Schizophrenia treatment; treatment and prevention of manic disorders; treatment and prevention of bipolar disorder; treatment and prevention of hallucinations and delusions in patients with alcoholism; treatment and prevention of hallucinations and delusions, manic episodes in drug addicts.
Dispersible tablets, 5 mg.
One tablet contains
active substance: olanzapine 5 mg.
Excipients: mannitol (E 421), aspartame (E 951), crospovidone, orange flavoring, colloidal anhydrous silica, sodium stearyl fumarate.
Round tablets, with a flat cylindrical surface, yellow.
6 mm in diameter, engraved with “5” on one side and smooth on the other (for a dosage of 5 mg).
Psychotropic drugs. Neuroleptics (Antipsychotics). Dibenzodiazepines and their derivatives. Olanzapine.
ATX code N05AH03
After oral administration, olanzapine is well absorbed and its maximum concentration in blood plasma is reached in 5 – 8 hours. The absorption of olanzapine is independent of food intake. At plasma concentrations of 7 to 1000 ng / ml, about 93% of olanzapine is bound to plasma proteins, mainly albumin and 1-acid glycoprotein.
Olanzapine is metabolized in the liver by conjugation and oxidation. The major circulating metabolite is 10-N-glucuronide, which theoretically does not penetrate the GEB. Cytochromes P450-CYP1A2 and P450-2D6 are involved in the formation of N-desmethyl and 2-hydroxymethyl metabolites of olanzapine. The activity of the CYP2D6 isoenzyme does not affect the level of olanzapine metabolism. The main pharmacological activity of the drug is due to olanzapine. Olanzapine is excreted in breast milk. The mean dose (mg / kg) given to the child when the mother’s Css is reached is 1.8% of the mother’s olanzapine concentration (mg / kg).
The mean elimination half-life of olanzapine in women was longer than in men (36.7 and 32.3 hours, respectively), while the clearance was lower (18.9 and 27.3 l / h, respectively). The safety profile of olanzapine (5-20 mg) was comparable in both women (n = 467) and men (n = 869).
Pharmacokinetics in special clinical cases
The pharmacokinetics of olanzapine vary depending on gender, age, and smoking.
Olanzapine is an antipsychotic, antimanic, mood-stabilizing drug that acts on various receptor systems.
The affinity of olanzapine (Ki; <100 nM) for the following multiple receptors was experimentally established: serotonin 5HT2A / 2C, 5HT3, 5HT6, dopamine D1, D2, D3, D4, D5, muscarinic cholinergic receptors M1-M5 and α1. The drug selectively reduces the excitability of mesolimbic (A10) dopaminergic neurons, and at the same time has a negligible effect on the striatal (A9) nerve pathways involved in the regulation of motor functions. Olanzapine reduces the conditioned protective reflex (a test that characterizes antipsychotic activity) at doses lower than the doses that cause catalepsy (a disorder that reflects a side effect on motor function). Enhances the anti-anxiety effect during the anxiolytic test. Provides reduction of both productive (including delusions, hallucinations), and negative frustration.
Indications for use
– for the treatment of exacerbations and maintenance therapy of schizophrenia and similar psychotic disorders in patients with severe productive (eg, delusions, hallucinations, thought disorder, hostility and suspicion) and / or negative (eg, emotional flatness, emotional and social isolation, depletion, symptomatology , as well as concomitant secondary affective disorders. Zolafren-swift is intended to maintain clinical improvement with continued therapy in patients who experienced an initial effect of treatment.
– long-term maintenance therapy of patients who have shown good results in treatment at the initial stage of therapy
– for the treatment of manic episodes from moderate to severe severity.
– prevention of recurrence of affective bipolar disorder
Method of application and dose
Zolafren Swift tablets are soluble in saliva and can be easily swallowed. As the tablet is very fragile, it should be taken immediately after opening the blister. In addition, just before taking the drug, the tablets can be dissolved in a full glass of water or other beverage (orange or apple juice, milk or coffee).
The recommended starting dose of olanzapine is 10 mg daily
the initial dose is 15 mg per day, given as a single dose in monotherapy, or 10 mg per day in combination therapy
prevention of recurrence of affective bipolar disorder: the recommended starting dose is 10 mg / day. Patients receiving olanzapine to treat episodes of mania to avoid recurrence should continue treatment with the same dose. In the event of a new episode of mania, mixed episode or episode of depression, olanzapine treatment should be continued (dose optimization if necessary), and additional treatment for affective symptoms should be used if there is medical evidence.
During the treatment of schizophrenia, episodes of mania and to avoid recurrence of affective bipolar disorder, the daily dose may be increased depending on the clinical condition of the patient from 5 to 20 mg / day. The increase in the recommended dose is indicated only after re-assessment of the clinical condition and should be carried out no more than once a day. Zolafren-swift can be taken regardless of the diet, as food does not affect its action. If olanzapine is scheduled to end, the dose should be reduced gradually
the minimum starting dose (5 mg / day) has not been experimentally confirmed, therefore, according to clinical indications, caution should be exercised when using the drug in patients older than 65 years.
hepatic and / or renal impairment: In such patients, a lower starting dose (5 mg) should be used. In moderate hepatic insufficiency (Child-Pugh class A or B), the starting dose should be 5 mg and increased with caution.
The initial dose and volume of dosage used in female patients are not subject to adjustment in contrast to the dosage used in male patients.
The starting dose and dosage levels in non-smoking patients are not adjustable in contrast to the dosage used in smoking patients.
If there is more than one factor that can provoke a slowdown in metabolism (female, elderly, non-smoker), a reduction in the starting dose should be considered.
According to clinical studies, the most commonly reported adverse reactions ( 1%) include drowsiness, weight gain, eosinophilia, increased prolactin, cholesterol, glucose and triglyceride levels, glucosuria, increased appetite, dizziness, akathisia, parkinitis, parkinsonism , anticholinergic effects, transient asymptomatic increase in hepatic transaminases, rash, asthenia, fatigue and edema.
very common (≥10%), common (≥1%, <10%), sometimes (≥0.1%, <1%), rare (≥0.01%, <0.1%), extremely rare <0.01%).
- weight gain (≥7% of body weight)
- increase in plasma prolactin levels
- orthostatic hypotension
- weight gain (≥15% of body weight)
- eosinophilia, leukopenia (including neutropenia)
- transient asymptomatic increase in hepatic aminotransferases (ALT, AST), especially in the early stages of treatment
- increase in alkaline phosphatase (ALP)
- increase in cholesterol levels ≥6.2 mmol / l compared to baseline <5.17 mmol / l on an empty stomach
- increase in triglyceride level ≥2.26 mmol / l compared to baseline <1.69 mmol / l
- increase in glucose level ≥7 mmol / l compared to baseline <5.56 mmol / l on an empty stomach
- increase in gamma-glutamyltransferase levels
- increase in uric acid levels
- increased appetite
- moderate transient anticholinergic effects, including constipation and dry mouth
- erectile dysfunction in men, decreased sexual desire in men and women
- rash, edema (including peripheral)
- asthenia, fatigue, fever
- weight gain (≥25% of body weight)
- leukopenia, neutropenia
- bradycardia, QT prolongation
- thromboembolism (including pulmonary embolism and deep vein thrombosis)
- photosensitivity reaction
- urinary incontinence, urinary retention
- amenorrhea, breast enlargement, galactorrhea in women, gynecomastia / breast enlargement in men
- increase in creatine phosphokinase, increase in total bilirubin
- nasal bleeding
- hepatitis (including hepatocellular, cholestatic or mixed liver damage)
- seizures / seizures
- allergic reaction (eg anaphylactoid reaction, angioneurotic edema, pruritus, urticaria)
- withdrawal symptoms7
- onset or exacerbation of diabetes mellitus, sometimes associated with ketoacidosis or coma, including several deaths
- hypertriglyceridemia, hypercholesterolemia
- convulsions in the presence in most cases of a history of seizures or risk factors for convulsions
- neuroleptic malignant syndrome
- dystonia (including eyeball movements)
- withdrawal syndrome in newborns
- tardive dyskinesia
- ventricular tachycardia / fibrillation, sudden death
- difficulty urinating
With long-term use of Zolafren-swift (at least 48 weeks), the ratio of patients with clinically significant changes in weight, glucose, total cholesterol, LDL, HDL or triglycerides increased over time. In patients who completed 9-12 courses of therapy, the growth rate of mean blood glucose slowed after approximately 6 months.
Adverse effects in special patient groups.
In clinical trials in elderly patients with dementia, Zolafren-swift treatment was associated with higher mortality and a higher incidence of cardiovascular adverse events compared with placebo. Very common adverse reactions (10%) in this group of patients include impaired gait and falls. Frequent adverse reactions (≥1%, <10%) were fever, lethargy, erythema, visual hallucinations, pneumonia and urinary incontinence.
In patients with drug-induced psychosis (dopamine agonist), hallucinations and worsening of parkinsonism symptoms were very common ( 10%) and more frequent than in the placebo group.
Patients with bipolar mania receiving Zolafren-swift in combination with lithium or valproate have developed neutropenia. Very common (10%) side effects in this group were weight gain, dry mouth, increased appetite, tremor, and frequent (<10% and ≥ 1%) speech disorders. During treatment with Zolafren-swift in combination with lithium or divalproex, weight gain ≥7% of baseline was observed in patients receiving acute therapy (up to 6 weeks). Long-term treatment with Zolafren-swift (up to 12 months) to prevent recurrence in patients with bipolar disorder was associated with an increase in body weight ≥7% from baseline in 39.9% of patients.
- hypersensitivity to the active substance or excipients of the drug
- patients at an established risk of glaucoma with a narrow anterior chamber angle
- Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
- lactation period
- children under 18 years
Olanzapine metabolism may be induced by tobacco smoking and carbamazepine, which may lead to decreased olanzapine concentrations.
If fluvoxamine or another CYP1A2 inhibitor, such as ciprofloxacin, is co-administered, a reduction in the initial dose of olanzapine should be considered. Dose reduction of olanzapine should be considered when initiating treatment with a CYP1A2 inhibitor.
Activated charcoal reduces the bioavailability of ingested olanzapine by 50-60% and activated charcoal should be taken at least 2 hours before or 2 hours after taking olanzapine.
Olanzapine may be an antagonist of direct and indirect dopamine agonists.
Caution should be exercised in patients who consume alcohol or take drugs that depress the activity of the central nervous system. Concomitant use of olanzapine and drugs used to treat Parkinson’s disease and dementia is not recommended.
Caution should be exercised when co-administering olanzapine with drugs that provoke QT prolongation.
During the use of antipsychotic drugs, improvement in the patient’s clinical condition may occur within days or weeks. During this period, the condition of patients should be closely monitored.
Psychosis and (or) behavioral disorders provoked by dementia
Olanzapine has not been approved as a drug for the treatment of patients with symptoms of psychosis and (or) behavioral disorders caused by dementia. This group of patients is not recommended to be treated with this drug due to increased mortality and risk of cerebrovascular disorders.
The use of olanzapine in the treatment of psychosis caused by dopamine agonists in patients with Parkinson’s disease is not recommended.
Neuroleptic malignant syndrome (CNS):
CNS is a potentially life-threatening condition associated with the use of antipsychotic drugs. Rare cases of CNS have also been reported with olanzapine. Clinical symptoms of CNS: very high temperature, muscle cramps, impaired consciousness, as well as signs of instability of the autonomic nervous system (irregular pulse or fluctuations in blood pressure, tachycardia, profuse sweating and cardiac arrhythmia). In addition, creatine phosphokinase activity may increase, myoglobinuria (rhabdomyolysis) and acute renal failure may develop. If the patient develops signs and symptoms indicating CNS, or fever for no apparent reason, without other clinical symptoms of CNS, all antipsychotic drugs, including olanzapine, should be discontinued.
Hyperglycemia and diabetes mellitus:
Rarely, hyperglycaemia and / or the development or worsening of symptoms of diabetes mellitus have been reported with isolated cases of ketoacidosis or coma, including death. In some cases, weight gain has been reported, which may be a predisposing factor. Appropriate monitoring of the clinical condition is also recommended, in accordance with accepted principles of antipsychotic treatment. Patients taking any antipsychotic drug, including Zolafren, should be monitored for early detection of signs and symptoms of hyperglycemia (such as excessive thirst, excessive urination, excessive appetite, and weakness), and patients with diabetes mellitus or predisposing risk factors. diabetes should be monitored regularly to detect impaired glycemic control. Body weight should be monitored regularly.
Change in lipid concentration:
Lipid side effects have been reported in placebo-controlled clinical trials in patients taking olanzapine. In the event of changes in lipid levels, appropriate treatment should be used, especially in patients with impaired lipid metabolism and in patients with risk factors for the development of such disorders. Patients receiving any antipsychotic drug, including Zolafrena Swift, should have their lipid levels monitored regularly in accordance with accepted principles of antipsychotic treatment.
Although the anticholinergic activity of olanzapine was detected in vitro, clinical trials have shown a low incidence of associated symptoms. However, due to the limited clinical experience of olanzapine in patients with intercurrent disease, caution should be exercised when prescribing to patients with prostate hypertrophy, paralytic obstruction, and similar conditions.
Transient and asymptomatic elevations of hepatic transaminases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are common, especially at the initial stage of drug use. Caution should be exercised in patients with elevated ALT and / or AST activity; who have signs and symptoms of liver failure; in whom there is a previously observed limitation of the functional reserve of the liver, as well as in patients taking drugs with hepatotoxic effects. If during treatment there is an increase in the activity of ALT and (or) AST, then you should perform a control analysis and reduce the dosage. In patients diagnosed with hepatic inflammation (including hepatocellular and cholestatic liver disease and mixed liver disease), olanzapine treatment should be discontinued.
Caution should be exercised with patients who for any reason have decreased white blood cell counts and / or neutrophilic granulocytes, with patients taking neutropenia medications, with patients with impaired function and / or toxic bone marrow damage provoked by intercurrent , radiotherapy or chemotherapy and with patients with hypereosinophilia or myeloproliferative disease. Neutropenia is common in patients taking olanzapine and valproate concomitantly.
Transient (transient) thromboembolism of the venous system has been reported during the use of antipsychotic drugs. Therefore, in such patients with schizophrenia, who often have risk factors for venous thromboembolism, all possible risk factors for thromboembolism should be identified and appropriate precautions taken before or during treatment with Zolofren-swift.
General activity of the central nervous system:
Based on the fact that Zolofren Swift acts primarily on the central nervous system, caution should be exercised when using it with other drugs acting on the central nervous system, as well as with alcohol. Antagonistic effects of olanzapine on direct and indirect dopamine agonists are possible.
Seizures / seizures.
Zolofren-swift should be used with caution in patients with a history of seizures / seizures or risk factors that lower the seizure threshold. In rare cases (most of which have a history of seizures or risk factors for seizures), seizures / seizures have been reported in patients taking Zolofren Swift.
If signs and symptoms of tardive dyskinesia occur in patients taking olanzapine, dose reduction or discontinuation should be considered. After stopping the drug, the symptoms may temporarily worsen or barely appear.
Rare cases of postural hypotension in elderly patients have been reported in clinical trials. As with other antipsychotic drugs, periodic monitoring of blood pressure is recommended in patients over 65 years of age.
Sudden coronary death:
Post-marketing surveillance has reported sudden cardiac death in patients taking Zolofren Swift. A retrospective observational cohort study found a similar, dose-dependent, twofold increase in the risk of sudden death in patients taking atypical antipsychotics compared with sudden death in patients not taking antipsychotics.
Zolafren Swift tablets contain aspartame, which is a source of phenylalanine. May be dangerous for patients with phenylketonuria.
Zolafren Swift tablets contain mannitol.
Due to the lack of experience with Zolafren-swift during pregnancy and the lack of appropriate clinical trials, the drug should be prescribed during pregnancy only if the potential benefit to the patient far outweighs the potential risk to the fetus. Patients should be advised to notify their physician of the onset or planning of pregnancy during treatment with Zolafren Swift.
If exposed to antipsychotics (including Zolafrena Swift) in the third trimester of pregnancy, newborns are at risk of developing adverse reactions, including extrapyramidal symptoms and / or withdrawal symptoms, which may vary in severity and duration. Cases of agitation, hypertension, hypotension, tremor, drowsiness, respiratory or eating disorders have been reported. Therefore, newborns should be closely monitored.
Features of the drug’s effect on the ability to drive a vehicle or potentially dangerous mechanisms
Because olanzapine may cause drowsiness and dizziness, patients should avoid potentially hazardous activities during treatment.
There have been cases of death with a single dose not exceeding 450 mg, but there have also been cases of a favorable outcome with a single oral dose of about 2 g.
Symptoms: tachycardia, agitation, aggression, dysarthria, various extrapyramidal symptoms and decreased consciousness: from sedation to coma. Also reported: delirium, convulsions, coma, neuroleptic malignant syndrome, respiratory depression, dyspnea, hypertension or hypotension, arrhythmia (<2% of overdose cases), cardiac and respiratory arrest.
Treatment: There is no specific antidote for Zolafren Swift. Provoking vomiting is not recommended. Standard overdose procedures may be required (gastric lavage, administration of activated charcoal). Co-administration of activated charcoal showed a decrease in the bioavailability of Zolafren-Swift when ingested to 50-60%.
Symptomatic treatment in accordance with the clinical condition and control of vital organ functions, including treatment of hypotension, circulatory collapse and maintenance of respiratory function, are indicated. Epinephrine, dopamine, and other sympathomimetics with beta-agonist activity should not be used, as stimulation of beta-adrenoceptors may exacerbate hypotension. It is necessary to monitor the cardiovascular system to identify possible arrhythmias. Careful medical supervision and monitoring should continue until the patient recovers.
Release form and packaging
14 tablets (for a dosage of 5 mg) or 7 tablets (for a dosage of 10 mg, 15 mg and 20 mg) are placed in a contour cellular packing from a film polyamide / aluminum / polyvinylchloride (PA / Aluminum / PVC /) and aluminum foil
2 (for a dosage of 5 mg) and 4 (for a dosage of 10 mg, 15 mg and 20 mg) contour cellular packings together with the instruction on medical application in the state and Russian languages place in a pack from a cardboard.
Store in the original package, in a dry, protected from light place at a temperature not exceeding 25 0C.
Keep out of reach of children!
Do not use after the expiration date.
Terms of leave from pharmacies
According to the recipe