natgillin/translations-raw huggingface dataset:
4. 4).
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).
8 4. 8 Bivirkninger
4.8 Undesirable effects
4. 4).
Post-injection syndrome events have occurred with ZYPADHERA leading to symptoms consistent with olanzapine overdose (see sections 4.2 and 4.4).
De kliniske tegn og symptomer inkluderede symptomer på sedation (fra mild sedation til koma) og/ eller delirium (herunder forvirring, desorientering, ophidselse/ uro, angst og anden kognitiv svækkelse).
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).
Andre bemærkede symptomer inkluderer ekstrapyramidale symptomer, dysartri, ataksi, aggression, svimmelhed, svaghed., hypertension og krampe.
Other symptoms noted include extrapyramidal symptoms, dysarthria, ataxia, aggression, dizziness, weakness, hypertension and convulsion.
I kliniske forsøg med ZYPADHERA var den eneste bivirkning, som blev rapporteret med en statistisk signifikant højere frekvens i ZYPADHERAgruppen end i placebogruppen, sedation (ZYPADHERA 8. 2%, placebo 2. 0%).
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
Blandt alle de patienter, som blev behandlet med ZYPADHERA, blev sedation rapporteret af 4. 7%.
Among all ZYPADHERA treated patients, sedation was reported by 4.7% of patients.
I kliniske forsøg med ZYPADHERA var incidensen af bivirkninger relateret til injektionsstedet omkring 8%.
In clinical trials with ZYPADHERA the incidence of injection site related adverse events was approximately 8%.
Andre rapporterede bivirkningsreaktioner var (efter faldende hyppighed): knudelignende reaktioner, erytemlignende reaktioner, ikke- specifikke bivirkningsreaktioner relateret til injektionsstedet, irritation, ødemlignende reaktioner, suggilation, blødning og anæstesi.
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.
Disse bivirkningsreaktioner opstod hos omkring 0, 1 til 1, 1% af patienterne.
These events occurred in about 0.1 to 1.1% of patients.
De bivirkninger, som er nævnt nedenfor, er set efter administration af oral olanzapin, men kan forekomme efter administration af ZYPADHERA.
The undesirable effects listed below have been observed following administration of oral olanzapine but may occur following administration of ZYPADHERA.
Meget almindelig (≥ 10%), almindelig (≥ 1% og < 10%), ikke almindelig (≥ 0, 1% og < 1%), sjælden (≥ 0, 01% og < 0, 1%), meget sjælden (< 0, 01%), ikke kendt (kan ikke estimeres ud fra forhåndenværende data).
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).
Krampeanfald, hvor
Nervous system disorders Somnolence
Meget almindelig Hjerte
Dizziness Akathisia6 Parkinsonism6 Dyskinesia6
Almindelig Akatisi6 Parkinsonisme6 Dyskinesi6
Seizures where in most cases a history of seizures or risk factors for seizures were reported Neuroleptic malignant syndrome (see section 4.4) Dystonia (including oculogyration) Tardive dyskinesia Discontinuation symptoms7
Ikke kendt der i de fleste tilfælde var tidligere krampeanfald eller observeret risikofaktorer Malignt neuroleptikasyndrom (se pkt.
9
Knogler, led, muskler og bindevæv Rhabdomyolyse Nyrer og urinveje Vandladningsbesvær Det reproduktive system og mammae Priapismus Almene symptomer og reaktioner på administrationsstedet Asteni Træthed Ødemer Undersøgelser Forhøjede plasmaprolaktinniveau er8
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
Høje niveauer af kreatininfosfokinase Forøget total bilirubin
High creatine phosphokinase Increased total bilirubin
10 1 Klinisk signifikant vægtøgning blev observeret på tværs af alle Body Mass Index (BMI) kategorier ved baseline.
Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories.
Vægtøgning ≥ 7% af kropsvægt ved baseline var meget almindeligt, og vægtøgning ≥ 15% af kropsvægt ved baseline var almindeligt.
Weight gain ≥ 7% of baseline body weight was very common and ≥ 15% of baseline body weight was common.
Patienter med en vægtøgning på ≥ 25% af deres kropsvægt ved baseline ved langvarig behandling var meget almindeligt.
Patients gaining ≥ 25% of their baseline body weight with long-term exposure were very common.
4 Observeret for fastende normalt niveau ved baseline (< 5, 56 mmol/ l), der blev øget til højt niveau (≥ 7 mmol/ l).
10 4 Observed for fasting normal levels at baseline (< 5.56 mmol/ l) which increased to high (≥ 7 mmol/ l).
Langvarig behandling (mindst 48 uger) Andelen af patienter, som havde klinisk signifikante bivirkninger i form af vægtøgning, glucose, total/ LDL/ HDL kolesterol eller triglycerider, steg over tid.
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.
Hos voksne patienter som fuldførte en 9 - 12 måneders behandling faldt hastigheden hvormed den gennemsnitlige blodglucoseværdi steg efter omkring 4- 6 måneder.
In adult patients who completed 9-12 months of therapy, the rate of increase in mean blood glucose slowed after approximately 4-6 months.
I kliniske forsøg med patienter med lægemiddelinduceret psykose (dopaminagonist) i forbindelse med Parkinsons sygdom, var hyppigheden af rapporter om forværring af Parkinson symptomatologi og hallucinationer meget almindeligt og oftere end med placebo.
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.
Under behandling med olanzapin sammen med lithium eller valproat forekom en stigning på ≥ 7% af legemsvægt ved baseline hos 17, 4% af patienterne ved akut behandling (op til 6 uger).
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).
11 tilbagefald hos patienter med bipolar sygdom blev forbundet med en stigning på ≥7% af legemsvægt ved baseline hos 39, 9% af patienterne.
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.
Klinisk signifikant vægtøgning (≥ 7%) synes at forekomme hyppigere i den unge population sammenlignet med voksne patienter i tilsvarende behandling.
The
Størrelsen af vægtøgningen og andelen af unge patienter, som havde en klinisk signifikant vægtøgning, var højere ved langvarig behandling (mindst 24 uger) end ved kortvarig behandling.
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.
Hyppighederne er defineret som følger:
The frequency terms listed are defined as follows:
9 Øget vægt ≥ 7% af legemsvægt (kg) ved baseline var meget almindelig og ≥ 15% af legemsvægt ved baseline var almindelig.
9 Weight gain ≥ 7% of baseline body weight (kg) was very common and ≥ 15% of baseline body weight was common.
Ved langvarig behandling (mindst 24 uger) fik omkring halvdelen af de unge patienter en vægtøgning ≥ 15%, og næsten en tredjedel fik en vægtøgning ≥ 25% af deres kropsvægt ved baseline.
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.
10 De observerede normalniveauer ved baseline (< 1. 016 mmol/ l ved faste) steg til høje niveauer (≥ 1. 467 mmol/ l), og triglyceridniveauerne ved faste, der lå ved grænsen ved baseline (≥ 1. 016 mmol/ l
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).
11 Ændringer i de totale kolesterolniveauer fra normale ved baseline (< 4. 39 mmol/ l ved faste) til høje (≥ 5. 17 mmol/ l) var almindelige.
11 Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/ l) to high (≥ 5.17 mmol/ l) were observed commonly.
Ændringer i de totale kolesterolniveauer ved faste fra grænsetilfælde ved baseline (≥ 4. 39 - < 5. 17 mmol/ l) til høje (≥ 5. 17 mmol/ l) var meget almindelige.
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.
12 Forhøjede plasmaprolaktinniveauer blev rapporteret hos 47, 4% af de unge patienter.
12 Elevated plasma prolactin levels were reported in 47.4% of adolescent patients.
4. 4).
If signs and symptoms of overdose consistent with post injection syndrome are observed, appropriate supportive measures should be taken (see section 4.4).
Reference information vedrørende oral olanzapin er angivet nedenfor, selvom overdosis er mindre sandsynlig med parenteral end med oral medicinering:
While overdose is less likely with parenteral than oral medication, reference information for oral olanzapine overdose is presented below:
12 Tegn og symptomer Meget almindelige symptomer på overdosering (forekomst > 10%) inkluderer takykardi, agitation/ aggressivitet, dysartri, forskellige ekstrapyramidale symptomer og nedsat bevidsthedsniveau, som varierer fra sedation til koma.
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.
Andre medicinsk signifikante følgetilstande af overdosering inkluderer delirium, kramper, koma, muligt malignt neuroleptikasyndrom, respirationsbesvær, aspiration, hypertension eller hypotension, hjertearytmi (< 2% af overdoseringstilfældene) og kardiopulmonært stop.
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.
2 g oral olanzapin.
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.
Symptomatisk behandling og overvågning af de vitale organers funktion bør indledes afhængig af den kliniske tilstand, inklusive behandling af hypotension og kredsløbssvigt samt understøttende behandling af den respiratoriske funktion.
Symptomatic treatment and monitoring of vital organ function should be instituted according to clinical presentation, including treatment of hypotension
Brug ikke adrenalin, dopamin eller andre sympatomimetiske midler med beta- agonistaktivitet, da beta- stimulation kan forværre hypotension.
Do not use epinephrine, dopamine, or other sympathomimetic agents with beta-agonist activity since beta stimulation may worsen hypotension.
I prækliniske undersøgelser udviste olanzapin affinitet (Ki; < 100 nM) til serotonin 5 HT2A/ 2C, 5 HT3, 5 HT6, dopamin D1, D2, D3, D4, D5, de kolinerge muskarine receptorer m1- m5, de α1- adrenerge receptorer og histamin H1- receptorerne.
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.
Olanzapin udviste større affinitet til serotonin 5HT2 - end til dopamin D2- receptorerne i in vitro- undersøgelser og større 5 HT2 - end D2- aktivitet i in vivo- modeller.
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.
Elektrofysiologiske undersøgelser viste, at olanzapin selektivt reducerede ” firing ” ved de mesolimbiske (A10) dopaminerge neuroner, hvorimod det kun havde lille påvirkning af de striatale (A9) baner for motorisk funktion.
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.
I behandlingen og vedligeholdelsesbehandlingen af skizofreni er effekten af ZYPADHERA i overensstemmelse med den anerkendte effekt af den orale formulering af olanzapin.
The effectiveness of ZYPADHERA in the treatment and maintenance treatment of schizophrenia is consistent with the established effectiveness of the oral formulation of olanzapine.
Dette niveau var i overensstemmelse med det, som blev fundet ved behandling med oral olanzapin.
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.
I alt 1469 patienter med skizofreni blev inkluderet i 2 pivotalstudier:
A total of 1469 patients with schizophrenia were included in 2 pivotal trials:
Det første, som var et 8- uger placebokontrolleret forsøg, blev udført med voksne patienter (n=404), som havde akutte psykotiske symptomer.
The first, an 8-week, placebo controlled trial conducted in adult patients (n=404) who were experiencing acute psychotic symptoms.
Det samlede resultat af Positive and Negative Symptom Score (PANSS) viste signifikant bedring fra baseline (den gennemsnitlige totale PANSS var
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).
I forhold til besøg indikerede den gennemsnitlige ændring i PANSS fra baseline til endpoint, at på dag 3 havde patienterne i behandlingsgrupperne 300 mg/ 2 uger og 405 mg/ 4 uger statistisk signifikant større reduktioner i PANSS sammenlignet med placebo (henholdsvis - 8, 6, - 8, 2 og - 5, 2).
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).
Alle 3 ZYPADHERA - behandlingsgrupper viste statistisk signifikant større bedring end placebo fra slutningen af uge 1.
All 3 ZYPADHERA treatment groups showed statistically significantly greater improvement than placebo beginning by end of Week 1.
Det andet var et langtidsstudie med klinisk stabile patienter (n=1065) (gennemsnitlig, total PANSS var 54, 33 til 57, 75 ved baseline), som initialt blev behandlet med oral olanzapin i 4 til 8 uger og derpå skiftet til at fortsætte med oral olanzapin eller til ZYPADHERA i 24 uger.
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.
ZYPADHERA behandlingsgrupperne med 150 mg og 300 mg, som blev givet hver anden uge (doserne er lagt sammen til analysebrug), og 405 mg, som blev givet hver 4. uge, blev ikke dårligere end med de kombinerede doser på 10, 15 og 20 mg oral olanzapin (doserne er lagt sammen til analysebrug).
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
Dette blev bestemt som hastigheden af forværringen af symptomerne på skizofreni (eksacerbationsrater på henholdsvis 10%, 10% og 7%).
13 exacerbation of symptoms of schizophrenia (respective exacerbation rates, 10%, 10% 7%).
Den kombinerede behandlingsgruppe med 150 mg og 300 mg/ 2 uger var ikke dårligere end behandlingsgruppen med 405 mg/ 4 uger (eksacerbationsrate på 10% for hver gruppe) 24 uger efter randomiseringen.
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.
Pædiatrisk population ZYPADHERA er ikke blevet undersøgt i den pædiatriske population.
Paediatric population ZYPADHERA has not been studied in the paediatric population.
Erfaringen med unge (alder 13 – 17 år) omfatter mindre end 200 unge og er begrænset til kortvarige effektdata ved skizofreni (6 uger) og mani i forbindelse med bipolar I- sygdom (3 uger).
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.
Oral olanzapin blev brugt i en fleksibel dosis, som begyndte med 2, 5 mg, og som gik op til 20 mg daglig.
Oral olanzapine was used as a flexible dose starting with 2.5 and ranging up to 20 mg/ day.
4. 4 og 4. 8) var større hos de unge end hos de voksne.
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.
Den overvejende cirkulerende metabolit er 10- N- glucuronid.
The major circulating metabolite is the 10-N-glucuronide.
Cytokrom P450- CYP1A2 og P450- CYP2D6 bidrager til dannelsen af N- desmethyl og 2- hydroxymethyl metabolitter, der udviser signifikant mindre farmakologisk aktivitet in vivo end olanzapin i dyreundersøgelser.
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.
Frigivelsen formindskes i løbet af otte til tolv uger Det er ikke nødvendigt med antipsykotisk supplering ved initieringen af behandling med ZYPADHERA (se pkt. 4. 2).
Antipsychotic supplementation is not required at the initiation of ZYPADHERA treatment (see section 4.2).
1000 ng/ ml.
The plasma protein binding of olanzapine is about 93% over the concentration range of 7 to about 1000 ng/ mL.
14 α1- syre- glycoprotein i plasma.
In plasma, olanzapine is bound to albumin and α 1-acid glycoprotein.
Olanzapins plasmaclearance efter oral indgift af olanzapin er lavere hos kvinder (18, 9 l/ time) end hos mænd (27, 3 l/ time) og hos ikke- rygere (18, 6 l/ time) end hos rygere (27, 7 l/ time).
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).
Lignende farmakokinetiske forskelle mellem mænd og kvinder samt rygere og ikke- rygere blev observeret i kliniske forsøg med ZYPADHERA.
Similar pharmacokinetic differences between males and females and smokers and nonsmokers were observed in ZYPADHERA clinical trials.
Efter gentagne i. m. injektioner med 150 til 300 mg ZYPADHERA hver anden uge var 10 til 90 percentilen af olanzapins steady state- plasmakoncentration mellem 4, 2 og 73, 2 ng/ ml.
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.
Olanzapins plasmakoncentrationer, som blev observeret for dosisintervallet fra 150 mg hver 4. uge til 300 mg hver 2. uge, viser øget systemisk eksponering af olanzapin med øgede doser af ZYPADHERA.
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.
I løbet af den initiale tre måneders behandling med ZYPADHERA blev set akkumulering af olanzapin, men der var ingen yderligere akkumulering ved langtidsbehandling (12 måneder) hos de patienter, som blev injiceret med op til 300 mg hver anden uge.
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.
Der er ikke udført specifikke undersøgelser hos ældre med ZYPADHERA.
No specific investigations have been conducted in the elderly with ZYPADHERA.
Selv om ZYPADHERA ikke kan tilrådes til behandling af den ældre population før et veltålt og effektivt dosisregime ved brug af oral olanzapin er fastsat, var den gennemsnitlige eliminationshalveringstid forlænget (51, 8 versus 33, 8 timer), og clearance var reduceret (17, 5 versus 18, 2 l/ time) hos raske ældre (65 år og derover) versus ikke ældre personer.
In healthy elderly (65 and over) versus non-elderly subjects, the mean elimination half-life was prolonged (51.8 versus
Hos 44 patienter med skizofreni > 65 år blev en dosis fra 5 til 20 mg/ dag ikke forbundet med nogen anden bivirkningsprofil.
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.
Hos patienter med nedsat nyrefunktion (creatininclearance < 10 ml/ min) versus raske forsøgspersoner var der ingen signifikant forskel i den gennemsnitlige halveringstid for elimination (37, 7 versus 32, 4 timer) eller clearance (21, 2 versus 25, 0 l/ time).
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).
57% af radioaktivt mærket olanzapin fandtes i urinen, især som metabolitter.
A mass balance study showed that approximately 57% of radiolabelled olanzapine appeared in urine, principally as metabolites.
4. 2).
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).
Det tilsvarende blev fundet for raske ikke rygere (henholdsvis 48, 8 timer og 14, 1 l/ time).
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).
4. 2).
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).
De væsentligste fund i studier af toksicitet efter gentagne doser (rotter, hunde) i et 2- års karcinogenicitetstudie med rotter og i reproduktionstoksicitetsstudier (rotter og kaniner) var begrænset til reaktioner på injektionsstedet, for hvilke der ikke kunne bestemmes NOAEL (No Observed Adverse Effect Level).
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.