Security Profile Summary
Adults
The most frequent (noted in ≥1% of patients) adverse reactions due to the use of olanzapine in clinical studies were drowsiness, weight gain, eosinophilia, increased concentrations of prolactin, cholesterol, glucose and triglycerides (see "Specific guidance"), glucosuria, increased appetite, dizziness, akathisia, parkinsonism, leukopenia, neutropenia (see section "Special instructions"), dyskinesia, orthostatic hypotension, aichiholinergic effects, transient asymptomatic increase in activity hepatic aminotransferases (see section "Special instructions"), rash, asthenia, fatigue, fever, arthralgia, increased activity of alkaline phosphatase, increased activity of γ-glutamyltransferase, hyperuricemia, increased activity of creatine phosphokinase and edema.
Table list of undesirable reactions
The table below lists the adverse reactions and laboratory observations noted in clinical studies and spontaneous reports.In each frequency category, unwanted reactions are arranged in decreasing order of severity. The following frequency categories are used: very often (≥ 1/10), often (≥1 / 100 to <1/10), infrequently (≥1 / 1000 to <1/100), rarely (≥1 / 10,000 to (< 1/1 000), very rarely (<1/10 000), is unknown (it is impossible to determine based on available data).
| Often | Often | Infrequently | Rarely | Unknown |
| Co the sides of the blood and lymphatic system |
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| EosiMr.officilia Leukopenia10 Neutropenia10 |
| Thrombocytopethe11 |
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| Co side of the immune system |
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| Hypersensitivityethe11 |
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| Co sides of metabolism and nutrition |
| Weight gain1 | Increase concentrations cholesterol2, 3 Enhancementse glucose concentrations4 Increase in the concentration of triglycerides2,5 Glucosuria Increased appetite
| Development or exacerbation of diabetes mellitus, sometimes accompanied by ketoacidosis or coma, including several deaths11 (see section "Special instructions")
| Hypothermia12 |
|
| Co the sides of the nervous system |
| Drowsiness | Dizziness Akathisia6 Parkinsonism6 Dyskinesia6 | Convulsions in patients with a history of seizures or in the presence of risk factors for seizures11 Dystonia (including the oculogic crisis)11 PLate dyskinesia11 Amnesia9 Dysatria
| Malignant yeyroleptichesky syndrome (see section "Special instructions")12 Symptoms canceling7,12 |
|
| Co sides of the heart |
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| Bradycardia Interval lengthening QTs (see section "Special instructions") | Ventricular tachycardia/ fibrillation ventricles, sudden death (see section "Special indications")11 |
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| Co sides of blood vessels |
| Orthostatic hypotension10 |
| Thromboembolism (including pulmonary embolism and deep vein thrombosis) (see section "Special instructions") |
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| Co side of the respiratory system, chest and mediastinal organs |
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| Hocoboe bleeding9 |
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|
| Co side of the gastrointestinal tract |
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| Light, transient anticholinergic effects, including constipation and dry mouth | Bloating9 | Pancreatit11 |
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| Co sides of the liver and bile ducts |
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| The transient asymptomatic increase in hepatic aminotransferase activity (ALT, ACT), especially in the early period of treatment (see section "Special instructions") |
| Hepatitis (including hepatocellular, cholestAcute and mixed liver damage)11 |
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| Co skin and subcutaneous tissue |
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| Rash | Reaction photosensitizerof the Alopecia |
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| Co side musculoskeletal and connective tissue |
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| Arthralgia9 |
| Rhabdomyolysis11 |
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| Co hand kidney and urinary tract |
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| Urinary incontinence, urinary retention Delayed onset of urination11 |
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| Bebeltart.ь, the puerperium period and perinatal conditions |
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| The withdrawal syndrome in newborns (see section " pregnancy and during breastfeeding ") |
| Co the side of the genitals and the mammary gland |
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| Erectile dysfunction in men Reduction of libido in men and women | Amenorrhea Breast enlargement Dalaktorrhea in women Gynecomastia / Breast Augmentation in Men | Priapism12 |
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| Are common disorders and disorders at the site of administration |
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| Asthenia Fatigue Edema Fever10 |
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| Laboratory data |
| Increase in prolactin concentration in plasma8 | Increase in activity of alkaline phosphatase10 Increase in activity of creatine phosphokinase11 Increase in γ-glutamyltransferase activity10 Hyperuricemia10 | Increase in the concentration of total bilirubin |
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1 In all patient groups, regardless of the initial body mass index, a clinically significant increase in body weight was observed. After a short course of therapy (munitscyan duration - 47 days) weight gain ≥7% of the initial value was observed very often (22.2%), ≥15% often (4.2%) and ≥25% infrequently (0.8%). Have napatients receiving long-term treatment (at least 48 weeks), an increase in ≥7, ≥15 and ≥25% were very frequent (64.4, 31.7 and 12.3% respectively).
2The average increase in the concentration of lipids on an empty stomach (cholesterol, low density lipoprotein (LPN)P), triglycerides) was more pronounced in patients without initial signs of lipid metabolism disorders.
3Chaone hundred per centbThere was an increase in the concentration of cholesterol from normal values nat(<5.17 mmol / l) to elevated (≥6.2 mmol / L). Change in concentration commono cholesterol on an empty stomach from border indicators (≥5.17- <6.2 mmol / l) to of theekshennyh (≥6,2 mmol / l) was very frequent.
4Haone observed an increase in fasting glucose concentration from normal values (<5.56 mmol / l) to elevated (≥7 mmol / L). Change in fasting glucose concentration from borderline indicators (≥5.56 - <7 mmol / l) to elevated (≥7 mmol / l) was very frequent.
5 Often there was an increase in the concentration of triglycerides on an empty stomach from normalh(<1.69 mmol / l) to elevated≥2.26 mmol / l). Change in fasting triglyceride concentration from borderline indicators (≥1.69 - <2.26 mmol / l) to elevated (≥ 2.26 mmol / l) was very frequent.
6The frequency of parkinsonism and dystonia in patients taking olMr.Zapin in clinical studies was quantitatively higher but statistically significant from placeboe fromlichalas. In patients who took olanzapine, parkinsonism, akathisia, dystonia were less frequent than in patients who received Podds and endsMr.doses of haloperidol. In view of lack of detailed information on the presence of patients in the anamnesiseth e sharp and late etostapyramide locomotor disorders, it is currently impossible to conclude that olanzapine to a lesser degree causes the development of tardive dyskinesia and (or) other late extraPiramidic syndromes.
7With a sharp abolition of olanzapine, symptoms such as sweating, insomnia, tremors, anxiety, nausea, and vomiting were observed.
8In clinical studies of up to 12 weeks, the concentration of prolactin in the plasma exceeded the upper limit of normal in about 30% of the naqipatients with normal initial values of prolactin. Most of these paqiincreased prolactin concentration was mild, and did not exceed 2 upper bounds of the norm.
9NotdesiredSprucee phenomenon, revealed in clinical studies in the Integral Database olanzapine data.
10According to the values in the clinical studies in the Olanzapine Integral Database.
11 Hlucrative phenomenon, revealed by post-registration observation, frequency of the mouthis anodized using the Integral olanzapine database.
12The undesirable phenomenon, revealed at Pregistration, frequency of the mouththe upper limit of the 95% confidence interval using The integrated olanzapine database.
Long-term exposure (at least 48 weeks)
The proportion of patients who experienced undesirable clinically significant changes in body weight, glucose, total / LDL cholesterol or triglyceride levels increased over time. In adults who underwent a 9-12-month course of therapy, the rate of increase in mean glucose concentration in the blood decreased after 6 months.
Additional information about special patient groups
In clinical studies in elderly patients with dementia, olanzapine therapy compared with placebo resulted in an increased incidence of fatal outcomes and cerebrovascular unwanted reactions (see also "Specific guidance").Very frequent undesirable reactions caused by the use of olanzapine in this group of patients were gait and fall disturbances. Often observed pneumonia, fever, lethargy, erythema, visual hallucinations and urinary incontinence.
In clinical studies in patients with drug (dopamine receptor agonists) psychosis due to Parkinson's disease, very often (more often than with placebo), the deterioration of parkinsonian symptoms and hallucinations was reported.
In one clinical trial in patients with bipolar mania, combined therapy with valproic acid and olanzapine in 4.1% of cases resulted in neutropenia, a potential causative factor could be a high plasma concentration of valproic acid. The use of olanzapine with lithium or valproic acid resulted in an increased frequency (≥10%) of tremor, dry mouth, increased appetite and weight gain. In addition, the disorder of speech was often reported. When combined therapy with olanzapine and lithium or valproate semitriya, an increase in body weight ≥7% of the initial body weight was observed in 17.4% of patients in a short course of treatment (up to 6 weeks).Long-term therapy with olanzapine (up to 12 months) in order to prevent relapse in patients with bipolar disorder led to an increase of ≥7% of the baseline body weight in 39.9% of patients.
Children
Olanzapine is not indicated for the treatment of children and adolescents under the age of 18 years.
Despite the fact that clinical studies aimed at comparing adolescents with adults were not conducted, the data obtained in studies in adolescents were compared with the results of studies in adults.
The presented table summarizes the undesirable reactions observed in adolescents (aged 13-17 years) with a higher frequency compared with adults or undesirable reactions found only in adolescents in the context of short-term clinical trials. A clinically significant increase in body weight (≥7%) is more likely to occur in adolescents than in adults (with comparable exposures). The amount of weight gain and the proportion of adolescents with a clinically significant increase in body weight is higher for long-term exposures (at least 24 weeks) than for short-term exposures.
In each frequency category, unwanted reactions are arranged in decreasing order of severity.The following frequency categories are used: very often (≥1 / 10), often (≥1 / 100 to <1/10).
From the side of metabolism and nutrition
Very often: weight gain13, an increase in the concentration of triglycerides14, increased appetite.
Often: increased cholesterol concentration15.
From the nervous system
Very often: sedation (including hypersomnia, lethargy, drowsiness).
From the gastrointestinal tract
Often: dry mouth.
From the liver and biliary tract
Very often: increased activity of hepatic aminotransferases (ALT / AST, see section "Special instructions").
Laboratory data
Very often: a decrease in the concentration of total bilirubin, an increase in GGT activity, an increase in the plasma concentration of prolactin16
13After a short course of therapy (median duration - 22 day) weight gain ≥7% of the initial value (kg) was observed very often (40,6%), ≥15% often (7.1%) and ≥25% infrequently (2.5%). With long-term treatment (according to less at least 24 weeks), an increase in ≥7% was noted in 89.4% of cases, ≥15% - 55.3% and ≥25% - 29.1% of cases from the initial body weight.
14 Often an increase in fasting triglyceride concentration from normal values (<1.016 mmol / L) to elevated (≥1,467 mmol / L) and changes in fasting triglyceride concentration from borderline indicators (≥1,016 - <1.467 mmol / L) to elevated (≥1.467 mmol / l) was very frequent.
15Often there was an increase in cholesterol concentration from normal fasting values (<4.39 mmol / l) to elevated (≥5.17 mmol / l). Change in the total fasting cholesterol concentration from borderline indicators (≥4.39- <5.17 mmol / l) to byvyshenMr.th (≥5.17 mmol / l) was very frequent.
16An increased plasma concentration of prolactin was found in 47.4% of adolescents.