qanastek/EMEA-V3 huggingface dataset:
Trudexa, 40 mg every other week, was studied in patients with moderately to severely active psoriatic arthritis in two placebo-controlled studies, Studies VI and VII.
zz It- teħid ta ’ 40 mg Trudexa ġimgħa iva u ġimgħa le ġie studjat f’ pazjenti li jbatu minn artrite psorjatika attiva minn moderata sa severa f’ żewġ studji kontrollati bil- plaċebo, Studji VI u VII.
Study VI with 24 week duration, i dic
Studju VI li dam 24 ġimgħa, tratta 313 pazjent adult li kellhom rispons mhux adegwat għall- kura b’ mediċina anti -
treated 313 adult patients who had an inadequate response to non-steroidal anti-inflammatory drug therapy and of these, approximately 50% were taking methotrexate.
ori infjammatorja mhux sterojdi, u minn dawn, bejn wieħed u ieħor 50% kienu qegħdin jieħdu methotrexate.
Me
Studju VII li dam 12 - il ġimgħa, tratta 100 pazjent li kellhom rispons mhux adegwat għat- terapija DMARD.
There is insufficient evidence of the efficacy of Trudexa in patients with ankylosing spondylitis-like psoriatic arthropathy due to the small number of patients studied (see Table 7).
t aw Minħabba n- numru żgħir ta ’ pazjenti studjati, m’ hemmx biżżejjed evidenza fuq l- effikaċja ta ’ Trudexa f’ pazjenti li jbatu minn artrite psorjatika li tixbaħ lill- infjammazzjoni tal- vertebri li jirriżulta fil - vertebri jitwaħħlu flimkien (ankylosing spondylitis) (ara Tabella 7).
Table 7:
ux Tabella 7:
ACR Response in Placebo-Controlled Psoriatic Arthritis Studies (Percent of Patients)
Rispons għall- ACR fi Studji ta ’ l- Artrite Psorjatika kontrollati bil- Plaċebo (Persentaġġ ta ’ Pazjenti)
Study VI
Studju VI
Study VII
Studju VII
16
ad
Trudexa
Plaċebo
Placebo
Humira Plaċebo
Trudexa
Humira
N=151
N=151 N=49 ’ g ħ
Week 12
Ġimgħa 12
58% ***
16% 58% ***
Week 24 ACR 50
Ġimgħa 24 ACR 50
57%
N/ A 57%
***
im
2%
2% 36%
Week 24
Ġimgħa 24 ACR 70
39%
N/ A 39%
0%
1% li l
0% ***
0% 20%
tho *** p < 0.001 for all comparisons between Trudexa and placebo
*** p < 0. 001 għall- paraguni kollha bejn Humira u l plaċebo
p < 0.05 for all comparisons between Trudexa and placebo
p < 0. 05 f għall- paraguni kollha bejn Humira u l plaċebo ina
N/ A not applicable
N/ A ma japplikax
au ACR responses in Study VI were similar with and without concomitant methotrexate therapy.
Ir- risponsi għall- ACR fi Studju VI kienu simili kemm flimkien mal- kura b’ methotrexate, kif ukoll diċ
Trudexa treated patients demonstrated improvement in physical function as assessed by HAQ and Short Form Health Survey (SF 36), from base-line to week 24.
Pazjenti kkurati b’ Trudexa urew titjib fil- funzjoni fiżika kif stimat bl- HAQ u l- istudju tas- saħħa fil - forma il- qasira (SF 36), mil- linja bażi sa ġimgħa 24. me
r Ankylosing spondylitis
Infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis)
ge Trudexa 40 mg every other week was assessed in 393 patients in two randomised, 24 week double− blind, placebo− controlled studies in patients with active ankylosing spondylitis (mean lon baseline score of disease activity [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)] was 6.3 in all groups) who have had an inadequate response to conventional therapy.
It- teħid ta ’ 40 mg Trudexa ġimgħa iva u ġimgħa le kien stimat fi 393 pazjent f’ żewġ studji double - blind, kontrollati bil- plaċebo li ħadu 24 ġimgħa u li saru b’ ordni addoċċ fuq pazjenti li jbatu minn ott
The blinded period was followed by an open− label period no
Il- perijodu blinded ġie segwit b’ perijodu open- label, li matulu l- pazjenti rċevew 40 mg Trudexa taħt il- ġilda ġimgħa iva u ġimgħa le Pr
Subjects (n = 215, 54.7%) who failed to achieve ASAS 20 at Weeks 12, or 16 or 20 received early escape open-label adalimumab 40 mg every other week subcutaneously and were subsequently treated as non-responders in the double-blind statistical analyses. t uc
għal perijodu addizzjonali ta 28 ġimgħa. suġġetti (n = 215, 54. 7%) li ma laħqux l- ASAS 20 f’ ġimgħat 12, jew 16 jew 20 irċevew 40 mg adalimumab ħruġ kmieni open- label taħt il- ġilda ġimgħa iva u ġimgħa le, u kienu sussegwentament trattati bħala pazjenti li ma jirrispondux għal kura fl- analiżi ta ’ l - istatistika double - blind.
In the larger study (VIII) with 315 patients, results showed statistically significant improvement of the signs and symptoms of ankylosing spondylitis in patients treated with Trudexa compared to placebo.
18 Fl- istudju ikbar (VIII) bi 315 pazjent, ir- riżultati urew titjib statistikament sinifikanti tas- sinjali u s - sintomi ta ’ infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis) f’ pazjenti kkurati b’ Trudexa, meta pparagunat mal- plaċebo.
Significant response was first observed at Week 2 and maintained through 24 weeks (Table 8). rod
Rispons sinifikanti ġie osservat l- ewwel f’ Ġimgħa 2 u nżamm tul 24 ġimgħa (Tabella 8).
Table 8 - Efficacy Responses in Placebo-Controlled AS Study – Study VIII Reduction of Signs and Symptoms lP
at Tabella 8 – Risponsi ta ’ l- Effikaċja fi Studju AS kontrollat bil- Plaċebo Effikaċja – Studju VIII Tnaqqis fisSinjali u s- Sintomi
Response ASASa 20 na
Rispons
Placebo N=107
Plaċebo N=107
dic
16% 21%
Week 2 Week 12 Week 24
Ġimgħa 24
ASAS 50 Me
aw ASAS 50
Week 2 Week 12 Week 24
Ġimgħa 12 Ġimgħa 24
ASAS 70
ux ASAS 70
BASDAIb 50
BASDAI 50 ’ g ħ
Week 12 Week 24
Ġimgħa 12 Ġimgħa 24
***, ** Statistically significant at p < 0.001, < 0.01 for all comparisons between Trudexa and placebo at Weeks 2, 12 and 24 a ASsessments in Ankylosing Spondylitis
***, ** Statistikament sinifikanti f’ p < 0. 001, < 0. 01 għall- paraguni kollha bejn Trudexa u l - im
ed b Bath Ankylosing Spondylitis Disease Activity Index
plaċebo f’ Ġimgħa 2, 12 u 24 a Stima f ’ Ankylosing Spondylitis b Indiċi ta ’ l- Attività tal- Mard Bath Ankylosing Spondylitis li l
Trudexa treated patients had significantly greater improvement at Week 12 which was maintained through Week 24 in both the SF36 and Ankylosing Spondylitis Quality of Life Questionnaire
Pazjenti kkurati b’ Trudexa kellhom titjib akbar sinifikanti f’ Ġimgħa 12, li nżamm tul Ġimgħa 24 kemm fl- SF36, kif ukoll fil- kwistjunarju dwar il- kwalità tal- ħajja Ankylosing Spondylitis (ASQoL). ina
tho placebo controlled study (IX) of 82 adult patients with active ankylosing spondylitis.
Tendenzi simili (mhux kollha statistikament sinifikanti) ġew osservati fl- istudju iżgħar double- blind kontrollat bil- plaċebo li sar b’ ordni addoċċ (IX) ta ’ 82 pazjent adult li jbatu b’ infjammazzjoni tal - vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis). diċ
Crohn’ s Disease
Il- Marda Crohn (Crohn’ s Disease)
478 of the enrolled patients (32%) were defined as having a
Is- sigurtà u l- effikaċja ta ’ Trudexa ġew stimati f ’’ il fuq minn 1400 pazjent li jbatu mill- marda Crohn me
r severe disease (CDAI score > 300 and concomitant corticosteroid and/ or immunosuppressants)
478 mill- pazjenti reġistrati (32%) ġew dikjarati bħala li jbatu minn marda severa (riżultat ta ’ CDAI > 300 u t- teħid fl- istess waqt ta ’ corticosteroid u/ jew immunosoppressanti) li tikkorrespondi mal - ott
ge corresponding to the population defined in the indication (see section 4.1).
popolazzjoni definite fl- indikazzjoni (ara sezzjoni 4. 1).
Concomitant stable doses of aminosalicylates, corticosteroids, and/ or immunomodulatory agents were permitted and 79% of patients continued to receive at least one of these medications. lon Induction of clinical remission (defined as CDAI < 150) was evaluated in two studies, CLASSIC I and GAIN.
Dożi stabbli ta ’ aminosalicylates, corticosteroids, u/ jew aġenti immunomodulatorji mittieħda fl- istess waqt, kienu permessi u 79% tal - pazjenti komplew jirċievu mill- inqas waħda minn dawn il- mediċini. od
In CLASSIC I, 299 TNF-antagonist naive patients were randomised to one of four treatment groups; placebo at weeks 0 and 2, 160 mg Trudexa at week 0 and 80 mg at week 2, 80 mg at week 0 and 40 mg at week 2, and 40 mg at week 0 and 20 mg at week 2.
Il- qlib għall- aħjar fl- istat kliniku (definit bhala CDAI < 150) ġie evalwat f’ żewġ studji, CLASSIC I u GAIN.
In GAIN, 325 patients who had lost no
Fi CLASSIC I, 299 pazjent li qatt ma ħadu antagonist ta ’ TNF ġew imqassma bl- addoċċ Pr
response or were intolerant to infliximab were randomised to receive either 160 mg Trudexa at week 0 and 80 mg at week 2 or placebo at weeks 0 and 2.
f’ wieħed minn erbgħa gruppi ta ’ nies li kienu qegħdin jieħdu l- kura; plaċebo f’ ġimgħat 0 u 2, 160 mg Trudexa f’ ġimgħa 0 u 80 mg f’ ġimgħa 2, 80 mg f’ ġimgħa 0 u 40 mg f’ ġimgħa 2, u 40 mg f’ ġimgħa 0 u 20 mg f’ ġimgħa 2.
The primary non-responders were excluded from the studies and therefore these patients were not further evaluated. t uc
Dawk il- pazjenti li ma wrewx rispons mill- ewwel ġew esklużi mill- istudji u għalhekk dawn il- pazjenti ma ġewx evalwati aktar.
Maintenance of clinical remission was evaluated in CHARM.
19 Il- fatt jekk ġiex mantenut it- titjib kliniku ġie evalwat f’ CHARM.
In CHARM, 854 patients received open-label 80 mg at week 0 and 40 mg at week 2.
F’ CHARM, 854 pazjent irċevew 80 mg f’ ġimgħa 0 u 40 mg f’ ġimgħa 2, open label.
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.
F’ ġimgħa 4, il- pazjenti ġew imqassma bl- addoċċ biex jingħataw 40 mg ġimgħa iva u ġimgħa le, 40 mg kull ġimgħa, jew plaċebo għal tul ta ’ studju totali ta’ 56 ġimgħa.
Patients in clinical rod
Pazjenti li kellhom rispons kliniku (tnaqqis f ’ CDAI ≥ 70) f’ ġimgħa 4 ġew
response (decrease in CDAI ≥ 70) at week 4 were stratified and analysed separately from those not in clinical response at week 4.
at isseparati minn ma ’ l- oħrajn u ġew analizzati separatement minn dawk li ma kellhomx rispons kliniku f’ ġimgħa 4.
Corticosteroid taper was permitted after week 8.
It- tnaqqis tal- corticosteroid ftit ftit sakemm jitwaqqaf totalment, kien permess wara
CLASSIC I and GAIN induction of remission and response rates are presented in Table 9. lP Me
ori preżentati f’ Tabella 9.
Induction of Clinical Remission and Response (Percent of Patients)
t (Persentaġġ ta ’ Pazjenti)
CLASSIC I:
aw
Naive Patients
Pazjenti li qatt ma ħadu infliximab Plaċebo Trudexa Trudexa
Infliximab Experienced Patients
Pazjenti li kienu diġà ħadu infliximab qabel Plaċebo Trudexa
Trudexa 160/ 80 mg
160/ 80 mg N=76
ed Week 4
Ġimgħa 4
N=76
N=159
N=159
ad36% *
ris Clinical remission
Titjib kliniku
Clinical response (CR-
Rispons kliniku (CR- 100)
49%**
’ g ħ
tho 100) All p-values are pairwise comparisons of proportions for Trudexa versus placebo * p < 0.001 **
Il- valuri- p kollha huma paraguni magħmula għal kull par ta ’ proporzjonijiet għal Trudexa kontra l - plaċebo im
au p < 0.01
* p < 0. 001 ** p < 0. 01
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.
Rati simili ta ’ titjib ġew osservati għad- dożaġġ tal- bidu ta’ 160/ 80 mg u 80/ 40 mg milħuqa sa ġimgħa 8 li l
r ge In CHARM, at week 4, 58% (499/ 854) of patients were in clinical response and were assessed in the primary analysis.
F’ CHARM, f’ ġimgħa 4, 58% (499/ 854) tal- pazjenti kellhom rispons kliniku u ġew assessjati fl- analiżi primarja.
Maintenance of remission and response rates are presented in Table 10.
Minn dawk li kellhom rispons kliniku f’ ġimgħa 4, 48% kienu ġew esponuti għal kura oħra għal kontra TNF fil- passat.
Table 10:
Iż- żamma tar- rati tat- titjib u tar- rispons huma preżentati f’ Tabella 10.
Maintenance of Clinical Remission and Response (Percent of Patients) no
Ir - riżultati tat- titjib kliniku baqgħu relattivament kostanti, irrispettivament mill- esponimenti għal diċ
Placebo
antagonist ta ’ TNF li kien hemm fil- passat. me ott od Pr
40 mg Trudexa
20 Tabella 10:
every other week
40 mg Trudexa ġimgħa iva u ġimgħa le
every week
40 mg Trudexa kull ġimgħa
Week 26
at Ġimgħa 26
Clinical remission
zz Titjib kliniku Rispons kliniku (CR- 100)
47%*
40% * 52% *
52%*
ori
Patients in steroid-free remission rod
Pazjenti li kellhom titjib mingħajr sterojdi għal > =90 ġurnataa
for > =90 daysa Week 56 Clinical remission
t Ġimgħa 56
Clinical response (CR-100)
aw Titjib kliniku Rispons kliniku (CR- 100)
Patients in steroid-free remission for > =90 daysa na
Pazjenti li kellhom titjib mingħajr sterojdi għal > =90 ġurnataa
* p < 0.001 for Trudexa versus placebo pairwise comparisons of proportions ** p < 0.02 for Trudexa versus placebo pairwise comparisons of proportions a i
ux * p < 0. 001 għall- paraguni magħmula bejn kull par ta ’ proporzjonijiet għal Trudexa kontra l- plaċebo ** p < 0. 02 għall- paraguni magħmula bejn kull par ta ’ proporzjonijiet għal Trudexa kontra l- plaċebo
Of those receiving corticosteroids at baseline dic
ad a Minn dawk li jirċievu l- corticosteroids fil- linja bażi
Among patients who were not in response at week 4, 43% of Trudexa maintenance patients responded by week 12 compared to 30% of placebo maintenance patients.
Mill- pazjenti li ma kellhomx rispons f’ ġimgħa 4, 43% tal- pazjenti li baqgħu jingħataw Trudexa biex ’ g ħ imantnu l- istat tagħhom kellhom rispons sa ġimgħa 12 meta komparati ma 30% ta ’ pazjenti li jirċievu l- plaċebo biex imantnu l- istat tagħhom.
These results suggest that some patients who have not responded by week 4 benefit from continued maintenance therapy through week Me
Terapija li im
Therapy continued beyond 12 weeks did not result in significantly more responses (see section 4.2).
tkompliet wara ġimgħa 12 ma wasslitx għal numru ikbar b’ mod sinifikanti ta ’ aktar risponsi (ara sezzjoni 4. 2).
Quality of Life
Kwalità ta’ Ħajja li l
In CLASSIC I and GAIN, statistically significant improvement in the disease-specific inflammatory bowel disease questionnaire (IBDQ) total score was achieved at week 4 in patients randomised to
Fi CLASSIC I u GAIN, f’ ġimgħa 4, ġie milħuq riżultat totali li wera titjib li hu statistikament sinifikanti fil- kwestjonarju għall- mard speċifiku dwar il- marda ta ’ l- infjammazzjoni tal- musrana ina
19 Trudexa 80/ 40 mg and 160/ 80 mg compared to placebo and was seen at weeks 26 and 56 in CHARM as well among the adalimumab treatment groups compared to the placebo group.
(IBDQ), u dan f’ pazjenti li ġew magħżula bl- addoċċ u ngħataw 80/ 40 mg u 160/ 80 mg Trudexa meta mqabbel mal- plaċebo, u dan deher f’ ġimgħat 26 u 56 f’ CHARM, kif ukoll fil- gruppi tal- kura b’ adalimumab meta mqabbla mal- grupp tal- plaċebo. diċ
Formation of anti-adalimumab antibodies is associated with increased clearance and reduced efficacy
Il- formazzjoni ta ’ anti- korpi kontra adalimumab hija assoċjata ma ’ żieda fit- tneħħija u tnaqqis fl - me
ed of adalimumab.
effikaċja ta ’ adalimumab.
There is no apparent correlation between the presence of anti-adalimumab antibodies and adverse events.
Ma jidher li hemm l- ebda korrelazzjoni bejn il- preżenza ta’ anti- korpi kontra adalimumab u effetti avversi.
ris Patients in Studies I, II and III were tested at multiple timepoints for antibodies to adalimumab during the 6 to 12 month period.
Pazjenti fi Studji I, II u III ġew ittestjati għal anti- korpi kontra adalimumab f’ diversi ħinijiet waqt il - ott
In patients not given
Fil- provi pivotali, anti- korpi kontra adalimumab kienu identifikati fi 58/ 1053 (5. 5%) pazjent ikkurati b’ adalimumab, imqabbla ma ’ 2/ 370 (0. 5%) fuq il- plaċebo.
tho concomitant methotrexate, the incidence was 12.4%, compared to 0.6% when adalimumab was used as add-on to methotrexate.
F’ pazjenti li ma ngħatawx methotrexate flimkien ma ’ adalimumab, l- inċidenza kienet ta ’ 12. 4%, imqabbla ma ’ 0. 6% meta adalimumab kien użat addizzjonalment ma ’ methotrexate. od
In patients with psoriatic arthritis, adalimumab antibodies were identified in 38/ 376 subjects (10%)
F’ pazjenti li jbatu minn artrite psorjatika, anti- korpi ta ’ adalimumab ġew identifikati fi 38/ 376 suġġett (10%) ikkurati b’ adalimumab.
au treated with adalimumab.
F’ pazjenti li ma ngħatawx ukoll methotrexate flimkien ma ’ Pr
In patients not given concomitant methotrexate, the incidence was 13.5% (24/ 178 subjects), compared to 7% (14 of 198 subjects) when adalimumab was used as add-on to methotrexate.
adalimumab, l- inċidenza kienet ta ’ 13. 5% (24/ 178 suġġett), meta pparagunat ma ’ 7% (14 minn 198 suġġett) meta adalimumab kien użat addizzjonalment ma ’ methotrexate.
r ge In patients with ankylosing spondylitis antibodies were identified in 17/ 204 subjects (8.3%) treated with adalimumab.
F’ pazjenti li jbatu minn infjammazzjoni tal- vertebri li tirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis), ġew identifikati anti- korpi fi 17/ 204 suġġett (8. 3%) ikkurati b’ adalimumab.
In patients not given concomitant methotrexate, the incidence was 16/ 185 (8.6%), compared to 1/ 19 (5.3%) when adalimumab was used as add-on to methotrexate. lon In patients with Crohn’ s disease, adalimumab antibodies were identified in 7/ 269 subjects (2.6%) treated with adalimumab.
21 F’ pazjenti li ma ngħatawx ukoll methotrexate flimkien ma ’ adalimumab, l- inċidenza kienet ta ’ 16/ 185 (8. 6%), meta pparagunat ma ’ 1/ 19 (5. 3%) meta adalimumab kien użat addizzjonalment ma ’ methotrexate.
Because immunogenicity analyses are product-specific, comparison of antibody rates with those from no
F’ pazjenti li jbatu mill- marda Crohn (Crohn’ s disease), anti- korpi ta ’ kontra adalimumab ġew
other products is not appropriate.
at identifikati f’ 7/ 269 suġġett (2. 6%) ikkurati b’ adalimumab.
5.2 Pharmacokinetic properties t
ori 5. 2 Tagħrif farmakokinetiku
After subcutaneous administration of a single 40 mg dose, absorption and distribution of adalimumab uc
Wara t- teħid taħt il- gilda ta ’ doża waħda ta ’ 40 mg, l- assorbiment u d- distribuzzjoni ta ’ adalimumab
was slow, with peak serum concentrations being reached about 5 days after administration.
t kien bil- mod, bl- ogħla punt ta ’ konċentrazzjoni fis- serum jintlaħaq madwar 5 ijiem wara li jittieħed.
The average absolute bioavailability of adalimumab estimated from three studies following a single 40 mg rod
Il -
subcutaneous dose was 64%.
aw biodisponibiltà medja assoluta ta ’ adalimumab stimata minn tliet studji wara t- teħid ta ’ doża waħda ta ’ 40 mg taħt il- ġilda kienet ta ’ 64%.
After doses of 0.5 mg/ kg (~40 mg), clearances ranged from 11 to 15 ml/ hour, the distribution volume (Vss) ranged from 5 to 6 litres and the mean terminal phase half- life was approximately two weeks.
Wara dożi ta ’ 0. 5 mg/ kg (~40 mg), it - tneħħija mill- ġisem varjat minn 11 sa 15 ml/ siegħa, il- volum ta ’ distribuzzjoni (Vss) varja minn 5 sa
rheumatoid arthritis patients ranged from 31-96% of those in serum.
ux 6 litri u l- half- life medja tal- fażi terminali kienet ta ’ bejn wieħed u ieħor gimagħtejn.
Following subcutaneous administration of 40 mg of Trudexa every other week in rheumatoid arthritis (RA) patients the mean steady-state trough concentrations were approximately 5 µg/ ml (without na
Il - konċentrazzjoni ta ’ adalimumab fil- fluwidu sinovjali ta ’ ħafna pazjenti li jbatu minn artrite rewmatika varjaw minn 31- 96% minn dawk fis- serum.
concomitant methotrexate) and 8 to 9 µg/ ml (with concomitant methotrexate), respectively.
ad Wara t- teħid ta ’ Trudexa 40 mg taħt il- ġilda ġimgħa iva u ġimgħa le f’ pazjenti li jbatu minn artrite rewmatika (AR), il- konċentrazzjoni minimali medja fissa kienet ta ’ bejn wieħed u ieħor 5µg/ ml ’ g ħ (mingħajr t- teħid konkomitanti ta ’ methotrexate) u minn 8 sa 9 µg/ ml (bit- teħid konkomitanti ta’ methotrexate), rispettivament.
The serum adalimumab trough levels at steady-state increased roughly proportionally with dose following 20, 40 and 80 mg every other week and every week subcutaneous dosing. i dic
Il- livelli minimali fissi fis- serum ta ’ adalimumab żdiedu bejn wieħed u ieħor proporzjonalment mad- doża wara t- teħid ta ’ 20, 40 u 80 mg ġimgħa iva u ġimgħa le u dożaġġ ta ’ injezzjoni taħt il- ġilda kull ġimgħa. im
A loading dose of 160 mg Trudexa on week 0 followed by 80 mg Me
F’ pazjenti li jbatu mill- marda Crohn (Crohn’ s disease), id- doża kbira ta ’ 80 mg Trudexa f’ ġimgħa 0 segwita b’ 40 mg Trudexa f’ ġimgħa 2 tilħaq konċentrazzjonijiet minimali tas- serum f’ adalimumab ta ’ li l
Trudexa on week 2 achieves serum adalimumab trough concentrations of approximately 12 µg/ ml during the induction period.
Doża kbira ta ’ 160 mg Trudexa f’ ġimgħa 0 segwita b’ 80 mg Trudexa f’ ġimgħa 2 tilħaq konċentrazzjonijiet minimali tas- serum f’ adalimumab ta ’ bejn wieħed u ieħor 12 µg/ ml matul il- perijodu tal- bidu.
Mean steady-state trough levels of approximately 7 µg/ ml were observed in Crohn’ s disease patients who received a maintenance dose of 40 mg Trudexa every other week.
F’ pazjenti li jbatu mill- marda Crohn (Crohn’ s ina
Population pharmacokinetic analyses with data from over 1300 RA patients revealed a trend toward higher apparent clearance of adalimumab with increasing body weight.
Analiżi tal- farmakokinetika tal- populazzjoni bi stħarriġ fuq ’ il fuq minn 1300 pazjent bl- AR wera diċ
After adjustment for weight differences, gender and age appeared to have a minimal effect on adalimumab clearance.
xaqlib lejn turija aktar għolja ta ’ tneħħija ta ’ adalimumab mill- ġisem, aktar ma jiżdied il- piż tal- ġisem.
The serum
Wara aġġustamenti li saru għal differenzi fil- piż, irriżulta li s- sess u l- eta ’ kellhom effett minimu fuq it- tneħħija ta ’ adalimumab.
20 levels of free adalimumab (not bound to anti-adalimumab antibodies, AAA) were observed to be lower in patients with measurable AAA.
Ġie osservat li l- livelli fis- serum ta ’ adalimumab ħieles (mhux imwaħħal ma anti- korpi ta ’ kontra adalimumab, AAA) kienu aktar baxxi f’ pazjenti b’ livelli AAA li jitkejlu. me
Trudexa has not been studied in children or in patients with hepatic or renal impairment.
Trudexa ma ġiex studjat fuq tfal jew pazjenti li jbatu minn indeboliment tal- fwied jew indeboliment renali.
5.3 Preclinical safety data
5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina ott
ed Non-clinical data reveal no special hazard for humans based on studies of single dose toxicity, repeated dose toxicity, and genotoxicity.
Informazzjoni li mhix klinika, magħmula fuq studji ta ’ l- effett tossiku ta ’ doża waħda, l- effett tossiku ta ’ dożi ripetuti u tal- ġenotossiċità, ma turi l- ebda periklu speċjali għall- bnedmin. od
ris An embryo-foetal developmental toxicity/ perinatal developmental study has been performed in cynomologous monkeys at 0, 30 and 100 mg/ kg (9-17 monkeys/ group) and has revealed no evidence of harm to the foetuses due to adalimumab.
Sar studju fuq l- effett tat- tossiċità waqt l- iżvilupp embrijo- fetali/ l- iżvilupp fiż- żmien immedjatament qabel jew wara t- twelid, fuq xadini ċinomologi li b ’ 0, 30 u 100mk/ kg (9- 17 – il xadina/ grupp) u dan ma wera l- ebda evidenza ta ’ dannu kkaġunat b’ adalimumab fuq il- feti.
Carcinogenicity studies, and standard assessment of
Ma sarux studji karċinoġeniċi, Pr
tho fertility and postnatal toxicity, were not performed with adalimumab due to the lack of appropriate models for an antibody with limited cross-reactivity to rodent TNF and the development of neutralizing antibodies in rodents.
u stima stàndard ta ’ fertilità u tossiċità wara t- twelid b’ adalimumab, u dan minħabba nuqqas ta ’ mudelli adegwati għal anti- korp li jirreaġixxu ukoll għat- TNF tal- bhejjem gerriema u l- iżvilupp ta ’ anti- korpi li jinnewtraliżżaw fil- bhejjem gerriema.
au 6.
22 6.
r ge Mannitol Citric acid monohydrate Sodium citrate lon Sodium dihydrogen phosphate dihydrate Disodium phosphate dihydrate Sodium chloride Polysorbate 80 no
zz Sodium citrate Sodium dihydrogen phosphate dihydrate Disodium phosphate dihydrate
Sodium hydroxide Water for injections.
ori Sodium chloride Polysorbate 80 Sodium hydroxide
6.2 Incompatibilities t uc
t Ilma għall- injezzjonijiet
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. rod
Minħabba li ma sarux studji li juru liema huma l- prodotti li ma jablux miegħu, dan il- prodott
6.3 Shelf life
ux mediċinali m’ għandux jitħallat ma ’ prodotti mediċinali oħrajn.
18 months lP
6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
6.4 Special precautions for storage
ad 18- il xahar ’ g ħ 6. 4 Prekawzjonijiet speċjali għall- ħażna
Do not freeze. na
Tagħmlux fil- friża. im
6.5 Nature and contents of container i
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
Trudexa 40 mg solution for injection in single-use vial (type I glass), fitted with rubber stoppers, dic
Trudexa 40 mg soluzzjoni għall- injezzjoni f’ kunjett li jintuża għal darba waħda biss (ħġieġ tip I), komplut bis- siġilli tal- lastku, magħluq bil- pressa bl- aluminju u bis- siġilli flip- off. li l
Me
Pakketti ta: ina
6.6 Special precautions for disposal
6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema diċ
Any unused product or waste material should be disposed of in accordance with local requirements.
Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa ’ wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali. me
Abbott Laboratories Ltd.
Abbott Laboratories Ltd. ott
Queenborough Kent ME11 5EL United Kingdom
Queenborough Kent ME11 5EL Renju Unit od
MARKETING AUTHORISATION NUMBER(S)
NUMRU( I) TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ Pr
1 September 2003
23 1 ta ’ Settembru 2003
r {MM/ YYYY}
at {XX/ SSSS}
ge lon not uc rod lP i na dic Me
zz ori t aw ux ad ’ g ħ im li l ina diċ me ott od Pr
Trudexa 40 mg solution for injection in pre-filled syringe
Trudexa 40 mg soluzzjoni għall- injezzjoni f’ siringa mimlija għal- lest
ed Each 0.8 ml single dose pre-filled syringe contains 40 mg of adalimumab.
zz Kull siringa mimlija għal- lest b’ doża waħda ta ’ 0. 8 ml fiha 40 mg adalimumab.
ris Adalimumab is a recombinant human monoclonal antibody expressed in Chinese Hamster Ovary cells.
ori waħda, espress fiċ- ċelluli ta ’ l- ovarji tal- ħamster ċiniż.
au Solution for injection in pre-filled syringe.
Soluzzjoni għall- injezzjoni f’ siringa mimlija għal- lest.
4.
ux 4.
r ge 4.1 Therapeutic indications
ad 4. 1 Indikazzjonijiet terapewtiċi ’ g ħ Artrite rewmatika
Rheumatoid arthritis lon Trudexa in combination with methotrexate, is indicated for:
Trudexa, flimkien ma ’ methotrexate, huwa indikat għall -: im
the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the no
• kura ta ’ artrite rewmatika attiva minn moderata sa severa f’ pazjenti adulti, meta r- rispons tagħhom għal mediċini anti- rewmatiċi li jaffetwaw il- proċess tal- mard, inkluż methotrexate, ma kienx adegwat. li l
response to disease-modifying anti-rheumatic drugs including methotrexate has been inadequate. the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate. t uc
• kura ta ’ artrite rewmatika attiva u progressiva severa f’ adulti li ma jkunux ingħataw kura b’ methotrexate qabel. ina
Trudexa can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate. rod
Trudexa jista ’ jingħata waħdu f’ każ ta ’ intolleranza għal methotrexate, jew f’ każ li t- tkomplija tal- kura b’ methotrexate ma tkunx tajba. diċ
Trudexa has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function, when given in combination with methotrexate.
Ġie ppruvat li, meta jingħata flimkien ma ’ methotrexate, Trudexa jnaqqas ir- rata li biha tipprogressa l - ħsara fil- ġogi kif imkejjel permezz ta ’ X- ray, u li jtejjeb il- funzjoni fiżika. me
Psoriatic arthritis lP
Artrite Psorjatika
Ankylosing spondylitis i
Infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis) od
Trudexa is indicated for the treatment of adults with severe active ankylosing spondylitis who have dic
Pr
Trudexa is indicated for treatment of severe, active Crohn’ s disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/ or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies.
Trudexa huwa indikat għall- marda Crohn severa u attiva f’ pazjenti li, minkejja terapija sħiħa u adekwata li jkunu ingħataw b’ xi corticosteroid u/ jew b’ xi immunosoppressiv, xorta ma kellhomx
For induction treatment, Trudexa should be given in combination with corticosteroids.
Għall- kura tal- bidu, Trudexa għandu jingħata flimkien ma ’ corticosteroids.
23 4.2 Posology and method of administration
at 4. 2 Pożoloġija u metodu ta ’ kif għandu jingħata
Trudexa treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or Crohn’ s disease.
zz Il- kura b’ Trudexa għandha tinbeda u tiġi ssorveljata minn tobba speċjalisti li għandhom esperjenza fid- dijanjosi u fil- kura ta ’ l- artrite rewmatika, ta ’ l- artrite psorjatika, ta ’ l- infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis) jew tal- marda Crohn (Crohn’ s
ed After proper training in injection technique, patients may self-inject with Trudexa if their physician determines that it is appropriate and with medical follow-up as necessary.
t infushom b’ Trudexa jekk it- tabib tagħhom jiddeċiedi li dan hu tajjeb għalihom, u jekk ikun hemm
ris During treatment with Trudexa, other concomitant therapies (e. g., corticosteroids and/ or immunomodulatory agents) should be optimised.
Matul il- kura b’ Trudexa, terapiji oħra (eż., corticosteroids u/ jew aġenti immunomodulatorji) għandhom jiġu aġġustati għall- aħjar effett.
Rheumatoid arthritis
ad Artrire rewmatika
au The recommended dose of Trudexa for adult patients with rheumatoid arthritis is 40 mg adalimumab administered every other week as a single dose via subcutaneous injection.
Id- doża ta ’ Trudexa rrakkomandata għal pazjenti adulti li jbatu minn artrite rewmatika hija ta ’ 40 mg ’ g ħ adalimumab li tittieħed bħala doża waħda ġimgħa iva u ġimgħa le, permezz ta ’ injezzjoni taħt il- ġilda.
Methotrexate should be continued during treatment with Trudexa.
Methotrexate għandu jitkompla waqt il- kura b’ Trudexa.
r Glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs, or analgesics can be continued
Mediċini glukokortikojdi, saliċilati u mediċini anti- infjammatorji mhux sterojdi, jew mediċini im
ge during treatment with Trudexa.
analġeżiċi jistgħu jitkomplew waqt il- kura b’ Trudexa.
Regarding combination with disease modifying anti-rheumatic drugs other than methotrexate see sections 4.4 and 5.1. lon In monotherapy, some patients who experience a decrease in their response may benefit from an increase in dose intensity to 40 mg adalimumab every week.
Rigward it- teħid flimkien ta ’ Trudexa ma ’ mediċini anti- rewmatiċi li jaffetwaw il- proċess tal- mard, minbarra methotrexate, ara sezzjoni 4. 4 u 5. 1. li l
Psoriatic arthritis and ankylosing spondylitis no
Artrite Psorjatika u infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis) diċ
The recommended dose of Trudexa for patients with psoriatic arthritis and ankylosing spondylitis is 40 mg adalimumab administered every other week as a single dose via subcutaneous injection. t
Id- doża ta ’ Trudexa rrakkomandata għal pazjenti li jbatu minn artrite psorjatika u infjammazzjoni tal - vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis), hija ta ’ 40 mg adalimumab li tittieħed bħala doża waħda ġimgħa iva u ġimgħa le, permezz ta ’ injezzjoni taħt il- ġilda. me
Continued therapy should be carefully reconsidered in a patient not responding within this time period. rod
Wieħed għandu jirrikonsidra b’ attenzjoni jekk għandhiex titkompla l- kura f’ każ ta’ pazjent li ma jkunx irrisponda f’ dan il- perijodu ta ’ żmien. ott
The recommended Trudexa induction dose regimen for adult patients with severe Crohn’ s disease is lP
Id- dożaġġ irrakkomandat biex tinbeda l- kura b’ Trudexa fuq pazjenti adulti li jbatu mill- marda Crohn od
80 mg at week 0 followed by 40 mg at week 2.
(Crohn’ s disease) severa huwa ta ’ 80 mg f’ ġimgħa 0 segwiti b’ 40 mg f’ ġimgħa 2.
In case there is a need for a more rapid response to therapy, the regimen 160 mg at week 0 (dose can be administered as four injections in one day or as two injections per day for two consecutive days), 80 mg at week 2, can be used with the awareness that the risk for adverse events is higher during induction. na
jumejn konsekuttivi) u 80 mg f’ ġimgħa 2 jista ’ jingħata però, f’ dan il- każ, wieħed għandu jżomm f’ moħħu l- fatt li r- riskju ta ’ effetti avversi waqt il- bidu tat- terapija ikun ogħla.
Trudexa may be re-administered.
26 marda jerġgħu joħorġu, Trudexa jista ’ jerġa ’ jingħata.
24 Some patients who have not responded by week 4 may benefit from continued maintenance therapy through week 12.
ori titkompla sa ġimgħa 12.
Serious infections: i dic
Infezzjonijiet serji:
In clinical trials an increased risk of serious infections in patients receiving Trudexa has been shown, and reports from the post-marketing setting support this finding.
27 Fi provi kliniċi, irriżulta riskju akbar ta ’ infezzjonijiet serji f’ pazjenti li jirċievu Trudexa, u rapporti li saru wara li l- prodott tpoġġa fis- suq jikkonfermaw dan.
25 Before initiation of therapy with Trudexa, all patients must be evaluated for both active or inactive (latent) tuberculosis infection.
ori Qabel tinbeda l- kura b’ Trudexa, il- pazjenti kollha għandhom jiġu evalwati għall- infezzjoni tat - tuberkulosi kemm attiva kif ukoll mhux attiva (rieqda).
ed are reminded of the risk of false negative tuberculin skin test results, especially in patients who are severely ill or immunocompromised.
t medika fid- dettall, bl- istorja personali tat- tuberkulosi jew esponimenti għal pazjenti b’ tuberkulosi
ris If active tuberculosis is diagnosed, Trudexa therapy must not be initiated (see section 4.3).
Testijiet xierqa għall- iċċekjar, jiġifieri test tal- ġilda għat- tuberkolina u X- ray tas - sider, għandhom isiru fuq il- pazjenti kollha (rakkomandazzjonijiet lokali jistgħu japplikaw).
If latent tuberculosis is diagnosed, appropriate anti-tuberculosis prophylaxis in accordance with local
ux Min jagħti l- mediċina huwa mfakkar fir- riskju ta ’ testijiet negattivi tal- ġilda għat- tuberkolina foloz, speċjalment f’ pazjenti li huma morda serjament jew li għandhom immunità kompromessa.
au wasting/ weight loss, low grade fever) suggestive of a tuberculosis infection occur during or after therapy with Trudexa.
Il- pazjenti għandhom ikunu avżati biex jitolbu parir mediku jekk sinjali/ sintomi (eż, sogħla persisitenti, telf ta ’ muskoli/ tnaqqis fil- piż, deni ta ’ grad baxx) li jindikaw infezzjoni tat- tuberkulosi ifeġġu waqt jew wara t- terapija b’ Trudexa. li l
ge There have been reports of serious and severe opportunistic infections associated with Trudexa therapy, for example pneumocystis carinii pneumonia, disseminated histoplasmosis, listeriosis and lon aspergillosis.
Kien hemm rapporti ta ’ infezzjonijiet opportunistiċi serji u severi assoċjati mat- terapija b’ Trudexa, per eżempju pnewmonja pneumocystis carinii, histoplasmosis mifruxa, listeriosis u aspergillosis.
If a patient receiving Trudexa shows prolonged/ atypical symptoms/ signs of infections or general deterioration, prevalent opportunistic conditions must be considered. no
tul/ atipiċi, għandhom jiġu kkunsdrati kundizzjonijiet opportunistiċi prevalenti.
Hepatitis B Reactivation
Riattivazzjoni ta ’ Epatite B me
Patients at risk for HBV t uc
Persuni li jġorru l- HBV u li jkollhom bżonn il - ott
infection should be evaluated for prior evidence of HBV infection before initiating Trudexa therapy.
kura b’ Trudexa għandhom jiġu monitorjati għal sinjali u sintomi ta ’ infezzjoni HBV attiva matul it - terapija u għal ħafna xhur wara li titwaqqaf it- terapija.
Carriers of HBV who require treatment with Trudexa should be closely monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination rod
M’ hawnx informazzjoni adegwata fuq il- kura ta ’ pazjenti li jġorru l- HBV permezz ta ’ terapija anti- virali flimkien ma ’ terapija b’ antagonist ta ’ TNF od
Adequate data of treating patients who are carriers of HBV with anti-viral therapy in conjunction with TNF-antagonist therapy to prevent HBV reactivation are not available.
biex tiġi evitata r- riattivazzjoni ta ’ l- HBV.
In patients who develop HBV reactivation, Trudexa should be stopped and effective anti-viral therapy with appropriate supportive treatment should be initiated. lP
Pr
TNF-antagonists including Trudexa have been associated in rare cases with new onset or exacerbation na
Min jagħti l -
Prescribers should exercise caution in considering the use of Trudexa in patients with pre-existing or recent-onset central nervous system demyelinating disorders. i dic
28 mediċina għandu joqgħod attent meta jikkunsidra l- użu ta ’ Trudexa fuq pazjenti li diġà għandhom jew li qabduhom riċentement, disturbi li jaffetwaw il- myelin fis- sistema ċentrali nervuża.
Serious allergic adverse reactions have not been reported with subcutaneous administration of Trudexa Me
at Matul provi kliniċi, ma ġewx irrappurtati reazzjonijiet avversi serji bl- użu ta ’ Trudexa taħt il- ġilda.
during clinical trials.
zz kliniċi.
In postmarketing, serious allergic reactions including anaphylaxis have been reported very rarely following Trudexa administration.
Wara li l- prodott tqiegħed fis- suq, reazzjonijiet allerġiċi serji, li jinkludu l- anafilassi, ġew irrappurtati f’ każi rari ħafna wara li ttieħed Trudexa.
If an anaphylactic reaction or other serious allergic reaction occurs, administration of Trudexa should be discontinued immediately and appropriate therapy initiated.
Jekk ikun hemm reazzjoni anafilattika jew reazzjoni allerġika serja oħra, it- teħid ta ’ Trudexa għandu jitwaqqaf immedjatament, u għandha
26 The needle cover of the syringe contains natural rubber (latex).
L- għatu tal- labra tas- siringa fih lastiku naturali (latex).
This may cause severe allergic reactions in patients sensitive to latex.
Dan jista ’ jikkaġuna reazzjonijiet allerġiċi
Immunosuppression
aw Immunosoppressjoni
In a study of 64 patients with rheumatoid arthritis that were treated with Trudexa, there was no
Fi studju ta ’ 64 pazjent li jbatu minn artrite rewmatika li kienu kkurati b’ Trudexa, ma kien hemm l -
ed evidence of depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or change in enumeration of effector T-and B cells and NK-cells, monocyte/ macrophages, and neutrophils.
ux ebda evidenza ta ’ tnaqqis ta ’ sensitività eċċessiva imdewma, tnaqqis tal- livelli ta ’ immunoglobuli, jew tibdil fin- numri ta ’ ċelloli effettivi T u B u ċelloli NK, monoċistiċi / makrofaġi, u newtrofili.
ris Malignancies and lymphoproliferative disorders
ad Tumuri malinni u disturbi li jaffetwaw it- tkattir tal- limfoċiti
tho In the controlled portions of clinical trials of TNF-antagonists, more cases of malignancies including lymphoma have been observed among patients receiving a TNF-antagonist compared with control patients.
Fil- porzjonijiet kontrollati tal- provi kliniċi ta ’ antagonisti ta ’ TNF, ġew osservati aktar każi ta ’ tumuri ’ g ħ malinni, inkluż limfoma, f’ pazjenti li jirċievu xi anagonist ta ’ TNF, meta ipparagunati ma ’ pazjenti kontrollati.
Furthermore, there is an increased background lymphoma risk in rheumatoid arthritis patients with long-standing, highly active, inflammatory
Barra minn hekk, hemm sfond ta ’ riskju akbar ta ’ limfoma f’ pazjenti li jbatu minn artrite rewmatika b’ mard infjammatorju li jkun ilu u li hu attiv ħafna, li jikkomplika l- istima tar- riskju.
With the current knowledge, a possible risk for the development of lymphomas or other malignancies in patients treated with a TNF-antagonist cannot be excluded.
possibilità ta ’ żvilupp ta ’ tumuri limfoma jew tumuri malinni oħra f’ pazjenti kkurati b’ xi antagonist ta ’ TNF.
r No studies have been conducted that include patients with a history of malignancy or that continue
Ma saru l- ebda studji li jinkludu pazjenti bi storja ta ’ tumuri malinni jew fejn tkompliet il- kura fuq li l
Thus additional caution should be exercised in considering Trudexa treatment of these patients (see section 4.8). lon In an exploratory clinical trial evaluating the use of another anti-TNF agent, infliximab, in patients with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in the lung or head and neck, were reported in infliximab-treated patients compared with control patients.
Għalhekk, wieħed għandu joqgħod aktar attent meta jikkunsidra l- kura b’ Trudexa ta’ dawn il- pazjenti (ara sezzjoni 4. 8). ina
All patients had a history of heavy smoking.
pparagunati ma ’ pazjenti kontrollati.
Therefore, caution should be exercised when using any no
Il- pazjenti kollha kienu jpejpu ħafna.
TNF-antagonist in COPD patients, as well as in patients with increased risk for malignancy due to heavy smoking.
Għalhekk, għandha tiġi eżerċitata l- attenzjoni meta jintuża kwalukwe antagonist ta ’ TNF f’ pazjenti li jbatu minn COPD, kif ukoll f’ pazjenti li għandhom riskju akbar ta ’ tumur malinn minħabba li jpejpu ħafna. me
Haematologic reactions t uc
Reazzjonijiet ematoloġiċi
Adverse events of the haematologic system, including medically significant cytopoenia (e. g. rod
Effetti avversi tas- sistema ematoloġika, li jinkludu ċitopenja li hi medikament sinifikanti (eż ott
thrombocytopaenia, leucopaenia) have been infrequently reported with Trudexa.
thrombocytopaenia, lewkopenja) ma ġewx irrappurtati frekwentament b’ Trudexa.
Discontinuation of Trudexa therapy should be considered in patients with confirmed significant haematologic lP
Il- pazjenti kollha għandhom ikunu avżati biex ifittxu l- attenzjoni medika jekk jiżviluppaw sinjali u sintomi li jindikaw tibdil fil- livelli taċ- ċelloli tad- demm (eż deni persistenti, tbenġil, ħruġ ta ’ demm, sfurija) waqt li jkunu od
abnormalities.
qegħdin jirċievu Trudexa.
virus vaccination were observed in a study in 226 adult subjects with rheumatoid arthritis who were treated with adalimumab or placebo.
M’ hawn l- ebda informazzjoni dwar it -
No data are available on the secondary transmission of infection by live vaccines in patients receiving Trudexa.
29 trasmissjoni sekondarja ta ’ l- infezzjoni permezz ta ’ vaċċini ħajjin f’ pazjenti li jirċievu Trudexa.
vaccinations, except for live vaccines.
Insuffiċjenza tal- qalb konġestiva
In a clinical trial with another TNF-antagonist worsening congestive heart failure and increased mortality due to congestive heart failure have been observed.
zz insuffiċjenza tal- qalb konġestiva marret għall- agħar ġew irrappurtati ukoll f’ pazjenti li jirċievu Trudexa.
Trudexa is contraindicated in moderate to severe heart failure (see section 4.3).
ori moderata sa severa (ara sezzjoni 4. 3).
Treatment with Trudexa must be discontinued in patients who develop new or worsening symptoms of congestive heart failure.
Il- kura b’ Trudexa għandha titwaqqaf f’ pazjenti li jiżviluppaw sintomi ġodda jew li jiggravawlhom is- sintomi eżistenti ta ’ insuffiċjenza tal- qalb konġestiva.
27 Autoimmune processes
t Proċessi awtoimmuni
Treatment with Trudexa may result in the formation of autoimmune antibodies.
aw Il- kura b’ Trudexa tista ’ tirriżulta fil- formazzjoni ta’ anti- korpi awtoimmuni.
ed given (see section 4.8).
ux jkun pożittiv għall- anti- korpi kontra DNA li hi double stranded, m’ għandhiex tingħata aktar kura b’ Trudexa (ara sezzjoni 4. 8).
Concurrent administration of TNF-antagonists and anakinra
ad L- għoti flimkien ta ’ antagonisti ta ’ TNF u anakinra
Because of
Fi studji kliniċi fejn intużaw flimkien anakinra u antagonist ieħor ta ’ TNF, etanercept, ġew osservati ’ g ħ infezzjonijiet serji, u ma kienx hemm żieda ta ’ xi benefiċju kliniku meta pparagunat ma ’ l- għoti ta ’ etanercept waħdu.
Therefore, the combination of adalimumab and anakinra is not recommended.
Għalhekk, l- għoti flimkien ta’ nadalimumab u anakinra m’ huwiex im
au Surgery
Kirurġija li l
A
Pazjent li ina
r patient who requires surgery while on Trudexa should be closely monitored for infections, and
jkollu bżonn operazzjoni waqt li jkun qiegħed jieħu Trudexa, għandu jiġi monitorjat mill- qrib għall - infezzjonijiet, u għandhom jittieħdu l- azzjonijiet xierqa.
ge appropriate actions should be taken.
Imblukkar tal- musrana ż- żgħira
There is limited safety experience in patients undergoing arthroplasty while receiving Trudexa. lon Small bowel obstruction
Il- fatt li ma jkunx hemm rispons għall- kura tal- marda Crohn (Crohn’ s disease) jista ’ jindika l - me
Failure to respond to treatment for Crohn’ s disease may indicate the presence of fixed fibrotic stricture that may require surgical treatment.
preżenza ta ’ kontrazzjoni fissa riżultat ta ’ fibrożi u jista ’ jkun li jkun hemm bżonn ta ’ kura kirurġika.
Available data suggest that Trudexa does not worsen or cause no
Informazzjoni li għandna turi li Trudexa ma tikkaġunax kontrazzjonijiet eżistenti biex imorru għall - agħar, u lanqas ma tikkawżahom.
strictures.
4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu ott
4.5 Interaction with other medicinal products and other forms of interaction t
l- effett farmaċewtiku tal- prodott
Trudexa has been studied both in rheumatoid arthritis and psoriatic arthritis patients taking Trudexa as uc
Trudexa ġie studjat kemm f’ pazjenti li jbatu bl- artrite rewmatika u bl- artrite psorjatika li jieħdu od
Antibody formation was lower when Trudexa was given together with methotrexate in comparison with use as monotherapy.
Il - formazzjoni ta ’ anti- korpi kienet iktar baxxa meta Trudexa ingħata flimkien ma ’ methotrexate, meta pparagunat ma ’ l- użu ta ’ Trudexa waħdu bħala kura.
Administration of Trudexa without methotrexate resulted in increased formation of antibodies, rod
Pr
4.6 Pregnancy and lactation lP
4. 6 Tqala u Treddigħ
For Trudexa, no clinical data on exposed pregnancies are available
30 Għall- Trudexa m’ hemmx tagħrif kliniku dwar l- użu waqt it- tqala.
In a developmental toxicity study conducted in monkeys, there was no indication of maternal toxicity, na
Fi studju dwar it- tossiċità fl- iżvilupp li sar fuq ix- xadini, ma kien hemm l- ebda indikazzjoni ta ’ tossiċità fl- omm, fl- embriju jew ta ’ teratoġeniċità.
embryotoxicity or teratogenicity.
at sezzjoni 5. 3).
Due to its inhibition of TNFα, adalimumab administered during pregnancy could affect normal immune responses in the newborn.
zz Minħabba li adalimumab jimpedixxi t- TNFα, it- teħid tiegħu waqt it- tqala jista ’ jaffetwa r- risponsi immuni normali tat- tarbija tat- twelid.
Me
ori jużawh sa mill- inqas ħames xhur wara l- aħħar trattament ta ’ Trudexa.
It is not known whether adalimumab is excreted in human milk or absorbed systemically after ingestion.
t aw M’ huwiex magħruf jekk adalimumab joħroġx mill- ħalib uman jew jekk jiġix assorbit b’ mod sistemiku wara li jittieħed.
28 However, because human immunoglobulins are excreted in milk, women must not breast-feed for at least five months after the last Trudexa treatment.
Madanakollu, minħabba li l- immunoglobulini umani joħorġu mill- ħalib, in- nisa m’ għandhomx
4.7 Effects on ability to drive and use machines
ux ireddgħu għal mill- inqas ħames xhur wara l- aħħar trattament ta ’ Trudexa.
No studies on the effects on the ability to drive and use machines have been performed.
4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
ed 4.8 Undesirable effects
ad Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni. ’ g ħ 4. 8 Effetti mhux mixtieqa
ris Clinical Trials
Provi Kliniċi im
These
Trudexa ġie studjat f’ 5293 pazjent fi provi kontrollati u open- label li damu sejrin sa 60 xahar.
tho trials included rheumatoid arthritis patients with short term and long standing disease as well as psoriatic arthritis, ankylosing spondylitis and Crohn’ s disease patients.
Dawn il- provi inkludew pazjenti li jbatu minn artrite rewmatika, kemm f’ dawk li ma jkunux ilhom u dawk li jkunu ilhom bil- marda, kif ukoll pazjenti li jbatu minn artrite psorjatika, infjammazzjoni tal- vertebri li jirriżulta fil- vertebri jitwaħħlu flimkien (ankylosing spondylitis) u l- marda Crohn (Crohn’ s disease). li l