natgillin/translations-raw huggingface dataset:
The median lethal doses were approximately 210 mg/ kg (mice) and 175 mg/ kg (rats).
trebuie continuat (cu ajustarea dozelor dacă
Dogs tolerated single oral doses up to 100 mg/ kg without mortality.
starea clinică impune, se suplimentează dispoziţ ie.
Clinical signs included sedation, ataxia, tremors, increased heart rate, labored respiration, miosis, and anorexia.
pentru tratamentul simptomelor modifică de ia,
In monkeys, single oral doses up to 100 mg/ kg resulted in prostration and, at higher doses, semi-consciousness.
În cursul tratamentului schizofreniei, episoadelor maniacale şprevenirii recurenţ din tulbură
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.
bipolare, doza zilnică poate fi ajustată funcţ de starea clinică
Tolerance developed to the CNS depression.
individuală în intervalul 5– 20 mg/ zi., ş
Growth parameters were decreased at high doses.
Creş terea dozei peste cea iniţ recomandată indicată
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.
este
Haematologic toxicity:
numai după evaluare clinică o
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.
Olanzapina se poate administra, indiferent de orarul meselor, deoarece absorbţ medicamentului nu este afectată alimente.
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).
Întreruperea tratamentului cu olanzapină face prin reducerea gradată dozei.
In cytopenic dogs, there were no adverse effects on progenitor and proliferating cells in the bone marrow.
Olanzapina nu este recomandata pentru utilizare la copii şadolescenţ vârsta sub 18 ani datorită
Reproductive toxicity Olanzapine had no teratogenic effects.
lipsei datelor privind siguranţşeficacitatea.
Sedation affected mating performance of male rats.
În studiile clinice pe termen scurt, la pacienţ
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).
adolescenţs- a raportat o amplitudine mai mare a creş în greutate, a alteră profilului lipidicş
In the offspring of rats given olanzapine, delays in fetal development and transient decreases in offspring activity levels were seen.
4. 4, 4. 8, 5. 1 ş5. 2). prolactinemiei decât în studiile la pacienţ
83 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.
Nu este indicată folosirea de rutină unei doze iniţ scă (5mg/ zi), dar aceasta trebuie luată
Carcinogenicity Based on the results of studies in mice and rats, it was concluded that olanzapine is not carcinogenic.
considerare la pacienţ în vârstă 65 de ani sau mai mult, atunci când factorii clinici o justifică pct 4. 4).
PHARMACEUTICAL PARTICULARS
Pacienţ cu afecţ renale ş
6.1 List of excipients
La aceş pacienţ
Lactose monohydrate Powdered cellulose Pregelatinised maize starch Maize starch Colloidal anhydrous silica Magnesium stearate
În caz de insuficienţ în ială zută clasa Child– Pugh A sau B), doza iniţ va fi de 5 mg şpoate fi crescută
6.2 Incompatibilities
moderată (ciroză
Not applicable.
cu precauţ ie.
6.3 Shelf life
modificarea dozei iniţ iale.
2 years.
Fumatori
6.4 Special precautions for storage
La nefumatori, în comparaţ cu fumatorii, nu este necesară
This medicinal product does not require any special storage conditions.
modificarea dozei iniţ iale.
6.5 Nature and contents of container
In cazul prezenţ mai multor factori ce pot determina metabolizarea mai lentă medicamentului (sex
Blister pack (OPA/ Al/ PVC, Al-foil):
feminin, vârstăînaintatănefumator), se va lua în considerare scă
14, 28, 35, 56 or 70 tablets in a box.
derea dozei iniţ În funcţ de iale. ie
Not all pack sizes may be marketed.
terea dozelor se va face cu prudenţ( vezi cap 4. 5 ş5. 2.). ă
6.6 Special precautions for disposal
necesită terapeutice, creş
Any unused product or waste material should be disposed of in accordance with local requirements.
Hipersensibilitate la substanţactivă la oricare dintre ingredienţ produsului.
7.
ii
MARKETING AUTHORISATION HOLDER
Atenţ ri şprecauţ speciale pentru utilizare 4. 4
KRKA, d. d., Novo mesto, Š marješ cesta 6, 8501 Novo mesto, Slovenia ka
În timpul tratamentului antipsihotic, ameliorarea stă clinice a pacientului poate să
8.
rii
MARKETING AUTHORISATION NUMBER(S)
necesite câteva
EU/ 1/ 07/ 415/ 027-031
zile până câteva să mâni.
DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION
ei i/ sau alte tulbură de comportament ri pentru a fi utilizată tratamentul psihozelor ş tulbură de
Date of first authorisation:
Olanzapina nu este autorizată
27 September 2007.
în i/ sau
84 10.
rilor
DATE OF REVISION OF THE TEXT
comportament asociate demenţ şnu se recomandată acest grup special de pacienţ deoarece
Detailed information on this product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu
În studii clinice controlate ţi creş cu placebo (cu o durată 6- 12 să mâni) la pacienţvârstnici (vârsta medie 78 ani) cu psihoze ş
85 1.
tere
NAME OF THE MEDICINAL PRODUCT
la pacienţ trataţ olanzapină
Zalasta 5 mg orodispersible tablets
comparativ cu cei la care s- a administrat placebo (3, 5%, respectiv
Each orodispersible tablet contains 5 mg olanzapine.
Incidenţcrescută deceselor nu a fost asociată doza de olanzapină
Excipient:
administrată (doza
Each orodispersible tablet contains 0.50 mg aspartame.
medie zilnică mg) sau cu durata tratamentului.
For a full list of excipients, see section 6.1.
terea mortalită includ vârsta > 65 ani, disfagia, sedarea, malnutriţ ş ţ
PHARMACEUTICAL FORM
deshidratarea, afecţ
Orodispersible tablet.
etiologie) sau
Tablets are round, slightly biconvex, yellow marbled tablets with possible individual spots.
Cu toate acestea, independent de factorii de risc a enumeraţ incidenţdeceselor a fost mai mare în rândul pacienţ trataţ olanzapină
4.
i,
CLINICAL PARTICULARS
comparativ
4.1 Therapeutic indications
cu cei la care s- a administrat placebo.
Adults Olanzapine is indicated for the treatment of schizophrenia.
S- a înregistrat o creş de 3 ori a tere EACV la pacienţ trataţ olanzapină
Olanzapine is effective in maintaining the clinical improvement during continuation therapy in patients who have shown an initial treatment response.
comparativ cu cei la care s- a administrat placebo (1, 3%,
Olanzapine is indicated for the treatment of moderate to severe manic episode.
Toţ
In patients whose manic episode has responded to olanzapine treatment, olanzapine is indicated for the prevention of recurrence in patients with bipolar disorder (see section 5.1).
prezentat evenimente adverse cerebrovasculare aveau factori de risc pre- existenţ Vârsta > 75 ani ş demenţde tip vascular/ mixtă fost identificaţ factori de risc asociaţ
4.2 Posology and method of administration
i tratamentului cu olanzapină
Adults Schizophrenia:
pentru apariţ EACV.
The recommended starting dose for olanzapine is 10 mg/ day.
În aceste studii clinice nu s- a stabilit eficacitatea olanzapinei. ia
Manic episode:
Boala Parkinson Nu se recomandă
The starting dose is 15 mg as a single daily dose in monotherapy or 10 mg daily in combination therapy (see section 5.1).
utilizarea olanzapinei în tratamentul psihozei asociate cu agoniş dopaminergici la tii
The recommended starting dose is 10 mg/ day.
pacienţ cu boala Parkinson.
For patients who have been receiving olanzapine for treatment of manic episode, continue therapy for preventing recurrence at the same dose.
În studiile clinice, s- a raportat foarte frecvent şmai frecvent decât cu
If a new manic, mixed, or depressive episode occurs, olanzapine treatment should be continued (with dose optimisation as needed), with supplementary therapy to treat mood symptoms, as clinically indicated.
agravarea simptomatologiei parkinsoniene şa halucinaţ (vezi ş4. 8 Reacţ i iilor
During treatment for schizophrenia, manic episode and recurrence prevention in bipolar disorder, daily dosage may subsequently be adjusted on the basis of individual clinical status within the range 5- 20 mg/ day.
olanzapina nu a fost mai eficace decât placebo în tratamentul simptomelor psihotice.
An increase to a dose greater than the recommended starting dose is advised only after appropriate clinical reassessment and should generally occur at intervals of not less than 24 hours.
În aceste studii clinice, iniţ a fost necesar ca pacienţ să stabili la cea mai mică
86 Olanzapine can be given without regards for meals as absorption is not affected by food.
(agonist dopaminergic) şsă mână aceleaşmedicaţ şdoze de antiparkinsoniană
Gradual tapering of the dose should be considered when discontinuing olanzapine.
S- a iniţ administrarea de olanzapină o doză
Zalasta orodispersible tablet should be placed in the mouth, where it will rapidly disperse in saliva, so it can be easily swallowed.
2, 5 mg/ zi care a fost crescută treptat până maxim 15 mg/ zi, în funcţ de aprecierea investigatorului.
Removal of the intact orodispersible tablet from the mouth is difficult.
SNM este o afecţ care pune viaţîn pericol, asociată medicaţ antipsihotică Cazuri rare
Since the orodispersible tablet is fragile, it should be taken immediately on opening the blister.
raportate ca SNM au fost, de asemenea, asociate cu tratamentul cu olanzapinăManifestă clinice
Alternatively, it may be dispersed in a full glass of water immediately before administration.
ale SNM sunt hiperpirexie, rigiditate muscularăalterarea stă mintale şsemne de instabilitate
Olanzapine orodispersible tablet is bioequivalent to olanzapine tablets, with a similar rate and extent of absorption.
ş vegetativă (puls neregulat sau oscilaţ tensionale, tahicardie, diaforeză i disritmii cardiace).
It has the same dosage and frequency of administration as olanzapine tablets.
inexplicabilă ră manifestă clinice ale SNM, toate medicamentele antipsihotice, inclusiv
Olanzapine orodispersible tablets may be used as an alternative to olanzapine tablets.
olanzapina, trebuie întrerupte.
Children and adolescents Olanzapine is not recommended for use in children and adolescents below 18 years of age due to a lack of data on safety and efficacy.
Hiperglicemie şdiabet zaharat i Rar s– au raportat hiperglicemie ş i/ sau apariţ sau agravarea diabetului, asociate ocazional cu ia ţ cetoacidoza sau coma, inclusiv cazuri letale (vezi pct.
A greater magnitude of weight gain, lipid and prolactin alterations has been reported in short term studies of adolescent patients than in studies of adult patients (see sections 4.4, 4.8, 5.1 and 5.2).
Se recomandămonitorizarea adecvatăîn special la pacienţ diabetici şla cei cu factori de risc de apariţ a diabetului cl
Elderly A lower starting dose (5 mg/ day) is not routinely indicated but should be considered for those 65 and over when clinical factors warrant (see also section 4.4).
Alteră ale profilului lipidic ri În studiile clinice placebo- controlate, la pacienţ în tratament cu olanzapină apă modifică ale
Renal and/ or hepatic impairment A lower starting dose (5 mg) should be considered for such patients.
Alteră lipidelor trebuie să controlate după
In cases of moderate hepatic insufficiency (cirrhosis, Child-Pugh Class A or B), the starting dose should be 5 mg and only increased with caution.
de vedere clinic, în special la pacienţ cu dislipidemii precum şla pacienţ cu factori de risc pentru apariţ tulbură lipidice. ia rilor
Gender The starting dose and dose range need not be routinely altered for female patients relative to male patients.
Cu toate că olanzapina a demonstrat activitate anticolinergică vitro, experienţdin studiile clinice a
Smokers The starting dose and dose range need not be routinely altered for non-smokers relative to smokers.
Cu toate acestea, deoarece
When more than one factor is present which might result in slower metabolism (female gender, geriatric age, non-smoking status), consider ation should be given to decreasing the starting dose.
experienţclinică olanzapină pacienţ cu boli asociate este limitatăse recomandă
Dose escalation, when indicated, should be conservative in such patients.
prescrierea medicamentului la pacienţ cu hipertrofie de prostatăileus paralitic şafecţ înrudite.
In cases where dose increments of 2.5 mg are considered necessary, Zalasta tablets should be used.
Este necesară
(See sections 4.5 and 5.2.)
i prudenţla pacienţ cu ii valori ale ALAT ş
4.3 Contraindications
i/ sau ASAT crescute, la pacienţ
Hypersensitivity to the active substance or to any of the excipients.
cu semne şsimptome de insuficienţhepaticăla ă
Patients with known risk for narrow-angle glaucoma.
pacienţ cu afecţ pre- existente care se asociază o rezervă
4.4 Special warnings and precautions for use
funcţ ională hepaticălimitată i la
During antipsychotic treatment, improvement in the patient's clinical condition may take several days to some weeks.
În caz de valori crescute ale ALAT ş
Patients should be closely monitored during this period.
monitorizarea ştrebuie luată considerare reducerea ASAT în t
In placebo-controlled clinical trials (6-12 weeks
impul tratamentului, trebuie instituită i
87 duration) of elderly patients (mean age 78 years) with dementia-related psychosis and/ or disturbed behaviours, there was a 2-fold increase in the incidence of death in olanzapine-treated patients compared to patients treated with placebo (3.5% vs.
În cazurile în care s- a diagnosticat o hepatită (incluzând forme prin afectare hepatocelularăprin, colestază prin mecanism mixt), tratamentul cu olanzapină
1.5%, respectively).
trebuie întrerupt.
The higher incidence of death was not associated with olanzapine dose (mean daily dose 4.4 mg) or duration of treatment.
indiferent de cauzăla pacienţ trataţcu medicamente cunoscute că
Risk factors that may predispose this patient population to increased mortality include age > 65 years, dysphagia, sedation, malnutrition and dehydration, pulmonary conditions (e. g., pneumonia, with or without aspiration), or concomitant use of benzodiazepines.
74
However, the incidence of death was higher in olanzapine-treated than in placebo-treated patients independent of these risk factors.
provocată boli concomitente, radioterapie sau chimioterapie şla pacienţ cu
In the same clinical trials, cerebrovascular adverse events (CVAE e. g., stroke, transient ischemic attack), including fatalities, were reported.
hipereozinofilie sau cu boli mieloproliferative.
There was a 3-fold increase in CVAE in patients treated with olanzapine compared to patients treated with placebo (1.3% vs.
În cazul în care olanzapina s- a administrat concomitent cu valproat s- a raportat frecvent neutropenie (vezi pct.
0.4%, respectively).
4. 8).
All olanzapine- and placebo-treated patients who experienced a cerebrovascular event had pre-existing risk factors.
Întreruperea tratamentului La întreruperea bruscă tratamentului cu olanzapinăau fost raportate foarte rar (< 0, 01%) simptome
Age > 75 years and vascular/ mixed type dementia were identified as risk factors for CVAE in association with olanzapine treatment.
La întreruperea
The efficacy of olanzapine was not established in these trials.
reducerea gradată dozei. a
Parkinson's disease The use of olanzapine in the treatment of dopamine agonist associated psychosis in patients with Parkinson's disease is not recommended.
În studiile clinice, la pacienţ trataţ olanzapină
In clinical trials, worsening of Parkinsonian symptomatology and hallucinations were reported very commonly and more frequently than with placebo (see section 4.8), and olanzapine was not more effective than placebo in the treatment of psychotic symptoms.
i cu
Olanzapine was started at 2.5 mg/ day and titrated to a maximum of 15 mg/ day based on investigator judgement.
comparativ cu cei la care s- a administrat placebo
Neuroleptic Malignant Syndrome (NMS) NMS is a potentially life-threatening condition associated with antipsychotic medicinal product.
clinic a intervalului QTc (corecţ
Rare cases reported as NMS have also been received in association with olanzapine.
tip Fridericia a intervalului QT [QTcF] ia
Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia).
≥ milisecunde [msec] în orice moment post- evaluare iniţ la pacienţ cu valori iniţ ale 500 QTcF < 500 msec) a fost mai puţ frecventă
Additi onal signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.
1%), fă diferenţsemnificative asupra la ră e
If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all antipsychotic medicines, including olanzapine must be discontinued.
Cu toate acestea, similar altor antipsihotice, este necesară
Hyperglycaemia and diabetes Hyperglycaemia and/ or development or exacerbation of diabetes occasionally associated with ketoacidosis or coma has been reported rarely, including some fatal cases (see section 4.8).
când olanzapina se prescrie în asociere cu medicamente cunoscute ca prelungind intervalul QTc, în ă special la pacienţ vârstnici, la pacienţ cu sindrom QT prelungit congenital, cu insuficienţcardiacă
In some cases, a prior increase in body weight has been reported which may be a predisposing factor.
congestivăhipertrofie cardiacăhipokaliemie sau hipomagneziemie.
Appropriate clinical monitoring is advisable particularly in diabetic patients and in patients with risk factors for the development of diabetes mellitus for which regular glucose control is recommended.
,
Lipid alterations Undesirable alterations in lipids have been observed in olanzapine-treated patients in placebo- controlled clinical trials (see section 4.8).
Nu s- a stabilit o relaţ cauzală
Lipid alterations should be managed as clinically appropriate, particularly in dyslipidemic patients and in patients with risk factors for the development of lipids disorders.
cu olanzapinăCu toate acestea, deoarece pacienţ cu schizofrenie prezintă
Anticholinergic activity While olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical trials revealed a low incidence of related events.
pentru tromboembolism venos, toţ
88 Hepatic function Transient, asymptomatic elevations of hepatic transaminases, ALT, AST have been seen commonly, especially in early treatment.
i factorii de risc de TEV, ca de exemplu imobilizarea pacienţ
Caution should be exercised in patients with elevated ALT and/ or AST, in patients with signs and symptoms of hepatic impairment, in patients with pre-existing conditions associated with limited hepatic functional reserve, and in patients who are being treated with potentially hepatotoxic medicines.
ii
In the event of elevated ALT and/ or AST during treatment, follow- up should be organised and dose reduction should be considered.
surile preventive necesare.
In cases where hepatitis (including hepatocellular, cholestatic or mixed liver injury) has been diagnosed, olanzapine treatment should be discontinued.
Activitatea generală asupra SNC Ca urmare a efectelor olanzapinei în primul rând asupra sistemului nervos central (SNC), este necesară
Neutropenia has been reported commonly when olanzapine and valproate are used concomitantly (see section 4.8).
prudenţatunci când aceasta se administrează asociere cu alte medicamente cu acţ centrală i
Discontinuation of treatment Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting have been reported very rarely (< 0.01%) when olanzapine is stopped abruptly.
Deoarece prezintă antagonism dopaminergic in vitro, olanzapina poate să ioneze acţ antagonist faţde efectele agoniş dopaminergici direcţşindirecţ
However, as with other antipsychotics, caution should be exercised when olanzapine is prescribed with medicines known to increase QTc interval, especially in the elderly, in patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalaemia or hypomagnesaemia.
Olanzapina trebuie utilizată prudenţla pacienţ cu antecedente convulsive sau la cei expuşunor
Thromboembolism Temporal association of olanzapine treatment and venous thromboembolism has very rarely (< 0.01%) been reported.
La pacienţ trataţ olanzapină raportat rareori
A causal relationship between the occurrence of venous thromboembolism and treatment with olanzapine has not been established.
În majoritatea acestor cazuri s- au raportat antecedente convulsive sau factori de ia risc pentru convulsii.
However, since patients with schizophrenia often present with acquired risk factors for venous thromboembolism all possible risk factors of VTE e. g. immobilisation of patients, should be identified and preventive measures undertaken.
Diskinezie tardivă ă În studiile comparative cu durată un an sau mai puţ olanzapina s- a asociat cu o frecvenţmai micăsemnificativă
General CNS activity Given the primary CNS effects of olanzapine, caution should be used when it is taken in combination with other centrally acting medicines and alcohol.
Cu toate acestea, riscul de diskinezie tardivă
As it exhibits in vitro dopamine antagonism, olanzapine may antagonize the effects of direct and indirect dopamine agonists.
creş odată expunerea pe termen lung ş în consecinţ dacă un pacient tratat cu olanzapină ă
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.
semne sau simptome de diskinezie tardivătrebuie luată considerare reducerea dozei sau
Seizures have been reported to occur rarely in patients when treated with olanzapine.
întreruperea medicamentului.
In most of these cases, a history of seizures or risk factors for seizures was reported.
Simptomele se pot accentua în timp sau apar chiar după tratamentului.
Tardive Dyskinesia In comparator studies of one year or less duration, olanzapine was associated with a statistically significant lower incidence of treatment emergent dyskinesia.
În studiile clinice cu olanzapină pacienţ vârstnici s- a observat rareori hipotensiune arterială
However the risk of tardive dyskinesia increases with long term exposure, and therefore if signs or symptoms of tardive dyskinesia appear in a patient on olanzapine, a dose reduction or discontinuation should be considered.
ii
These symptoms can temporally deteriorate or even arise after discontinuation of treatment.
posturalăSimilar altor antipsihotice, se recomandă
89 Postural hypotension Postural hypotension was infrequently observed in the elderly in olanzapine clinical trials.
determinarea periodică tensiunii arteriale la a
Studies in patients aged 13-17 years showed various adverse reactions, including weight gain, changes in metabolic parameters and increases in prolactin levels.
între 13 ş ani au evidenţ diverse reacţ adverse, efectuate la pacienţ vârsta cuprinsă
Long-term outcomes associated with these events have not been studied and remain unknown (see sections 4.8 and 5.1).
4. 8 ş5. 1). i
Aspartame Zalasta orodispersible tablets contain aspartame, a source of phenylalanine.
intoleranţereditară galactozădeficienţde lactază galactoză.
May be harmful for people with phenylketonuria.
Lapp sau sindrom de malabsorbţ de glucoză ie -
4.5 Interaction with other medicinal products and other forms of interaction
Interacţ cu alte medicamente şalte forme de interacţ 4. 5
Interaction studies have only been performed in adults.
Studiile privind interacţ iunile s- au efectuat doar la adulţ i.