qanastek/EMEA-V3 huggingface dataset:
3 Observed for fasting normal levels at baseline (< 5.17 mmol/ l) which increased to high (6.2 mmol/ l).
3 Innotat g al livelli normali waqt is- sawm fil- linja ba i (< 5. 17 mmol/ l) li diedu g al g oljin (6. 2 mmol/ l).
Changes in total fasting cholesterol levels from borderline at baseline (5.17- < 6.2 mmol/ l) to high (6.2 mmol/ l) were very common.
Tibdil fil- livelli tal- kolesterol totali waqt is- sawm mil- limitu tan- normal fil- linja ba i (5. 17 mmol/ l - < 6. 2 mmol/ l) g al g oljin (6. 2 mmol/ l) kienu komuni afna.
4 Observed for fasting normal levels at baseline (< 5.56 mmol/ l) which increased to high (7 mmol/ l).
9 4 Innotat g al livelli normali waqt is- sawm fil- linja ba i (< 5. 56 mmol/ l) li diedu g al g oljin (7 mmol/ l).
Changes in fasting glucose from borderline at baseline (5.56 - < 7 mmol/ l) to high (7 mmol/ l) were very common.
Tibdil fil- livelli taz- zokkor waqt is- sawm mil- limitu tan- normal fil- linja ba i (5. 56 - < 7 mmol/ l) g al g oljin (7m mol/ l) kienu komuni afna.
5 Observed for fasting normal levels at baseline (< 1.69 mmol/ l) which increased to high (2.26 mmol/ l).
5 Innotat g al livelli normali waqt is- sawm fil- linja ba i (< 1. 69 mmol/ l) li diedu g al g oljin (2. 26 mmol/ l).
Changes in fasting triglycerides from borderline at baseline (1.69 mmol/ l - < 2.26 mmol/ l) to high (2.26 mmol/ l) were very common.
Tibdil fit- trigli eridi waqt is- sawm mil- limitu tan- normal fil- linja ba i (1. 69 mmol/ l - < 2. 26 mmol/ l) g al g oljin (2. 26 mmol/ l) kienu komuni afna.
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 klini i, l- in idenza tal- marda ta' Parkinson u distonja f 'pazjenti kkurati b ’ olanzapine kienet numerikament og la, imma statistikament mhux differenti b’ mod sinifikattiv mill- pla ebo.
Olanzapine-treated patients had a lower incidence of parkinsonism, akathisia and dystonia compared with titrated doses of haloperidol.
Parkinson, ta 'l- akati ja u tad- distonja aktar
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 'rif dettaljat dwar passat pri -
9 7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been reported when olanzapine is stopped abruptly.
7 ew irrapportati sintomi akuti b al g araq, insomnja, rog da, ansjetà, tqallig u rimettar meta olanzapine jitwaqqaf f' daqqa.
8 Associated clinical manifestations (e. g., gynaecomastia, galactorrhoea, and breast enlargement) were rare.
8 Kienu rari l- manifestazzjonijiet klini i asso jati (e. ginekomastja, galaktorea, u tkabbir tas- sider).
In most patients, levels returned to normal ranges without cessation of treatment.
Fil- bi a l- kbira tal- pazjenti, il- livelli re g u lura g an- normal ming ajr 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.
Espo izzjoni g al perijodu twil ta ’ mien (g allinqas 48 img a) Il- proporzjon ta ’ pazjenti li kellhom tibdil avvers, klinikament sinifikanti fi - ieda fil- pi, fil- glucose, fil- kolesterol totali/ LDL/ HDL jew trigli eridi died ma - mien.
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 spi aw 9- 12- il xahar ta ’ terapija, ir- rata ta - ieda fil- medja tal- glucose fid- demm naqset wara kwa i 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 section 4.4).
Tag rif addizzjonali dwar popolazzjonijiet spe jali Fi studji klini i f’ pazjenti anzjani bid- demenzja, trattament b 'olanzapine kien asso jat ma ’ in idenza og la ta ’ mwiet u reazzjonijiet avversi erebro- vaskulari meta mqabbla mal- pla ebo (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 afna asso jati ma ’ l- u u ta’ olanzapine f’ dan il- grupp ta ’ pazjenti kienu mixi mhux normali u waqg at.
Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and urinary incontinence were observed commonly.
Il- pulmonite, i - ieda fit- temperatura tal - isem, il - letar ija, l- eritema, l- allu inazzjonijiet vi ivi u l- inkontinenza ta ’ l- awrina kienu komunement osservati.
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 klini i f’ pazjenti b’ psiko i dovuta g al medi ina (agonist ta' dopamine) asso jata mal- marda ta ’ Parkinson, id- deterjorament fis- sintomi tal- marda ta ’ Parkinson u fl- allu inazzjonijiet, kienu rrapportati b 'komuni afna u aktar ta ’ spiss milli bil- pla ebo. mod
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 wie ed f' pazjenti b' manija bipolari, terapija b’ valproate flimkien ma 'olanzapine rri ultat f' idenza ta '
Olanzapine administered with lithium or valproate resulted in increased levels (≥ 10%) of tremor, dry mouth, increased appetite, and weight gain.
(> 10%) ta 'da, nixfa fil - alq, ieda fl- aptit, u ieda fil- pi.
Speech disorder was also reported commonly.
Disturb fid- diskors kien ukoll rog komunement rappurtat.
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).
Waqt trattament b’ olanzapine flimkien ma ’ lithium jew divalproex, ieda ta '7% mil- linja ba i tal- pi tal - isem se et f' 17. 4% tal- pazjenti waqt it- trattament akut (sa 6 img at).
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.
Trattament b ’ olanzapine g al mien twil (sa 12- il xahar) bl- g an ta 'f'
Children and adolescents Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years.
pazjenti b 'mard bipolari kien asso jat ma' ieda ta '7% mil- linja ba i tal- pi tal - isem f' 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.
ewx imwettqa studji klini i mag mulin biex iqabblu l- adolexxenti ma '
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 ejja ti bor 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 ew identifikati biss waqt studji klini i ta ’ terminu qasir f' pazjenti adolexxenti. ieda fil- pi klinikament sinifikanti
Clinically significant weight gain (7%) appears to occur more frequently in the adolescent population compared to adults with comparable exposures.
10 (7%) tidher li sse aktar frekwentement fil- popolazzjoni ta '
The 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 ’ ieda fil- pi u l - proporzjon ta ’ pazjenti adolexxenti li kellhom ieda fil- pi klinikament sinifikanti kienu akbar b’ espo izzjoni g al perijodu twil ta ’ mien (g allinqas 24 img a) milli b’ espo izzjoni g al perijodu qasir ta ’ mien..
The frequency terms listed are defined as follows:
It- termini ta 'frekwenza elenkati huma mfissra kif ej:
Very common (10%), common (1% and < 10%).
Komuni afna (10%), komuni (1% u < 10%).
Weight gain9, elevated triglyceride levels10, increased appetite.
Disturbi fil- metaboli mu u n- nutrizzjoni Komuni afna: ieda fil- pi 9, livelli elevati ta' trigli eridi10, ieda fl- aptit.
Common:
11 Komuni:
Elevated cholesterol levels11 Nervous system disorders Very common:
Livelli g olja ta 'kolesterol Disturbi fis- sistema nervu a Komuni afna:
Sedation (including: hypersomnia, lethargy, somnolence).
Sedazzjoni (inklu i: ipersomnja, letar ija, sedazzjoni, sonnolenza).
Dry mouth Hepato-biliary disorders Very common:
Disturbi gastro- intestinali Komuni: alq xott Disturbi fil- fwied u fil- marrara Komuni afna: ieda ta 'Investigazzjonijiet
Elevations of hepatic transaminases (ALT/ AST; see section 4.4).
transaminases tal- fwied (ALT/ AST; ara sezzjoni 4. 4).
Investigations Very common:
Komuni afna:
9 Weight gain 7% of baseline body weight (kg) was very common and 15% of baseline body weight was common.
Tnaqqis fil- bilirubin totali, ieda ta 'GGT, livelli elevati ta' 9 ieda fil- pi ta '7% mil- linja ba i tal- pi tal - isem (kg) kienet komuni afna u ta' 15% mil- linja ba i tal- pi tal - isem 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’ espo izzjoni g al perijodu twil ta ’ mien (g allinqas 24 img a) kwa i nofs il- pazjenti adolexxenti iedu 15% u kwa i terz iedu 25% mill- pi ba ilari tag hom.
Among adolescent patients, mean weight gain was greatest in patients who were overweight or obese at baseline.
Fost il- pazjenti adolexxenti, il- medja ta - ieda fil- pi kienet l- i jed f’ pazjenti li b ala pi ba ilari kellhom pi ejjed jew kienu obe i.
10 Observed for fasting normal levels at baseline (< 1.016 mmol/ l) which increased to high (1.467 mmol/ l) and changes in fasting triglycerides from borderline at baseline (1.016 mmol/ l - < 1.467 mmol/ l) to high (1.467 mmol/ l).
10 Innotat g al livelli normali waqt is- sawm fil- linja ba i (< 1. 016 mmol/ l) li diedu g al g oljin (1. 467 mmol/ l) u tibdil fit- trigli eridi waqt is- sawm mil- limitu tan- normal fil- linja ba i (1. 016 mmol/ l - < 1. 467 mmol/ l) g al g oljin (1. 467 mmol/ l).
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 ba i (< 4. 39 mmol/ l) g al g oljin (5. 17 mmol/ l) kienu 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 ba i (4. 39 - < 5. 17 mmol/ l) g al g oljin (5. 17 mmol/ l) kienu komuni afna.
12 Elevated plasma prolactin levels were reported in 47.4% of adolescent patients.
12 F '47. 4% tal- pazjenti adolexxenti ew irrapportati livelli g oljin ta' prolactin fil- pla ma.
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.
Sinjali u sintomi Sintomi komuni afna meta ittie det do a e essiva (> 10% in idenza) jinkludu takikardija, a itazzjoni/ aggressività, di artrija, sintomi ekstrapiramidali varji, u telf tas- sensi li tvarja minn sedazzjoni sa 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 o ra morbu i ta 'a e essiva li huma medicament sinifikanti jinkludu d- delirju, il - do konvul joni, koma, possibilment Sindromu Newrolettiku Malinn, depressjoni respiratorja, aspirazzjoni fil- passa respiratorju, pressjoni tad- demm g olja jew baxxa, ta bit tal- qalb irregolari (< 2% tal - ka ijiet ta' a e essiva) u arrest kardjopulmonari. ew rappurtati ka ijiet fatali b 'i akuti u
Fatal outcomes have been reported for acute overdoses as low as 450 mg but survival has also been reported following acute overdose of 1,500 mg.
e essivi baxxi daqs 450 mg i da kien hemm ukoll ka fejn pazjent baqa aj wara do a e essiva akuta ta '1, 500 mg.
Management of overdose There is no specific antidote for olanzapine.
L- Immani ar ta 'Do a E essiva Ma hemm ebda antidotu spe ifiku g al olanzapine.
Standard procedures for management of overdose may be indicated (i. e. gastric lavage, administration of activated charcoal).
Jistg u jkunu ndikati l- mi uri tas- soltu g all- immani ar ta 'a e essiva (li huma l - asil gastriku, te id ta' am
The concomitant administration of activated charcoal was shown to reduce the oral bioavailability of olanzapine by 50 to 60%.
It- te id flimkien mal- fa am attivat wera li jnaqqas il- biodisponibilità orali ta' olanzapine b '50% sa 60%.
Symptomatic treatment and monitoring of vital organ function should be instituted according to clinical presentation, including treatment of hypotension and circulatory collapse and support of respiratory function.
klinika, inklu it- trattament g all- pressjoni baxxa u kolass ta - irkolazzjoni u sosteniment pulmonari.
Do not use epinephrine, dopamine, or other sympathomimetic agents with beta- agonist activity since beta stimulation may worsen hypotension.
Tu ax epinephrine, dopamine, jew sustanzi o ra simpatomimati i b '
Cardiovascular monitoring is necessary to detect possible arrhythmias.
istimulazzjoni beta tista' taggrava l- pressjoni baxxa.
Close medical supervision and monitoring should continue until the patient recovers.
G andha tkompli s- supervi joni medika mill - qrib u l- monitora jitkompla sakemm il- pazjent jirkupra.
N05A H03.
Grupp farmako- terapewtiku: antipsikotiku, kodi i 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 hija sustanza antipsikotika, kontra l- manija u stabilizzatur tal- burdata li turi profil farmakolo iku ta 'firxa wiesa' sistemi ta 'etturi.
In preclinical studies, olanzapine exhibited a range of receptor affinities (Ki; < 100 nM) for serotonin 5HT2A/ 2C, 5HT3, 5HT6; dopamine D1, D2, D3, D4, D5; cholinergic muscarinic receptors m1-m5; α 1 adrenergic; and histamine H1 receptors.
Fi studji ta 'qabel l- u u kliniku, olanzapine wera firxa ta' affinitajiet g ar- ri etturi (Ki; < 100 nM) serotoni i 5HT2A/ 2C, 5HT3, 5HT6; dopamine D1, D2, D3, D4, D5: ri etturi muskarini i koliner i i m1- m5; ∝ 1 adrener i i; u ri etturi ta '
Animal behavioral studies with olanzapine indicated 5HT, dopamine, and cholinergic antagonism, consistent with the receptor-binding profile.
olanzapine indikaw antagoni mu g al 5HT, g al dopamine, u g al dak koliner iku, konsistenti mal - profil tar- ri ettur li jorbot.
Olanzapine demonstrated a greater in vitro affinity for serotonin 5HT2 than dopamine D2 receptors and greater 5HT2 than D2 activity in vivo, models.
Olanzapine wera affinità akbar in vitro g al serotonin 5HT2 milli g ar - ri etturi ta ’ dopamine D2 u attività in vivo akbar g al 5HT2 milli g al 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.
Olanzapine naqset ir- rispons kundizzjonat u ta '
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.
skansar, test indikattiv ta 'l- attività antipsikotika, f' i do
Unlike some other antipsychotic agents, olanzapine increases responding in an “ anxiolytic” test.
Kuntrarju g all- medi ini o ra antipsikoti i, olanzapine i id ir- rispons f 'anksjolitiku. test
In a single oral dose (10 mg) Positron Emission tomography (PET) study in healthy volunteers, olanzapine produced a higher 5HT2A than dopamine D2 receptor occupancy.
Fi studju b 'a wa da orali (10 mg) fejn intu at it- tomografija bl- Emissjoni tal- Pozitroni (PET) do f' voluntiera b' ithom, olanzapine ipprodu a okkupanza ta '
In addition, a Single Photon Emission Computed Tomography (SPECT) imaging study in schizophrenic patients revealed that olanzapine-responsive patients had lower striatal D2 occupancy than some other antipsychotic- and risperidone-responsive patients, while being comparable to clozapine-responsive patients.
Ma 'dan, studju b ’ (SPECT) f' pazjenti ski ofreni i wera li l- pazjenti li jirreagixxu g al olanzapine kellhom okkupanza strijatali D2 anqas milli f 'pazjenti li rrispondew g al xi antipsikoti i o ra jew g al risperidone, waqt li kienu komparabbli g all- pazjenti li irrispondew g al clozapine.
In two of two placebo and two of three comparator controlled trials with over 2,900 schizophrenic patients presenting with both positive and negative symptoms, olanzapine was associated with statistically significantly greater improvements in negative as well as positive symptoms.
pazjenti ski ofreni i li g andhom kemm sintomi negattivi kif ukoll sintomi po ittivi, olanzapine kien asso jat ma 'titjib akbar, statistikament sinifikanti, f' sintomi negattivi kif ukoll po ittivi.
In a multinational, double-blind, comparative study of schizophrenia, schizoaffective, and related disorders which included 1,481 patients with varying degrees of associated depressive symptoms (baseline mean of 16.6 on the Montgomery-Asberg Depression Rating Scale), a prospective secondary analysis of baseline to endpoint mood score change demonstrated a statistically significant improvement (p= 0.001) favouring olanzapine (-6.0) versus haloperidol (-3.1).
F’ studju komparattiv, double- blind u multinazzjonali ta ’ ski ofrenija, ta ’ manifestazzjonijiet ski oaffettivi u disturbi relatati o ra li kien jinkludi 1, 481 pazjent li kellhom gravità differenti ta ’ l - asso jati sintomi dipressivi (medja ta ’ punte g ta ’ 16. 6 me ud fil- bidu tal- kura skond l- iskala li tivvaluta d- dipressjoni ta ’ Montgomery- Asberg), anali i prospettiva sekondarja tat- tibdil fil- punte ta ’ l- atte ament bejn il- bidu u fl- a ar tal- kura wriet titjib statistikament sinifikanti (p=0. 001) favur olanzapine (- 6. 0) kontra haloperidol (- 3. 1).
In patients with a manic or mixed episode of bipolar disorder, olanzapine demonstrated superior efficacy to placebo and valproate semisodium (divalproex) in reduction of manic symptoms over 3 weeks.
minn 3 img at.
Olanzapine also demonstrated comparable efficacy results to haloperidol in terms of the proportion of patients in symptomatic remission from mania and depression at 6 and 12 weeks.
Olanzapine wera wkoll ri ultati effika ji li jistg u ji u kumparati ma 'termini tal- proporzjon ta' pazjenti f '
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.
Fi studju ta 'terapija ta' pazjenti trattati flimkien b’ lithium jew b’ valproate g al minimu ta' img atejn, i - jieda ta 'olanzapine 10 mg (terapija flimkien ma ’ lithium jew valproate) wara 6 img at irri ultat f'
In a 12-month recurrence prevention study in manic episode patients who achieved remission on olanzapine and were then randomised to olanzapine or placebo, olanzapine demonstrated statistically significant superiority over placebo on the primary endpoint of bipolar recurrence.
Fi studju ta' 12- il xahar ta' prevenzjoni ta' rikorrenza f 'pazjenti b' episodju ta' manija, li kienu di à ikkontrollati b’ olanzapine, imbag ad kienu mog tija ming ajr g a la olanzapine jew il- pla ebo,
Olanzapine also showed a statistically significant advantage over placebo in terms of preventing either recurrence into mania or recurrence into depression.
12 olanzapine wera superjorita sinifikanti u statistikament superjuri fuq il- pla ebo fuq l- g an ewlieni tar - rikorrenza bipolari. olanzapine uriet ukoll vanta statistiku u sinifikanti fuq il- pla ebo fil - prevenzjoni, kemm f 'attakki odda ta' manija kif ukoll f' attakki odda ta 'depressjoni.
In a second 12-month recurrence prevention study in manic episode patients who achieved remission with a combination of olanzapine and lithium and were then randomised to olanzapine or lithium alone, olanzapine was statistically non-inferior to lithium on the primary endpoint of bipolar recurrence (olanzapine 30.0%, lithium 38.3%; p = 0.055).
Fit- tieni studju ta' 12- il xhar dwar ir- rikorrenza preventiva f 'pazjenti b' episodju ta' manija li kienu ikkontrollati b’ olanzapine u l- lithium flimkien, kienu mbag ad mqassmin ming ajr g a la u mog tija olanzapine jew il- lithium wa du. olanzapine kien statistikament mhux inferjuri g all- lithium fuq l - g an ewlieni ta 'rikorrenza bipolari (olanzapine 30. 0%, lithium 38. 3%; p = 0. 055).
12 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.
Fi studju ta '18- il xhar f' pazjenti b 'manija jew b' episodji m allta stabilizzati fuq olanzapine flimkien ma 'stabilizzatur tal- burdata (lithium jew valproate), l- u u fit- tul ta' olanzapine flimkien ma ’ lithium jew l- valproate ma kienx statistikament sinifikanti superjuri g all- lithium jew g all- valproate wa du biex jittardja r- rikorrenza bipolari, kif definit skond il- kriterji (dijanjosti i) tas- sindromu.
Paediatric population The experience in adolescents (ages 13 to 17 years) is limited to short term efficacy data in schizophrenia (6 weeks) and mania associated with bipolar I disorder (3 weeks), involving less than 200 adolescents.
Popolazzjoni pedjatrika L- esperjenza fl- adolexxenti (minn 13 sa 17- il sena) hija limitata g al dejta dwar l- effika ja g al mien qasir fl- iski ofrenja (6 img at) u manija asso jata ma '
Olanzapine was used as a flexible dose starting with 2.5 and ranging up to 20 mg/ day.
Waqt il- kura b '
During treatment with olanzapine, adolescents gained significantly more weight compared with adults.
olanzapine, l- adolexxenti iedu aktar fil- pi b 'sinifikanti meta mod
The magnitude of changes in fasting total cholesterol, LDL cholesterol, triglycerides, and prolactin (see sections 4.4 and 4.8) were greater in adolescents than in adults.
Il- grad ta 'tibdil fil- kolesterol totali waqt is- sawm, kolesterol tat- tip LDL,
There are no data on maintenance of effect and limited data on long term safety (see sections 4.4 and 4.8).
trigli eridi, u prolactin (ara sezzjonijiet 4. 4 u 4. 8) kien akbar fl- adolexxenti milli fl- adulti.
5.2 Pharmacokinetic properties
l- effett u hemm tag rif limitat dwar is- sigurtà fit- tul (ara sezzjonijiet
Olanzapine orodispersible tablets may be used as an alternative to olanzapine coated tablets.
5. 2 Tag rif farmakokinetiku
Olanzapine is well absorbed after oral administration, reaching peak plasma concentrations within 5 to 8 hours.
Olanzapine hija assorbita sew wara li tittie ed mill - alq, til aq l- og la kon entrazzjonijiet fil- pla ma fi mien 5 sa 8 sig at.
The absorption is not affected by food.
L- assorbiment ma ji ix affetwat mill- ikel.
Absolute oral bioavailability relative to intravenous administration has not been determined
Il- biodisponibilità assoluta orali relattiva g al amministrazzjoni fil- vina ma 'kienitx determinata.
The major circulating metabolite is the 10-N-glucuronide, which does not pass the blood brain barrier.
Il- prodott metaboliku li l- aktar ji irkola huwa 10- N- glukoronide, li ma jaqsamx il- barriera bejn id- demm u l- mo.
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.
farmakolo ika in vivo milli olanzapine fi studji fuq l- annimali.
The predominant pharmacologic activity is from the parent olanzapine.
L- attività farmakolo ika predominanti ejja minn olanzapine nnifsu.
After oral administration, the mean terminal elimination half-life of olanzapine in healthy subjects varied on the basis of age and gender.
Wara li jittie ed mill - alq, il- medja tal- half life ta' l- eliminazzjoni terminali ta 'olanzapine f' etti b 'ithom varjat fuq il- ba i ta'
In healthy elderly (65 and over) versus non-elderly subjects, the mean elimination half-life was prolonged (51.8 versus 33.8 hr) and the clearance was reduced (17.5 versus 18.2 l/ hr).
F' anzjani b 'ithom (65 u fuqhom) f'
The pharmacokinetic variability observed in the elderly is within the range for the non-elderly.
paragun ma 'pazjenti mhux anzjani, il- half life ta'
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 'pazjenti ski ofreni i li g andhom > 65 sena, id- dosa minn 5 sa 20 mg / urnata ma kienx 44 asso jat ma' profil distint ta '
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).
F' pazjenti femminili f 'paragun ma' dawk maskili l- medja tal- half life ta' l- eliminazzjoni iet kemmxejn mtawla (36. 7 kontra 32. 3 sig at) u t- tne ija tnaqqset (18. 9 kontra 27. 3 l/ hr).
However, olanzapine (5-20 mg) demonstrated a comparable safety profile in female (n=467) as in male patients (n=869).
Madankollu, olanzapine (5- 20 mg) wera profil ta' sigurtà' kumparabbli f 'pazjenti nisa (n=467) u f' pazjenti r iel (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).
mard tal- kliewi (tne ija tal- krejatinina < 10 ml/ min) f '
A mass balance study showed that approximately 57% of radiolabelled olanzapine appeared in urine, principally as metabolites.
Studju ta ’ tqabbil tal- pi ijiet wera bejn wie ed u ie or 57% ta 'olanzapine radjuattiv fl- urina, prin ipalment b ala prodotti 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).
F' pazjenti li jpejpu u g andhom disfunzjoni tal- fwied afifa, il- half life ta' l- eliminazzjoni medja (39. 3 sieg a) twalet u t- tne ija (18. 0 l/ hr) tnaqqset b al f 'pazjenti b' ithom li ma jpejpux (48. 8 sieg a u sa 14. 1 l/ hr, rispettivament).
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).
13 F' pazjenti li ma jpejpux f 'paragun ma' dawk li jpejpu (ir iel u nisa) il- medja tal- half life ta' l - eliminazzjoni kien imtawwal (38. 6 kontra 30. 4 sieg a) u l- clearance tnaqqset (18. 6 kontra 27. 7 l/ hr).
The plasma clearance of olanzapine is lower in elderly versus young subjects, in females versus males, and in non-smokers versus smokers.
Il- clearance ta 'olanzapine mill- pla ma huwa anqas f' nisa f' paragun ma 'iel, u f'
However, the magnitude of the impact of age, gender, or
pazjenti anzjani f 'paragun ma'
13 smoking on olanzapine clearance and half-life is small in comparison to the overall variability between individuals.
ta' l- età, is- sess, jew tat- tipjip fuq il- clearance ta' olanzapine u fuq il- half life huwa g ir f 'paragun mal- varjabilità totali ta' bejn individwi.
In a study of Caucasians, Japanese, and Chinese subjects, there were no differences in the pharmacokinetic parameters among the three populations.
Fi studju ta' pazjenti kawkasi, appuni i, u ini i, ma kien hemm ebda differenzi fil- parametri farmakokineti i fost it- tliet popolazzjonijiet.
The plasma protein binding of olanzapine was about 93% over the concentration range of about 7 to about 1000 ng/ ml.
Ir- rabta mal- proteina fil- pla ma ta' olanzapine kienet madwar 93% fuq il- firxa tal- kon entrazzjoni ta 'l- albumina u ∝1- acid - madwar 7 sa xi 1000 ng/ ml.
Olanzapine is bound predominantly to albumin and α 1-acid-glycoprotein.
Olanzapine hija fil- bi a ’ l kbira marbuta ma 'glycoprotein.
The pharmacokinetics of olanzapine are similar between adolescents and adults.
olanzapine fl- adolexxenti u fl- adulti hija
In clinical studies, the average olanzapine exposure was approximately 27% higher in adolescents.
Fi studji klini i, il- medja ta' espo izzjoni g al olanzapine kienet bejn wie ed u ie or ta '27% og la fl- adolexxenti.
Demographic differences between the adolescents and adults include a lower average body weight and fewer adolescents were smokers.
Id- differenzi demografi i bejn l- adolexxenti u l- adulti jinkludu medja anqas ta 'pi tal - isem u anqas adolexxenti kienu jpejpu.
Such factors possibly contribute to the higher average exposure observed in adolescents.
Fatturi b al dawn x 'medja ta' espo izzjoni og la osservata fl- adolexxenti.
5.3 Preclinical safety data
aktarx li jikkontribwixxu g all -
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.
Tossi ità akuta (do a wa da) Sinjali ta' tossi ità orali fir- rodenti kienu simili g as- sustanzi newroletti i qawwija: attività baxxa, koma, rog da, konvul jonijiet kloni i, salivazzjoni, u tnaqqis fi - jieda tal- pi.
The median lethal doses were approximately 210 mg/ kg (mice) and 175 mg/ kg (rats).
Id- do i medjani li jwasslu g all- mewt kienu bejn wie ed u ie or 210 mg/ kg (rieden) u 175 mg/ kg (firien).
Dogs tolerated single oral doses up to 100 mg/ kg without mortality.
Il- klieb fel u do i orali b’ wa diet sa 100 mg/ kg ming ajr mortalità.
In monkeys, single oral doses up to 100 mg/ kg resulted in prostration and, at higher doses, semi-consciousness.
Sinjali klini i inkludew sedazzjoni, atassja, rog da, jieda fir- rata tal- qalb, diffikultà fir- respirazzjoni, tidjiq tal- pupilla ta 'ajn, u l- anoreksja. l- g Fix- xadini, do i orali b’ wa diet sa 100 mg/ kg irri ultaw f' 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.
Fi studji sa 3 xhur fil - rieden u sa sena fil- firien u fil- klieb, l- effetti li ippredominaw kienu d - depressjoni CNS, effetti antikoliner i i, u di ordnijiet periferali ematolo i i. viluppat it- tolleranza g ad- depressjoni CNS.
Tolerance developed to the CNS depression.
Il- parametri ta 'vilupp kienu mnaqqsa b' i g oljin.
Growth parameters were decreased at high doses.
konsistenti ma '
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.
prolaktin elevat fil- firien inkludew tnaqqis fil- pi ta '
Haematologic toxicity:
Tossi ità ematolo ika:
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 ematolo i i nstabu f 'spe i, inklu i tnaqqis relatat kull mad- do a fil- lewko iti li ji irkolaw fil - rieden u tnaqqis mhux spe ifiku fil- lewko iti li ji irkolaw fil- firien; madankollu, ma nstabet l- ebda prova ta' itotossi ità tal- mudullun.
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).
Newtropenja, trombo itopenja jew l- anemija riversibbli viluppaw fi ftit klieb ittrattati b 'jew 10 mg/ kg / urnata 8 (espo izzjoni totali ta' olanzapine [erja ta t il- kurva] hija 12 sa 15- il darba aktar minn dik ta' el ra mog ti do a ta 'mg).
In cytopenic dogs, there were no adverse effects on progenitor and proliferating cells in the bone marrow.
Fi klieb fejn l- g add ta - elluli tad- demm huwa anqas minn normal, ma kien 12 hemm ebda effetti avversi fuq elloli pro enituri u elloli proliferanti tal- mudullun.
Reproductive toxicity Olanzapine had no teratogenic effects.
Tossi ità fuq is- sistema riproduttiva Olanzapine ma kellha ebda effetti terato eni i.
Sedation affected mating performance of male rats.
Is- sedazzjoni affettwat il - ila ta ’ tg ammir tal- firien ta 'sess maskili.
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).
I - ikli estruwi kienu affettwati b 'i ta' mg/ kg (3 darbiet id- do a massima fil -
In the offspring of rats given olanzapine, delays in fetal development and transient decreases in offspring activity levels were seen.
do
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.
1. 1
Carcinogenicity Based on the results of studies in mice and rats, it was concluded that olanzapine is not carcinogenic.
Fil- frie tal- firien mog tija olanzapine, kienu osservati dewmien fl - i vilupp tal- fetu u tnaqqis g al xi mien fl- attività tal- frie.
14 6.
14 Muta eni ità Olanzapine ma ikkaw atx muta eni ità jew klasto eni ità f '
PHARMACEUTICAL PARTICULARS
6 TAG RIF FARMA EWTIKU
Gelatin Mannitol (E421) Aspartame (E951) Sodium methyl parahydroxybenzoate (E219) Sodium propyl parahydroxybenzoate (E217)
Gelatin Mannitol (421) Aspartame (E951) Sodium methyl parahydroxybenzoate (E219) Sodium propyl parahydroxybenzoate (E217)
Not applicable.
Ma jg oddx f 'il- ka dan
Store in the original package in order to protect from light and moisture.
A en fil- pakkett ori inali sabiex tilqa ’ mid- dawl u mill- umdità.
6.5 Nature and contents of container
6. 5 In- natura tal- kontenitur u ta 'dak li hemm o fih
Aluminium blister strips in cartons of 28, 35, 56 or 70 orodispersible tablets per carton.
28,
Not all pack sizes may be marketed.
kollha jkunu g all- skop kummer jali.
No special requirements.
L- ebda ti ijiet spe jali
MARKETING AUTHORISATION HOLDER
ID- DETENTUR TA 'L- AWTORIZZAZZJONI G AT- TQEG ID FIS- SUQ
MARKETING AUTHORISATION NUMBER(S)
NUMRU( I) TA 'L- AWTORIZZAZZJONI G AT- TQEG ID FIS- SUQ
DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION
DATA TA 'L- EWWEL AWTORIZZAZZJONIJI/ TI DID TA' L- AWTORIZZAZZJONI
3 February 2000 Date of latest renewal:
3 ta' Frar 2000 Data ta ’ l- a ar ti did:
DATE OF REVISION OF THE TEXT
DATA TA 'META
ZYPREXA VELOTAB 10 mg orodispersible tablets
ZYPREXA VELOTAB 10 mg pilloli li jin allu fil - alq
Each orodispersible tablet contains 10 mg olanzapine.
Kull pillola li tin all fil - alq g andha 10 mg olanzapine.
Each orodispersible tablet contains 0.80 mg aspartame, 0.15 mg sodium methyl parahydroxybenzoate, 0.05 mg sodium propyl parahydroxybenzoate.
Kull pillola li tin all fil - alq fiha 0. 80 mg aspartame 0. 15 mg sodium methyl parahydroxybenzoate 0. 05 mg sodium propyl parahydroxybenzoate.
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.
Waqt it- trattament g as- ski ofrenja, g al episodju ta' manija u g all- prevenzjoni tar- rikorrenza fid - di ordni bipolari, d- do a ta 'kuljum jista' sussegwentement ji i a ustat fuq il- ba i ta 'l- istat kliniku individwali minn 5 mg sa 20 mg / urnata. jieda g al do a akbar mid- do a tal- bidu rakkomandata g andha ting ata biss wara rivalutazzjoni klinika xierqa u eneralment g andha ssir f' intervalli ta '
An increase to a dose greater than the recommended starting dose is advised only after
Olanzapine tista '
16 appropriate clinical reassessment and should generally occur at intervals of not less than 24 hours.
ting ata fuq l- ikel jew fuq stonku vojt g ax l -
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.
18 Psiko i relatata mad- demenzja u/ jew disturbi fil- komportament Olanzapine mhux approvat g at- trattament tal- psiko i relatata mad- demenzja u/ jew disturbi fil - komportament, u mhux irrakkomandat g all- u u f’ dan il- grupp partikolari ta ’ pazjenti, dovut g al ieda fil- mortalità u r- riskju ta ’ in ident erebro- vaskulari.
Lipid alterations should be managed as clinically appropriate, particularly in dyslipidemic patients and in patients with risk factors for the development of lipids disorders.
Tibdil fil- livell tax- xa mijiet g andu ji i kkontrollat b’ mod klinikamet xieraq spe jalment f’ pazjenti b’ ammonti mhux normali ta ’ xa mijiet fid- demm u f’ pazjenti li g andhom fatturi ta ’ riskju g all- i vilupp ta ’ disturbi fix- xa mijiet.
18 Anticholinergic activity While olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical trials revealed a low incidence of related events.
19 Attività antikoliner ika Waqt li olanzapine wera attività antikoliner ika in vitro, ersperjenza waqt il- provi klini i uriet in idenza baxxa ta 'rajjiet relatati.
Seizures have been reported to occur rarely in patients when treated with olanzapine.
Fil- ma oranza ta '
In most of these cases, a history of seizures or risk factors for seizures were reported.
a essjonijiet jew fatturi ta' riskju g al a essjonijiet kienu rappurtati.
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.
Diskajne ja Tardiva Fi studji komparattivi li damu sena jew anqas, olanzapine kien asso jat ma 'idenza mnaqqsa ta' in diskajne ja f 'ultat tat- trattament b'
The clinical consequences are likely to be limited, but clinical monitoring is recommended and an increase of olanzapine dose may be considered if necessary (See section 4.2).
Il- konsegwenzi klini i x 'aktarx huma limitati, imma hija rakkomandata l - osservazzjoni klinika u tista' i kkunsidrata jieda fid- do a ta 'Sezzjoni 4. 2).
Inhibition of CYP1A2 Fluvoxamine, a specific CYP1A2 inhibitor, has been shown to significantly inhibit the metabolism of olanzapine.
I - jieda medja f’ olanzapine Cmax wara t- te id ta '
The mean increase in olanzapine AUC was 52% and 108% respectively.
I - jieda medja fl- AUC ta' olanzapine kienet 52% u 108% rispettivament.
A lower starting dose of olanzapine should be considered in patients who are using fluvoxamine or any other CYP1A2 inhibitors, such as ciprofloxacin.
21 ju aw fluvoxamine jew xi inibituri o ra ta' CYP1A2, b al ciprofloxacin.
A decrease in the dose of olanzapine should be considered if treatment with an inhibitor of CYP1A2 is initiated.
G andha ti i kkunsidrata tnaqqis fid- do a ta' olanzapine jekk jinbeda xi trattament b 'inibitur ta' CYP1A2.
20 Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have not been found to significantly affect the pharmacokinetics of olanzapine.
Fluvoxetine (inibitur CYP2D6), do i b’ wa diet t 'anta idi (aluminium, magnesium) jew cimetidine ma nstabux li jaffettwaw sinifikatament il- komportament farmakokinetiku ta' olanzapine.
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.
Pazjenti g andhom jing ataw parir biex ma jreddawx tarbija jekk qed jie du olanzapine.
21 transient asymptomatic elevations of hepatic transaminases (see section 4.4), rash, asthenia, fatigue and oedema.
l- olanzapine kienu sonnolenza, ieda fil- pi, eosinofilja,
Nervous system disorders Somnolence Cardiac disorders
Disturbi fis- sistema nervu a Sonnolenza Disturbi fil- qalb
Vascular disorders
Bradikardija QTc imtawwal (ara sezzjoni 4. 4)
Bradycardia QTc prolongation (see section 4.4)
Takikardija / fibrillazzjoni ventrikulari, mewt g all- g arrieda (ara sezzjoni 4. 4)
Ventricular tachycardia/ fibrillation, sudden death (see section 4.4)
23 Disturbi vaskulari
22 Hepato-biliary disorders
Disturbi fil- fwied u fil- marrara
4 Observed for fasting normal levels at baseline (< 5.56 mmol/ l) which increased to high (7 mmol/ l).
4 Innotat g al livelli normali waqt is- sawm fil- linja ba i (< 5. 56 mmol/ l) li diedu g al g oljin (7 mmol/ l).
5 Observed for fasting normal levels at baseline (< 1.69 mmol/ l) which increased to high (2.26 mmol/ l).
24 5 Innotat g al livelli normali waqt is- sawm fil- linja ba i (< 1. 69 mmol/ l) li diedu g al g oljin (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 ew irrapportati sintomi akuti b al g araq, insomnja, rog da, ansjetà, tqallig u rimettar meta olanzapine jitwaqqaf f' daqqa.
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 ejja ti bor 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 ew identifikati biss waqt studji klini i ta ’ terminu qasir f' pazjenti adolexxenti. ieda fil- pi klinikament sinifikanti (7%) tidher li sse aktar frekwentement fil- popolazzjoni ta '
Clinically significant weight gain (7%) appears to occur more frequently in the adolescent population compared to adults with comparable exposures.
adulti li kellhom l- istess ammont ta ’ espo izzjoni g all- prodott.
Cardiovascular monitoring is necessary to detect possible arrhythmias.
26 biex tinduna b’ ta bit irregolari tal- qalb li jista ’ jse.
In a 12-month recurrence prevention study in manic episode patients who achieved remission on olanzapine and were then randomised to olanzapine or placebo, olanzapine demonstrated statistically significant superiority over placebo on the primary endpoint of bipolar recurrence.
Fi studju ta' 12- il xahar ta' prevenzjoni ta' rikorrenza f 'pazjenti b' episodju ta' manija, li kienu di à ikkontrollati b’ olanzapine, imbag ad kienu mog tija ming ajr g a la olanzapine jew il- pla ebo, olanzapine wera superjorita sinifikanti u statistikament superjuri fuq il- pla ebo fuq l- g an ewlieni tar - rikorrenza bipolari. olanzapine uriet ukoll vanta statistiku u sinifikanti fuq il- pla ebo fil - prevenzjoni, kemm f 'attakki odda ta' manija kif ukoll f' attakki odda ta 'depressjoni.
Olanzapine also showed a statistically significant advantage over placebo in terms of preventing either recurrence into mania or recurrence into depression.
Fit- tieni studju ta' 12- il xhar dwar ir- rikorrenza preventiva f 'pazjenti b' episodju ta' manija li kienu ikkontrollati b’ olanzapine u l- lithium flimkien, kienu mbag ad mqassmin ming ajr g a la u mog tija
In a second 12-month recurrence prevention study in manic episode patients who achieved remission with a combination of olanzapine and lithium and were then randomised to olanzapine or lithium alone, olanzapine was statistically non-inferior to lithium on the primary endpoint of bipolar recurrence (olanzapine 30.0%, lithium 38.3%; p = 0.055).
27 olanzapine jew il- lithium wa du. olanzapine kien statistikament mhux inferjuri g all- lithium fuq l - g an ewlieni ta' rikorrenza bipolari (olanzapine 30. 0%, lithium 38. 3%; p = 0. 055).
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.
Fi studju ta '18- il xhar f' pazjenti b 'manija jew b' episodji m allta stabilizzati fuq olanzapine flimkien ma 'stabilizzatur tal- burdata (lithium jew valproate), l- u u fit- tul ta' olanzapine flimkien ma ’ lithium jew l- valproate ma kienx statistikament sinifikanti superjuri g all- lithium jew g all- valproate wa du biex jittardja r- rikorrenza bipolari, kif definit skond il- kriterji (dijanjosti i) tas- sindromu.
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).
F' pazjenti li jpejpu u g andhom disfunzjoni tal- fwied afifa, il- half life ta' l- eliminazzjoni medja (39. 3 sieg a) twalet u t- tne ija (18. 0 l/ hr) tnaqqset b al f 'pazjenti b' ithom li ma jpejpux (48. 8 sa sieg a u 14. 1 l/ hr, rispettivament).
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).
F' pazjenti li ma jpejpux f 'paragun ma' dawk li jpejpu (ir iel u nisa) il- medja tal- half life ta' l - eliminazzjoni kien imtawwal (38. 6 kontra 30. 4 sieg a) u l- clearance tnaqqset (18. 6 kontra 27. 7 l/ hr).
The plasma clearance of olanzapine is lower in elderly versus young subjects, in females versus males, and in non-smokers versus smokers.
Il- clearance ta' olanzapine mill- pla ma huwa anqas f' pazjenti anzjani f 'paragun ma' su etti g ar, fin - nisa f' paragun ma 'iel, u f'
However, the magnitude of the impact of age, gender, or
dawk li ma jpejpux f 'paragun ma'
27 smoking on olanzapine clearance and half-life is small in comparison to the overall variability between individuals.
ta' l- età, is- sess, jew tat- tipjip fuq il- clearance ta' olanzapine u fuq il- half life huwa g ir f 'paragun mal- varjabilità totali ta' bejn individwi.
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).
bniedem) u l- parametri tar- riproduzzjoni kienu influwenzati fil- firien mog tija 3 mg/ kg (9 darbiet id - do a massima fil- bniedem).
In the offspring of rats given olanzapine, delays in fetal development and transient decreases in offspring activity levels were seen.
Fil- frie tal- firien mog tija olanzapine, kienu osservati dewmien fl - i vilupp tal- fetu u tnaqqis g al xi mien fl- attività tal- frie.
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.
testijiet ta' mutazzjoni tal- mikrobi kif ukoll testijiet fuq il- mammiferi kemm in vitro kif ukoll in vivo.
Carcinogenicity Based on the results of studies in mice and rats, it was concluded that olanzapine is not carcinogenic.
29 Kan ero eni ità Ibba at fuq ri ultati ta' studji fuq il - rieden u l- firien, kien konklu li olanzapine mhuwiex kan ero eniku.
Aluminium blister strips in cartons of 28, 35 56, or 70 orodispersible tablets per carton.
28,
ZYPREXA VELOTAB 15 mg orodispersible tablets
ZYPREXA VELOTAB 15 mg pilloli li jin allu fil - alq
Each orodispersible tablet contains 15 mg olanzapine.
Kull pillola li tin all fil - alq g andha 15 mg olanzapine.
For a full list of excipients, see section 6.1.
Kull pillola li tin all fil - alq 1. 20 mg aspartame 0. 225 mg sodium methyl parahydroxybenzoate 0. 075 mg sodium propyl parahydroxybenzoate G al- lista kompleta ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.