |
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Zyprexa 5 mg film-coated tablets 28 pcs. 2018 rub. Buy |
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Zyprexa Zidis 5 mg dispersible tablets 28 pcs. 2045 RUB Buy |
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Zyprexa Zidis 10 mg dispersible tablets 28 pcs. 4233 RUB Buy |
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Reviews of Zyprexa Zidis 4233 RUB Buy |
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Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
