natgillin/translations-raw huggingface dataset:
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.
ni
72 Olanzapine can be given without regards for meals as absorption is not affected by food.
jo
Children and adolescents Olanzapine is not recommended for use in children and adolescents below 18 years of age due to a lack of data on safety and efficacy.
afiniteto za serotoninske 5- HT2 kot za dopaminske receptorje D2, v modelih in vivo pa več aktivnost jo 5- HT 2 kot D2.
A greater magnitude of weight gain, lipid and prolactin alterations has been reported in short term studies of adolescent patients than in studies of adult patients (see sections 4.4, 4.8, 5.1 and 5.2).
Elektrofiziološ raziskave so pokazale, da je olanzapin selektivno zmanjš prož mezolimbič (A10) dopaminergič nih
Elderly A lower starting dose (5 mg/ day) is not routinely indicated but should be considered for those 65 and over when clinical factors warrant (see also section 4.4).
ke nevronov, medtem ko je imel majhen uč na striatne (A9) nih inek
Renal and/ or hepatic impairment A lower starting dose (5 mg) should be considered for such patients.
poti, vpletene v motorič delovanje.
In cases of moderate hepatic insufficiency (cirrhosis, Child-Pugh Class A or B), the starting dose should be 5 mg and only increased with caution.
Gre za test,
Gender The starting dose and dose range need not be routinely altered for female patients relative to male patients.
no
Smokers The starting dose and dose range need not be routinely altered for non-smokers relative to smokers.
al
Dose escalation, when indicated, should be conservative in such patients.
ki pokaž antipsihotič delovanje pri manjš odmerkih od tistih, ki povzroč katalepsijo, tj. uč
(See sections 4.5 and 5.2.)
e
4.3 Contraindications
no
Hypersensitivity to the active substance or to any of the excipients.
ih
Patients with known risk for narrow-angle glaucoma.
ijo
4.4 Special warnings and precautions for use
inek,
Patients should be closely monitored during this period.
ki kaž na motorič než
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.
e
In the same clinical trials, cerebrovascular adverse events (CVAE e. g., stroke, transient ischemic attack), including fatalities, were reported.
ne
0.4%, respectively).
elene uč inke.
Age > 75 years and vascular/ mixed type dementia were identified as risk factors for CVAE in association with olanzapine treatment.
Za razliko od nekaterih drugih antipsihotikov olanzapin poveč
The efficacy of olanzapine was not established in these trials.
odzivanje v "anksiolitičnem" testu.
Olanzapine was started at 2.5 mg/ day and titrated to a maximum of 15 mg/ day based on investigator judgement.
Pri pozitronski emisijski tomografiji (PET) s posameznim peroralnim odmerkom (10 mg) pri zdravih prostovoljcih je olanzapin povzroč več zasedenost receptorjev 5- HT 2A kot dopaminskih receptorjev
Neuroleptic Malignant Syndrome (NMS) NMS is a potentially life-threatening condition associated with antipsychotic medicinal product.
il
Hyperglycaemia and diabetes Hyperglycaemia and/ or development or exacerbation of diabetes occasionally associated with ketoacidosis or coma has been reported rarely, including some fatal cases (see section 4.8).
jo
Lipid alterations Undesirable alterations in lipids have been observed in olanzapine-treated patients in placebo- controlled clinical trials (see section 4.8).
D2.
Lipid alterations should be managed as clinically appropriate, particularly in dyslipidemic patients and in patients with risk factors for the development of lipids disorders.
Slikovna raziskava SPECT (Single Photon Emission Computed Tomography) je pri bolnikih s shizofrenijo razkrila, da je bila zasedenost striatnih receptorjev D 2 pri bolnikih, ki so se odzivali na olanzapin, manjš kot pri bolnikih, ki so se odzivali na nekatere druge antipsihotike in na risperidon, a medtem ko je bila primerljiva z bolniki, ki so se odzivali na klozapin.
Anticholinergic activity While olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical trials revealed a low incidence of related events.
Pri dveh od dveh s placebom kontroliranih in dveh od treh primerjalno kontroliranih preizkuš anjih na več 2900 bolnikih s shizofrenijo, ki so imeli tako pozitivne kot negativne simptome, je olanzapin kot statistič znač izboljš negativne in tudi pozitivne simptome.
However, as clinical experience with olanzapine in patients with concomitant illness is limited, caution is advised when prescribing for patients with prostatic hypertrophy, or paralytic ileus and related conditions.
al
In cases where hepatitis (including hepatocellular, cholestatic or mixed liver injury) has been diagnosed, olanzapine treatment should be discontinued.
V dvojno slepi primerjalni raziskavi shizofrenije ter shizoafektivnih in sorodnih motenj, v kateri je sodelovalo več av in skupaj 1481 bolnikov z različ
74 Neutropenia Caution should be exercised in patients with low leukocyte and/ or neutrophil counts for any reason, in patients receiving medicines known to cause neutropenia, in patients with a history of drug-induced bone marrow depression/ toxicity, in patients with bone marrow depression caused by concomitant illness, radiation therapy or chemotherapy and in patients with hypereosinophilic conditions or with myeloproliferative disease.
drž
Discontinuation of treatment Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting have been reported very rarely (< 0.01%) when olanzapine is stopped abruptly.
č
QT interval In clinical trials, clinically meaningful QTc prolongations (Fridericia QT correction [QTcF] ≥ 500 milliseconds [msec] at any time post baseline in patients with baseline QTcF < 500 msec) were uncommon (0.1% to 1%) in patients treated with olanzapine, with no significant differences in associated cardiac events compared to placebo.
nimi stopnjami pridruž
Thromboembolism Temporal association of olanzapine treatment and venous thromboembolism has very rarely (< 0.01%) been reported.
depresivnih enih
General CNS activity Given the primary CNS effects of olanzapine, caution should be used when it is taken in combination with other centrally acting medicines and alcohol.
simptomov (izhodišna srednja vrednost 16, 6 na Montgomery- Asbergovi lestvici ocenjevanja č depresije), je prospektivna sekundarna analiza spremembe od izhodišne do konč ocenene
In most of these cases, a history of seizures or risk factors for seizures was reported.
67 razpolož pokazala statistič znač izboljš (p = 0, 001) v korist olanzapina (– 6) v primerjavi
Tardive Dyskinesia In comparator studies of one year or less duration, olanzapine was associated with a statistically significant lower incidence of treatment emergent dyskinesia.
ilno
Postural hypotension Postural hypotension was infrequently observed in the elderly in olanzapine clinical trials.
anje
Long-term outcomes associated with these events have not been studied and remain unknown (see sections 4.8 and 5.1).
s haloperidolom (– 3, 1).
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Pri bolnikih z manič ali meš epizodo bipolarne motnje je olanzapin v treh tednih veliko bolj
4.5 Interaction with other medicinal products and other forms of interaction
no
Interaction studies have only been performed in adults.
ano
Potential interactions affecting olanzapine Since olanzapine is metabolised by CYP1A2, substances that can specifically induce or inhibit this isoenzyme may affect the pharmacokinetics of olanzapine.
uč inkovito zmanjš jakost manič simptomov kot placebo in seminatrijev valproat (divalproeks).
Induction of CYP1A2 The metabolism of olanzapine may be induced by smoking and carbamazepine, which may lead to reduced olanzapine concentrations.
nih
Inhibition of CYP1A2 Fluvoxamine, a specific CYP 1A2 inhibitor, has been shown to significantly inhibit the metabolism of olanzapine.
Odstotek bolnikov, zdravljenih z olanzapinom v simptomatski remisiji manije in depresije, je bil po 6 in 12 tednih primerljiv z odstotkom bolnikov, ki so se zdravili s haloperidolom.
The mean increase in olanzapine AUC was 52% and 108% respectively.
V raziskavi, v kateri so vsaj dva tedna spremljali sočasno zdravljenje bolnikov z litijem ali valproatom, je dodatek 10 mg olanzapina bolj zmanjš jakost simptomov manije po 6 tednih kot pri monoterapiji z litijem ali al valproatom.
A decrease in the dose of olanzapine should be considered if treatment with an inhibitor of CYP 1A2 is initiated.
V 12- meseč raziskavi o ponovitvi bolezni pri bolnikih z manič epizodo, ki so z zdravljenjem z
Decreased bioavailability Activated charcoal reduces the bioavailability of oral olanzapine by 50 to 60% and should be taken at least 2 hours before or after olanzapine.
ni
Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have not been found to significantly affect the pharmacokinetics of olanzapine.
no
Potential for olanzapine to affect other medicinal products Olanzapine may antagonise the effects of direct and indirect dopamine agonists.
olanzapinom dosegli remisijo, nato pa so jim naključ predpisali jemanje olanzapin ali placebo, je bil no olanzapin ob primarni konč toč ponovitve bipolarne motnje statistič znač boljšod placeba.
Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e. g.
no
Olanzapine showed no interaction when co-administered with lithium or biperiden.
ilno
Therapeutic monitoring of valproate plasma levels did not indicate that valproate dosage adjustment is required after the introduction of concomitant olanzapine.
i
General CNS activity Caution should be exercised in patients who consume alcohol or receive medicinal products that can cause central nervous system depression.
Statistič znač prednost pred placebom je dosegel tudi pri prepreč
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).
no
QTc interval Caution should be used if olanzapine is being administered concomitantly with medicinal products known to increase QTc interval (see section 4.4).
ilno
76 4.6 Pregnancy and lactation
evanju ponovnega pojava
Pregnancy:
manije ali depresije.
There are no adequate and well-controlled studies in pregnant women.
V drugi 12- meseč raziskavi o prepreč
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.
ni
In a study in lactating, healthy women, olanzapine was excreted in breast milk.
evanju ponovitve bolezni pri bolnikih z manič epizodo, ki so no
Patients should be advised not to breast feed an infant if they are taking olanzapine.
z zdravljenjem s kombinacijo olanzapina in litija dosegli remisijo, nato pa so jim naključ predpisali no samo olanzapin ali samo litij, je bil olanzapin ob primarni konč toč ponovitve bipolarne motnje primerljiv z litijem (olanzapin 30%, litij 38, 3%; p = 0, 055).
4.7 Effects on ability to drive and use machines
ni
No studies on the effects on the ability to drive and use machines have been performed.
ki
4.8 Undesirable effects
V 18- meseč raziskavi o soč
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.
ni
The frequency terms listed are defined as follows:
asnem zdravljenju bolnikov z manič
10%), common (≥ 1% and < 10%), uncommon (≥ 0.1% and < 1%), rare (≥ 0.01% and
ali meš epizodo, stabiliziranih no ano
< 0.1%), very rare (< 0.01%), not known (cannot be estimated from the data available).
z olanzapinom in s stabilizatorjem razpolož (litijem ali valproatom), dolgotrajno soč
Very common
enja
Common
asno
Uncommon
ene
Not known
nih)
Blood and the lymphatic system disorders Immune system disorders
no
Eosinophilia
ilno
Leukopenia Neutropenia
samo z litijem ali samo z valproatom.
Thrombocytopenia Allergic reaction
Zdravljenje so zač z 2, 5 mg in odmerek postopno poveč
Metabolism and nutrition
eli
disorders
evali do 20 mg
Weight gain1
na dan.
Elevated cholesterol levels 2,3 Elevated glucose levels 4 Elevated triglyceride levels2,5 Glucosuria Increased appetite
Vrednosti skupnega holesterola, merjenega na teše, holesterola LDL in trigliceridov ter ravni prolaktina (gl. poglavji 4. 4 in 4. 8) so se bolj poveč pri mladostnikih kot pri odraslih.
Development or exacerbation of diabetes occasionally associated with ketoacidosis or coma, including some fatal cases (see section 4.4) Hypothermia
Podatkov ale o vzdrž evalnem uč ni, podatkov o dolgoroč varnosti ni dovolj (gl. poglavji 4. 4 in 4. 8)
Nervous system disorders Somnolence
5. 2 Farmakokinetič lastnosti ne
Dizziness Akathisia6
Hrana na absorpcijo ne vpliva.
Seizures where in most cases a history of
V krvi je glavni presnovek 10- N- glukuronid, ki ne prehaja skozi krvnomož
77
Citokroma P450 CYP1A2 in P450 CYP2D6 prispevata k
Cardiac disorders
V raziskavah na ž
Parkinsonism6 Dyskinesia 6
ivalih so bili presnovki in
seizures or risk factors for seizures were reported Neuroleptic malignant syndrome (see section 4.4) Dystonia (including oculogyration) Tardive dyskinesia Discontinuation symptoms7
Prevladujoč farmakološ aktivnost
Vascular disorders
k
Bradycardia QT c prolongation (see section 4.4)
o o
Ventricular tachycardia/ fibrillation, sudden death (see section 4.4)
ko
Orthostatic hypotension
povzroč olanzapin.
Thromboembolism (including pulmonary embolism and deep vein thrombosis)
a
Gastrointestinal disorders
ni
Mild, transient anticholinergic effects including constipation and dry mouth
as
Pancreatitis
anja
Hepato-biliary disorders
zdravih osebah razlikoval glede na starost in spol.
Transient, asymptomatic elevations of hepatic transaminases (ALT, AST), especially in early treatment (see section 4.4)
Pri zdravih starejš osebah (65 let in več je bil v primerjavi z mlajš osebami srednji razpolovni
Hepatitis (including hepatocellular, cholestatic or mixed liver injury)
ih
Rash
imi
Photosensitivity reaction Alopecia
č izloč podaljš (51, 8 v primerjavi s 33, 8 ure), oč pa zmanjš (17, 5 v primerjavi z as
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 levels 8 1
anja an
High creatine phosphokinase Increased total bilirubin
istek
Increased alkaine phosphatase
an
Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories.
18, 2 l/ h).
Weight gain ≥ 7% of baseline body weight was very common and ≥
Farmakokinetič variabilnost, opaž pri starejš je v okvirih razpona za mlajš Pri 44
15% of baseline body
na
78
e.
6 In clinical trials, the incidence of parkinsonism and dystonia in olanzapine-treated patients was numerically higher, but not statistically significantly different from placebo.
bolnikih s shizofrenijo, starejš od 65 let, odmerjanje od 5 do 20 mg/ dan ni pokazalo razlike v profilu ih než elenih učinkov.
8 Associated clinical manifestations (e. g., gynaecomastia, galactorrhoea, and breast enlargement) were rare.
68 Pri ž kimi je bil srednji razpolovni č izloč nekoliko podaljš (36, 7 v
In most patients, levels returned to normal ranges without cessation of treatment.
enskah v primerjavi z moš
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.
an
Very common adverse reactions associated with the use of olanzapine in this patient group were abnormal gait and falls.
primerjavi z 32, 3 ure), oč istek pa zmanjš (18, 9 v primerjavi s 27, 3 l/ h).
Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and urinary incontinence were observed commonly.
Vendar je olanzapin (5 do an 20 mg) pokazal primerljiv profil varnosti tako pri bolnicah (n = 467) kot pri bolnikih (n = 869).
In clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with Parkinson’ s disease, worsening of Parkinsonian symptomatology and ha llucinations were reported very commonly and more frequently than with placebo.
Pri bolnikih z okvarjenim ledvič delovanjem (kreatininski oč
Speech disorder was also reported commonly.
istek < 10 ml/ min) v primerjavi z
Long-term olanzapine treatment (up to 12 months) for recurrence prevention in patients with bipolar disorder was associated with an increase of  from baseline body weight in 39.9% of 7% patients.
zdravimi osebami ni bilo znač razlike v srednjem razpolovnem č izloč (37, 7 v primerjavi z 32, 4 ure) ali v oč
79 Children and adolescents Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years.
asu
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.
anja
The frequency terms listed are defined as follows:
istku (21, 2 v primerjavi s 25, 0 l/ h).
Very common (≥ 10%), common (≥ 1% and < 10%).
Raziskava ravnovesja snovi je pokazala, da se približ 57% radioaktivno označ
Metabolism and nutrition disorders Very common:
enega olanzapina pojavi v urinu, predvsem v obliki presnovkov.
Weight gain9, elevated triglyceride levels10, increased appetite.
Pri kadilcih z blagimi motnjami v jetrnem delovanju je bil srednji razpolovni č izloč (39, 3 ure) podaljš oč
11 Common:
anja
Elevated cholesterol levels Nervous system disorders Very common:
an, istek (18 l/ h) pa zmanjš v primerjavi z zdravimi nekadilci (48, 8 ure oziroma 14, 1 l/ h). an
Sedation (including: hypersomnia, lethargy, somnolence).
V primerjavi med kadilci in nekadilci (moš in ž kimi nekadilcih podaljš (38, 6 v primerjavi s 30, 4 ure),
Gastrointestinal disorders Common:
enskami) je bil srednji razpolovni oč
Dry mouth Hepato-biliary disorders Very common:
č izloč pri as anj
Elevations of hepatic transaminases (ALT/ AST; see section 4.4).
an
Investigations Very common:
istek pa zmanjš
9 Weight gain ≥ 7% of baseline body weight (kg) was very common and ≥ 15% of baseline body weight was common.
(18, 6 v primerjavi s 27, 7 l/ h). an
Among adolescent patients, mean weight gain was greatest in patients who were overweight or obese at baseline.
istek olanzapina je bil manjšpri starejš v primerjavi z mlajš pri ž Plazemsk
4.9 Overdose
i oč i
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.
imi,
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.
enskah v
80 Management of overdose There is no specific antidote for olanzapine.
primerjavi z moš kimi in pri nekadilcih v primerjavi s kadilci.
Standard procedures for management of overdose may be indicated (i. e. gastric lavage, administration of activated charcoal).
Vendar pa je vpliv starosti, spola ali istek in razpolovni č olanzapina majhen v primerjavi s povpreč variabilnostjo med kajenja na oč posamezniki.
The concomitant administration of activated charcoal was shown to reduce the oral bioavailability of olanzapine by 50 to 60%.
Raziskava, v kateri so sodelovali parametrih.
Do not use epinephrine, dopamine, or other sympathomimetic agents with beta- agonist activity since beta stimulation may worsen hypotension.
belci, Japonci in Kitajci, ni pokazala razlik
PHARMACOLOGICAL PROPERTIES
v farmakokinetič nih
5.1 Pharmacodynamic properties
Olanzapin se vež predvsem na albumin in kisli glikoprotein alfa 1.
N05AH03.
no no
In preclinical studies, olanzapine exhibited a range of receptor affinities (Ki; < 100 nM) for serotonin 5 HT2A/ 2C, 5 HT3, 5 HT6; dopamine D1, D2, D3, D4, D5; cholinergic muscarinic receptors m1-m5; α adrenergic; and histamine H1 receptors.
e
In a single oral dose (10 mg) Positron Emission tomography (PET) study in healthy volunteers, olanzapine produced a higher 5 HT2A than dopamine D2 receptor occupancy.
Mladostniki Farmakokinetika olanzapina je bila pri mladostnikih (starih od 13 do 17 let) podobna kot pri odraslih.
In addition, a SPECT imaging study in schizophrenic patients revealed that olanzapine-responsive patients had lower striatal D2 occupancy than some other antipsychotic- and risperidone-responsive patients, while being comparable to clozapine-responsive patients.
Pri mladostnikih je
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.
nih
In a multinationational, double-blind, comparative study of schizophrenia, schizoaffective, and related disorders which included 1,481 patients with varying degrees of associated depressive symptoms (baseline mean of 16.6 on the Montgomery-Asberg Depression Rating Scale), a prospective secondary analysis of baseline to endpoint mood score change demonstrated a statistically significant improvement (p=0.001) favouring olanzapine (-6.0) versus haloperidol (-3.1).
no
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.
bila povpreč telesna masa manjš manj mladostnikov je bilo kadilcev.
In a co-therapy study of patients treated with lithium or valproate for a minimum of 2 weeks, the addition
Mož je, da taki dejavniki
81 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.
na
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.
a,
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).
no
There are no data on maintenance of effect and limited data on long term safety (see sections 4.4 and 4.8).
vplivajo na več povpreč izpostavljenost, ki so jo opazili pri mladostnikih.
5.2 Pharmacokinetic properties
jo
Olanzapine is well absorbed after oral administration, reaching peak plasma concentrations within 5 to 8 hours.
no
In female versus male subjects the mean elimination half life was somewhat prolonged (36.7 versus 32.3 hr) and the clearance was reduced (18.9 versus 27.3 l/ hr).
5. 3 Predklinič podatki o varnosti ni
However, olanzapine (5-20 mg) demonstrated a comparable safety profile in female (n=467) as in male patients (n=869).
Akutna toksič (toksič po enkratnem odmerku)