natgillin/translations-raw huggingface dataset:
I et forsøg, hvor 64 patienter med reumatoid artrit blev behandlet med Humira, var der ingen tegn på nedsat forsinket hypersensitivitet, nedsatte immunglobulinniveauer eller forandring i antallet af effektor T -, B, - NK- celler, monocytter/ makrofager og neutrofiler.
In a study of 64 patients with rheumatoid arthritis that were treated with Humira, there was no evidence of depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or change in enumeration of effector T-, B, -NK-cells, monocyte/ macrophages, and neutrophils.
Alle patienter og specielt patienter, som tidligere har fået omfattende immuno- suppresiv behandling eller psoriasispatienter, der tidligere har været behandlet med PUVA, skal undersøges for ikke - melanom hudkræft inden og under behandling med Humira.
All patients, and in particular patients with a medical history of extensive immunosuppressant therapy or psoriasis patients with a history of PUVA treatment should be examined for the presence of non- melanoma skin cancer prior to and during treatment with Humira.
Sjældne tilfælde af pancytopeni herunder aplastisk anæmi er rapporteret efter behandling med TNF - antagonister.
Rare reports of pancytopenia including aplastic anaemia have been reported with TNFantagonists.
88 thrombocytopeni, leukopeni) er rapporteret i sjældne tilfælde efter behandling med Humira.
Adverse events of the haematologic system, including medically significant cytopoenia (e. g. thrombocytopaenia, leucopaenia) have been infrequently reported with Humira.
Vaccinationer
It is recommended that polyarticular juvenile idiopathic arthritis patients, if possible, be brought up to date with all immunisations in agreement with current immunisation guidelines prior to initiating Humira therapy.
Der blev observeret et lignede antistof respons på den 23- valente standard pneumokok vaccine og den trivalente influenza virus vaccine i et forsøg med 226 voksne individer med reumatoid artrit, som blev behandlet med adalimumab eller placebo.
88 Vaccinations Similar antibody responses to the standard 23-valent pneumococcal vaccine and the influenza trivalent virus vaccination were observed in a study in 226 adult subjects with rheumatoid arthritis who were treated with adalimumab or placebo.
Hjerteinsufficiens I et klinisk forsøg med en anden TNF- antagonist er der observeret forværring af hjerteinsufficiens og forøget mortalitet som følge af hjerteinsufficiens.
In a clinical trial with another TNF-antagonist worsening congestive heart failure and increased mortality due to congestive heart failure have been observed.
(Se punkt 4. 5).
See section 4.5).
89 Tyndtarms- obstruktion
Small bowel obstruction
Antistofdannelsen var lavere ved Humira i kombination med methotrexat i forhold til ved behandling med Humira alene.
Antibody formation was lower when Humira was given together with methotrexate in comparison with use as
Svimmelhed (inklusive vertigo, synsforstyrrelser og træthed) kan forekomme efter administration af Humira se pkt 4. 8
Dizziness (including vertigo, vision disorder and fatigue) may occur following administration of Humira see (Section 4.8).
Humira blev undersøgt hos 6593 patienter i kontrollerede og åbne forsøg i op til 60 måneder.
Humira was studied in 6,593patients in controlled and open label trials for up to 60 months.
Disse forsøg omfattede både patienter med reumatoid artrit med kortere og længere sygdomsforløb, med polyartikulær juvenil idiopatisk artrit og patienter med psoriasisartrit, ankyloserende spondylitis, Crohns sygdom og psoriasis.
These trials included rheumatoid arthritis patients with short term and long standing disease, polyarticular juvenile idiopathic arthritis as well as psoriatic arthritis, ankylosing spondylitis, Crohn’ s disease and psoriasis patients.
90 Den del af patienterne, som ophørte med behandling på grund af bivirkninger i løbet af den dobbeltblindede, kontrollerede del af de pivotale forsøg udgjorde 4, 5% for patienter, der fik Humira, og 4, 5% for kontrolbehandlede patienter.
The proportion of patients who discontinued treatment due to adverse events during the double-blind, controlled portion of pivotal studies was 4.5% for patients taking Humira and 4.5% for control treated patients.
Bivirkninger, hvor kausaliteten i det mindste er muligt relateret til adalimumab for de pivotale forsøg, både klinisk og laboratoriemæssigt, er opført efter organklassesystem og hyppighed (meget almindelig ≥ 1/ 10; almindelig ≥ 1/ 100 til < 1/ 10; usædvanlig ≥ 1/ 1. 000 til < 1/ 100 og sjælden ≥ 1/ 10, 000 til < 1/ 1000) i tabel 1 nedenfor.
90 ≥ 1/ 100 to < 1/ 10; uncommon ≥ 1/ 1000 to < 1/ 100and rare ≥ 1/ 10,000 to < 1/ 1,000) in Table 1 below.
91 Systemorganklasser Undersøgelser
System Organ Class Investigations
Sygdomme i åndedrætsorganer, brysthule og mediastinum
91 System Organ Class Respiratory, thoracic and mediastinal disorders
92 Systemorganklasser Gastrointestinale sygdomme
Gastrointestinal disorders
Infektiøse og parasitære sygdomme
92 System Organ Class Infections and infestations
93 Systemorganklasser Godartede, ondartede og uspecificerede svulster
Neoplasms benign, malignant and unspecified
Reaktioner ved injektionsstedet
93 Injection site reactions
I de pivotale kontrollerede forsøg var infektionshyppigheden 1, 58 pr. patientår hos Humira - behandlede patienter og 1, 39 pr. patientår hos placebo - og aktiv kontrolbehandlede patienter.
In the pivotal controlled trials, the rate of infection was 1.58per patient year in the Humira treated patients and 1.42 per patient year in the placebo and active control-treated patients.
94 I kontrollerede og åbne forsøg med Humira blev der rapporteret alvorlige infektioner (herunder dødelige infektioner, som forekom sjældent), inklusive rapporter om tuberkulose (herunder miliærtuberkulose og ekstra- pulmonær tuberkulose) og invasive opportunistiske infektioner (f. eks. dissemineret eller ekstrapulmonal histoplasmose, blastomykose, kokcidioimykose, pneumocytis, candidiasis, aspergillose og listeriose).
In controlled and open label studies with Humira, serious infections (including fatal infections, which occurred rarely) have been reported, which include reports of tuberculosis (including miliary and extra-pulmonary locations) and invasive opportunistic infections (e. g. disseminated or extrapulmonary histoplasmosis, blastomycosis, coccidioidomycosis, pneumocystis, candidiasis, aspergillosis and listeriosis).
1. 000 patient- år blandt 3853 Humirabehandlede patienter mod en hyppighed på 4, 3 (1, 8, 10, 4) pr.
During the controlled portions of pivotal Humira trials at least 12 weeks in duration in patients with moderately to severely active rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’ s disease and psoriasis, malignancies, other than lymphoma and non-melanoma skin cancer, were observed at a rate (95% confidence interval) of 5.9 (3.5, 9.9) per 1,000 patient-years among 3,853 Humira treated patients versus a rate of 4.3 (1.8, 10.4) per 1,000 patient-years among 2,183 control patients (median duration of treatment was 5.5 months for Humira and 3.9 months for control-treated patients).
1. 000 patient- år blandt 2. 183 kontrolpatienter (gennemsnitlig varighed af behandlingen var 5, 5 måneder for Humira og 3, 9 måneder for de kontrol- behandlede patienter).
The rate (95% confidence interval) of non-melanoma skin cancers was 8.8 (5.7, 13.5) per 1000 patient-years among Humira-treated patients and 2.6 (0.8, 8.0) per 1,000 patient-years among control patients.
Hos disse hudkræfttilfælde forekom planocellulært karcinom med en hyppighed (95% konfidensinterval) på 2, 5 (1, 1, 5, 6) pr.
The rate (95% confidence interval) of lymphomas was 0.8 (0.2, 3.3) per 1000 patient-years among Humira-treated patients and 0.9 (0.1, 6.1) per 1,000 patient-years among control patients.
1000 patient- år.
The observed rate of non-melanoma skin cancers is approximately 9.0 per 1,000 patient years, and the observed rate of lymphomas is approximately 1.1 per 1,000 patient years.
Der er ved post- marketing erfaring fra januar 2003, hovedsageligt hos patienter med reumatoid artrit rapporteret en hyppighed af andre maligniteter end lymfomer og ikke- melanom hudkræft på cirka 1, 7 pr.
In post-marketing experience from January 2003, predominately in patients with rheumatoid arthritis, the reported rate of malignancies other than lymphomas and non-melanoma skin cancers is approximately 1.7 per 1,000 patient years.
Autoantistoffer
94 Autoantibodies
Forhøjelsen af ALAT var sammenlignelig hos patienter, der modtog adalimumab eller placebo i de kontrollerede kliniske forsøg for psoriasis.
Psoriasis clinical trials: in controlled psoriasis clinical trials, elevations of ALT were similar in patients receiving adalimumab or placebo
4. 9 Overdosering
95 4.9 Overdose
Adalimumab modulerer også de biologiske responser, som induceres eller reguleres af TNF, herunder ændringer i niveauerne af de adhæsionsmolekyler, som er ansvarlige for leukocytmigrationen (ELAM - 1, VCAM- 1 og ICAM- 1 med en IC50 på 0, 1- 0, 2 nM).
Adalimumab also modulates biological responses that are induced or regulated by TNF, including changes in the levels of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, and ICAM-1 with an IC50 of0.1-0.2 nM).
96 Farmakodynamiske virkninger
Pharmacodynamic effects
Et hurtigt fald i CRP- niveau blev også observeret hos patienter med polyartikulær juvenil idiopatisk artrit.
A rapid decrease in CRP levels was also observed in patients with polyarticular juvenile idiopathic arthritis
RA- forsøg III evaluerede 619 patienter, der var ≥ 18 år, med moderat til alvorlig aktiv reumatoid artrit, som havde haft et ikke- effektivt respons på methotrexat i doser på 12, 5 til 25 mg eller som var intolerante over for 10 mg methotrexat hver uge.
RA study III evaluated 619 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 years old, and who had anineffective response to methotrexate at doses of 12.5 to 25 mg or have
Det primære end- point i RA- forsøg
The primary end point in RA studies I, II and III and the secondary endpoint in RA study IV was the percent of patients who achieved an ACR 20 response at Week 24 or 26.
97 V var procentdelen af patienter, som opnåede et ACR 50 respons i uge 52.
The primary endpoint in RA study V was the percent of patients who achieved an ACR 50 response at Week 52.
Ra- forsøg IIIa **
RA Study IIIa**
I tillæg hertil blev behandlingseffekt bedømt ved ACR- respons opretholdt hos størstedelen af patienterne, som blev fulgt i det åbne forlængelsesforsøg til uge 104.
In addition, ACR response rates were 97 maintained in the majority of patients followed in the open-label extension phase to Week 104.
I RA- forsøg V med patienter med reumatoid artrit på et tidligt stadium, som var methotrexat- naive, førte kombinationsbehandlingen med Humira og methotrexat til hurtigere og signifikant større ACR respons end methotrexat- monoterapi og Humira- monoterapi i uge 52, og effekten blev opretholdt i 104 uger (se tabel 4).
In RA study V with early rheumatoid arthritis patients who were methotrexate naïve, combination therapy with Humira and methotrexate led to faster and significantly greater ACR responses than methotrexate monotherapy and Humira monotherapy at week 52 and responses were sustained at Week 104 (see Table 4).
98 Tabel 4 ACR Respons i RA- forsøg V (Procentdel af patienter)
Table 4 ACR Responses in RA Study V (percent of patients)
p- værdia
62.6% 56.0%
p- værdib
54.4% 49.3%
p- værdic
72.8% 69.4%
54, 4% 49, 3%
45.9% 42.8%
72, 8% 69, 4%
41.2% 36.9%
0, 013 0, 002
61.6% 59.0%
0, 043 0, 140
0.317 0.162
< 0, 001 < 0, 001
25.9% 28.1%
I RA- forsøg III, hvor de Humira- behandlede patienter havde haft reumatoid artrit gennemsnitlig i 11 år, blev den strukturelle ødelæggelse af leddene vurderet radiografisk og udtrykt som ændringer i modificeret Sharp Score (TSS) og dennes delkomponenter, erosionsscore og ledspalteforsnævring (JSN).
In RA study III, where Humira treated patients had a mean duration of rheumatoid arthritis of approximately 11 years, structural joint damage was assessed radiographically and expressed as change in modified Total Sharp Score (TSS) and its components, the erosion score and joint space narrowing score.
Tabel 5 Gennemsnitlige radiografiske ændringer gennem 12 måneder i RA- forsøg III
98 Table 5 Radiographic Mean Changes Over 12 Months in RA Study III
Total Sharp- score Erosion score JSNd score
Total Sharp Score Erosion score JSNd score
99 I RA- forsøg V blev strukturel ledskade vurderet radiografisk og udtrykt som ændringer i modificeret Total Sharp Score (se tabel 6).
In RA study V, structural joint damage was assessed radiographically and expressed as change in modified Total Sharp Score (see Table 6).
Tabel 6 Gennemsnitlige radiografiske ændringer i uge 52 i forsøg V
Table 6 Radiographic Mean Changes at Week 52 in RA Study V
I RA- forsøg III blev forbedringer i fysisk funktion opretholdt gennem 260 uger (60 måneder) med åben behandling.
99 In RA study III, improvement in physical function was maintained through Week 260 (60 months) of open-label treatment.
Effekten blev opretholdt i 104 uger.
In RA study V, the improvement in the HAQ disability index and the physical component of the SF 36 showed greater improvement (p < 0.001) for Humira/ methotrexate combination therapy versus methotrexate monotherapy and Humira monotherapy at week 52, which was maintained through Week 104.
100 Patienterne fortsatte på faste doser NSAID’ er og/ eller prednison (≤ 0, 2 mg/ kg/ dag eller maksimalt 10 mg/ dag) I den åbne indkøringsfase fik alle patienter 24 mg/ m2 op til et maksimum på 40 mg Humira hver anden uge i 16 uger.
In the OL LI phase all patients received 24 mg/ m2 up to a maximum of 40 mg Humira every other week for 16 weeks.
Tabel 8 Pædiatriske ACR- responser i JIA- forsøget
100 Table 8 Ped ACR Responses in the JIA study
Stratum Fase Åben indkøringsfase uge 16
Stratum Phase OL-LI 16 week
101 resultater anbefales Humira til anvendelse i kombination med MTX og til anvendelse som monoterapi til patienter, som ikke egner sig til behandling med MTX (se afsnit 4. 2).
Taking these results into consideration, Humira is recommended for use in combination with MTX and for use as monotherapy in patients for whom MTX use is not appropriate (see section 4.2).
Humira givet i doser af 40 mg hver anden uge blev undersøgt hos patienter med moderat til alvorlig aktiv psoriasisartrit i to placebokontrollerede PsA- forsøg, forsøgne I og II.
Humira, 40 mg every other week, was studied in patients with moderately to severely active psoriatic arthritis in two placebo-controlled studies, PsA I and II.
Tabel 9 ACR respons i placebokontrollerede psoriasisartrit forsøg (Procentdel af patienter)
101 Table 9 ACR Response in Placebo-Controlled Psoriatic Arthritis Studies (Percent of Patients)
PsA- forsøg VI
PsA Study I
PsA- forsøg VII
PsA Study II
Behandling med Humira reducerede den udviklingshastighed, hvormed de perifere led destrueredes, sammenlignet med behandling med placebo som målt ved ændring i forhold til baseline i mTSS (gennemsnit ± SD) 0, 8 ± 2, 5 i placebogruppen (ved uge 24) sammenlignet med 0, 0 ± 1, 9; (p < 0, 001) i Humira- gruppen (ved uge 48). Af de forsøgspersoner, som blev behandlet med Humira uden at vise radiografisk progression fra baseline til uge 48 (n=102), viste 84% fortsat ingen radiografisk progression i løbet af de 144 ugers behandling.
Humira treatment reduced the rate of progression of peripheral joint damage compared with placebo treatment as measured by change from baseline in mTSS (mean ± SD) 0.8 ± 2.5 in the placebo group (at Week 24) compared with 0.0 ± 1.9( p < 0.001) in the Humira group (at Week 48).
102 Ankyloserende spondylitis
Ankylosing spondylitis
Tabel 10 - Effekt respons i placebo- kontrolleret AS forsøg – forsøg I Reduktion af tegn og symptomer
102 Table 10 Efficacy Responses in Placebo-Controlled AS Study – Study I Reduction of Signs and Symptoms
103 Crohns sygdom
Crohn’ s disease
Vedligeholdelse af klinisk remission blev undersøgt i CD- forsøg III (CHARM).
103 Maintenance of clinical remission was evaluated in CD Study III (CHARM).
Ved uge 4 blev patienterne randomiseret til 40 mg hver anden uge, 40 mg hver uge, eller placebo gennem hele forsøgsforløbet på 56 uger.
At Week 4 patients were randomised to 40 mg every other week, 40 mg every week, or placebo with a total study duration of 56 weeks.
Tabel 11 viser rater for induktion af remission og respons i CD- forsøg Iog CD- forsøg II.
CD Study I and CD Study II induction of remission and response rates are presented in Table 9.
Lignende remissions- rater sås for 160/ 80 mg og 80/ 40 mg induktionsregimerne ved uge 8, mens bivirkninger oftere sås i gruppen med 160/ 80 mg.
Similar remission rates were observed for the 160/ 80 mg and 80/ 40 mg induction regimens by week 8 and adverse events were more frequently noted in the 160/ 80 mg group.
104 Tabel 12 Vedligeholdelse af klinisk remission og respons (Procent af patienterne)
104 Table 12 Maintenance of Clinical Remission and Response (Percent of Patients)
Disse resultater tyder på, at nogle patienter, som ikke har responderet ved uge 4, har fordel af fortsat vedligeholdelsesbehandling til og med uge 12.
These results suggest that some patients who have not responded by Week 4 benefit from continued maintenance therapy through week 12.
I CD- forsøg I og CD- forsøg II, blev der opnået statistisk signifikante forbedringer i total score i det sygdoms- specifikke tarm- sygdoms- spørgeskema (IBDQ) ved uge 4 for patienter randomiseret til Humira 80/ 40 mg og 160/ 80 mg sammenlignet med placebo, og i CD- forsøg III blev det set ved uge 26 og 56, såvel som blandt den adalimumab- behandlede- grupper sammenlignet med placebo- gruppen.
In CD Stusy I and CD Study II, statistically significant improvement in the disease-specific inflammatory bowel disease questionnaire (IBDQ) total score was achieved at Week 4 in patients randomised to Humira 80/ 40 mg and 160/ 80 mg compared to placebo and was seen at Weeks 26 and 56 in CD Study III as well among the adalimumab treatment groups compared to the placebo group.
105 efterfulgt af 40 mg hver anden uge (med start en uge efter den første dosis) i 16 uger.
105 by 40 mg every other week (starting one week after the initial dose) for 16 weeks.
Tabel 13 Ps Forsøg I (REVEAL) Resultater af effekt ved uge 16 Humira 40 mg hver Placebo anden uge N=398 N=814 N (%) n (%)
Table 13 Ps Study I (REVEAL)-Efficacy Results at 16 Weeks
Patienterne blev genrandomiseret til placebo ved uge 33 sammenlignet med 5%, som fortsatte på Humira, p < 0, 001.
In Psoriasis Study I, 28% of patients who were PASI 75 responders and were re-randomised to placebo at Week 33 compared to 5% continuing on Humira, p < 0.001, experienced “ loss of adequate response” (PASI score after Week 33 and on or before Week 52 that resulted in a < PASI 50 response relative to baseline with a minimum of a 6-point increase in PASI score relative to week 33).
106 Immunogenicitet
106 Immunogenicity
Adalimumab- niveauet i serum ved steady- state- lavpunktet blev forøget omtrent proportionalt med doser på 20, 40 og 80 mg ved subkutan dosering hver anden uge og hver uge.
The serum adalimumab trough levels at steady-state increased roughly proportionally with dose following 20, 40 and 80 mg subcutaneous dosing every other week and every week Following the administration of 24 mg/ m2 (up to a maximum of 40 mg) subcutaneously every other week to patients with polyarticular juvenile idiopathic arthritis (JIA) the mean trough steady-state (values measured from Week 20 to 48) serum adalimumab concentration was 5.6 ± 5.6 µg/ mL (102 %CV) Humira monotherapy and 10.9 ± 5.2 µg/ mL (47.7% CV) with concomitant methotrexate.
Hos patienter med Crohns sygdom, blev der i induktionsperioden med induktionsregime på 80 mg Humira i uge 0 fulgt af 40 mg Humira i uge 2, opnået laveste serum- adalimumab koncentrationer på
In patients with Crohn’ s disease, the loading dose of 80 mg Humira on Week 0 followed by 40 mg Humira on Week 2 achieves serum adalimumab trough concentrations of approximately 5.5 µg/ ml
107 ca.
107 during the induction period.
Ved et induktionsregime på 160 mg Humira i uge 0 fulgt af 80 mg Humira i uge 2 blev opnået laveste serum- adalimumab- koncentrationer på ca.
A loading dose of 160 mg Humira on Week 0 followed by 80 mg Humira on week 2 achieves serum adalimumab trough concentrations of approximately 12 µg/ ml during the induction period.
Mannitol Citronsyremonohydrat Natriumcitrat Natriumdihydrogenfosfatdihydrat Dinatriumfosfatdihydrat Natriumklorid Polysorbat 80 Natriumhydroxid Vand til injektionsvæske
Mannitol Citric acid monohydrate Sodium citrate Sodium dihydrogen phosphate dihydrate Disodium phosphate dihydrate Sodium chloride Polysorbate 80 Sodium hydroxide Water for injections.
108 6. 4 Særlige opbevaringsforhold
6.4 Special precautions for storage
6. 5 Emballagetype og pakningsstørrelser
108 6.5 Nature and contents of container
Humira, 40 mg injektionsvæske, opløsning i engangs fyldt pen til patient brug.
Humira 40 mg solution for injection in single-use pre-filled pen for patient use.
Pakninger af: • 1 fyldt pen med 1 alkoholserviet i en blisterpakning. • 2 fyldte pen med 1 alkoholserviet i en blisterpakning. • 4 fyldte pen med 1 alkoholserviet i en blisterpakning. • 6 fyldte pen med 1 alkoholserviet i en blisterpakning.
Packs of: • 1 pre-filled pen with 1 alcohol pad in a blister. • 2 pre-filled pen, each with 1 alcohol pad, in a blister. • 4 pre-filled pen, each with 1 alcohol pad, in a blister. • 6 pre-filled pen, each with 1 alcohol pad, in a blister.
, HUMIRA 40 mg opløsning til injektionsvæske indeholder ikke konserveringsmidler; derfor skal ikke anvendt lægemiddel eller affald heraf bør bortskaffes i overensstemmelse med lokale retningslinjer.
HUMIRA 40 mg solution for injection does not contain preservatives; therefore, any unused product or waste material should be disposed of in accordance with local requirements.
109 BILAG II
109 ANNEX II
110 A.
110 A.
Abbott Biotechnology Ltd.
Abbott Biotechnology Ltd.
Road No.
Road No.
2, Km.
2, Km.
59. 2 Barceloneta Puerto Rico 00617 USA
59.2 Barceloneta Puerto Rico 00617
Abbott Biotechnology Deutschland GmbH Max- Planck- Ring 2 D- 65205 Wiesbaden Tyskland
Abbott Biotechnology Deutschland GmbH Max-Planck-Ring 2 D-65205 Wiesbaden Germany
Inden markedsføring skal indehaveren af markedsføringstilladelsen sikre sig, at det uddannelsesprogram, der er implementeret for de nuværende godkendte indikationer, udvides med potentielle udskrivere af den nye indikation, juvenil idiopatisk artrit.
Prior to launch, the MAH shall ensure that the Educational programme implemented for currently authorised indications is extended to the potential prescribers concerned by the new indication, Juvenile Idiopathic Arthritis.
Dette program skal sikre, at læger, som har til hensigt at udskrive Humira, er klar over:
This programme shall ensure that physicians who intend to prescribe Humira are aware of:
- risiko for alvorlige infektioner, sepsis, tuberkulose og andre opportunistiske infektioner
- the risk of serious infections, sepsis, tuberculosis and other opportunistic infections
- risiko for hjerteinsufficiens
- the risk of heart failure
- risiko for demyeliserende sygdom i centralnervesystemet
- the risk of central nervous system demyelination
- risiko for maligne sygdomme
- the risk of malignancies
Patientkortet gives til patienter, der bruger Humira
- the Patient Alert Card is to be given to patients using Humira
Som vedtaget i version 2. 0 af Risk Management Plan (RMP), som findes i Modul 1. 8. 2 af ansøgning om markedsføringstilladelse og i enhver opdatering af RMP, der efterfølgende er vedtaget af CHMP.
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the pharmacovigilance plan, as agreed in version 4.0 of the Risk Management Plan (RMP) presented in Module 1.8.2 of the marketing Authorisation Application and any subsequent updates of the RMP agreed by the CHMP.