natgillin/translations-raw huggingface dataset:
Sedation (including: hypersomnia, lethargy, somnolence).
Sedare (incluzând hipersomnie, letargie, sedare, somnolenţ Tulbură gastro- intestinale ri Frecvente:
Gastrointestinal disorders Common:
Tulbură hepatobiliare ri
Dry mouth Hepato-biliary disorders Very common:
Foarte frecvente:
Elevations of hepatic transaminases (ALT/ AST; see section 4.4).
Creş ale valorilor transaminazelor hepatice (ALAT/ ASAT, vezi pct.
Investigations Very common:
4. 4). teri Investigaţ diagnostice ii Foarte frecvente:
Decreased total bilirubin, increased GGT, elevated plasma prolactin levels12.
Scă derea valorilor bilirubinei totale, creş terea valorilor GGT, concentraţ plasmatice ii crescute ale prolactinei 12.
9 Weight gain ≥ 7% of baseline body weight (kg) was very common and ≥ 15% of baseline body weight was common.
terea în greutate ≥ faţde masa corporală ială fost foarte frecventăiar creş 9
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.
faţde masa corporală ială fost frecventăÎn cazul expunerii îndelungate (cel puţ 24
Among adolescent patients, mean weight gain was greatest in patients who were overweight or obese at baseline.
să mâni), aproximativ jumă dintre pacienţ adolescenţ avut o creş în greutate ≥15% ş
10 Observed for fasting normal levels at baseline (< 1.016 mmol/ l) which increased to high (≥ 1.467 mmol/ l) and changes in fasting triglycerides from borderline at baseline (≥ 1.016 mmol/ l - < 1.467 mmol/ l) to high (≥ 1.467 mmol/ l).
10 aproape o treime o creş ≥25% faţde masa corporală ialăÎn cadrul pacienţ adolescenţ ă
11 Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/ l) to high (≥ 5.17 mmol/ l) were observed commonly.
11
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.
(≥1, 016 mmol/ l - < 1, 467 mmol/ l) la valori crescute (≥
12 Elevated plasma prolactin levels were reported in 47.4% of adolescent patients.
12 Concentraţ plasmatice crescute ale prolactinei au fost raportate la 47, 4% dintre pacienţ adolescenţ i.
4.9 Overdose
4. 9 Supradozare
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.
Simptomele de supradozare foarte frecvente (incidenţ a > 10%) includ tahicardie, agitaţie/ agresivitate, disartrie, diferite simptome extrapiramidale şnivel de conş ă
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.
S- au raportat
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.
cazuri letale în urma supradozajului acut cu numai 450 mg, dar s- a raportat şsupravieţ supradozaj acut cu 1500 mg.
10 Management of overdose There is no specific antidote for olanzapine.
Nu exista un antidot specific pentru olanzapinăNu se recomandă
Induction of emesis is not recommended.
Se pot lua rsă
Standard procedures for management of overdose may be indicated (i. e. gastric lavage, administration of activated charcoal).
mă surile standard de tratament al intoxicaţ acute (de ex. lavajul gastric, administrarea de carbune iei activat).
The concomitant administration of activated charcoal was shown to reduce the oral bioavailability of olanzapine by 50 to 60%.
Administrarea concomitentă căa rbunelui activat reduce biodisponibilitatea orală a olanzapinei cu 50- 60%.
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.
În funcţ de starea clinicăse va institui tratament simptomatic şmonitorizarea funcţ vitale,
Do not use epinephrine, dopamine, or other sympathomimetic agents with beta- agonist activity since beta stimulation may worsen hypotension.
Este necesară
Cardiovascular monitoring is necessary to detect possible arrhythmias.
unor posibile aritmii.
Close medical supervision and monitoring should continue until the patient recovers.
Supravegherea şmonitorizarea medicală recuperarea pacientului.
PHARMACOLOGICAL PROPERTIES
PROPRIETĂ FARMACOLOGICE TI
5.1 Pharmacodynamic properties
5. 1 Proprietă farmacodinamice ti
Pharmacotherapeutic group: antipsychotics: diazepines, oxazepines and thiazepines, ATC code:
Cod ATC:
N05AH03.
N05AH03
Olanzapine is an antipsychotic, antimanic and mood stabilising agent that demonstrates a broad pharmacologic profile across a number of receptor systems.
Olanzapina este un agent antipsihotic, antimaniacal şstabilizator al dispoziţ cu profil farmacologic larg, ce include mai multe sisteme de receptori.
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.
1
Animal behavioral studies with 1 olanzapine indicated 5HT, dopamine, and cholinergic antagonism, consistent with the receptor- binding profile.
11 Studiile comportamentale cu olanzapină animale au ară că
Olanzapine demonstrated a greater in vitro affinity for serotonin 5HT2 than dopamine D2 receptors and greater 5 HT2 than D2 activity in vivo, models.
serotoninic (5 HT), dopaminic şcolinergic, în concordanţcu profilul afinită faţde receptori.
Electrophysiological studies demonstrated that olanzapine selectively reduced the firing of mesolimbic (A10) dopaminergic neurons, while having little effect on the striatal (A9) pathways involved in motor function.
Olanzapina a micş un ră
Olanzapine reduced a conditioned avoidance response, a test indicative of antipsychotic activity, at doses below those producing catalepsy, an effect indicative of motor side-effects.
activitate antipsihoticăîn doze mai mici decât cele ce produc catalepsie, efect ce indică
Unlike some other antipsychotic agents, olanzapine increases responding in an “ anxiolytic” test.
Spre deosebire de alţ i agenţi antipsihotici, olanzapina determină raspuns crescut un la un test „ anxiolitic “.
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.
oralăunică mg) a avut un grad mai mare de ocupare a receptorilor 5- HT2A, (10
In addition, a SPECT imaging study in schizophrenic patients revealed that olanzapine-responsive patients had lower striatal D2 occupancy than some other antipsychotic- and risperidone-responsive patients, while being comparable to clozapine-responsive patients.
În plus, un studiu de imagisticăSPECT la pacienţ schizofrenie a i cu ară că tat pacienţ responsivi la olanzapină un grad de ocupare a receptorilor striaţD2 mai mic
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.
amelioră superioare, semnificativ statistic, atât pentru simptomele negative, cât şpentru cele pozitive.
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).
La pacienţ cu episod maniacal sau mixt din tulburarile bipolare, olanzapina a demonstrat eficacitate ii superioară ă placebo şfaţde valproatul semisodic (divalproex) în privinţreducerii iă
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.
Olanzapina a demonstrat, de asemenea, 3 ptă
Olanzapine also demonstrated comparable efficacy results to haloperidol in terms of the proportion of patients in symptomatic remission from mania and depression at 6 and 12 weeks.
Într– un studiu de terapie
In a co-therapy study of patients treated with lithium or valproate for a minimum of 2 weeks, the addition
litiu sau valproat, timp de minimum 2 să mâni, i cu
11 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.
olanzapinei 10 mg (în tratament combinat cu litiu sau valproat) a dus, după să mâni de tratament, 6 ptă la o reducere mai mare a simptomelor maniacale, decat în cazul monoterapiei cu litiu sau cu valproat.
In a 12-month recurrence prevention study in manic episode patients who achieved remission on olanzapine and were then randomised to olanzapine or placebo, olanzapine demonstrated statistically significant superiority over placebo on the primary endpoint of bipolar recurrence.
tratament cu olanzapinăş care au fost apoi randomizaţ pe olanzapinăsau placebo, olanzapina a
Olanzapine also showed a statistically significant advantage over placebo in terms of preventing either recur rence into mania or recurrence into depression.
demonstrat o superioritate semnificativăstatistic faţ placebo pe parametrul principal - recurenţ
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).
Olanzapina a demonstrat de asemenea un avantaj semnificativ statistic faţ rii placebo în prevenirea recurenţ episoadelor maniacale sau depresive. elor Într- un al doilea studiu de 12 luni de prevenire a recurenţ episoadelor maniacale la pacienti aflaţ
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.
cu olanzapină i litiu sau valproat nu a fost superior, semnificativ statistic, monoterapiei cu litiu sau valproat în amânarea recurenţ bipolare, definită
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.
în tratamentul schizofreniei (6 să mâni) şal maniei ascociate tulbură bipolare I (3 să mâni), ce
Olanzapine was used as a flexible dose starting with 2.5 and ranging up to 20 mg/ day.
În timpul tratamentului cu olanzapinăadolescenţ au
During treatment with olanzapine, adolescents gained significantly more weight compared with adults.
crescut semnificativ mai mult în greutate faţde adulţ Amplitudinea modifică valorilor
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.
colesterolului total în condiţ de repaus alimentar, a colesterolului LDL, trigliceridelor şprolactinei
There are no data on maintenance of effect and limited data on long term safety (see sections 4.4 and 4.8).
4. 4 ş4. 8) a fost mai mare la adolescenţ
5.2 Pharmacokinetic properties
i decât la adulţ Nu există
Olanzapine is well absorbed after oral administration, reaching peak plasma concentrations within 5 to 8 hours.
4. 4
The absorption is not affected by food.
Olanzapina se absoarbe bine după
Absolute oral bioavailability relative to intravenous administration has not been determined.
Biodisponibilitatea orală
Olanzapine is metabolized in the liver by conjugative and oxidative pathways.
Metabolitul principal circulant este
The major circulating metabolite is the 1 0-N-glucuronide, which does not pass the blood brain barrier.
derivatul 10– N– glucuronid, ce nu trece bariera hematoencefalicăCitocromii P450– CYP1A2 şP450 –
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.
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
The predominant pharmacologic activity is from the parent olanzapine.
Olanzapina,
After oral administration, the mean terminal elimination half-life of olanzapine in healthy subjects varied on the basis of age and gender.
în forma nemodificatăare cea mai mare activitate farmacologicăLa voluntarii să toş după
In healthy elderly (65 and over) versus non-elderly subjects, the mean elimination half-life was prolonged (51.8 versus 33.8 hr) and the clearance was reduced (17.5 versus 18.2 l/ hr).
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
The pharmacokinetic variability observed in the elderly is within the range for the non-elderly.
La 44 de pacienţ schizofrenie în vârstă
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.
peste 65 de ani, dozele între 5 ş20 mg/ zi nu au produs un profil deosebit al reacţ adverse.
In female versus male subjects the mean elimination half life was somewhat prolonged (36.7 versus 32.3 hr) and the clearance was reduced (18.9 versus 27.3 l/ hr).
La subiecţ de sex feminin, în comparaţ cu cei de sex masculin, timpul mediu de înjumă ţ
However, olanzapine (5-20 mg) demonstrated a comparable safety profile in female (n=467) as in male patients (n=869).
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
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).
(clearance- ul creatininei < 10 ml/ min) faţde subiecţ să toş nu
A mass balance study showed that approximately 57% of radiolabelled olanzapine appeared in urine, principally as metabolites.
La subiecţ fumă cu insuficienţhepatică oarătimpul mediu de înjumă ţ ă
12 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).
(39, 3 ore) a fost prelungit şclearance– ul (18 l/ orăa fost redus, în comparaţ cu subiecţ plasmat
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).
eliminare plasmatică fost prelungit (38, 6 ore faţde 30, 4 ore) şclearance– ul a fost redus (18, 6 l/ oră ă
The plasma clearance of olanzapine is lower in elderly versus young subjects, in females versus males, and in non-smokers versus smokers.
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
However, the magnitude of the impact of age, gender, or smoking on olanzapine clearance and half-life is small in comparison to the overall variability between individuals.
clearance– ului ştimpului de injumă ţ este mic, în comparaţ cu variabilitatea individuală generală.
In a study of Caucasians, Japanese, and Chinese subjects, there were no differences in the pharmacokinetic parameters among the three populations.
i caucazieni, japonezi şchinezi, nu au existat diferenţale parametrilor Intr– un stud
The plasma protein binding of olanzapine was about 93% over the concentration range of about 7 to about 1000 ng/ ml.
Legarea olanzapinei de proteinele plasmatice a fost de circa 93% în concentraţ cuprinse între aproximativ 7 ng/ ml şaproximativ 1000 ng/ ml.
Olanzapine is bound predominantly to albumin and α -acid-glycoprotein.
Olanzapina se leagă predominant i α– glicoproteina acidă.
Paediatric population Adolescents (ages 13 to 17 years):
Adolescenţ( vârsta între 13 ş17 ani):
The pharmacokinetics of olanzapine are similar between adolescents and adults.
Farmacocinetica olanzapinei este similară adolescenţş
In clinical studies, the average olanzapine exposure was approximately 27% higher in adolescents.
adulţ În studiile clinice, expunerea medie la olanzapină fost cu aproximativ 27% mai mare la
Demographic differences between the adolescents and adults include a lower average body weight and fewer adolescents were smokers.
adolescenţ Diferenţ demografice dintre adolescenţşadulţinclud o greutate corporală
Such factors possibly contribute to the higher average exposure observed in adolescents.
mică i faptul că puţ adolescenţerau fumă Este posibil ca asemenea factori să
5.3 Preclinical safety data
13 Toxicitate acută doză
Acute (single-dose) toxicity Signs of oral toxicity in rodents were characteristic of potent neuroleptic compounds: hypoactivity, coma, tremors, clonic convulsions, salivation, and depressed weight gain.
Dozele letale ţ scă
The median lethal doses were approximately 210 mg/ kg (mice) and 175 mg/ kg (rats).
oareci) ş175 mg/ kg (ş med
Dogs tolerated single oral doses up to 100 mg/ kg without mortality.
unice de până 100 mg/ kg fă mortalitate.
Clinical signs included sedation, ataxia, tremors, increased heart rate, labored respiration, miosis, and anorexia.
Semnele clinice au inclus sedare, ataxie, tremor, puls
In monkeys, single oral doses up to 100 mg/ kg resulted in prostration and, at higher doses, semi-consciousness.
La maimuţ dozele orale unice de până 100 mg/ kg au
Repeated-dose toxicity In studies up to 3 months duration in mice and up to 1 year in rats and dogs, the predominant effects were CNS depression, anticholinergic effects, and peripheral haematological disorders.
provocat o stare de prostraţ ş la doze mai mari, semiconş a.
Tolerance developed to the CNS depression.
În studii cu durata de până
Growth parameters were decreased at high doses.
trei luni pe ş oareci şde până un
Reversible effects consistent with elevated prolactin in rats included decreased weights of ovaries and uterus and morphologic changes in vaginal epithelium and in mammary gland.
La
Haematologic toxicity:
. tere ş
Effects on haematology parameters were found in each species, including dose-related reductions in circulating leukocytes in mice and non-specific reductions of circulating leukocytes in rats; however, no evidence of bone marrow cytotoxicity was found.
obolani, efectele reversibile concordante cu creşterea prolactinei au inclus reducerea greutăii ovarelor şa uterului şmodifică morfologice ale epiteliului vaginal şale glandei mamare.
Reversible neutropenia, thrombocytopenia, or anemia developed in a few dogs treated with 8 or 10 mg/ kg/ day (total olanzapine exposure [AUC] is 12- to 15-fold greater than that of a man given a 12-mg dose).
La câţ câini trataţ 8 sau 10 mg/ kg pe zi (expunere totală olanzapină ASC -
In cytopenic dogs, there were no adverse effects on progenitor and proliferating cells in the bone marrow.
La câinii citopenici nu s- au evidenţ efecte adverse asupra iat celulelor progenitoare şproliferante din mă
Reproductive toxicity Olanzapine had no teratogenic effects.
Toxicitate asupra funcţ de reproducere iei efecte teratogene.
Sedation affected mating performance of male rats.
reproducerii.
Estrous cycles were affected at doses of 1.1 mg/ kg (3 times the maximum human dose) and reproduction parameters were influenced in rats given 3 mg/ kg (9 times the maximum human dose).
Ciclurile estrale au fost afectate la doze de 1, 1 mg/ kg (de 3 ori mai mari decât doza maximă om), iar parametrii de reproducere au fost influenţ i la ş
In the offspring of rats given olanzapine, delays in fetal development and transient decreases in offspring activity levels were seen.
Mutagenicitate Olanzapina nu a fost mutagenă clastogenă întreaga gamă teste standard, ce a inclus teste de
13 Mutagenicity Olanzapine was not mutagenic or clastogenic in a full range of standard tests, which included bacterial mutation tests and in vitro and in vivo mammalian tests.
mutaţ bacteriene şteste in vitro şin vivo la mamifere.
Carcinogenicity Based on the results of studies in mice and rats, it was concluded that olanzapine is not carcinogenic.
Carcinogenitate Pe baza rezultatelor studiilor pe ş oareci şş i obolani, s– a dovedit căolanzapina nu este carcinogenă.
PHARMACEUTICAL PARTICULARS
PROPRIETĂ FARMACEUTICE TI
Lactose monohydrate Powdered cellulose Pregelatinised maize starch Maize starch Colloidal anhydrous silica Magnesium stearate
Monohidrat de lactoză Pulbere de celuloză Amidon din porumb - pregelatinizat Amidon din porumb Siliciu coloidal anhidru Stearat de magneziu
6.2 Incompatibilities
ţ 6. 2 Incompatibilităi
6.4 Special precautions for storage
14 6. 4 Precauţ speciale pentru pă
This medicinal product does not require any special storage conditions.
Nu este cazul.
6.5 Nature and contents of container
Natura şconţ 6. 5
Blister pack (OPA/ Al/ PVC, Al-foil):
inutul ambalajului
14, 28, 35, 56 or 70 tablets in a box.
Blistere (OPA/ Al/ PVC, folie de Al): cutie cu 14, 28, 35, 56 sau 70 comprimate.
Not all pack sizes may be marketed.
Potenţ nu sunt disponibile toate formele farmaceutice. ial,
Any unused product or waste material should be disposed of in accordance with local requirements.
Produsele neutilizate şresturile de materiale se vor îndepă conform legislaţ în vigoare.
MARKETING AUTHORISATION HOLDER
DEŢINĂTORUL AUTORIZAŢ DE PUNERE PE PIAŢ IEI
8.
Ă 8.
MARKETING AUTHORISATION NUMBER(S)
NUMĂRUL AUTORIZAŢ DE PUNERE PE PIAŢ IEI
27 September 2007.
Data primei autoriză 27 Septembrie 2007. ri:
14 Detailed information on this product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu
Medicamentului (EMEA) http: // www. emea. europa. eu
Each tablet contains 5 mg olanzapine.
Fiecare comprimat conţ 5 mg olanzapină
Each tablet contains 80.9 mg lactose.
Fiecare comprimat conţ 80, 9 mg lactoză
Tablets are round, slightly biconvex, slightly yellow tablets with possible individual yellow spots and an inscription “ 5”.
ionate “ 5 ”.
16 Olanzapine can be given without regards for meals as absorption is not affected by food.
16 indiferent de orarul meselor, deoarece absorbţ medicamentului nu este afectată alimente.
During antipsychotic treatment, improvement in the patient's clinical condition may take several days to some weeks.
În timpul tratamentului antipsihotic, ameliorarea stă clinice a pacientului poate să
17 with olanzapine compared to patients treated with placebo (1.3% vs.
17 EACV la pacienţ trataţ olanzapină
18 Neutropenia Caution should be exercised in patients with low leukocyte and/ or neutrophil counts for any reason, in patients receiving medicines known to cause neutropenia, in patients with a history of drug-induced bone marrow depression/ toxicity, in patients with bone marrow depression caused by concomitant illness, radiation therapy or chemotherapy and in patients with hypereosinophilic conditions or with myeloproliferative disease.
4. 8).
19 Lactose Zalasta tablets contain lactose.
19
Therapeutic monitoring of valproate plasma levels did not indicate that valproate dosage adjustment is required after the introduction of concomitant olanzapine.
Monitorizarea terapeutică concentraţ plasmatice ale valproatului nu a indicat necesitatea unei