natgillin/translations-raw huggingface dataset:
4. 2).
Platelet counts should be monitored when combining romiplostim with other medicinal products for the treatment of ITP in order to avoid platelet counts outside of the recommended range (see section 4.2).
5. 1).
Corticosteroids, danazol, and azathioprine use may be reduced or discontinued when given in combination with romiplostim (see section 5.1).
4. 2).
Platelet counts should be monitored when reducing or discontinuing other ITP treatments in order to avoid platelet counts below the recommended range (see section 4.2).
Der foreligger ikke kliniske data for eksponeringen for romisplostim under graviditet.
For romiplostim no clinical data on exposed pregnancies are available.
5. 3).
Studies in animals have shown reproductive toxicity, such as transplacental passage and increased foetal platelet counts in rats (see section 5.3).
5 Romiplostim bør ikke anvendes under graviditet, medmindre det er absolut nødvendigt.
Romiplostim should not be used during pregnancy unless clearly necessary.
Der foreligger ikke data vedrørende udskillelse af romiplostim i modermælk hos mennesker.
There are no data on excretion of romiplostim in human milk.
Udskillelse er dog sandsynlig, og risiko for barnet kan ikke udelukkes.
However, excretion is likely and a risk to the suckling child cannot be excluded.
Beslutningen om, hvorvidt amning skal fortsætte/ afbrydes, eller hvorvidt behandling med romiplostim skal fortsætte/ seponeres, bør træffes under hensyntagen til fordelen for barnet ved amning og fordelen for kvinden ved behandling med romiplostim.
5 A decision on whether to continue/ discontinue breast-feeding or to continue/ discontinue therapy with romiplostim should be made taking into account the benefit of breast-feeding to the child and the benefit of romiplostim therapy to the woman.
Patienterne skal dog informeres om, at nogle patienter i kliniske undersøgelser har oplevet milde til moderate forbigående anfald af svimmelhed, hvilket kan påvirke evnen til at føre motorkøretøj eller betjene maskiner.
However, patients should be informed that in clinical trials mild to moderate, transient bouts of dizziness were experienced by some patients, which may affect the ability to drive or use machines.
En analyse af alle de voksne ITP- patienter, som fik romiplostim i fire kontrollerede og fem ikke - kontrollerede kliniske undersøgelser, viste, at den samlede bivirkningsforekomst hos patienter, der blev behandlet med romiplostim var 91, 5% (248/ 271).
Based on an analysis of all adult ITP patients receiving romiplostim in 4 controlled and 5 uncontrolled clinical studies, the overall subject incidence of all adverse events for romiplostim-treated subjects was 91.5% (248/ 271).
I tabellen nedenfor ses de bivirkninger, som investigatorerne vurderede var associeret med behandlingen, og som blev observeret med en forekomst på > 1% (n = 271).
The adverse events listed in the table below are those deemed treatment related by investigators and which occur at a > 1% incidence (n = 271).
Hyppighederne defineres som: meget almindelig (≥ 1/ 10) og almindelig (≥ 1/ 100 til < 1/ 10).
Very common (≥ 1/ 10) and Common (≥ 1/ 100 to < 1/ 10).
De alvorligste bivirkninger skal anføres først.
Within each MedDRA system organ class and frequency grouping, undesirable effects are presented in order of decreasing incidence.
MedDRA
MedDRA system organ class Blood and lymphatic system disorders Psychiatric disorders
Knoglemarvslidelse * Trombocytopeni *
Common Bone marrow disorder* Thrombocytopenia* Insomnia
Insomni
Headache
Nervesystemet
Dizziness Paraesthesia Migraine
Hovedpine
Vascular disorders Respiratory, thoracic and mediastinal disorders
Svimmelhed Paræstesi Migræne
Flushing Pulmonary embolism*
Vaskulære sygdomme Luftveje, thorax og mediastinum Mave- tarm- kanalen
Gastrointestinal disorders
Rødmen Lungeemboli * Kvalme Diarré Mavesmerter Dyspepsi Obstipation
Nausea Diarrhoea Abdominal pain Dyspepsia Constipation
Pruritus Ekkymose Udslæt
Pruritis Ecchymosis Rash
Artralgi Myalgi Smerte i ekstremitet Muskelkrampe Rygsmerter Knoglesmerter
Arthralgia Myalgia Pain in extremity Muscle spasm Back pain Bone pain
MedDRA
6 MedDRA system organ class General disorders and administration site conditions
Træthed Blodudtrædning på injektionsstedet Smerte på injektionsstedet Perifert ødem Influenzalignende sygdom Smerte Asteni Pyreksi Kulderystelser Hæmatomer på injektionsstedet Hævelse på injektionsstedet
Common Fatigue Injection site bruising Injection site pain Oedema peripheral Influenza like illness Pain Asthenia Pyrexia Chills Injection site haematoma Injection site swelling
4. 4.
Injury, poisoning and procedural complications * see section 4.4
Endvidere har man vurderet, at de bivirkninger, der angives nedenfor, er associeret til romiplostim - behandling.
In addition the events listed below have been deemed to be related to romiplostim treatment.
I en analyse af alle de voksne ITP- patienter, som fik romiplostim i fire kontrollerede og fem ikke - kontrollerede kliniske undersøgelser, blev tre tilfælde af trombocytose, n = 271, rapporteret.
Based on an analysis of all adult ITP patients receiving romiplostim in 4 controlled and 5 uncontrolled clinical studies, 3 events of thrombocytosis were reported, n = 271.
4. 4).
Based on an analysis of all adult ITP patients receiving romiplostim in 4 controlled and 5 uncontrolled clinical studies, 4 events of thrombocytopenia after cessation of treatment were reported, n = 271 (see section 4.4).
I kliniske undersøgelser måtte romiplostim- behandlingen seponeres hos fire ud af 271 patienter pga. aflejring af retikulin i knoglemarven.
In clinical studies, romiplostim treatment was discontinued in 4 of the 271 patients because of bone marrow reticulin deposition.
4. 4).
In 6 additional patients reticulin was observed upon bone marrow biopsy (see section 4.4).
Antistoffer mod romiplostim blev undersøgt i kliniske undersøgelser.
In clinical studies, antibodies to romiplostim were examined.
Af de 271 voksne ITP- patienter, som fik romiplostim i kliniske undersøgelser af ITP, udviklede én patient antistoffer, som var i stand til at neutralisere romiplostims aktivitet, men disse antistoffer krydsreagerede ikke med endogent TPO.
Of the 271 adult ITP patients receiving romiplostim in the ITP clinical programme one patient developed antibodies capable of neutralising the activity of romiplostim but these antibodies did not cross react with endogenous TPO.
Cirka 4 måneder senere blev patienten testet negativ for neutraliserende antistoffer mod romiplostim.
Approximately 4 months later, the patient tested negative for neutralising antibodies to romiplostim.
6) med henblik på antistof- testning.
If formation of neutralising antibodies is suspected, contact the local representative of the Marketing Authorisation Holder (see section 6 of the Package Leaflet) for antibody testing.
I tidlige kliniske undersøgelser var den maksimale dosis af romiplostim 30 µg/ kg.
In early clinical studies, the maximum dose of romiplostim was 30 µg/ kg.
Den blev senere reduceret til 10 µg/ kg, da der ikke var nogen yderligere klinisk fordel ved doser over dette niveau.
This was later reduced to 10 µg/ kg due to lack of additional clinical benefit of doses above this level.
7 Der sås ingen bivirkninger hos rotter, som fik en enkelt dosis på 1000 µg/ kg, eller hos aber efter gentagen indgivelse af 500 µg/ kg romiplostim (henholdsvis 100 eller 50 gange den maksimale kliniske dosis på 10 µg/ kg).
No adverse effects were seen in rats given a single dose of 1000 μ g/ kg or in monkeys after repeated administration of romiplostim at 500 µg/ kg (100 or 50 times the maximum clinical dose of 10 µg/ kg, respectively).
I tilfælde af overdosering kan trombocyttallet overstige det normale værdiområde.
7 In the event of overdose, platelet counts may increase above the normal range.
4. 2).
Platelet counts should be monitored and appropriate treatment should be given (see section 4.2).
ATC- kode:
Antihemorrhagics, ATC code:
Romiplostim er et Fc- peptid- fusionsprotein (peptibody), som signalerer og aktiverer intracellulære transkriptionsveje via trombopoietin (TPO) - receptoren (også betegnet cMpl) til at øge trombocytproduktion.
Romiplostim is an Fc-peptide fusion protein (peptibody) that signals and activates intracellular transcriptional pathways via the thrombopoietin (TPO) receptor (also known as cMpl) to increase platelet production.
Peptibody- molekylet består af et humant immunglobulin IgG1 Fc- domæne med hver enkeltkædet underenhed bundet kovalent ved C- terminalen til en peptidkæde med to TPO - receptorbindende domæner.
The peptibody molecule is comprised of a human immunoglobulin IgG1 Fc domain, with each single-chain subunit covalently linked at the C-terminus to a peptide chain containing 2 TPO receptor-binding domains.
Ingen anti- romiplostim - antistoffer krydsreagerede med endogent TPO i prækliniske og kliniske undersøgelser.
In pre-clinical and clinical studies no anti-romiplostim antibodies cross reacted with endogenous TPO.
I kliniske undersøgelser resulterede behandling med romiplostim i dosisafhængige forøgelser af trombocyttal.
In clinical studies, treatment with romiplostim resulted in dose-dependent increases in platelet count.
Den maksimale virkning på trombocyttal ses efter 10- 14 dage og er uafhængig af dosis.
Time to reach the maximum effect on platelet count is approximately 10-14 days, and is independent of the dose.
Efter en enkelt subkutan dosis på 1 til 10 µg/ kg romiplostim hos ITP- patienter var det maksimale trombocyttal 1, 3 til 14, 9 gange højere end trombocyttallet ved baseline over en periode på 2 til 3 uger, og responsen varierede fra patient til patient.
After a single subcutaneous dose of 1 to 10 µg/ kg romiplostim in ITP patients, the peak platelet count was 1.3 to 14.9 times greater than the baseline platelet count over a 2 to 3 week period and the response was variable among patients.
Trombocyttallene for patienter med ITP, som modtog 6 ugentlige doser på 1 eller 3 µg/ kg romiplostim, lå for de fleste patienters vedkommende inden for området 50 til 450 x 109/ l.
The platelet counts of ITP patients who received 6 weekly doses of 1 or 3 µg/ kg of romiplostim were within the range of 50 to 450 x 109/ l for most patients.
Af de 271 patienter, som fik romiplostim i de kliniske undersøgelser vedrørende ITP, var 55 (20%) 65 år eller derover, og 27 (10%) var 75 år eller derover.
Of the 271 patients who received romiplostim in ITP clinical studies, 55 (20%) were age 65 and over, and 27 (10%) were 75 and over.
I undersøgelse S1 (212) indgik ikke- splenektomerede patienter, som havde en utilfredsstillende respons på tidligere behandlinger, eller som var intolerante over for tidligere behandlinger.
Study S1 (212) evaluated patients who were non-splenectomised and had an inadequate response or were intolerant to prior therapies.
Tidligere behandlinger inkluderede kortikosteroider (90% af alle patienter), immunglobuliner (76%), rituximab (29%), cytotoksiske behandlinger (21%), danazol (11%) og azathioprin (5%).
Prior treatments included corticosteroids (90% of all patients), immunoglobulins (76%), rituximab (29%), cytotoxic therapies (21%), danazol (11%), and azathioprine (5%).
Medianværdien for patienternes trombocyttal var 19 x 109/ l ved optagelse i undersøgelsen.
Patients had a median platelet count of 19 x 109/ l at study entry.
Tidligere behandlinger inkluderede kortikosteroider (98% af alle patienter), immunglobuliner (97%), rituximab (71%), danazol (37%), cytotoksiske behandlinger
Prior treatments included corticosteroids (98% of all patients), immunoglobulins (97%), rituximab (71%), danazol (37%), cytotoxic therapies (68%), and azathioprine (24%).
Median for patienternes trombocyttal var 14 x 109/ l ved optagelse i undersøgelsen.
Patients had a median platelet count of 14 x 109/ l at study entry.
Patienterne (≥ 18 år) blev randomiseret i forholdet 2: 1 til at modtage en begyndelsesdosis af romiplostim på 1 µg/ kg eller placebo.
Patients (≥ 18 years) were randomised in a 2:1 ratio to receive a starting dose of romiplostim 1 µg/ kg or placebo.
Doserne blev justeret for at fastholde (50 til 200 x 109/ l) trombocyttal.
Doses were adjusted to maintain (50 to 200 x 109/ l) platelet counts.
I begge undersøgelser blev virkningen bestemt ud fra stigningen i andelen af patienter med en varig trombocyt- respons.
In both studies, efficacy was determined by an increase in the proportion of patients who achieved a durable
Median for den gennemsnitlige ugentlige dosis for splenektomerede patienter var 3 µg/ kg, og den var 2 µg/ kg for ikke- splenektomerede patienter.
The median average weekly dose for splenectomised patients was 3 µg/ kg and for non-splenectomised patients was 2 µg/ kg.
Efter de første 4 ugers opretholdt romiplostim trombocyttal ≥ 50 x 109/ l hos mellem 50% og 70% af patienterne i den 6 måneder lange behandlingsperiode i de placebokontrollerede undersøgelser.
Following the first 4-weeks of study romiplostim maintained platelet counts ≥ 50 x 109/ l in between 50% to 70% of patients during the 6 month treatment period in the placebo-controlled studies.
I placebogruppen opnåede 0% til 7% af patienterne en trombocytrespons i løbet af den 6 måneder lange behandlingsperiode.
In the placebo group, 0% to 7% of patients were able achieve a platelet count response during the 6 months of treatment.
Ikke- splenektomerede patienter
non-splenectomised patients
Splenektomerede patienter
splenectomised patients
undersøgelse 1 og 2
studies 1 & 2
Antal (%) patienter med
(%) patients with
romiplostim (n = 41)
romiplostim (n = 41)
placebo romiplostim placebo (n = 21) (n = 42) (n = 21)
Placebo romiplostim Placebo romiplostim (n = 21) (n = 42) (n = 21) (n = 83)
placebo (n = 42)
Placebo (n = 42)
varig trombocyt - responsa
durable platelet responsea
25 (61%)
25 (61%)
76%)
(45%, 76%)
24%)
(0%, 24%)
54%)
(24%, 54%)
Antal (%) patienter med generel trombocyt - responsb
(%) patients with overall platelet responseb
Middelværdi for antal uger med trombocyt - responsc
Mean no. weeks with platelet responsec
(SD) p- værdi Antal (%) patienter, som
(SD) p-value
krævede ” rescue ” - behandlingd
(%) patients requiring rescue therapiesd
Antal (%) patienter med varig
(%) patients with durable
placebo romiplostim placebo romiplostim (n = 21) (n = 42) (n = 21) (n = 83)
Placebo romiplostim Placebo romiplostim (n = 21) (n = 42) (n = 21) (n = 83)
trombocyt - respons ved stabil dosise
platelet response with stable dosee
0 (0%) 13 (31%) 0 (0%) 34 (41%)
0 (0%) 13 (31%) 0 (0%) 34 (41%)
(35%,
0 (0%)
67%)
(35%, 67%)
47%) 16%)
(0%, 16%) (18%, 47%) (0%, 16%) (30%, 52%)
52%)
(0%, 8%)
Varig trombocytrespons defineres som et ugentligt trombocyttal ≥ 50 x 109/ l seks gange eller mere i undersøgelsesugerne 18- 25 og fravær af ” rescue ” - behandlinger i hele behandlingsperioden. b Generel trombocytrespons defineres som opnåelse af varige eller forbigående trombocytresponser.
Durable platelet response was defined as weekly platelet count ≥ 50 x 109/ l for 6 or more times for study weeks 18-25 in the absence of rescue therapies any time during the treatment period. b Overall platelet response is defined as achieving durable or transient platelet responses.
Forbigående trombocytrespons defineres som ugentlige trombocyttal ≥ 50 x 109/ l 4 gange eller mere i uge 2- 25 af undersøgelsen, men uden en varig trombocytrespons.
Transient platelet response was defined as weekly platelet count ≥ 50 x 109/ l for 4 or more times during study weeks 2-25 but without durable platelet response.
Det er muligt, at patienterne ikke har en ugentlig respons inden for 8 uger efter indgift af eventuelle ” rescue ” - lægemidler. c Antal uger med trombocytrespons defineres som antallet af uger med trombocyttal ≥ 50 x 109/ l i uge 2- 25 af undersøgelsen.
Patient may not have a weekly response within 8 weeks after receiving any rescue medicinal products. c Number of weeks with platelet response is defined as number of weeks with platelet counts ≥ 50 x 109/ l during study weeks 2-25.
Det er muligt, at patienterne ikke har en ugentlig respons inden for 8 uger efter indgift af eventuelle ” rescue ” - lægemidler. d ” Rescue ” - behandlinger defineres som enhver behandling, som gives for at forhøje trombocyttallene.
Patient may not have a weekly response within 8 weeks after receiving any rescue medicinal products. d Rescue therapies defined as any therapy administered to raise platelet counts.
Patienter, som har behov for ” rescue ” - lægemidler, blev ikke taget i betragtning for varig trombocytrespons.
Patients requiring rescue medicinal products were not considered for durable platelet response.
Tilladte ” rescue ” - behandlinger i denne undersøgelse var IVIG, trombocyttransfusion, anti- D immunglobulin og kortikosteroider. e Stabil dosis defineres som dosis uforandret inden for ± 1 µg/ kg i de sidste 8 uger med behandling.
Rescue therapies allowed in the study were IVIG, platelet transfusions, anti-D immunoglobulin, and corticosteroids. e Stable dose defined as dose maintained within ± 1 µg/ kg during the last 8 weeks of treatment.
I begge placebokontrollerede, dobbeltblindede undersøgelser fik patienter, som allerede fik medicinsk behandling for ITP i henhold til en konstant doseringsplan, lov til at fortsætte med disse medicinske behandlinger under hele undersøgelsen (kortikosteroider, danazol og/ eller azathioprin).
In both placebo-controlled, double-blind studies, patients already receiving ITP medical therapies at a constant dosing schedule were allowed to continue receiving these medical treatments throughout the study (corticosteroids, danazol and/ or azathioprine).
Enogtyve ikke- splenektomerede patienter og 18 splenektomerede patienter fik en anden samtidig tilladt medicinsk behandling (primært kortikosteroider) for ITP ved undersøgelsesstart.
Twenty-one non-splenectomised and 18 splenectomised patients received on-study ITP medical treatments (primarily corticosteroids) at the start of study.
For alle (100%) splenektomerede patienter, som fik romiplostim, kunne dosis reduceres med mere end 25%, eller samtidig medicinsk behandling af ITP kunne ophøre ved afslutningen af behandlingsperioden sammenlignet med 17% af de patienter, som blev behandlet med placebo.
All (100%) splenectomised patients who were receiving romiplostim were able to reduce the dose by more than 25% or discontinue the concurrent ITP medical therapies by the end of the treatment period compared to 17% of placebo treated patients.
4. 5).
Seventy-three percent of non-splenectomised patients receiving romiplostim were able to reduce the dose by more than 25% or discontinue concurrent ITP medical therapies by the end of the study compared to 50% of placebo treated patients (see section 4.5).
Alle klinisk signifikante (≥ grad 3) blødningshændelser forekom ved trombocyttal < 30 x 109/ l.
All clinically significant (≥ grade 3) bleeding events occurred at platelet counts < 30 x 109/ l.
Alle blødningshændelser (≥ grad 2) forekom ved trombocyttal < 50 x 109/ l.
All bleeding events ≥ grade 2 occurred at platelet counts < 50 x 109/ l.
Der blev ikke observeret nogen statistisk signifikante forskelle i den samlede forekomst af blødningshændelser mellem Nplate- behandlede og placebo- behandlede patienter.
No statistically significant differences in the overall incidence of bleeding events were observed between Nplate and placebo treated patients.
I de to placebokontrollerede undersøgelser rapporterede ni patienter blødningshændelser, som blev betragtet som alvorlige (5 (6, 0%) romiplostim, 4 (9, 8%) placebo; odds ratio (romiplostim/ placebo) = 0, 59; 95% CI = (0, 15, 2, 31)).
In the two placebo-controlled studies, 9 patients reported a bleeding event that was considered serious (5 [6.0%] romiplostim, 4 [9.8%] placebo; Odds Ratio [romiplostim/ placebo] = 0.59; 95% CI = (0.15, 2.31)).
Blødningshændelser, som var grad 2 eller højere, blev rapporteret af 15% af de patienter, som blev behandlet med romiplostim, og 34% af de patienter, som blev behandlet med placebo; (odds ratio (romiplostim/ placebo) = 0, 35; 95% CI = (0, 14, 0, 85)).
Bleeding events that were grade 2 or higher were reported by 15% of patients treated with romiplostim and 34% of patients treated with placebo (Odds Ratio; [romiplostim/ placebo] = 0.35; 95% CI = (0.14, 0.85)).
Romiplostims farmakokinetik involverede target- medieret aflejring, hvilket antageligt medieres af TPO- receptorer på trombocytter og andre celler af trombopoietisk afstamning, såsom megakaryocytter.
The pharmacokinetics of romiplostim involved target-mediated disposition, which is presumably mediated by TPO receptors on platelets and other cells of the thrombopoietic lineage such as megakaryocytes.
Efter subkutan indgivelse af 3 til 15 µg/ kg romiplostim blev maksimale romiplostim- serum- niveauer hos ITP- patienter nået efter 7 - 50 timer (median 14 timer).
After subcutaneous administration of 3 to 15 μ g/ kg romiplostim, maximum romiplostim serum levels in ITP patients were obtained after 7-50 hours (median 14 hours).
Romiplostims serum- niveauer synes at stå i omvendt forhold til trombocyttal.
Romiplostim serum levels appear inversely related to platelet counts.
Romiplostims fordelingsvolumen efter intravenøs indgift af romiplostim faldt non- lineært fra 122; 78, 8; til 48, 2 ml/ kg for intravenøse doser på henholdsvis 0, 3; 1, 0 og 10 µg/ kg hos raske forsøgspersoner.
The volume of distribution of romiplostim following intravenous administration of romiplostim decreased nonlinearly from 122, 78.8, to 48.2 ml/ kg for intravenous doses of 0.3, 1.0 and 10 μ g/ kg, respectively in healthy subjects.
Denne non- lineære reduktion i fordelingsvolumen svarer til den (megakaryocyt og trombocyt) target- medierede binding af romiplostim, som kan være mættet ved de højere anvendte doser.
This non-linear decrease in volume of distribution is in line with the (megakaryocyte and platelet) target-mediated binding of romiplostim, which may be saturated at the higher doses applied.
Halveringstiden for romiplostim hos patienter med ITP varierede mellem 1 og 34 dage (median 3, 5 dage).
Elimination half-life of romiplostim in ITP patients ranged from 1 to 34 days (median, 3.5 days).
Elimineringen af romiplostim i serum afhænger delvist af TPO- receptoren på trombocytterne.
The elimination of serum romiplostim is in part dependent on the TPO receptor on platelets.
I en anden klinisk undersøgelse relateret til ITP sås der ikke akkumulering i serumkoncentrationer efter 6 ugentlige doser romiplostim (3 µg/ kg).
In another ITP clinical study, no accumulation in serum concentrations was observed after 6 weekly doses of romiplostim (3 μ g/ kg).
Romiplostims farmakokinetik for patienter med nyre - og leverinsufficiens er ikke blevet undersøgt.
Pharmacokinetics of romiplostim in patients with renal and hepatic impairment has not been investigated.
Der var også en stimulatorisk effekt på leukocyt - produktionen, da de perifere blodtal for neutrofiler, lymfocytter, monocytter og eosinofiler steg en anelse.
There was also a stimulatory effect on leukocyte production, as peripheral blood counts for neutrophils, lymphocytes, monocytes, and eosinophils were mildly increased.
Sammenlignet med placebo- behandlede patienter påvirkede romiplostim i øvrigt hverken de røde eller de hvide blodlegemers afstamninger i de pivotale fase 3- undersøgelser.
Additionally, in the phase 3 pivotal studies, romiplostim did not affect the red blood cell and white blood cells lineages relative to placebo treated subjects.
Selvom højere doser blev testet i dyreforsøg, kan sikkerhedsmargen ikke med sikkerhed fastslås pga. forskellene mellem laboratoriearterne og
Although high doses were tested in the animal studies, due to differences between the laboratory species and humans with regard to the sensitivity for
11 mennesker mht. følsomheden over for romiplostims farmakodynamiske virkning og virkningen af de neutraliserende antistoffer.
11 the pharmacodynamic effect of romiplostim and the effect of neutralising antibodies, safety margins cannot be reliably estimated.
Karcinogenese:
Carcinogenesis:
Reproduktionstoksicitet:
Reproductive toxicology:
I undersøgelser af embryo- føtal udvikling hos rotter og mus sås udelukkende nedsat maternel legemsvægt hos mus.
In embryo-foetal development studies in mice and rats, reductions in maternal body weight were found only in mice.