qanastek/EMEA-V3 huggingface dataset:
Potential for olanzapine to affect other medicinal products Olanzapine may antagonise the effects of direct and indirect dopamine agonists.
Olanzapine jista ’ jantagonizza l- effetti ta ’ l- agonisti diretti jew indiretti ta ’ dopamine.
Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e. g.
Olanzapine ma jimpedixxix l- isoenzimi CYP450 prinċipali in vitro (eż.
Thus no particular interaction is expected as verified through in vivo studies where no inhibition of metabolism of the following active substances was found: tricyclic antidepressant (representing
Għalhekk, mhux mistenni li jseħħ xi effett partikolari ta ’ mediċini jew ta ’ affarijiet oħra fuq l- effett farmaċewtiku ta ’ olanzapine kif ivverifikat minn studji in vitro fejn ma nstabet ebda inibizzjoni tal - metaboliżmu tas- sustanzi attivi li ġejjin: antidepressiv triċikliku (li jirrapreżenta l- aktar is- sensiela ta ’ reazzjonijiet ta ’ CYP2D6), warfarin (CYP2C9), theophylline (CYP1A2) jew diazepam (CYP3A4 u 2C19).
Olanzapine showed no interaction when co-administered with lithium or biperiden.
Olanzapine ma wera ebda effett farmaċewtiku fuq lithium jew biperiden meta ngħata flimkien magħhom.
Therapeutic monitoring of valproate plasma levels did not indicate that valproate dosage adjustment is required after the introduction of concomitant olanzapine.
Il- monitoraġġ terapewtiku tal- livelli ta ’ valproate fil- plażma ma indikax li aġġustament fid- dożaġġ ta ’ valproate huwa meħtieġ wara l- introduzzjoni ta ’ olanzapine fl- istess waqt.
General CNS activity Caution should be exercised in patients who consume alcohol or receive medicinal products that can cause central nervous system depression.
Attività ġenerali ta ’ CNS Għandha tittieħed kawtela f’ pazjenti li jieħdu l- alkoħol jew prodotti mediċinali li jistgħu jikkawżaw depressjoni tas- sistema nervuża ċentrali.
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).
Mhux irrakkomandat l- użu konkomitanti ta ’ olanzapine ma ’ prodotti mediċinali kontra l- Parkinson f’ pazjenti bil- marda ta ’ Parkinson u d- demenzja (ara sezzjoni 4. 4).
QTc interval Caution should be used if olanzapine is being administered concomitantly with medicinal products known to increase QTc interval (see section 4.4).
L- Intervall QTc Għandha tintuża l- kawtela jekk olanzapine qiegħed jingħata flimkien ma ’ prodotti mediċinali magħrufa li jtawlu l- intervall QTc (ara sezzjoni 4. 4).
There are no adequate and well-controlled studies in pregnant women.
Mhemm l- ebda studju adegwat u kkontrollat tajjeb f’ nisa waqt it- tqala.
Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during treatment with olanzapine.
Il- pazjenti għandhom jingħataw parir biex jgħarrfu lit- tabib tagħhom jekk jinqabdu tqal jew jekk qed jippjanaw li jinqabdu tqal waqt il- kura b’ olanzapine.
Nevertheless, because human experience is limited, olanzapine should be used in pregnancy only if the potential benefit justifies the potential risk to the foetus.
Madanakollu, minħabba li l- esperjenza fil- bniedem hija limitata, olanzapine għandu jintuża biss waqt it- tqala jekk il- benefiċju potenzjali jiġġustifika r- riskju potenzjali fuq il- fetu.
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.
Rapporti spontanji kienu rrapportati b’ mod rari ħafna dwar rogħda, ipertonja, letarġija u ngħas, fi trabi mwielda lill- ommijiet li użaw olanzapine waqt l- aħħar 3 xhur tat- tqala.
In a study of oral olanzapine in breast-feeding, healthy women, olanzapine was excreted in breast milk.
Fi studju ta ’ olanzapine mill- ħalq f’ nisa b’ saħħithom li qed ireddgħu, olanzapine ħareġ fil- ħalib tas - sider.
Mean infant exposure (mg/ kg) at steady state was estimated to be 1.8% of the maternal olanzapine dose (mg/ kg).
L- espożizzjoni medja tat- tarbija (mg/ kg) f’ steady- state ġie stmat li kienet 1. 8% tad- doża ta ’ olanzapine fl- omm (mg/ kg).
As olanzapine may cause somnolence and dizziness, patients should be cautioned about operating machinery, including motor vehicles.
Minħabba li olanzapine jista ’ jikkawża sonnolenza u sturdament, il- pazjenti għandhom jiġu avżati dwar l- użu ta ’ magni, inklużi l - karozzi.
Patients should be advised not to drive or operate machinery for the remainder of the day after each injection due to the possibility of a post-injection syndrome event leading to symptoms consistent with olanzapine overdose (see section 4.4).
Il- pazjenti għandhom jingħataw parir li ma jsuqux jew iħaddmu magni għall- bqija tal- ġurnata wara kull injezzjoni minħabba l- possibiltà li jkun hemm avveniment ta ’ sindromu ta ’ wara l- injezzjoni li jwassal għal sintomi konsistenti ma ’ doża eċċessiva ta ’ olanzapine (ara sezzjoni 4. 4).
Post-injection syndrome events have occurred with ZYPADHERA leading to symptoms consistent with olanzapine overdose (see sections 4.2 and 4.4).
Avvenimenti ta ’ sindromu ta ’ wara l- injezzjoni li jwasslu għal sintomi konsistenti ma ’ doża eċċessiva ta ’ olanzapine (ara sezzjoni 4. 4) seħħew b’ ZYPADHERA.
Clinical signs and symptoms included symptoms of sedation (ranging from mild in severity up to coma) and/ or delirium (including confusion, disorientation, agitation, anxiety and other cognitive impairment).
Fost is- sinjali u s- sintomi kliniċi nsibu sintomi ta ’ sedazzjoni (li jvarjaw minn ħfief fis- severità sa koma) u/ jew delirju (inklużi konfużjoni, diżorjentament, aġitazzjoni, ansjetà u indeboliment konoxxittiv ieħor).
Other adverse reactions observed in patients treated with ZYPADHERA were similar to those seen with oral olanzapine.
Reazzjonijiet avversi oħra li ġew osservati f’ pazjenti kkurati b’ ZYPADHERA kienu simili għal dawk innutati b’ olanzapine mill- ħalq.
In clinical trials with ZYPADHERA, the only adverse reaction reported at a statistically significantly higher rate in the ZYPADHERA group than in the placebo group was
Fi studji kliniċi b’ ZYPADHERA, is- sedazzjoni kienet l- unika reazzjoni avversa rrapportata b’ rata ogħla b’ mod statistikament sinifikanti fil- grupp ta ’ ZYPADHERA milli fil- grupp tal- plaċebo (ZYPADHERA 8. 2%, plaċebo 2. 0%).
Among all ZYPADHERA treated patients, sedation was reported by 4.7% of patients.
Fil- pazjenti kollha kkurati b’ ZYPADHERA, is- sedazzjoni ġiet irrapportata minn 4. 7% tal- pazjenti.
In clinical trials with ZYPADHERA the incidence of injection site related adverse events was approximately 8%.
Fi studji kliniċi b’ ZYPADHERA l- inċidenza ta ’ avvenimenti avversi relatati mas- sit ta ’ l- injezzjoni kien madwar 8%.
The most commonly reported injection site related adverse event was pain (5%); some other injection site adverse events reported were (in decreasing frequency): nodule type reactions, erythema type reactions, non-specific injection site reactions, irritation, oedema type reactions, bruising, haemorrhage, and anesthesia.
L- aktar avveniment avvers li ġie rrapportat b’ mod komuni relatat mas- sit ta ’ l - injezzjoni kien l- uġigħ (5%); xi avvenimenti avversi oħra relatati mas- sit ta ’ l- injezzjoni li ġew irrapportati kienu (b’ frekwenza li tonqos): reazzjonijiet tat- tip nodulari, reazzjonijiet tat- tip eritemiku, reazzjonijiet fis- sit ta ’ l- injezzjoni li mhumiex speċifiċi, irritazzjonijiet, reazzjonijiet tat- tip edimiku, tbenġil, emorraġija u anesteżija.
These events occurred in about 0.1 to 1.1% of patients.
Dawn l- avvenimenti seħħew f’ madwar 0. 1 sa 1. 1% tal- pazjenti.
The undesirable effects listed below have been observed following administration of oral olanzapine but may occur following administration of ZYPADHERA.
L- effetti mhux mixtieqa ta ’ hawn taħt ġew osservati wara li ngħata olanzapine mill- ħalq iżda jistgħu jseħħu wara li jingħata ZYPADHERA.
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.
Adulti L- aktar reazzjonijiet avversi li ġew irrapportati b’ mod frekwenti (jidhru f ’ > 1% tal- pazjenti) assoċjati ma ’ l- użu ta ’ olanzapine fi studji kliniċi kienu sonnolenza, żieda fil- piż, eosinofilja, livelli għolja ta ’ prolactin, kolesterol, glucose u trigliċeridi (ara sezzjoni 4. 4), glikosurja, żieda fl- aptit, sturdament, akatiżja, parkinsoniżmu (ara sezzjoni 4. 4), diskineżja, pressjoni baxxa mal- waqfien, effetti antikolinerġiċi, livelli għolja ta ’ transaminases tal- fwied temporanji u mingħajr sintomi (ara sezzjoni 4. 4), raxx, astenja, għaja u edema.
The following table lists the adverse reactions and laboratory investigations observed from spontaneous reporting and in clinical trials.
It- tabella li ġejja telenka r- reazzjonijiet avversi u t- testijiet tal- laboratorju osservati f’ irrapportar spontanju u f’ studji kliniċi.
The frequency terms listed are defined as follows:
It- termini ta ’ frekwenza elenkati huma mfissra kif ġej:
Very common (≥ 10%), common (≥ 1% and < 10%), uncommon (≥ 0.1% and < 1%), rare (≥ 0.01% and < 0.1%), very rare (< 0.01%), not known (cannot be estimated from the data available).
Komuni ħafna (> 10%), komuni (> 1% u < 10%), mhux komuni (> 0. 1% u < 1%), rari (> 0. 01% u < 0. 1%), rari ħafna (< 0. 01%), mhux magħrufa (ma jistawx jiġu stmati mill- informazzjoni li hemm disponibbli).
Development or exacerbation of diabetes occasionally associated with ketoacidosis or coma, including some fatal cases (see section 4.4) Hypothermia
Żvilupp jew iggravar tad- dijabete, xi kultant assoċjata ma ’ ketoaċidożi jew koma inklużi xi każijiet fatali (ara sezzjoni 4. 4) Ipotermja
Nervous system disorders Somnolence
Disturbi fis- sistema nervuża
9
9 Sonnolenza Disturbi fil- qalb
Ventricular tachycardia/ fibrillation, sudden death (see section 4.4)
Takikardija / fibrillazzjoni ventrikulari, mewt għal għarrieda (ara sezzjoni 4. 4)
Transient, asymptomatic elevations of hepatic transaminases (ALT, AST), especially in early treatment (see section 4.4)
Livelli għolja ta ’ transaminases tal- fwied (ALT, AST) temporanji u mingħajr sintomi, speċjalmet fil - bidu tal- kura (ara sezzjoni 4. 4)
Hepatitis (including hepatocellular, cholestatic or mixed liver injury)
Epatite (inkluż ħsara fil- fwied tat- tip epatoċellulari, kolestatiku jew imħallta)
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 levels8 1
Disturbi muskolu- skeltrali u tal- connective tissue Rabdomijoliżi Disturbi fil- kliewi u fis- sistema urinarja Eżitazzjoni urinarja Disturbi fis- sistema riproduttiva u fis- sider Prijapiżmu Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata Astenja Għaja Edema Investigazzjonijiet Livelli elevati ta ’
High creatine phosphokinase Increased total bilirubin
phosphokinase għoli Żieda fil- bilirubin
Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories.
Ġiet osservata żieda fil- piż klinikament sinifikanti fil- kategoriji kollha fil- linja bażi ta ’ l- Indiċi tal - Massa tal- Ġisem (BMI).
Patients gaining ≥ 25% of their baseline body weight with long-term exposure were very common.
Wara espożizzjoni għal tul ta ’ żmien, il - pazjenti li żiedu ≥ 25% mil- linja bażi tal- piż tal- ġisem tagħhom kienu komuni ħafna.
Changes in total fasting cholesterol levels from borderline at baseline (≥ 5.17 - < 6.2 mmol) to high (≥ 6.2 mmol) were very common.
Tibdil fil- livelli tal- kolesterol totali waqt is- sawm mil- limitu tan- normal fil- linja bażi (≥ 5. 17 mmol/ l - < 6. 2 mmol/ l) għal għoljin (≥ 6. 2 mmol/ l) kienu komuni.
10 4 Observed for fasting normal levels at baseline (< 5.56 mmol/ l) which increased to high (≥ 7 mmol/ l).
4 Innotat għal livelli normali waqt is- sawm fil- linja bażi (< 5. 56 mmol/ l) li żdiedu għal għoljin (≥ 7 mmol/ l).
6 In clinical trials, the incidence of parkinsonism and dystonia in olanzapine-treated patients was numerically higher, but not statistically significantly different from placebo.
6 Fi studji kliniċi, l- inċidenza ta ’ parkinsoniżmu u distonja f’ pazjenti kkurati b’ olanzapine kienet numerikament ogħla, iżda mhux differenti mill- plaċebo b’ mod statistikament sinifikanti.
Olanzapine-treated patients had a lower incidence of parkinsonism, akathisia and dystonia compared with titrated doses of haloperidol.
Pazjenti kkurati b’ olanzapine kellhom inċidenza ta ’ parkinsoniżmu, akatiżja u distonja aktar baxxa meta mqabbel ma ’ dożi aġġustati bil- mod ta ’ haloperidol.
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.
Fl- assenza ta ’ tagħrif dettaljat dwar passat diġà eżistenti ta ’ disturbi individwali akuti u tardivi ta ’ moviment ekstrapiramidali, fil- preżent ma jistax jiġi konkluż li olanzapine jipproduċi anqas diskineżja tardiva u/ jew sindromi ekstrapiramidali tardivi oħra.
7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been reported when olanzapine is stopped abruptly.
7 Sintomi akuti bħal għaraq, insomnja, rogħda, ansjetà, tqalligħ u rimettar ġew irrapportati meta olanzapine jitwaqqaf f’ daqqa.
8 Associated clinical manifestations (e. g., gynaecomastia, galactorrhoea, and breast enlargement) were rare.
8 Manifestazzjonijiet kliniċi assoċjati (eż. ginekomastja, galaktorea, u tkabbir tas- sider) kienu rari.
In most patients, levels returned to normal ranges without cessation of treatment.
Fil - biċċa l- kbira tal- pazjenti, il- livelli reġgħu lura għan- normal mingħajr twaqqif ta ’ kura.
Long-term exposure (at least 48 weeks) The proportion of patients who had adverse, clinically significant changes in weight gain, glucose, total/ LDL/ HDL cholesterol or triglycerides increased over time.
Espożizzjoni fit- tul (għallinqas 48 ġimgħa) Il- proporzjon ta ’ pazjenti li kellhom tibdil avvers, klinikament sinifikanti, f’ żieda fil- piż, glucose, kolesterol totali/ LDL/ HDL jew trigliċeridi żdied maż- żmien.
In adult patients who completed 9-12 months of therapy, the rate of increase in mean blood glucose slowed after approximately 4-6 months.
F’ pazjenti adulti li spiċċaw 9- 12- il xahar ta ’ terapija, ir- rata taż- żieda fil- medja taz- zokkor fid- demm naqas wara madwar 4- 6 xhur.
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).
Tagħrif addizzjonali dwar popolazzjonijiet speċjali Fi studji kliniċi f’ pazjenti anzjani bid- demenzja, kura b’ olanzapine kienet assoċjata ma ’ inċidenza ogħla ta ’ mwiet u reazzjonijiet avversi ċerebrovaskulari meta mqabbla mal- plaċebo (ara wkoll sezzjoni 4. 4).
Very common adverse reactions associated with the use of olanzapine in this patient group were abnormal gait and falls.
Reazzjonijiet avversi komuni ħafna assoċjati ma ’ l- użu ta’ olanzapine f’ dan il- grupp ta ’ pazjenti kienu mixja abnormali u waqgħat.
Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and urinary incontinence were observed commonly.
Il- pulmonite, iż- żieda fit- temperatura tal- ġisem, il- letarġija, l - eritema, l- alluċinazzjonijiet viżivi u l- inkontinenza ta ’ l- awrina kienu osservati b’ mod komuni.
In clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with Parkinson’ s disease, worsening of Parkinsonian symptomatology and hallucinations were reported very commonly and more frequently than with placebo.
Fi studji kliniċi f’ pazjenti b’ psikożi dovuta għal mediċina (agonist ta ’ dopamine) assoċjata mal- marda ta ’ Parkinson, kienu rrapportati deterjorament tas- sintomatoloġija tal- marda ta ’ Parkinson u l - alluċinazzjonijiet b’ mod komuni ħafna u aktar spiss mill- plaċebo.
In one clinical trial in patients with bipolar mania, valproate combination therapy with olanzapine resulted in an incidence of neutropenia of 4.1%; a potential contributing factor could be high plasma valproate levels.
Fi studju kliniku wieħed f’ pazjenti b’ manija bipolari, terapija b’ valproate flimkien ma ’ olanzapine rriżultat f’ inċidenza ta ’ newtropenja ta ’ 4. 1%; fattur potenzjalment kontributorju jista ’ jkun livelli għolja ta ’ valproate fil- plażma.
Olanzapine administered with lithium or valproate resulted in increased levels (≥ 10%) of tremor, dry mouth, increased appetite, and weight gain.
Olanzapine flimkien ma ’ lithium jew valproate rriżulta f’ livelli ogħla (> 10%) ta ’ rogħda, nixfa fil- ħalq, żieda fl- aptit, u żieda fil- piż.
Speech disorder was also reported commonly.
Disturb fid- diskors kien ukoll irrappurtat b’ mod komuni.
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).
Kura
Long-term olanzapine treatment (up to 12 months) for recurrence prevention in patients with bipolar disorder was associated with an increase of ≥ 7% from baseline body weight in 39.9% of patients.
11 b’ olanzapine għal żmien twil (sa 12- il xahar) bl- għan ta 'prevenzjoni ta' episodji oħra f' pazjenti b' mard bipolari kien assoċjat ma 'żieda ta' ≥ 7% mil- linja bażi tal- piż tal- ġisem f' 39. 9% tal- pazjenti.
Although no clinical studies designed to compare adolescents to adults have been conducted, data from the adolescent trials were compared to those of the adult trials.
Għalkemm ma ġewx imwettqa studji kliniċi magħmulin biex iqabblu l- adolexxenti ma ’ l- adulti, tagħrif mill- istudji ta ’ l- adolexxenti ġie mqabbel ma ’ dak tal- istudji ta ’ l- adulti.
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.
It- tabella li ġejja tiġbor fil- qosor ir- reazzjonijiet avversi rrapportati b' frekwenza akbar f' pazjenti adolexxenti (minn 13 sa 17- il sena) milli f' pazjenti adulti jew reazzjonijiet avversi li ġew identifikati biss waqt studji kliniċi magħmula għal żmien qasir f' pazjenti adolexxenti.
The
Żieda fil- piż klinikament sinifikanti (≥ 7%) tidher li sseħħ aktar frekwentement fil- popolazzjoni ta 'l- adolexxenti meta mqabbla ma ’ l- adulti b’ espożizzjoni simili.
11 magnitude of weight gain and the proportion of adolescent patients who had clinically significant weight gain were greater with long-term exposure (at least 24 weeks) than with short-term exposure.
L- ammont ta ’ żieda fil- piż u l- proporzjon ta ’ pazjenti adolexxenti li kellhom żieda fil- piż klinikament sinifikanti kienu akbar b’ espożizzjoni fit- tul (għallinqas 24 ġimgħa) milli b’ espożizzjoni għal żmien qasir.
Elevations of hepatic transaminases (ALT/ AST; see section 4.4).
Livelli għolja ta ’ transaminases tal- fwied (ALT/ AST; ara sezzjoni 4. 4).
9 Weight gain ≥ 7% of baseline body weight (kg) was very common and ≥ 15% of baseline body weight was common.
9 Żieda fil- piż ta '> 7% mil- linja bażi tal- piż tal- ġisem (kg) kienet komuni ħafna u ta' ≥ 15% mil- linja bażi tal- piż tal- ġisem kienet komuni.
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.
B’ espożizzjoni fit- tul (għallinqas 24 ġimgħa), madwar nofs il - pazjenti adulti żiedu ≥ 15% u kważi terz żiedu ≥ 25% mil- linja bażi tal- piż tal- ġisem tagħhom.
Among adolescent patients, mean weight gain was greatest in patients who were overweight or obese at baseline.
Fost il - pazjenti adolexxenti, iż- żieda medja fil- piż kienet l- aktar f’ pazjenti li bħala linja bażi kellhom piż żejjed jew kienu obeżi.
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 Tibdil fil- livelli tal- kolesterol totali waqt is- sawm minn normal fil- linja bażi (< 4. 39 mmol/ l) għal għoljin (≥ 5. 17 mmol/ l) kienu osservati b’ mod komuni.
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.
Tibdil fil- livelli tal- kolesterol totali waqt is - sawm mil- limitu tan- normal fil- linja bażi (≥ 4. 39 - < 5. 17 mmol/ l) għal għoljin (≥ 5. 17 mmol/ l) kienu komuni ħafna.
12 Elevated plasma prolactin levels were reported in 47.4% of adolescent patients.
12 F' 47. 4% tal- pazjenti adolexxenti ġew irrapportati livelli għoljin ta ’ prolactin fil- plażma.
If signs and symptoms of overdose consistent with post injection syndrome are observed, appropriate supportive measures should be taken (see section 4.4).
Jekk jiġu osservati sinjali u sintomi ta ’ doża eċċessiva konsistenti mas- sindromu ta ’ wara l- injezzjoni, għandhom jittieħdu miżuri ta ’ għajnuna xierqa (ara sezzjoni 4. 4).
While overdose is less likely with parenteral than oral medication, reference information for oral olanzapine overdose is presented below:
Waqt li doża eċċessiva hija anqas probbabli b’ medikazzjoni li tingħata minn ġol- vini milli mill- ħalq, tagħrif għal referenza ta ’ doża eċċessiva ta ’ olanzapine mill- ħalq huwa ppreżentat hawn taħt:
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.
Sintomi komuni ħafna b’ doża eċċessiva (inċidenza ta ’ > 10%) jinkludu takikardija, aġitazzjoni/ aggressività, disartrija, sintomi ekstrapiramidali varji, u tnaqqis fil- livell ta ’ koxjenza li jvarja minn sedazzjoni għal koma.
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.
Sintomi morbużi oħra medikalment sinifikanti ta ’ doża eċċessiva jinkludu delirju, konvulżjoni, koma, possibiltà ta ’ sindromu newrolettiku malinn, depressjoni respiratorja, aspirazzjoni, pressjoni għolja jew baxxa, taħbit tal- qalb irregolari (< 2% tal- każijiet ta ’ doża eċċessiva) u arrest kardjopulmonari.
Fatal outcomes have been reported for acute oral overdoses as low as 450 mg but survival has also been reported following acute overdose of approximately 2 g of oral olanzapine.
Ġew irrappurtati każijiet fatali b’ dożi eċċessivi akuti baxxi daqs 450 mg iżda ġew irrapportati wkoll każijiet ta ’ sopravivenza wara doża eċċessiva akuta ta ’ madwar 2 g ta ’ olanzapine mill- ħalq.
Management of overdose There is no specific antidote for olanzapine.
L- Immaniġġar ta ’ doża eċċessiva M’ hemm l- ebda antidotu speċifiku għal olanzapine.
Symptomatic treatment and monitoring of vital organ function should be instituted according to clinical presentation, including treatment of hypotension
Kura sintomatika u monitoraġġ tal- funzjoni ta ’ l - organi vitali għandhom jiġu stabbiliti skont il- qagħda klinika, inkluż kura għall- pressjoni baxxa u kolass taċ- ċirkolazzjoni u sosteniment tal- funzjoni respiratorja.
Do not use epinephrine, dopamine, or other sympathomimetic agents with beta-agonist activity since beta stimulation may worsen hypotension.
Tużax epinephrine, dopamine, jew sustanzi oħra simpatomimatiċi b’ attività beta- agonista billi l- istimulazzjoni beta tista ’ taggrava l - pressjoni baxxa.
Cardiovascular monitoring is necessary to detect possible arrhythmias.
Huwa neċessarju l- monitoraġġ kardjovaskulari biex tinduna b’ taħbit irregolari tal - qalb li jista ’ jseħħ.
Close medical supervision and monitoring should continue until the patient recovers.
Is- superviżjoni medika u l- monitoraġġ mill- qrib għandhom jitkomplew sakemm il - pazjent jirkupra.
Pharmacotherapeutic group: diazepines, oxazepines and thiazepines, ATC code N05A H03.
Grupp farmako- terapewtiku: antipsikotiku, kodiċi ATC N05A H03.
Olanzapine is an antipsychotic, antimanic and mood stabilising agent that demonstrates a broad pharmacologic profile across a number of receptor systems.
Olanzapine huwa sustanza antipsikotika, kontra l- manija u stabilizzatur tal- burdata li juri profil farmakoloġiku wiesa ’ f’ numru ta ’ sistemi ta ’ riċetturi.
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 -1 adrenergic; and histamine H1 receptors.
Fi studji ta ’ qabel l- użu kliniku, olanzapine wera firxa ta ’ affinitajiet għar- riċetturi (Ki; < 100 nM) għal riċetturi ta ’ serotonin 5- HT2A/ 2C, 5- HT3, 5- HT6; dopamine D1, D2, D3, D4, D5; riċetturi muskariniċi kolinerġiċi m1- m5; α- 1 adrenerġiċi; riċetturi histamine H1.
Animal behavioural studies with olanzapine indicated 5HT, dopamine, and cholinergic antagonism, consistent with the receptor-binding profile.
Studji fuq l- imġiba ta ’ l - annimali b’ olanzapine indikaw antagoniżmu għal 5HT, dopamine, u dak kolinerġiku, konsistenti mal - profil ta ’ rbit mar- riċettur.
Olanzapine demonstrated a greater in-vitro affinity for serotonin 5-HT2 than dopamine D2 receptors and greater 5-HT2 than D2 activity in vivo, models.
Olanzapine wera affinità akbar in vitro għar- riċetturi ta ’ serotonin 5- HT2 milli ta ’ dopamine D2 u attività in vivo akbar għal 5- HT2 milli għal D2.
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.
Studji elettrofiżjoloġiċi wrew illi olanzapine b’ mod selettiv naqqas l- istumulazzjoni tan- newroni dopaminerġiċi mesolimbiċi (A10), waqt li kellu ftit effett fuq is- sekwenza tar- reazzjoni strijatali (A9) involuta fil- funzjoni motorjali.
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.
Olanzapine naqqas ir- rispons ta ’ ħrib kundizzjonat, test indikattiv ta ’ l- attività antipsikotika, f’ dożi anqas minn dawk li jwasslu għall- katalepsi, konsegwenza indikattiva ta ’ effett motorju mhux mixtieq.
Unlike some other antipsychotic agents, olanzapine increases responding in an “ anxiolytic” test.
Kuntrarju għal xi sustanzi antipsikotiċi oħra, olanzapine iżid ir- rispons f' test anksjolitiku.
The effectiveness of ZYPADHERA in the treatment and maintenance treatment of schizophrenia is consistent with the established effectiveness of the oral formulation of olanzapine.
L- effikaċja ta ’ ZYPADHERA fil- kura u fil- kura ta ’ manteniment ta ’ l- iskiżofrenja hija konsistenti ma ’ l- effikaċja stabbilita tal- formulazzjoni mill- ħalq ta ’ olanzapine.
In a Positron Emission Tomography (PET) study in patients treated with ZYPADHERA (300 mg/ 4 weeks), mean D2 receptor occupancy was 60% or higher at the end of a 6 month period, a level consistent with that found during treatment with oral olanzapine.
Fi studju ta ’ Tomografija bl- Emissjoni ta ’ Pożitroni (PET) f’ pazjenti kkurati b’ ZYPADHERA (300 mg/ 4 gimgħat), l- okkupanza medja ta ’ riċetturi D2 kienet ta ’ 60% jew ogħla fit- tmien ta ’ perijodu ta ’ 6 xhur, livell konsistenti ma ’ dak li nstab waqt kura ta ’ olanzapine mill- ħalq.
A total of 1469 patients with schizophrenia were included in 2 pivotal trials:
Total ta ’ 1469 pazjent b’ skiżofrenja ġew inklużi f’ 2 studji kruċjali:
The first, an 8-week, placebo controlled trial conducted in adult patients (n=404) who were experiencing acute psychotic symptoms.
L- ewwel, studju kkontrollat mill- plaċebo, li dam 8 gimgħat, f’ pazjenti adulti (n=404) li esperjenzaw sintomi psikotiċi akuti.
Patients were randomized to receive injections of ZYPADHERA 405 mg every 4 weeks, 300 mg every 2 weeks, 210 mg every 2 weeks, or placebo every 2 weeks.
Il- pazjenti ngħataw b’ mod arbitrarju injezzjonijiet ta ’ ZYPADHERA 405 mg kull 4 ġimgħat, 300 mg kull ġimagħtejn, 210 mg kull ġimagħtejn, jew plaċebo kull ġimagħtejn.
No oral antipsychotic supplementation was allowed.
Ma kienx permess it- tisħiħ b’ antipsikotiċi mill- ħalq.
Total Positive and Negative Symptom Scores (PANSS) showed significant improvement from baseline (baseline mean Total PANSS Score 101) to endpoint (mean changes -22.57, -26.32, -22.49 respectively) with each dose of ZYPADHERA (405 mg every 4 weeks, 300 mg every 2 weeks, and 210 mg every 2 weeks) as compared to placebo (mean change -8.51).
13 endpoint (tibdil medju - 22. 57, - 26. 32, - 22. 49 rispettivament) ma ’ kull doża ta ’ ZYPADHERA (405 mg kull 4 ġimgħat, 300 mg kull ġimagħtejn, u 210 mg kull ġimagħtejn) meta mqabbel ma ’ plaċebo (tibdil medju - 8. 51).
Visitwise mean change from baseline to endpoint in PANSS Total score indicated that by Day 3, patients in the 300 mg/ 2 weeks and 405 mg/ 4 weeks treatment groups had statistically significantly greater reductions in PANSS Total score compared to placebo (-8.6, -8.2, and -5.2, respectively).
Tibdil medju visitwise mil- linja bażi sa l- endpoint fil- punteġġ Totali PANSS indika li sa Jum 3, pazjenti fil- gruppi ta ’ kura ta ’ 300 mg/ ġimagħtejn u 405 mg/ 4 ġimgħat kellhom tnaqqis akbar b’ mod statistikament sinifikanti fil- punteġġ Totali PANSS imqabbel ma ’ plaċebo (- 8. 6, - 8. 2, u - 5. 2, rispettivament).
All 3 ZYPADHERA treatment groups showed statistically significantly greater improvement than placebo beginning by end of Week 1.
It- 3 gruppi ta ’ kura b’ ZYPADHERA wrew titjib akbar b’ mod statistikament sinifikanti mill- plaċebo li beda sa l- aħħar ta ’ Ġimgħa 1.
These results support efficacy for ZYPADHERA over 8 weeks of treatment and a drug effect that was observed as early as 1 week after starting treatment with ZYPADHERA.
Dawn ir- riżultati jsostnu effikaċja ta ’ ZYPADHERA fuq 8 ġimgħat ta ’ kura u effett tal- mediċina li ġie osservat bikri mill- 1 ġimgħa wara li nbdiet il- kura b’ ZYPADHERA.
The second, a long term study in clinically stable patients (n=1065) (baseline mean Total PANSS Score 54.33 to 57.75) who were initially treated with oral olanzapine for 4 to 8 weeks and then switched to continue on oral olanzapine or to ZYPADHERA for 24 weeks.
It- tieni, studju fit- tul f’ pazjenti klinikament stabbli (n=1065) (Punteġġ PANSS Totali medju mil- linja bażi 54. 33 sa 57. 75) li għall- ewwel kienu kkurati b’ olanzapine mill- ħalq għal 4 sa 8 ġimgħat u mbagħad inqalbu biex ikomplu jieħdu olanzapine mill- ħalq jew ZYPADHERA għal 24 gimgħa.
ZYPADHERA treatment groups of 150 mg and 300 mg given every 2 weeks (doses pooled for analysis) and 405 mg given every 4 weeks were non inferior to the combined doses of 10, 15 and 20 mg of oral olanzapine (doses pooled for analysis) as measured by rates of
Il- gruppi ta ’ kura ta ’ 150 mg u 300 mg ZYPADHERA mogħtija kull ġimagħtejn (dożi miġbura għall- analiżi) u 405 mg mogħtija kull 4 ġimgħat ma kinux inferjuri għad- dożi kkombinati ta ’ 10, 15 u 20 mg ta ’ olanzapine mill- ħalq (dożi miġbura għall- analiżi) kif imkejla bir- rati ta ’ iggravar tas- sintomi ta ’ skiżofrenja (rati ta ’ iggravar rispettivi, 10%, 10% 7%).
Exacerbation was measured by worsening of items on the PANSS derived BPRS Positive scale and hospitalization due to worsening of positive psychotic symptoms.
L- iggravar ġie mkejjel mill- oġġetti elenkati fl- iskala BPRS Pożittiva mnissla minn PANSS li marru għall- agħar, u mill- ammissjonijiet fl- isptar minħabba sintomi psikotiċi pożittivi li marru għall- agħar.
The combined 150 mg and 300 mg/ 2 week treatment group was non inferior to the 405 mg/ 4 week treatment group (exacerbation rates 10% for each group) at 24 weeks after randomisation.
Il- grupp ikkombinat ta ’ kura b’ 150 mg u 300 mg/ ġimagħtejn ma kienx inferjuri għall- grupp ta ’ kura b’ 405 mg/ 4 ġimgħat (rati ta ’ iggravar ta ’ 10% għal kull grupp) fl- 24 ġimgħa wara randomisation.
Paediatric population ZYPADHERA has not been studied in the paediatric population.
Popolazzjoni pedjatrika ZYPADHERA ma ġiex studjat f’ popolazzjoni pedjatrika.
The experience in adolescents (ages 13 to 17 years) is limited to short term oral olanzapine efficacy data in schizophrenia (6 weeks) and mania associated with bipolar I disorder (3 weeks), involving less than 200 adolescents.
L- esperjenza fl- adolexxenti (minn 13 sa 17 - il sena) hija limitata għal tagħrif dwar l- effikaċja għal żmien qasir fl- iskiżofrenja (6 ġimgħat) u manija assoċjata ma 'mard bipolari ta' tip I (3 ġimgħat), li involviet anqas minn 200 adolexxent.
Oral olanzapine was used as a flexible dose starting with 2.5 and ranging up to 20 mg/ day.
Olanzapine mill- ħalq intuża bħala doża flessibbli li tibda b' 2. 5 u titla 'sa 20 mg/ jum.
During treatment with oral olanzapine, adolescents gained significantly more weight compared with adults.
Waqt il- kura b' olanzapine mill- ħalq, l- adolexxenti żiedu b' mod sinifikanti aktar fil- piż meta mqabbel ma 'l- adulti.
There are no data on maintenance of effect and limited data on long term safety (see sections 4.4 and 4.8).
M' hemmx tagħrif dwar iż- żamma ta 'l- effett u hemm tagħrif limitat dwar is- sigurtà fit- tul (ara sezzjonijiet 4. 4 u 4. 8).
Olanzapine is metabolised in the liver by conjugative and oxidative pathways.
Olanzapine jiġi metabolizzat fil- fwied minn sensieli ta ’ reazzjonijiet konjugattivi u ossidattivi.
The major circulating metabolite is the 10-N-glucuronide.
Il - metabolit prinċipali li jiċċirkola huwa 10- N- glucuronide.
Cytochromes P450-CYP1A2 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.
Ċitokromi P450- CYP1A2 u P450- CYP2D6 jikkontribwixxu għall- formazzjoni tal- metaboliti N- desmethyl u 2- hydroxymethyl; it- tnejn urew attività farmakoloġika in vivo anqas b’ mod sinifikanti minn olanzapine fi studji fl- annimali.
The predominant pharmacologic activity is from the parent, olanzapine.
L- attività farmakoloġika predominanti tiġi mis- sustanza oriġinali, olanzapine.
After a single IM injection with ZYPADHERA the slow dissolution of the olanzapine pamoate salt in muscle tissue begins immediately and provides a slow continuous release of olanzapine for more than four weeks.
Wara injezzjoni waħda ta ’ ZYPADHERA ġol- muskoli t- taħlil bil- mod tal- melħ olanzapine pamoate fit- tessut tal- muskoli jibda minnufih u jipprovdi reħi ta ’ olanzapine bil- mod u kontinwu għal aktar minn erba ’ ġimgħat.
The release becomes diminishingly smaller within eight to twelve weeks.
Il- ħruġ jitnaqqas ħafna fi żmien tmien ġimgħat sa tnax- il ġimgħa.
Antipsychotic supplementation is not required at the initiation of ZYPADHERA treatment (see section 4.2).
Tisħiħ b’ antipsikotiċi mhux neċessarju fil- bidu ta ’ kura b’ ZYPADHERA (ara sezzjoni 4. 2).
The combination of the release profile and the dosage regimen (IM injection every two or four weeks) result in sustained olanzapine plasma concentrations.
Il- profil tar- reħi u r- rutina ta ’ dożaġġ (injezzjoni ġol- muskoli kull ġimagħtejn jew tlieta) f’ daqqa jirriżultaw f’ konċentrazzjonijiet sostenuti ta ’ olanzapine fil- plażma.
Plasma concentrations remain measurable for several months after each ZYPADHERA injection.
Il- konċentrazzjonijiet fil- plażma jistgħu jibqgħu jitkejlu għal ħafna xhur wara kull injezzjoni ta ’ ZYPADHERA.
The half-life of olanzapine after ZYPADHERA is 30 days compared to 30 hours following oral administration.
Il- half- life ta ’ olanzapine wara ZYPADHERA huwa ta ’ 30 jum imqabbel ma ’ 30 siegħa wara t- teħid mill- ħalq.
The absorption and elimination are complete approximately six to eight months after the last injection.
L - assorbiment u l- eliminazzjoni huma kompleti wara madwar sitt sa tmien xhur wara l- aħħar injezzjoni.
Oral olanzapine is rapidly distributed.
Olanzapine mill- ħalq jiġi distribwit b’ mod rapidu.
The plasma protein binding of olanzapine is about 93% over the concentration range of 7 to about 1000 ng/ mL.
L- irbit ta ’ olanzapine mal- proteini tal- plażma huwa madwar 93% fuq l- iskala tal- konċentrazzjoni ta ’ 7 sa madwar 1000 ng/ mL.
In plasma, olanzapine is bound to albumin and α 1-acid glycoprotein.
Fil- plażma, olanzapine jkun marbut ma ’ l- albumina u ma ’ α1- glikoproteina aċida.
Olanzapine plasma clearance after oral olanzapine is lower in females (18.9 l/ hr) versus males (27.3 l/ hr), and in non-smokers (18.6 l/ hr) versus smokers (27.7 l/ hr).
14 It- tneħħija ta ’ olanzapine mill- plażma wara li olanzapine ttieħed mill- ħalq hija aktar baxxa fin- nisa (18. 9 l/ siegħa) kontra l- irġiel (27. 3 l/ siegħa), u f’ minn ma jpejjipx (18. 6 l/ siegħa) kontra minn ipejjep (27. 7 l/ siegħa).
Similar pharmacokinetic differences between males and females and smokers and nonsmokers were observed in ZYPADHERA clinical trials.
Differenzi farmakokinetiċi simili bejn l- irġiel u n- nisa u minn ippejjep u minn ma jpejjipx ġew osservati fi studji kliniċi ta ’ ZYPADHERA.
However, the magnitude of the impact of gender, or smoking on olanzapine clearance is small in comparison to the overall variability between individuals.
Madanakollu, il- grad ta ’ l- impatt tas- sess, jew tipjip fuq it- tneħħija ta ’ olanzapine huwa żgħir f’ paragun mal- varjabbilità totali bejn l- individwi.
After repeated IM injections with 150 to 300 mg ZYPADHERA every two weeks, the 10th to 90th percentile of steady-state plasma concentrations of olanzapine were between 4.2 and 73.2 ng/ ml.
Wara injezzjonijiet repetuti ġol- muskoli b’ 150 sa 300 mg ZYPADHERA kull ġimagħtejn, l- 10 sa d- 90 perċentil ta ’ konċentrazzjonijiet ta ’ olanzapine fil- plażma f’ steady- state kienu bejn 4. 2 u 73. 2 ng/ ml.
The plasma concentrations of olanzapine observed across the dose range of 150mg every 4 weeks to 300mg every 2 weeks illustrate increased systemic olanzapine exposure with increased ZYPADHERA doses.
Il- konċentrazzjonijiet ta ’ olanzapine fil- plażma li ġew osservati fil- firxa kollha tad- doża ta ’ 150 mg kull 4 ġimgħat sa 300 mg kull ġimagħtejn juru żieda fl- espożizzjoni sistemika ta ’ olanzapine ma ’ żidiet fid- dożi ta ’ ZYPADHERA.
During the initial three months of treatment with ZYPADHERA, accumulation of olanzapine was observed but there was no additional accumulation during long-term use (12 months) in patients who were injected with up to 300 mg every two weeks.
Matul l- ewwel tliet xhur ta ’ kura b’ ZYPADHERA, ġiet osservata akkumulazzjoni ta ’ olanzapine iżda ma kienx hemm akkumulazzjoni addizzjonali matul l- użu fit- tul (12- il xahar) f’ pazjenti li kellhom injezzjoni sa 300 mg kull ġimagħtejn.
No specific investigations have been conducted in the elderly with ZYPADHERA.
Ma sarux investigazzjonijiet speċifiċi fl- anzjani b’ ZYPADHERA.
In healthy elderly (65 and over) versus non-elderly subjects, the mean elimination half-life was prolonged (51.8 versus
Għalkemm ZYPADHERA mhux irrakkomandat għall- kura fil- popolazzjoni anzjana sakemm ma tiġix stabbilita rutina ta ’ dożaġġ ittollerata tajjeb u effettiva b’ olanzapine mill- ħalq, f' anzjani b’ saħħithom (65 u fuqhom) kontra persuni mhux anzjani, il- medja tal- half- life ta ’ l- eliminazzjoni kien imtawwal (51. 8 kontra 33. 8 siegħa) u t - tneħħija kienet imnaqqsa (17. 5 kontra 18. 2 l/ siegħa).
The pharmacokinetic variability observed in the elderly is within the range for the non-elderly.
Il- varjabbilità farmakokinetika li ġiet osservata fl- anzjani hija fil- limiti ta ’ l- iskala għal persuni mhux anzjani.
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.
F’ 44 pazjenti b’ skiżofrenja > 65 sena, doża ta ’ 5 sa 20 mg/ jum ma ġietx assoċjata ma ’ l- ebda profil ta ’ ġrajjiet avversi li jintgħaraf.
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 hours) or clearance (21.2 versus 25.0 l/ hr).
F’ pazjenti b’ indeboliment tal- kliewi (tneħħija tal- krejatinina < 10 ml/ min) kontra pazjenti b’ saħħithom, ma kienx hemm differenza sinifikanti fil- medja tal- half- life ta ’ l- eliminazzjoni (37. 7 kontra 32. 4 siegħa) jew fit- tneħħija (21. 2 kontra 25. 0 l/ siegħa).
A mass balance study showed that approximately 57% of radiolabelled olanzapine appeared in urine, principally as metabolites.
Studju ta ’ bilanċ tal- massa wera li madwar 57% ta ’ olanzapine radjuattiv deher fl- urina, prinċipalment bħala metaboliti.
Although patients with renal impairment were not studied with ZYPADHERA, it is recommended that a well-tolerated and effective dosage regimen using oral olanzapine is established in patients with renal impairment before treatment with ZYPADHERA is initiated (see section 4.2).
Ghalkemm pazjenti b’ indeboliment tal- kliewi ma ġewx studjati b’ ZYPADHERA, huwa rrakkomandat li rutina ta ’ dożaġġ ittollerata tajjeb u effettiva b’ olanzapine mill- ħalq tiġi stabbilita f’ pazjenti b’ indeboliment tal- kliewi qabel ma tinbeda l- kura b’ ZYPADHERA (ara sezzjoni 4. 2).
In smoking subjects with mild hepatic dysfunction, mean elimination half-life (39.3 hours) of orally administered olanzapine was prolonged and clearance (18.0 l/ hr) was reduced analogous to non- smoking healthy subjects (48.8 hours and 14.1 l/ hr, respectively).
F' pazjenti li jpejpu u għandhom disfunzjoni tal- fwied ħafifa, il- medja tal- half life ta ’ l- eliminazzjoni (39. 3 siegħa) ta ’ olanzapine li ngħata mill- ħalq kienet imtawla u t- tneħħija (18. 0 l/ siegħa) kienet imnaqqsa bħal f' pazjenti b' saħħithom li ma jpejpux (48. 8 siegħa u 14. 1 l/ siegħa, rispettivament).
Although patients with hepatic impairment were not studied with ZYPADHERA, it is recommended that a well-tolerated and effective dosage regimen using oral olanzapine is established in patients with hepatic impairment before treatment with ZYPADHERA is initiated (see section 4.2).
Ghalkemm pazjenti b’ indeboliment tal- fwied ma ġewx studjati b’ ZYPADHERA, huwa rrakkomandat li rutina ta ’ dożaġġ ittollerata tajjeb u effettiva b’ olanzapine mill- ħalq tiġi stabbilita f’ pazjenti b’ indeboliment tal - fwied qabel ma tinbeda l- kura b’ ZYPADHERA (ara sezzjoni 4. 2).
In a study of oral olanzapine given to Caucasians, Japanese, and Chinese subjects, there were no differences in the pharmacokinetic parameters among the three populations.
Fi studju ta ’ olanzapine mill- ħalq f’ pazjenti Kawkasi, Ġappuniżi, u Ċiniżi, ma kien hemm ebda differenza fil- parametri farmakokinetiċi fost it- tliet popolazzjonijiet.
Preclinical safety studies were performed using olanzapine pamoate monohydrate.
Studji qabel l- użu kliniku dwar is- sigurtà saru bl- użu ta ’ olanzapine pamoate monohydrate.
The main findings found in repeat-dose toxicity studies (rat, dog), in a 2-year rat carcinogenicity study, and in toxicity to reproduction studies (rat, rabbit) were limited to injection site reactions for which no NOAEL could be determined.
Is- sejbiet ewlenin li nstabu fi studji ta ’ tossiċità b’ dożi rrepetuti (far, kelb), fi studju ta ’ karċinoġenità fil- far li dam sejjer sentejn, u fi studji ta ’ tossiċità fir- riproduzzjoni (far, fenek) kienu limitati għal reazzjonijiet fis- sit ta ’ l- injezzjoni li għalihom ma setax jiġi ddeterminat l- ebda NOAEL.
No new toxic effect resulting from systemic exposure to olanzapine could be identified.
L- ebda effett tossiku ġdid minħabba espożizzjoni sistemika għal olanzapine ma seta ’ jiġi identifikat.
However, systemic concentrations in these studies were generally less than that seen at effect levels in the oral studies; thus the information on oral olanzapine is provided below for reference.
Madanakollu, il - konċentrazzjonijiet sistemiċi f’ dawn l- istudji kien ġeneralment anqas minn dawk osservati fil- livelli ta ’ l- effett fl- istudji ta ’ olanzapine mill- ħalq; għaldaqstant it- tagħrif dwar olanzapine mill- ħalq huwa pprovdut hawn taħt għal referenza.
Acute (single-dose) toxicity Signs of oral toxicity in rodents were characteristic of potent antipsychotic compounds: hypoactivity, coma, tremors, clonic convulsions, salivation, and depressed weight gain.
Tossiċità akuta (b’ doża waħda) Sinjali ta ’ tossiċità orali fl- annimali gerriema kienu karatteristiċi tas- sustanzi antipsikotiċi qawwija: attività baxxa, koma, rogħda, konvulżjonijiet kloniċi, salivazzjoni, u tnaqqis fiż- żieda tal- piż.
The median lethal doses were approximately 210 mg/ kg (mice) and 175 mg/ kg (rats).
Id- dożi medjani letali kienu ta ’ madwar 210 mg/ kg (ġrieden) u 175 mg/ kg (firien).
Dogs tolerated single oral doses up to 100 mg/ kg without mortality.
Il- klieb ittolleraw dożi mill- ħalq b’ waħdiet sa 100 mg/ kg mingħajr mortalità.
Clinical signs included sedation, ataxia, tremors, increased heart rate, laboured respiration, miosis, and anorexia.
Sinjali kliniċi inkludew sedazzjoni, atassja, rogħda, żieda fir- rata tal- qalb, diffikultà fir- respirazzjoni, tidjiq tal- pupilla ta 'l- għajn, u l- anoreksja.
In monkeys, single oral doses up to 100 mg/ kg resulted in prostration and, at higher doses, semi-consciousness.
15 Fix- xadini, dożi mill- ħalq b’ waħdiet sa 100 mg/ kg irriżultaw f' prostrazzjoni u, f' dożi ogħla, f’ telf parzjali mis- sensi.
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.
Tossiċità b’ dożi rrepetuti Fi studji li damu sejrin mhux aktar minn 3 xhur fil- ġrieden u mhux aktar minn sena fil- firien u fil - klieb, l- effetti predominanti kienu d- depressjoni ta ’ CNS, effetti antikolinerġiċi, u disturbi ematoloġiċi periferali.
Tolerance developed to the CNS depression.
Kien hemm żviluppi fit- tolleranza għad- depressjoni ta ’ CNS.
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.
Effetti riversibbli konsistenti ma 'prolaktin elevat fil- firien inkludew tnaqqis fil- piż ta' l- ovarji u ta 'l- utru u tibdiliet morfoloġiċi fl- epitilju tal- vaġina u fil- glandoli tas- sider.
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.
Effetti fuq il- parametri ematoloġiċi nstabu f' kull speċi, inklużi tnaqqis relatat mad- doża ta ’ lewkoċiti li jiċċirkolaw fil- ġrieden u tnaqqis mhux speċifiku ta ’ lewkoċiti li jiċċirkolaw fil- firien; madanakollu, ma nstabet l- ebda evidenza ta 'ċitotossiċità tal- mudullun.
Reversible neutropenia, thrombocytopenia, or anaemia 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).
Newtropenja, tromboċitopenja jew anemija riversibbli żviluppaw fi ftit klieb ikkurati b '8 jew 10 mg/ kg/ jum (espożizzjoni totali ta' olanzapine [AUC] hija 12 sa 15- il darba aktar minn dik ta 'raġel mogħti doża ta' 12 mg).
In cytopenic dogs, there were no undesirable effects on progenitor and proliferating cells in the bone marrow.
Fi klieb b’ ċitopenja, ma kien hemm ebda effetti avversi fuq ċelloli proġenituri u ċelloli proliferanti tal- mudullun.
15 Olanzapine had no teratogenic effects.
Tossiċità fuq is- sistema riproduttiva Olanzapine ma kellu l- ebda effetti teratoġeniċi.
Oestrous 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).
Iċ- ċikli estruwi kienu affettwati b' dożi ta '1. 1 mg/ kg (3 darbiet id- doża massima fil - bniedem) u l- parametri tar- riproduzzjoni kienu influwenzati fil- firien mogħtija 3 mg/ kg (9 darbiet id - doża massima fil- bniedem).