natgillin/translations-raw huggingface dataset:
A decrease in the dose of olanzapine should be considered if treatment with an inhibitor of CYP 1A2 is initiated.
Experienţla adolescenţ( vârsta între 13 ş17 ani) este limitată date de eficacitate pe termen scurt
Decreased bioavailability Activated charcoal reduces the bioavailability of oral olanzapine by 50 to 60% and should be taken at least 2 hours before or after olanzapine.
la
Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have not been found to significantly affect the pharmacokinetics of olanzapine.
în tratamentul schizofreniei (6 să mâni) şal maniei ascociate tulbură bipolare I (3 să mâni), ce
Potential for olanzapine to affect other medicinal products Olanzapine may antagonise the effects of direct and indirect dopamine agonists.
ptă
Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e. g.
au inclus mai puţ de 200 adolescenţ Olanzapina a fost utilizată
1A2, 2D6, 2C9, 2C19, 3A4).
într- un interval de dozare flexibil
Olanzapine showed no interaction when co-administered with lithium or biperiden.
În timpul tratamentului cu olanzapinăadolescenţ au
Therapeutic monitoring of valproate plasma levels did not indicate that valproate dosage adjustment is required after the introduction of concomitant olanzapine.
ii
General CNS activity Caution should be exercised in patients who consume alcohol or receive medicinal products that can cause central nervous system depression.
ă
The concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with Parkinson's disease and dementia is not recommended (see section 4.4).
68
QTc interval Caution should be used if olanzapine is being administered concomitantly with medicinal products known to increase QTc interval (see section 4.4).
crescut semnificativ mai mult în greutate faţde adulţ Amplitudinea modifică valorilor
76 4.6 Pregnancy and lactation
i.
Pregnancy:
rilor
Nevertheless, because human experience is limited, olanzapine should be used in pregnancy only if the potential benefit justifies the potential risk to the foetus.
colesterolului total în condiţ de repaus alimentar, a colesterolului LDL, trigliceridelor şprolactinei
Spontaneous reports have been very rarely received on tremor, hypertonia, lethargy and sleepiness, in infants born to mothers who had used olanzapine during the 3rd trimester.
i
Lactation:
(vezi pct.
In a study in lactating, healthy women, olanzapine was excreted in breast milk.
4. 4 ş4. 8) a fost mai mare la adolescenţ
Mean infant exposure (mg/ kg) at steady state was estimated to be 1.8% of the maternal olanzapine dose (mg/ kg).
i
Patients should be advised not to breast feed an infant if they are taking olanzapine.
i decât la adulţ Nu există
4.7 Effects on ability to drive and use machines
referitoare la ii
Because olanzapine may cause somnolence and dizziness, patients should be cautioned about operating machinery, including motor vehicles.
4. 4
4.8 Undesirable effects
i ş4. 8). i
Adults The most frequently (seen in ≥ 1% of patients) reported adverse reactions associated with the use of olanzapine in clinical trials were somnolence, weight gain, eosinophilia, elevated prolactin, cholesterol, glucose and triglyceride levels (see section 4.4), glucosuria, increased appetite, dizziness, akathisia, parkinsonism (see section 4.4), dyskinesia, orthostatic hypotension, anticholinergic effects, transient asymptomatic elevations of hepatic transaminases (see section 4.4), rash, asthenia, fatigue and oedema.
ţ
The frequency terms listed are defined as follows:
5. 2 Proprietăi farmacocinetice
10%), common (≥ 1% and < 10%), uncommon (≥ 0.1% and < 1%), rare (≥ 0.01% and
Olanzapina se absoarbe bine după
< 0.1%), very rare (< 0.01%), not known (cannot be estimated from the data available).
administrarea oralăatingând concentraţ plasmatică
Very common
,
Common
ia
Uncommon
maximă
Not known
după
Blood and the lymphatic system disorders Immune system disorders
Absorbţ nu este influenţ de ingestia de alimente.
Eosinophilia
ată
Leukopenia Neutropenia
absolută
Thrombocytopenia Allergic reaction
comparaţ cu administrarea intravenoasă a fost determinată
Metabolism and nutrition
Metabolitul principal circulant este
disorders
în
Weight gain1
i
Elevated cholesterol levels 2,3 Elevated glucose levels 4 Elevated triglyceride levels2,5 Glucosuria Increased appetite
derivatul 10– N– glucuronid, ce nu trece bariera hematoencefalicăCitocromii P450– CYP1A2 şP450 –
Development or exacerbation of diabetes occasionally associated with ketoacidosis or coma, including some fatal cases (see section 4.4) Hypothermia
CYP2D6 contribuie la formarea metaboliţ N– demetil si 2– hidroximetil care, în studii pe animale, ilor au manifestat o activitate farmacologică vivo semnificativ mai mică
Nervous system disorders Somnolence
in
Dizziness Akathisia6
decât olanzapina.
Seizures where in most cases a history of
în forma nemodificatăare cea mai mare activitate farmacologicăLa voluntarii să toş după
77
.
Cardiac disorders
nă i,
Parkinsonism6 Dyskinesia 6
administrarea oralătimpul mediu de înjumă ţ
seizures or risk factors for seizures were reported Neuroleptic malignant syndrome (see section 4.4) Dystonia (including oculogyration) Tardive dyskinesia Discontinuation symptoms7
,
Vascular disorders
tă ire- eliminare plasmatică olanzapinei a variat în al
Bradycardia QT c prolongation (see section 4.4)
funcţ de vârstă i de sex. ie La vârstnicii (65 de ani şpeste) sanatoş în comparaţ cu subiecţ mai tineri, timpul mediu de înjumă ţ
Ventricular tachycardia/ fibrillation, sudden death (see section 4.4)
tă ire- eliminare plasmatică fost mai lung (51, 8 ore faţde 33, 8 ore), iar clearance– ul a fost a mai mic (17, 5 l/ oră ă 18, 2 l/ oră Variabilitatea farmacocinetică
Orthostatic hypotension
observată vârstnici se la
Thromboembolism (including pulmonary embolism and deep vein thrombosis)
La 44 de pacienţcu schizofrenie în vârstă
Gastrointestinal disorders
de
Mild, transient anticholinergic effects including constipation and dry mouth
peste 65 de ani, dozele între 5 ş20 mg/ zi nu au produs un profil deosebit al reacţ adverse.
Pancreatitis
iilor
Hepato-biliary disorders
tăire -
Transient, asymptomatic elevations of hepatic transaminases (ALT, AST), especially in early treatment (see section 4.4)
eliminare plasmatică fost ceva mai lung (36, 7 ore faţde 32, 3 ore), iar clearance– ul a fost mai mic a (18, 9 l/ oră ă 27, 3 l/ oră Totuş olanzapina (5– 20 mg/ zi) a demonstrat un profil de siguranţ faţde). i, asemă tor la femei (n= 467) şla bă i (n= 869). nă i rbaţ
Hepatitis (including hepatocellular, cholestatic or mixed liver injury)
ă
Skin and subcutaneous tissue disorders
ă La pacienţ cu insuficienţrenală
Rash
ii
Photosensitivity reaction Alopecia
(clearance- ul creatininei < 10 ml/ min) faţde subiecţ să toş nu
Musculoskeletal and connective tissue disorders Rhabdomyolysis Renal and urinary disorders Urinary hesitation Reproductive system and breast disorders Priapism General disorders and administration site conditions Asthenia Fatigue Oedema Investigations Elevated plasma prolactin levels 8 1
ii nă i,
High creatine phosphokinase Increased total bilirubin
au existat diferenţsemnificative privind timpul mediu de înjumă ţ
Increased alkaine phosphatase
tăire- eliminare plasmatică
Weight gain ≥ 7% of baseline body weight was very common and ≥
(37, 7 ore
15% of baseline body
faţde 32, 4 ore) sau clearance– ul medicamentului (21, 2 l/ oră ă 25 l/ oră Un studiu de bilanţ
78
ă
weight was common.
).
Patients gaining ≥ 25% of their baseline body weight with long-term exposure were very common.
masei a ară cătat aproximativ 57% din olanzapina marcată formămetabolizată.
2 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline.
La subiecţ fumă cu insuficienţhepatică oarătimpul mediu de înjumă ţ ă
4 Observed for fasting normal levels at baseline (< 5.56 mmol/ l) which increased to high (≥ 7 mmol/ l).
radioactiv a apă în urina, în principal sub rut
Changes in fasting glucose from borderline at baseline (≥ 5.56 - < 7 mmol/ l) to high (≥ 7 mmol/ l) were very common.
(39, 3 ore) a fost prelungit şclearance– ul (18 l/ orăa fost redus, în comparaţ cu subiecţ plasmat
5 Observed for fasting normal levels at baseline (< 1.69 mmol/ l) which increased to high (≥ 2.26 mmol/ l).
să toşnefumatori (48, 8 ore, respectiv 14, 1 l/ oră
Changes in fasting triglycerides from borderline at baseline (≥ 1.69 mmol/ l - < 2.26 mmol/ l) to high (≥ 2.26 mmol/ l) were very common.
La subiecţ nefumă în comparaţ cu cei fumă (barbaţşfemei), timpul mediu de înjumă ţ
6 In clinical trials, the incidence of parkinsonism and dystonia in olanzapine-treated patients was numerically higher, but not statistically significantly different from placebo.
tă ire -
Olanzapine-treated patients had a lower incidence of parkinsonism, akathisia and dystonia compared with titrated doses of haloperidol.
eliminare plasmatică fost prelungit (38, 6 ore faţde 30, 4 ore) şclearance– ul a fost redus (18, 6 l/ oră ă
In the absence of detailed information on the pre-existing history of individual acute and tardive extrapyramidal movement disorders, it can not be concluded at present that olanzapine produces less tardive dyskinesia and/ or other tardive extrapyramidal syndromes.
i
7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been reported when olanzapine is stopped abruptly.
faţde 27, 7 l/ oră
In most patients, levels returned to normal ranges without cessation of treatment.
Clearance– ul plasmatic al olanzapinei este mai mic la subiecţ vârstnici faţde cei tineri, la femei faţ ii de barbaţşla nefumă faţde fumă Totuş importanţ vârstei, sexului sau fumatului asupra tori ă
In adult patients who completed 9-12 months of therapy, the rate of increase in mean blood glucose slowed after approximately 4-6 months.
clearance– ului ştimpului de injumă ţ este mic, în comparaţ cu variabilitatea individuală generală.
Additional information on special populations In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher incidence of death and cerebrovascular adverse reactions compared to placebo (see also section 4.4).
ire
In clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with Parkinson’ s disease, worsening of Parkinsonian symptomatology and ha llucinations were reported very commonly and more frequently than with placebo.
ie
Olanzapine administered with lithium or valproate resulted in increased levels ( 10%) of tremor, dry mouth, increased appetite, and weight gain.
i caucazieni, japonezi şchinezi, nu au existat diferenţale parametrilor Intr– un stud
Speech disorder was also reported commonly.
iu pe subiecţ i
During treatment with olanzapine in combination with lithium or divalproex, an increase of  7% from baseline body weight occurred in 17.4% of patients during acute treatment (up to 6 weeks).
e
79 Children and adolescents Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years.
farmacocinetici între cele trei populaţ
The following table summarises the adverse reactions reported with a greater frequency in adolescent patients (aged 13-17 years) than in adult patients or adverse reactions only identified during short-term clinical trials in adolescent patients.
ii.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Legarea olanzapinei de proteinele plasmatice a fost de circa 93% în concentraţ cuprinse între aproximativ 7 ng/ ml şaproximativ 1000 ng/ ml.
The frequency terms listed are defined as follows:
Olanzapina se leagă predominant i α– glicoproteina acidă.
Very common (≥ 10%), common (≥ 1% and < 10%).
1
Metabolism and nutrition disorders Very common:
Adolescenţ( vârsta între 13 ş17 ani):
Weight gain9, elevated triglyceride levels10, increased appetite.
adulţ În studiile clinice, expunerea medie la olanzapină fost cu aproximativ 27% mai mare la
11 Common:
medie mai
Elevated cholesterol levels Nervous system disorders Very common:
mică i faptul că puţ adolescenţerau fumă Este posibil ca asemenea factori să
Sedation (including: hypersomnia, lethargy, somnolence).
ini i tori. contri
Gastrointestinal disorders Common:
o expunere medie mai mare observată rândul adolescenţ
Dry mouth Hepato-biliary disorders Very common:
5. 3 Date preclinice de siguranţ
Elevations of hepatic transaminases (ALT/ AST; see section 4.4).
69 Toxicitate acută doză
Investigations Very common:
Semnele de toxicitate orală roză
Decreased total bilirubin, increased GGT, elevated plasma prolactin levels12.
derea activită comătremor, convulsii clonice, salivaţ şpierdere în greutate.
9 Weight gain ≥ 7% of baseline body weight (kg) was very common and ≥ 15% of baseline body weight was common.
oareci) ş175 mg/ kg (ş med
With long-term exposure (at least 24 weeks), approximately half of adolescent patients gained ≥ 15% and almost a third gained ≥ 25% of their baseline body weight.
Semnele clinice au inclus sedare, ataxie, tremor, puls
Among adolescent patients, mean weight gain was greatest in patients who were overweight or obese at baseline.
rapid, respiraţ dificilămioză i anorexie.
11 Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/ l) to high (≥ 5.17 mmol/ l) were observed commonly.
La maimuţ dozele orale unice de până 100 mg/ kg au
Changes in total fasting cholesterol levels from borderline at baseline (≥ 4.39 - < 5.17 mmol/ l) to high (≥ 5.17 mmol/ l) were very common.
provocat o stare de prostraţ ş la doze mai mari, semiconş a.
12 Elevated plasma prolactin levels were reported in 47.4% of adolescent patients.
trei luni pe ş oareci şde până un
4.9 Overdose
an pe ş
Signs and symptoms Very common symptoms in overdose (> 10% incidence) include tachycardia, agitation/ aggressiveness, dysarthria, various extrapyramidal symptoms, and reduced level of consciousness ranging from sedation to coma.
La
Other medically significant sequelae of overdose include delirium, convulsion, coma, possible neuroleptic malignant syndrome, respiratory depression, aspiration, hypertension or hypotension, cardiac arrhythmias (< 2% of overdose cases) and cardiopulmonary arrest.
obolani, efectele reversibile concordante cu creşterea prolactinei au inclus reducerea greutăii ovarelor şa uterului şmodifică morfologice ale epiteliului vaginal şale glandei mamare.
Fatal outcomes have been reported for acute overdoses as low as 450 mg but survival has also been reported following acute overdose of 1,500 mg.
Toxicitatea hematologicăla fiecare specie s– au constatat efecte hematologice, inclusiv reduceri: dependente de doză leucocitelor circulante la ş oareci şreduceri nespecifice ale leucocitelor circulante la ş
80 Management of overdose There is no specific antidote for olanzapine.
obolani; totuş nu s- au evidenţ fenomene de citotoxicitate la nivelul mă
Induction of emesis is not recommended.
hematopoietice.
Standard procedures for management of overdose may be indicated (i. e. gastric lavage, administration of activated charcoal).
La câţ câini trataţ 8 sau 10 mg/ kg pe zi (expunere totală olanzapină ASC -
The concomitant administration of activated charcoal was shown to reduce the oral bioavailability of olanzapine by 50 to 60%.
de 12– 15 ori mai mare decât doza de 12 mg/ zi administrată om) a apă fenomene reversibile de
Symptomatic treatment and monitoring of vital organ function should be instituted according to clinical presentation, including treatment of hypotension and circulatory collapse and support of respiratory function.
neutropenie, trombocitopenie sau anemie.
Do not use epinephrine, dopamine, or other sympathomimetic agents with beta- agonist activity since beta stimulation may worsen hypotension.
La câinii citopenici nu s- au evidenţ efecte adverse asupra iat celulelor progenitoare şproliferante din mă
Cardiovascular monitoring is necessary to detect possible arrhythmias.
La ş Olanzapina nu prezintă
Close medical supervision and monitoring should continue until the patient recovers.
obolanii masculi, sedarea a micş performanţ orat
PHARMACOLOGICAL PROPERTIES
aţ obolanii ce au primit 3 mg/ kg (de
5.1 Pharmacodynamic properties
s– au constatat întârzieri
Pharmacotherapeutic group: antipsychotics: diazepines, oxazepines and thiazepines, ATC code:
fetale şreducerea tranzitorie a activită ii i
N05AH03.
ţ ii.
Olanzapine is an antipsychotic, antimanic and mood stabilising agent that demonstrates a broad pharmacologic profile across a number of receptor systems.
Mutagenicitate Olanzapina nu a fost mutagenă clastogenă întreaga gamă teste standard, ce a inclus teste de
In preclinical studies, olanzapine exhibited a range of receptor affinities (Ki; < 100 nM) for serotonin 5 HT2A/ 2C, 5 HT3, 5 HT6; dopamine D1, D2, D3, D4, D5; cholinergic muscarinic receptors m1-m5; α adrenergic; and histamine H1 receptors.
Carcinogenitate Pe baza rezultatelor studiilor pe ş oareci şş i obolani, s– a dovedit căolanzapina nu este carcinogenă.
Animal behavioral studies with 1 olanzapine indicated 5HT, dopamine, and cholinergic antagonism, consistent with the receptor- binding profile.
6. 1 Lista excipienţ ilor
In a single oral dose (10 mg) Positron Emission tomography (PET) study in healthy volunteers, olanzapine produced a higher 5 HT2A than dopamine D2 receptor occupancy.
Monohidrat de lactoză Pulbere de celuloză Amidon din porumb - pregelatinizat Amidon din porumb Siliciu coloidal anhidru Stearat de magneziu
In two of two placebo and two of three comparator controlled trials with over 2,900 schizophrenic patients presenting with both positive and negative symptoms, olanzapine was associated with statistically significantly greater improvements in negative as well as positive symptoms.
ţ 6. 2 Incompatibilităi
In a multinationational, double-blind, comparative study of schizophrenia, schizoaffective, and related disorders which included 1,481 patients with varying degrees of associated depressive symptoms (baseline mean of 16.6 on the Montgomery-Asberg Depression Rating Scale), a prospective secondary analysis of baseline to endpoint mood score change demonstrated a statistically significant improvement (p=0.001) favouring olanzapine (-6.0) versus haloperidol (-3.1).
Nu este cazul.
In patients with a manic or mixed episode of bipolar disorder, olanzapine demonstrated superior efficacy to placebo and valproate semisodium (divalproex) in reduction of manic symptoms over 3 weeks.
6. 3 Perioada de valabilitate
In a co-therapy study of patients treated with lithium or valproate for a minimum of 2 weeks, the addition
2 ani.
81 of olanzapine 10 mg (co-therapy with lithium or valproate) resulted in a greater reduction in symptoms of mania than lithium or valproate monotherapy after 6 weeks.
DATA REVIZUIRII TEXTULUI
Olanzapine also showed a statistically significant advantage over placebo in terms of preventing either recur rence into mania or recurrence into depression.
Informaţ detaliate asupra acestui produs sunt disponibile pe website- ul Agenţ Europene a
In a second 12-month recurrence prevention study in manic episode patients who achieved remission with a combination of olanzapine and lithium and were then randomised to olanzapine or lithium alone, olanzapine was statistically non-inferior to lithium on the primary endpoint of bipolar recurrence (olanzapine 30.0%, lithium 38.3%; p = 0.055).
ii
In an 18-month co-therapy study in manic or mixed episode patients stabilised with olanzapine plus a mood stabiliser (lithium or valproate), long-term olanzapine co-therapy with lithium or valproate was not statistically significantly superior to lithium or valproate alone in delaying bipolar recurrence, defined according to syndromic (diagnostic) criteria.
iei
Paediatric population The experience in adolescents (ages 13 to 17 years) is limited to short term efficacy data in schizophrenia (6 weeks) and mania associated with bipolar I disorder (3 weeks), involving less than 200 adolescents.
Medicamentului (EMEA) http: // www. emea. europa. eu
Olanzapine was used as a flexible dose starting with 2.5 and ranging up to 20 mg/ day.
Zalasta 20 mg comprimate
During treatment with olanzapine, adolescents gained significantly more weight compared with adults.
COMPOZIŢ CALITATIVĂŞ CANTITATIVĂ
The magnitude of changes in fasting total cholesterol, LDL cholesterol, triglycerides, and prolactin (see sections 4.4 and 4.8) were greater in adolescents than in adults.
I
There are no data on maintenance of effect and limited data on long term safety (see sections 4.4 and 4.8).
Fiecare comprimat conţ 20 mg olanzapină
5.2 Pharmacokinetic properties
Fiecare comprimat conţ 323, 5 mg lactoză
Olanzapine is well absorbed after oral administration, reaching peak plasma concentrations within 5 to 8 hours.
6. 1. ilor,
The absorption is not affected by food.
Comprimat.
Absolute oral bioavailability relative to intravenous administration has not been determined.
Comprimatele sunt rotunde, uş biconvexe, de culoare uş gă gă şinscripţ
Olanzapine is metabolized in the liver by conjugative and oxidative pathways.
or lbuie sau cu posibile pete individuale
The major circulating metabolite is the 1 0-N-glucuronide, which does not pass the blood brain barrier.
4. 1 Indicaţ terapeutice ii
Cytochromes P450- CYP 1A2 and P450-CYP2D6 contribute to the formation of the N-desmethyl and 2-hydroxymethyl metabolites, both exhibited significantly less in vivo pharmacological activity than olanzapine in animal studies.
Adulţi:
The predominant pharmacologic activity is from the parent olanzapine.
Olanzapina este indicată tratamentul schizofreniei. în
After oral administration, the mean terminal elimination half-life of olanzapine in healthy subjects varied on the basis of age and gender.
inerea amelioră clinice în timpul tratamentului de întreţ rii inere, la
The pharmacokinetic variability observed in the elderly is within the range for the non-elderly.
spuns clinic la tratamentul iniţ ial.
In 44 patients with schizophrenia 65 years of age, dosing from 5 to 20 mg/ day was not associated with any distinguishing profile of adverse events.
Olanzapina este indicată tratamentul episoadelor maniacale moderate spre severe. în
However, olanzapine (5-20 mg) demonstrated a comparable safety profile in female (n=467) as in male patients (n=869).
Olanzapina este indicată prevenirea recurenţ la pacienţ cu tulbură bipolare, al că episod maniacal a ră
In renally impaired patients (creatinine clearance < 10 ml/ min) versus healthy subjects, there was no significant difference in mean elimination half-life (37.7 versus 32.4 hr) or clearance (21.2 versus 25.0 l/ hr).
în
82 In smoking subjects with mild hepatic dysfunction, mean elimination half-life (39.3 hr) was prolonged and clearance (18.0 l/ hr) was reduced analogous to non-smoking healthy subjects (48.8 hr and 14.1 l/ hr, respectively).
elor
In non-smoking versus smoking subjects (males and females) the mean elimination half-life was prolonged (38.6 versus 30.4 hr) and the clearance was reduced (18.6 versus 27.7 l/ hr).
ii
The plasma clearance of olanzapine is lower in elderly versus young subjects, in females versus males, and in non-smokers versus smokers.
ri
In a study of Caucasians, Japanese, and Chinese subjects, there were no differences in the pharmacokinetic parameters among the three populations.
ror
Olanzapine is bound predominantly to albumin and α -acid-glycoprotein.
spuns la tratamentul cu olanzapină (vezi pct.
1
5. 1).
Paediatric population Adolescents (ages 13 to 17 years):
Schizofrenie: doza iniţ recomandată olanzapină
The pharmacokinetics of olanzapine are similar between adolescents and adults.
Prevenirea recurenţ în tulburarea bipolarăDoza iniţ recomandată de 10 mg/ zi.
In clinical studies, the average olanzapine exposure was approximately 27% higher in adolescents.
pentru tratamentul episoadelor maniacale, tratamentul de
Demographic differences between the adolescents and adults include a lower average body weight and fewer adolescents were smokers.
prevenire a recă derilor se continuă aceeaşdoză Dacă
Such factors possibly contribute to the higher average exposure observed in adolescents.
apare un nou episod maniacal, mixt sau este necesar) şdacă
5.3 Preclinical safety data
depresiv, tratamentul cu olanzapină