natgillin/translations-raw huggingface dataset:
The pharmacokinetic variability observed in the elderly is within the range for the non-elderly.
Variabilitatea farmacocinetic observat la vârstnici se încadreaz în domeniul de varia ie pentru subiec ii mai tineri.
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.
La 44 pacien i cu schizofrenie cu vârsta > 65 ani, dozele între 5 i 20 mg/ zi nu s- au asociat cu un profil remarcabil al evenimentelor adverse.
In female versus male subjects the mean elimination half life was somewhat prolonged (36.7 versus 32.3 hrs) and the clearance was reduced (18.9 versus 27.3 l/ hr).
La subiec ii de sex feminin comparativ cu cei de sex masculin, timpul mediu de înjum t ire plasmatic prin eliminare a fost ceva mai lung (36, 7 ore comparativ cu 32, 3 ore) i clearance- ul a fost
However, olanzapine (5-20 mg) demonstrated a comparable safety profile in female (n=467) as in male patients (n=869).
Cu toate acestea, olanzapina (5- 20 mg/ zi) a demonstrat un profil de siguran comparabil la femei (n=467) i la barba i (n=869).
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).
La pacien ii cu insuficien renal (clearance- ul creatininei < 10 ml/ min) comparativ cu subiec ii s n to i, nu au existat diferen e semnificative privind timpul mediu de înjum t ire plasmatic prin eliminare (37, 7 ore comparativ cu 32, 4 ore) sau clearance- ul medicamentului (21, 2 l/ or comparativ cu 25, 0 l/ or).
A mass balance study showed that approximately 57% of radiolabelled olanzapine appeared in urine, principally as metabolites.
Într- un studiu de echilibru al maselor (aport/ excre ie) s- a eviden iat c aproximativ 57% din olanzapina marcat radioactiv s- a reg sit în urin, în principal ca metaboli i.
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).
La subiec i fum tori cu insuficien hepatic u oar, timpul mediu de înjum t ire plasmatic prin eliminare (39, 3 ore) a fost prelungit i clearance- ul (18, 0 l/ or) a fost redus comparativ cu subiec ii s n to i nefum tori (48, 8 ore, respectiv 14, 1 l/ or).
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).
La subiec ii nefum tori, comparativ cu cei fum tori (b rba i i femei), timpul mediu de înjum t ire plasmatic prin eliminare a fost prelungit (38, 6 ore comparativ cu 30, 4 ore) i clearance- ul a fost redus (18, 6 l/ or comparativ cu 27, 7 l/ or).
However, the magnitude of the impact of age, gender, or
Clearance- ul plasmatic al olanzapinei este mai mic la subiec ii vârstnici comparativ cu cei tineri, la femei comparativ cu b rba i i la nefum tori comparativ cu fum tori.
13 smoking on olanzapine clearance and half-life is small in comparison to the overall variability between individuals.
Cu toate acestea, importan a impactului vârstei, sexului sau fumatului asupra clearance- ului i timpului de înjum t ire plasmatic este mic în compara ie cu variabilitatea interindividual general.
In a study of Caucasians, Japanese, and Chinese subjects, there were no differences in the pharmacokinetic parameters among the three populations.
Într- un studiu la subiec i caucazieni, japonezi i chinezi, nu au existat diferen e ale parametrilor farmacocinetici între cele trei popula ii.
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 aproximativ 93% în intervalul concentra iilor cuprinse între aproximativ 7 ng/ ml i aproximativ 1000 ng/ ml.
Olanzapine is bound predominantly to albumin and α 1-acid-glycoprotein.
Olanzapina se leag predominant de albumin i de 1- glicoproteina acid.
Paediatric population Adolescents (ages 13 to 17 years):
Popula ie pediatric Adolescen i (vârsta între 13 i 17 ani):
The pharmacokinetics of olanzapine are similar between adolescents and adults.
Farmacocinetica olanzapinei este similar la adolescen i i adul i.
In clinical studies, the average olanzapine exposure was approximately 27% higher in adolescents.
În studiile clinice, expunerea medie la olanzapin a fost cu aproximativ 27% mai mare la adolescen i.
Demographic differences between the adolescents and adults include a lower average body weight and fewer adolescents were smokers.
Diferen ele demografice dintre adolescen i i adul i includ o greutate corporal medie mai mic i faptul c mai pu ini adolescen i erau fum tori.
Such factors possibly contribute to the higher average exposure observed in adolescents.
Este posibil ca asemenea factori s contribuie la o expunere medie mai mare observat în rândul adolescen ilor.
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.
Toxicitate acut (dup doz unic) Semnele de toxicitate oral la roz toare au fost cele caracteristice pentru neurolepticele cu poten mare: hipoactivitate, com, tremor, convulsii clonice, saliva ie i pierdere în greutate.
The median lethal doses were approximately 210 mg/ kg (mice) and 175 mg/ kg (rats).
Dozele letale medii au fost de aproximativ 210 mg/ kg (oarece) i de 175 mg/ kg (obolan).
Dogs tolerated single oral doses up to 100 mg/ kg without mortality.
Câinii au tolerat doze orale unice de pân la 100 mg/ kg f r mortalitate.
Clinical signs included sedation, ataxia, tremors, increased heart rate, labored respiration, miosis, and anorexia.
Semnele clinice au inclus sedare, ataxie, tremor, frecven cardiac crescut, respira ie dificil, mioz i anorexie.
In monkeys, single oral doses up to 100 mg/ kg resulted in prostration and, at higher doses, semi-consciousness.
La maimu e, doze orale unice de pân la 100 mg/ kg au provocat o stare de prostra ie i, la doze mai mari, semicon tien.
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.
Toxicitate dup doze repetate În studii cu durata de pân la 3 luni la oarece i de pân la 1 an la obolan i câine, efectele predominante au fost deprimarea SNC, efecte anticolinergice i tulbur ri hematologice periferice.
Tolerance developed to the CNS depression.
Ca efect al deprim rii SNC se dezvolt toleran a.
Growth parameters were decreased at high doses.
La doze mari, parametrii de cre tere au fost sc zu i.
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 obolan, efectele reversibile concordante cu cre terea prolactinei au inclus reducerea greut ii ovarelor i a uterului i modific ri morfologice ale epiteliului vaginal i glandei mamare.
Haematologic toxicity:
Toxicitate hematologic:
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.
La câ iva câini trata i cu 8 sau
Reversible neutropenia, thrombocytopenia, or anemia developed in a few dogs treated with 8 or 10 mg/ kg/ day (total olanzapine exposure [area under the curve] is 12- to 15-fold greater than that of a man given a 12-mg dose).
14 10 mg/ kg i zi (expunere total la olanzapin [ASC] de 12- 15 ori mai mare decât pentru doza de 12 mg/ zi la om) s- au dezvoltat neutropenie, trombocitopenie sau anemie reversibile.
In cytopenic dogs, there were no adverse effects on progenitor and proliferating cells in the bone marrow.
La câinii cu citopenie nu au existat reac ii adverse asupra celulelor progenitoare i proliferante din m duva osoas.
Sedation affected mating performance of male rats.
La obolani masculi sedarea a afectat performan a func iei de reproducere.
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).
Perioada fertil a fost afectat la doze de 1, 1 mg/ kg (de 3 ori mai mari decât doza maxim la om), iar parametrii de reproducere au fost influen a i la obolanii c rora li s- au administrat 3 mg/ kg (de 9 ori doza maxim la om).
In the offspring of rats given olanzapine, delays in fetal development and transient decreases in offspring activity levels were seen.
La puii femelelor de obolan trata i cu olanzapin s- au observat întârzieri ale dezvolt rii fetale i reduceri tranzitorii ale activit ii puilor.
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.
Mutagenitate Olanzapina nu a prezentat poten ial mutagen sau clastogen în întreaga gam de teste standard, care au inclus teste de muta ii bacteriene i teste in vitro i in 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 la oarece i obolan, s- a concluzionat c olanzapina nu este carcinogen.
Gelatin Mannitol (E421) Aspartame (E951) Sodium methyl parahydroxybenzoate (E219) Sodium propyl parahydroxybenzoate (E217)
Gelatin Manitol (E421) Aspartam (E951) Metil parahidroxibenzoat de sodiu (E219) Propil parahidroxibenzoat de sodiu (E217)
Store in the original package in order to protect from light and moisture.
A se p stra în ambalajul original pentru a fi protejat de lumin
Aluminium blister strips in cartons of 28, 35, 56 or 70 orodispersible tablets per carton.
Benzi de blistere de aluminiu, în cutii de carton a 28, 35, 56 sau 70 comprimate orodispersabile pe cutie.
3 February 2000 Date of latest renewal:
3 Februarie 2000 Data ultimei reînnoiri a autoriza iei:
Each orodispersible tablet contains 10 mg olanzapine.
Fiecare comprimat orodispersabil con ine 10 mg olanzapin.
Each orodispersible tablet contains 0.80 mg aspartame, 0.15 mg sodium methyl parahydroxybenzoate, 0.05 mg sodium propyl parahydroxybenzoate.
Fiecare comprimat orodispersabil con ine aspartam 0, 80 mg, metil parahidroxibenzoat de sodiu 0, 15 mg, propil parahidroxibenzoat de sodiu 0, 05 mg.
16 appropriate clinical reassessment and should generally occur at intervals of not less than 24 hours.
17 reevaluarea clinic adecvat i nu trebuie realizat, în general, la intervale mai mici de 24 ore.
4.4 Special warnings and precautions for use
18 4. 4 Aten ion ri i precau ii speciale pentru utilizare
17 Dementia-related psychosis and/ or behavioural disturbances Olanzapine is not approved for the treatment of dementia-related psychosis and/ or behavioural disturbances and is not recommended for use in this particular group of patients because of an increase in mortality and the risk of cerebrovascular accident.
Psihoza asociat demen ei i/ sau alte tulbur ri de comportament Olanzapina nu este autorizat pentru a fi utilizat în tratamentul psihozelor asociate demen ei i/ sau tulbur rilor de comportament asociate demen ei i nu se recomandat la acest grup particular de pacien i din cauza cre terii mortalit ii i a riscului de accident cerebrovascular.
Lipid alterations Undesirable alterations in lipids have been observed in olanzapine-treated patients in placebo- controlled clinical trials (see section 4.8).
19 Alter ri ale lipidelor În studiile clinice controlate placebo s- au observat alter ri nedorite ale lipidelor în rândul pacien ilor trata i cu olanzapin (vezi pct.
18 Anticholinergic activity While olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical trials revealed a low incidence of related events.
Activitate anticolinergic Cu toate c olanzapina a demonstrat activitate anticolinergic in vitro, experien a din studiile clinice a eviden iat o frecven mic a evenimentelor legate de aceast ac iune.
Seizures Olanzapine should be used cautiously in patients who have a history of seizures or are subject to factors which may lower the seizure threshold.
20 Convulsii Olanzapina trebuie utilizat cu pruden la pacien ii cu antecedente convulsive sau la cei expu i unor factori care pot s scad pragul convulsivant.
19 Tardive Dyskinesia In comparator studies of one year or less duration, olanzapine was associated with a statistically significant lower incidence of treatment emergent dyskinesia.
Diskinezie tardiv În studiile comparative cu durat de un an sau mai pu in, olanzapina s- a asociat cu o frecven mai mic, semnificativ statistic, a diskineziei iatrogene.
20 Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have not been found to significantly affect the pharmacokinetics of olanzapine.
S- a constatat c fluoxetina (un inhibitor al CYP2D6), dozele unice de antiacide (aluminiu, magneziu) sau cimetidina nu afecteaz semnificativ farmacocinetica olanzapinei.
Mean infant exposure (mg/ kg) at steady state was estimated to be 1.8% of the maternal olanzapine dose (mg/ kg) Patients should be advised not to breast-feed an infant if they are taking olanzapine.
Pacientelor trebuie s li se recomande s nu al pteze în timpul tratamentului cu olanzapin.
4.8 Undesirable effects
22 4. 8 Reac ii adverse
21 transient asymptomatic elevations of hepatic transaminases (see section 4.4), rash, asthenia, fatigue and oedema.
4. 4), glucozuria, cre terea apetitului alimentar, ame eala, akatizia, parkinsonismul (vezi pct.
Orthostatic hypotension
23 Tulbur ri vasculare
22 Hepato-biliary disorders
Cre teri tranzitorii, asimptomatice ale transaminazelor hepatice (ALAT, ASAT), în special la ini ierea tratamentului (vezi pct.
5 Observed for fasting normal levels at baseline (< 1.69 mmol/ l) which increased to high (2.26 mmol/ l).
24 5 Observat pentru valori ini iale normale à jeun (< 1, 69 mmol/ l) care au atins valori crescute (2, 26 mmol/ l).
23 7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been reported when olanzapine is stopped abruptly.
7 Simptome acute precum transpira ii, insomnie, tremor, anxietate, grea atunci când olanzapina a fost întrerupt brusc.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
25 fost mai mari în cazul expunerii îndelungate (cel pu in 24 s pt mâni) decât în cazul expunerilor de scurt durat.
The frequency terms listed are defined as follows:
În cadrul fiec rei grupe de frecven, reac iile adverse sunt prezentate în ordinea descresc toare a gravit ii.
Very common (10%), common (1% and < 10%).
Frecven a evenimentelor listate este definit dup cum urmeaz: foarte frecvente (≥10%), frecvente (≥1% i < 10%).
24 Metabolism and nutrition disorders Very common:
Tulbur ri metabolice i de nutri ie Foarte frecvente:
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.
26 Trebuie instituit tratament simptomatic i monitorizarea func iilor vitale în func ie de starea clinic, incluzând tratamentul hipotensiunii arteriale i a colapsului circulator i sus inerea func iei respiratorii.
In a co-therapy study of patients treated with lithium or valproate for a minimum of 2 weeks, the addition 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.
27 valproat) a determinat, dup 6 s pt mâni, o reducere mai mare a simptomelor maniacale decât în cazul monoterapiei cu litiu sau cu valproat.
26 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.
Într- un studiu de tratament asociat, cu durata de 18 luni, la pacien i cu episoade maniacale sau mixte stabiliza i cu olanzapin i un stabilizator de dispozi ie (litiu sau valproat), asocierea de lung durat dintre olanzapin i litiu sau valproat nu a fost semnificativ statistic superioar monoterapiei cu litiu sau valproat în întârzierea recuren ei tulbur rii bipolare, definit conform criteriilor diagnostice.
27 smoking on olanzapine clearance and half-life is small in comparison to the overall variability between individuals.
Cu toate acestea, importan a impactului vârstei, sexului sau fumatului asupra clearance- ului i timpului de înjum t ire plasmatic este mic în compara ie cu variabilitatea interindividual general.
Reversible neutropenia, thrombocytopenia, or anemia developed in a few dogs treated with 8 or 10 mg/ kg/ day (total olanzapine exposure [area under the curve] is 12- to 15-fold greater than that of a man given a 12-mg dose).
29 10 mg/ kg i zi (expunere total la olanzapin [ASC] de 12- 15 ori mai mare decât pentru doza de 12 mg/ zi la om) s- au dezvoltat neutropenie, trombocitopenie sau anemie reversibile.
Store in the original package in order to protect from light and moisture.
A se p stra în ambalajul original pentru a proteja de lumin
Aluminium blister strips in cartons of 28, 35 56, or 70 orodispersible tablets per carton.
Benzi de blistere de aluminiu, în cutii de carton a 28, 35, 56 sau 70 comprimate orodispersabile per cutie.
Each orodispersible tablet contains 15 mg olanzapine.
Fiecare comprimat orodispersabil con ine 15 mg olanzapin.
Each orodispersible tablet contains 1.20 mg aspartame, 0.225 mg sodium methyl parahydroxybenzoate, 0.075 mg sodium propyl parahydroxybenzoate.
Fiecare comprimat orodispersabil con ine aspartam 1, 20 mg, metil parahidroxibenzoat de sodiu 0, 225 mg, propil parahidroxibenzoat de sodiu 0, 075 mg.
30 appropriate clinical reassessment and should generally occur at intervals of not less than 24 hours.
32 reevaluarea clinic adecvat i nu trebuie realizat, în general, la intervale mai mici de 24 ore.
4.4 Special warnings and precautions for use
33 4. 4 Aten ion ri i precau ii speciale pentru utilizare
31 Dementia-related psychosis and/ or behavioural disturbances Olanzapine is not approved for the treatment of dementia-related psychosis and/ or behavioural disturbances and is not recommended for use in this particular group of patients because of an increase in mortality and the risk of cerebrovascular accident.
Psihoza asociat demen ei i/ sau alte tulbur ri de comportament Olanzapina nu este autorizat pentru a fi utilizat în tratamentul psihozelor asociate demen ei i/ sau tulbur rilor de comportament asociate demen ei i nu se recomandat la acest grup particular de pacien i din cauza cre terii mortalit ii i a riscului de accident cerebrovascular.
Lipid alterations Undesirable alterations in lipids have been observed in olanzapine-treated patients in placebo- controlled clinical trials (see section 4.8).
34 Alter ri ale lipidelor În studiile clinice controlate placebo s- au observat alter ri nedorite ale lipidelor în rândul pacien ilor trata i cu olanzapin (vezi pct.
32 Anticholinergic activity While olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical trials revealed a low incidence of related events.
Activitate anticolinergic Cu toate c olanzapina a demonstrat activitate anticolinergic in vitro, experien a din studiile clinice a eviden iat o frecven mic a evenimentelor legate de aceast ac iune.
Seizures Olanzapine should be used cautiously in patients who have a history of seizures or are subject to factors which may lower the seizure threshold.
35 Convulsii Olanzapina trebuie utilizat cu pruden la pacien ii cu antecedente convulsive sau la cei expu i unor factori care pot s scad pragul convulsivant.
33 Tardive Dyskinesia In comparator studies of one year or less duration, olanzapine was associated with a statistically significant lower incidence of treatment emergent dyskinesia.
Diskinezie tardiv În studiile comparative cu durat de un an sau mai pu in, olanzapina s- a asociat cu o frecven mai mic, semnificativ statistic, a diskineziei iatrogene.
4.5 Interaction with other medicaments and other forms of interaction
4. 5 Interac iuni cu alte medicamente i alte forme de interac iune
34 Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have not been found to significantly affect the pharmacokinetics of olanzapine.
S- a constatat c fluoxetina (un inhibitor al CYP2D6), dozele unice de antiacide (aluminiu, magneziu) sau cimetidina nu afecteaz semnificativ farmacocinetica olanzapinei.
4.8 Undesirable effects
37 4. 8 Reac ii adverse
35 transient asymptomatic elevations of hepatic transaminases (see section 4.4), rash, asthenia, fatigue and oedema.
4. 4), glucozuria, cre terea apetitului alimentar, ame eala, akatizia, parkinsonismul (vezi pct.
Orthostatic hypotension
38 Tulbur ri vasculare
36 Hepato-biliary disorders
Cre teri tranzitorii, asimptomatice ale transaminazelor hepatice (ALAT, ASAT), în special la ini ierea tratamentului (vezi pct.
5 Observed for fasting normal levels at baseline (< 1.69 mmol/ l) which increased to high (2.26 mmol/ l).
39 5 Observat pentru valori ini iale normale à jeun (< 1, 69 mmol/ l) care au atins valori crescute (2, 26 mmol/ l).
37 7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been reported when olanzapine is stopped abruptly.
7 Simptome acute precum transpira ii, insomnie, tremor, anxietate, grea atunci când olanzapina a fost întrerupt brusc.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
40 fost mai mari în cazul expunerii îndelungate (cel pu in 24 s pt mâni) decât în cazul expunerilor de scurt durat.
38 Metabolism and nutrition disorders Very common:
Tulbur ri metabolice i de nutri ie Foarte frecvente:
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.
41 Trebuie instituit tratament simptomatic i monitorizarea func iilor vitale în func ie de starea clinic, incluzând tratamentul hipotensiunii arteriale i a colapsului circulator i sus inerea func iei respiratorii.
In a co-therapy study of patients treated with lithium or valproate for a minimum of 2 weeks, the addition 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.
42 valproat) a determinat, dup 6 s pt mâni, o reducere mai mare a simptomelor maniacale decât în cazul monoterapiei cu litiu sau cu valproat.
40 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.
Într- un studiu de tratament asociat, cu durata de 18 luni, la pacien i cu episoade maniacale sau mixte stabiliza i cu olanzapin i un stabilizator de dispozi ie (litiu sau valproat), asocierea de lung durat dintre olanzapin i litiu sau valproat nu a fost semnificativ statistic superioar monoterapiei cu litiu sau valproat în întârzierea recuren ei tulbur rii bipolare, definit conform criteriilor diagnostice.
41 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 subiec ii vârstnici comparativ cu cei tineri, la femei comparativ cu b rba i i la nefum tori comparativ cu fum tori.