qanastek/EMEA-V3 huggingface dataset:
Events reported during the infusion were primarily episodes of hypertension; events reported within 24 hours of finishing an infusion were headache and skin reactions (rash, urticaria).
Il- ġrajjiet irrapportati waqt l - infużjoni kienu primarjament episodji ta ’ pressjoni għolja; ġrajjiet irrapportati fi żmien 24 siegħa mill - infużjoni kienu wgigħ ta ’ ras u reazzjonijiet tal- ġilda (raxx, urtikarja).
These events were not treatment limiting.
Dawn il- ġrajjiet ma kinux jillimitaw il- kura.
The rate of anaphylactic reactions (occurring in a total of 6/ 3,778 patients, 0.2%) was several fold higher with the 4 mg/ kg dose, compared to the 8 mg/ kg dose.
Ir- rata ta ’ reazzjonijiet anafilattiċi (iseħħu f’ total ta ’ 6/ 3, 778 pazjent, 0. 2%) kienet bil- wisq ogħla bid - doża ta ’ 4 mg/ kg, meta mqabbla mad- doża ta ’ 8 mg/ kg.
Clinically significant hypersensitivity reactions associated with tocilizumab and requiring treatment discontinuation were reported in a total of 13 out of 3,778 patients (0.3%) treated with tocilizumab during the controlled and open label clinical studies.
Reazzjonijiet ta ’ sensittività eċċessiva assoċjati ma ’ tocilizumab li kienu klinikament sinifikanti u li ħtiegu twaqqif tal- kura, ġew irrapportati f’ total ta ’ 13 minn 3, 778 pazjent (0. 3%) ikkurat b’ tocilizumab matul l- istudji kliniċi kkontrollati u open label.
These reactions were generally observed during the second to fifth infusions of tocilizumab (see section 4.4).
Dawn ir- reazzjonijiet ġeneralment kienu osservati waqt it- tieni sal- ħames infużjoni ta ’ tocilizumab (ara sezzjoni 4. 4).
Immunogenicity A total of 2,876 patients have been tested for anti-tocilizumab antibodies in the controlled clinical trials.
Immunoġeniċità Fl- istudji kliniċi kkontrollati kien hemm total ta ’ 2, 876 pazjent li ġew ittestjati għall- antikorpi kontra tocilizumab.
Of the 46 patients (1.6%) who developed anti-tocilizumab antibodies, 6 had an associated medically significant hypersensitivity reaction, of which 5 led to permanent discontinuation of treatment.
Minn 46 pazjent (1. 6%) li żviluppaw antikorpi kontra tocilizumab, 6 kellhom reazzjoni ta ’ sensittività eċċessiva li kienet medikament sinifikanti, u minn dawn 5 waqqfu il- kura b’ mod permanenti.
In 30 patients (1.1%) who developed neutralising antibodies, no apparent correlation to clinical response was observed.
Fit- 30 pazjent (1. 1%) li żviluppaw antikorpi li jinnewtralizzaw, ġie osservat li milli jidher m’ hemm ebda korrelazzjoni mar- rispons kliniku.
Haematological abnormalities Decreases in neutrophil counts below 1 x 109/ l occurred in 3.4% of patients on tocilizumab 8 mg/ kg plus DMARDs compared to < 0.1% of patients on placebo plus DMARDs.
Anormalitajiet ematoloġiċi Tnaqqis fl- għadd ta ’ newtrofili taħt 1 x 109 / l seħħ f’ 3. 4% tal- pazjenti fuq tocilizumab 8 mg/ kg flimkien ma ’ DMARDs meta mqabbel ma ’ < 0. 1% tal- pazjenti fuq plaċebo flimkien ma ’ DMARDs.
Approximately half of the patients who developed an ANC < 1 x 109/ l did so within 8 weeks after starting therapy.
Madwar nofs il- pazjenti li żviluppaw ANC ta ’ < 1 x 109 / l għamlu hekk fi żmien 8 ġimgħat wara li bdiet it- terapija.
Decreases below 0.5 x 109/ l were reported in 0.3% patients receiving tocilizumab 8 mg/ kg plus DMARDs.
Tnaqqis taħt 0. 5 x 109 / l ġie rrapportat f’ 0. 3% tal- pazjenti li rċevew tocilizumab 8 mg/ kg flimkien ma ’ DMARDs.
There was no clear association between decreases in neutrophils and the occurrence of serious infections.
Ma kienx hemm assoċjazzjoni ċara bejn it- tnaqqis fin- newtrofili u l - okkorrenza ta ’ infezzjonijiet serji.
Decreases in platelet counts below 100 x 103/ μ l occurred in 1.7% of patients on tocilizumab 8 mg/ kg plus DMARDs compared to < 1% on placebo plus DMARDs.
Tnaqqis fl- għadd ta ’ plejtlits taħt 100 x 103 / μl seħħ f’ 1. 7% tal- pazjenti fuq tocilizumab 8 mg/ kg ma ’ DMARDs meta mqabbel ma ’ < 1% fuq plaċebo ma ’ DMARDs.
These decreases occurred without associated bleeding events.
Dan it- tnaqqis seħħ mingħajr assoċjazzjoni ta ’ ġrajjiet ta ’ fsada.
8 Hepatic transaminase elevations Transient elevations in ALT/ AST > 3 x ULN were observed in 2.1% of patients on tocilizumab 8 mg/ kg compared to 4.9% of patients on MTX and in 6.5% of patients who received 8 mg/ kg tocilizumab plus DMARDs compared to 1.5% of patients on placebo plus DMARDs.
Żidiet fil- livell ta ’ transaminase tal- fwied Żidiet temporanji fil- livelli ta ’ ALT/ AST ta ’ > 3 x ULN ġew osservati f’ 2. 1% tal- pazjenti fuq tocilizumab 8 mg/ kg meta mqabbla ma ’ 4. 9% tal- pazjenti fuq MTX u f’ 6. 5% tal- pazjenti li rċevew 8 mg/ kg tocilizumab ma ’ DMARDs meta mqabbla ma ’ 1. 5% tal- pazjenti fuq plaċebo ma ’ DMARDs.
The addition of potentially hepatotoxic drugs (e. g.
Iż- żjieda ta ’ mediċini potenzjalment epatotossiċi (eż.
MTX) to tocilizumab monotherapy resulted in increased frequency of these elevations.
MTX), ma ’ monoterapija ta ’ tocilizumab wasslet għal frekwenzi ogħla ta ’ dawn iż- żidiet.
Elevations of ALT/ AST > 5 x ULN were observed in 0.7% of tocilizumab monotherapy patients and 1.4% of tocilizumab plus DMARD patients, the majority of whom were discontinued permanently from tocilizumab treatment.
Żidiet ta ’ ALT/ AST > 5 x ULN ġew osservati f’ 0. 7% tal - pazjenti b’ monoterapija ta ’ tocilizumab u f’ 1. 4% tal- pazjenti b’ tocilizumab ma ’ DMARDs, fejn il - maġġoranza tagħhom twaqqfitilhom il- kura ta ’ tocilizumab b’ mod permanenti.
These elevations were not associated with clinically relevant increase in direct bilirubin, nor were they associated with clinical evidence of hepatitis or hepatic impairment.
Dawn iż- żidiet ma ġewx assoċjati ma ’ żidiet klinikament rilevanti ta ’ bilirubina diretta, u lanqas ma ġew assoċjati ma ’ evidenza klinika ta ’ epatite jew indeboliment epatiku.
Lipid parameters During the six month controlled trials, increases of lipid parameters such as total cholesterol, triglycerides, LDL cholesterol, and/ or HDL cholesterol have been reported commonly.
Parametri tal- lipidi Waqt il- provi kkontrollati ta ’ sitt xhur ġew irrapportati b’ mod komuni żidiet fil- parametri tal- lipidi bħal kolesterol totali, trigliċeridi, kolesterol LDL, u/ jew kolesterol HDL.
Approximately 24% of patients receiving RoActemra in clinical trials experienced sustained elevations in total cholesterol ≥ 6.2 mmol/ l, with 15% experiencing a sustained increase in LDL to ≥ 4.1 mmol/ l.
Madwar 24% tal- pazjenti li kienu qed jirċievu RoActemra fil- provi kliniċi kellhom esperjenza ta ’ żidiet sostenuti fil- kolesterol totali ta ’ ≥ 6. 2 mmol / l, bi 15% li kellhom żjieda sostenuta f’ LDL għal ≥ 4. 1 mmol / l.
Elevations in lipid parameters responded to treatment with lipid-lowering agents.
Żidiet fil - parametri tal- lipidi rrispondew għall- kura b’ sustanzi li jnaqqsu l- lipidi.
Malignancies The clinical data are insufficient to assess the potential incidence of malignancy following exposure to tocilizumab.
Tumuri malinni M’ hemmx biżżejjed tagħrif kliniku biex tiġi vvalutata l- inċidenza potenzjali ta ’ tumuri malinni wara espożizzjoni għal tocilizumab.
Long-term safety evaluations are ongoing.
Valutazzjonijiet ta ’ sigurtà fit- tul għadhom sejrin.
4.9 Overdose
9 4. 9 Doża eċċessiva
There are limited data available on overdose with RoActemra.
It- tagħrif dwar doża eċċessiva ta ’ RoActemra huwa limitat.
One case of accidental overdose was reported in which a patient with multiple myeloma received a single dose of 40 mg/ kg.
Ġie rrapportat każ wieħed ta ’ doża eċċessiva fejn aċċidentalment pazjent b’ majeloma multipla rċieva doża waħda ta ’ 40 mg/ kg.
No adverse reactions were observed.
Ma ġewx osservati reazzjonijiet avversi.
No serious adverse reactions were observed in healthy volunteers who received a single dose up to 28 mg/ kg, although dose limiting neutropenia was observed.
Ma ġewx osservati reazzjonijiet avversi serji f’ voluntiera b’ saħħithom li rċevew doża waħda sa 28 mg/ kg, għalkemm ġiet osservata newtropenja li kienet tillimita d- doża.
Immunosupressants, Interleukin inhibitors; ATC code:
Immunosoppressivi, inibituri ta ’ interleukin; Kodiċi ATC:
Mechanism of action Tocilizumab binds specifically to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R).
Mekkaniżmu ta ’ azzjoni Tocilizumab jintrabat b’ mod speċifiku mar- riċetturi IL- 6, kemm dawk li huma solubbli kif ukoll dawk li huma marbutin mal- membrana (sIL- 6R u mIL- 6R).
Tocilizumab has been shown to inhibit sIL-6R and mIL-6R-mediated signalling.
Instab li tocilizumab jimpedixxi s- sinjalar permezz ta ’ sIL- 6R u mIL- 6R.
IL-6 is a pleiotropic pro-inflammatory cytokine produced by a variety of cell types including T- and B-cells, monocytes and fibroblasts.
IL- 6 huwa ċitokin pro- infjammatorju b’ aktar minn effett wieħed magħmul minn ħafna tipi ta ’ ċelluli fosthom iċ- ċelluli T u B, monoċiti u fibroblasti.
IL-6 is involved in diverse physiological processes such as T-cell activation, induction of immunoglobulin secretion, induction of hepatic acute phase protein synthesis and stimulation of haemopoiesis.
IL- 6 huwa involut f’ diversi proċessi fiżjoloġiċi bħall- attivazzjoni taċ- ċelluli T, stimulazzjoni tas- sekrezzjoni ta ’ immunoglobulini, stimulazzjoni ta ’ sintesi ta ’ proteini tal- fwied f’ fażi akuta u stimulazzjoni ta ’ emopoesi.
IL-6 has been implicated in the pathogenesis of diseases including inflammatory diseases, osteoporosis and neoplasia.
IL- 6 ġie implikat fil- patoġenesi tal- mard fosthom mard infjammatorju, osteoporożi u neoplażja.
In clinical studies with tocilizumab, rapid decreases in CRP, erythrocyte sedimentation rate (ESR) and serum amyloid A (SAA) were observed.
Fi studji klinici b’ tocilizumab, ġie osservat tnaqqis rapidu f’ CRP, fir- rata ta ’ sedimentazzjoni ta ’ eritroċiti (ESR) u Amyloid A fis- serum (SAA).
Consistent with the effect on acute phase reactants, treatment with tocilizumab was associated with reduction in platelet count within the normal range.
Konsistenti mal- effett fuq is- sustanzi li jieħdu parti fir - reazzjoni tal- fażi akuta, kura b’ tocilizumab ġiet assoċjata ma ’ tnaqqis fl- għadd tal- plejtlits iżda li baqgħu fil- parametri normali.
Increases in haemoglobin levels were observed, through tocilizumab decreasing the IL-6 driven effects on hepcidin production to increase iron availability.
Ġew osservati żidiet fil- livelli ta ’ emoglobina, minħabba li tocilizumab inaqqas l- effetti kkawżati minn IL- 6 fuq il- produzzjoni ta ’ hepcidin biex tiżdied id- disponibilità tal - ħadid.
In tocilizumab-treated patients, decreases in the levels of CRP to within normal ranges were seen as early as week 2, with decreases maintained while on treatment.
F’ pazjenti kkurati b’ tocilizumab, tnaqqis fil- livelli ta ’ CRP għall- parametri normali dehru mill - ewwel fit- 2 gimgħa, bit- tnaqqis miżmum waqt il- kura.
9 Clinical efficacy The efficacy of tocilizumab in alleviating the signs and symptoms of RA was assessed in five randomised, double-blind, multi-centre studies.
Effikaċja klinika L- effikaċja ta ’ tocilizumab li ttaffi s- sinjali u s- sintomi ta ’ RA ġiet evalwata f’ ħames studji randomised, double- blind u multi- ċentri.
Studies I-V enrolled patients ≥ 18 years of age with active RA diagnosed according to the American College of Rheumatology (ACR) criteria and who had at least eight tender and six swollen joints at baseline.
Fi studji I- V idaħħlu pazjenti ≥ 18- il sena b’ RA attiva ddijanjostikata skond il- kriterji tal- Kulleġġ Amerikan tar- Rewmatoloġija (ACR) u li bħala linja bażi kellhom mill - anqas tmien ġogi muġugħin u sitta minfuħin.
In Study I, tocilizumab was administered intravenously every four weeks as monotherapy.
Fi Studju I, tocilizumab ingħata minn ġol- vina kull erba ’ ġimgħat bħala monoterapija.
In Studies II, III and V, tocilizumab was administered intravenously every four weeks in combination with MTX vs. placebo and MTX.
Fi Studji II, III u V, tocilizumab ingħata b’ mod minn ġol- vina kull erba ’ ġimgħat flimkien ma ’ MTX kontra plaċebo u MTX.
In Study IV, tocilizumab was administered intravenously every 4 weeks in combination with other DMARDs vs. placebo and other DMARDs.
Fi Studju IV, tocilizumab ingħata minn ġol- vina kull erba ’ ġimgħat flimkien ma ’ DMARDs oħra kontra plaċebo u DMARDs oħra.
The primary endpoint for each of the five studies was the proportion of patients who achieved an ACR 20 response at week 24.
Il- mira primarja ta ’ kull wieħed mill- ħames studji kienet il - proporzjon ta ’ pazjenti li kisbu rispons ta ’ ACR 20 fl- 24 gimgħa.
Study I evaluated 673 patients who had not been treated with MTX within six months prior to randomisation and who had not discontinued previous MTX treatment as a result of clinically important toxic effects or lack of response.
Studju I ivvaluta 673 pazjent li ma kienx ikkurat b’ MTX fi żmien sitt xhur qabel ir- randomizzazzjoni u li ma kienux waqqfu kura preċedenti ta ’ MTX minħabba effetti tossiċi klinikament importanti jew nuqqas ta ’ rispons.
The majority (67%) of patients were MTX-naïve.
Il- maġġoranza (67%) ta ’ pazjenti qatt ma ħadu MTX.
Doses of 8 mg/ kg of tocilizumab were given every four weeks as monotherapy.
Dożi ta ’ 8 mg/ kg ta ’ tocilizumab ingħataw kull erba ’ ġimgħat bħala monoterapija.
The comparator group was weekly MTX (dose titrated from 7.5 mg to a maximum of 20 mg weekly over an eight week period).
Il- grupp komparatur ingħata MTX darba fil- ġimgħa (dożi miżjuda minn 7. 5 mg sa massimu ta ’ 20 mg fil- ġimgħa fuq perijodu ta ’ tmien ġimgħat).
Study II, a two year study with planned analyses at week 24 and week 52, evaluated 1196 patients who had an inadequate clinical response to MTX.
Studju II, studju ta ’ sentejn b’ analiżi ppjanata fl- 24 ġimgħa u fit- 52 ġimgħa, ivvaluta 1196 pazjent li ma kellhomx rispons kliniku tajjeb għal MTX.
Doses of 4 or 8 mg/ kg of tocilizumab or placebo were given every four weeks as blinded therapy for 52 weeks in combination with stable MTX (10 mg to 25 mg weekly).
Dożi ta ’ 4 jew 8 mg/ kg ta ’ tocilizumab jew plaċebo ngħataw kull erba ’ ġimgħat bħala terapija fl- għama għal 52 ġimgħa flimkien ma ’ MTX stabbli (10 mg
The primary endpoint at week 24 was the proportion of patients who achieved an ACR 20 response.
Il- mira primarja f’ ġimgħa 24 kienet il- proporzjon ta ’ pazjenti li kisbu rispons ta ’ ACR 20.
At week 52 the co-primary endpoints were prevention of joint damage and improvement in physical function.
Fil- 52 ġimgħa l- miri ko- primarji kienu l- prevenzjoni ta ’ ħsara fil- ġogi u t- titjib fil - funzjoni fiżika.
Study III evaluated 623 patients who had an inadequate clinical response to MTX.
Studju III ivvaluta 623 pazjent li ma kellhomx rispons kliniku tajjeb għal MTX.
Doses of 4 or 8 mg/ kg tocilizumab or placebo were given every four weeks, in combination with stable MTX (10 mg to 25 mg weekly).
Dożi ta ’ 4 jew 8 mg/ kg ta ’ tocilizumab jew plaċebo ngħataw kull erba ’ ġimgħat, flimkien ma ’ MTX stabbli (10 mg sa 25 mg kull ġimgħa).
Study IV evaluated 1,220 patients who had an inadequate response to their existing rheumatologic therapy, including one or more DMARDs.
Studju IV ivvaluta 1, 220 pazjent li ma kellhomx rispons tajjeb għat- terapija rewmatoloġika li kienu qed jieħdu, fosthom wieħed jew aktar DMARDs.
Doses of 8 mg/ kg tocilizumab or placebo were given every four weeks in combination with stable DMARDs.
Dożi ta ’ 8 mg/ kg ta ’ tocilizumab jew plaċebo ngħataw kull erba ’ ġimgħat flimkien ma ’ DMARDs stabbli.
Study V evaluated 499 patients who had an inadequate clinical response or were intolerant to one or more TNF antagonist therapies.
Studju V ivvaluta 499 pazjent li ma kellhomx rispons kliniku tajjeb jew li kienu intolleranti għal wieħed jew aktar mit- terapiji antagonisti għal TNF.
The TNF antagonist therapy was discontinued prior to randomisation.
It- terapija antagonista għal TNF ġiet imwaqqfa qabel ma beda l- istudju.
Doses of 4 or 8 mg/ kg tocilizumab or placebo were given every four weeks in combination with stable MTX (10 mg to 25 mg weekly).
Dożi ta ’ 4 jew 8 mg/ kg ta ’ tocilizumab jew plaċebo ngħataw kull erba ’ ġimgħat flimkien ma ’ MTX b’ mod stabbli (10 mg sa 25 mg kull ġimgħa).
Clinical response In all studies, patients treated with tocilizumab 8 mg/ kg had statistically significant higher ACR 20, 50, 70 response rates at 6 months compared to control (Table 2).
Rispons kliniku Fl- istudji kollha, pazjenti kkurati b’ tocilizumab 8 mg/ kg kellhom rati ta ’ rispons ta ’ ACR 20, 50, 70 li kienu statistikament ogħla b’ mod sinifikanti fis- 6 xahar meta mqabbla mal- kontroll (Tabella 2).
In study I, superiority of tocilizumab 8 mg/ kg was demonstrated against the active comparator MTX.
Fi Studju I, intweriet is- superjorità ta ’ tocilizumab 8 mg/ kg kontra l- komparatur attiv MTX.
The treatment effect was similar in patients independent of rheumatoid factor status, age, gender, race, number of prior treatments or disease status.
L- effett tal- kura kien simili fil- pazjenti indipendentement mill- istat tal- fattur rewmatiku, l- età, is- sess, ir- razza, in- numru ta ’ kuri preċedenti jew l- istat tal- marda.
Time to onset was rapid (as early as week 2) and the magnitude of response continued to improve with duration of treatment.
Il- ħin biex il- kura tibda taħdem kien wieħed rapidu (mit- 2 ġimgħa) u l- ammont ta ’ rispons kompla jitjieb matul il- kura.
Continued durable responses were seen for over 24 months in the ongoing open label extension studies I, III, IV and V.
Reazzjonijiet kontinwi li jibqgħu għal tul ta ’ żmien dehru għal aktar minn 24 xahar fl- istudji open label ta ’ estensjoni I, III, IV u V li għadhom sejrin.
In patients treated with tocilizumab 8 mg/ kg, significant improvements were noted on all individual components of the ACR response including: tender and swollen joint counts; patients and physician global assessment; disability index scores; pain assessment and CRP compared to patients receiving placebo plus MTX or other DMARDs in all studies.
F’ pazjenti kkurati b’ tocilizumab 8 mg/ kg, ġie nnutat titjib sinifikanti fil- komponenti individwali kollha tar- rispons ta ’ ACR fosthom: għadd tal- ġogi muġugħin u minfuħin; assessjar globali tal- pazjenti u tat - tobba; punteġġi tal- indiċi ta ’ diżabilità; valutazzjoni tal- uġigħ u CRP meta mqabbla ma ’ pazjenti li rċevew plaċebo ma ’ MTX jew DMARDs oħra fl- istudji kollha.
Patients in studies I – V had a mean Disease Activity Score (DAS28) of 6.5 – 6.8 at baseline.
Pazjenti fl- studji I – V kellhom medja tal- Punteġġ ta ’ l- Attività tal- Marda (DAS28) ta ’ 6. 5– 6. 8 fil- linja bażi.
Significant reduction in DAS28 from baseline (mean improvement) of 3.1– 3.4 were observed in tocilizumab-treated patients compared to control patients (1.3-2.1).
Tnaqqis sinifikanti f’ DAS28 mil- linja bażi (titjib medju) ta ’ 3. 1– 3. 4 kien osservat f’ pazjenti kkurati b’ tocilizumab meta mqabbel mal- pazjenti ta ’ kontroll (1. 3- 2. 1).
10 tocilizumab (28 – 34%) compared to 1– 12% of control patients at 24 weeks.
Il- proporzjon ta ’ pazjenti li laħqu DAS28 ta ’ remissjoni klinika (DAS28 < 2. 6) kienet ogħla b’ mod sinifikanti f’ pazjenti li rċevew tocilizumab (28– 34%) meta mqabbel ma 1– 12% tal- pazjenti ta ’ kontroll f’ ġimgħa 24.
In study II, 47% of patients achieved a DAS28 < 2.6 at 52 weeks compared to 33% of patients at week 24.
Fi studju II, 47% tal- pazjenti laħqu DAS28 ta ’ < 2. 6 wara 52 ġimgħa meta mqabbel ma ’ 33% ta ’ pazjenti f’ ġimgħa 24.
In a pooled analysis of studies II, III and IV, the proportion of patients achieving an ACR 20, 50 and 70 response was significantly higher (59% vs.
F’ ġabra ta ’ analiżi ta ’ studji II, III u IV, il- proporzjon ta ’ pazjenti li kisbu rispons ta ’ ACR 20, 50 u 70 kien ogħla b’ mod sinifikanti (59% vs.
11%, respectively) in the tocilizumab 8 mg/ kg plus DMARD vs. the tocilizumab 4 mg/ kg plus DMARD group (p < 0.03).
11% rispettivament) b’ tocilizumab 8 mg/ kg flimkien ma ’ DMARD vs. il- grupp b’ tocilizumab 4 mg/ kg flimkien ma ’ DMARD (p < 0. 03).
Similarly the proportion of patients achieving a DAS 28 remission (DAS28 < 2.6) was significantly higher (31% vs.
B’ mod simili, il- proporzjon ta ’ pazjenti li kisbu DAS28 ta ’ remissjoni (DAS28 < 2. 6) kien ogħla b’ mod sinifikanti (31% vs.
16% respectively) in patients receiving tocilizumab 8 mg/ kg plus DMARD than in patients receiving tocilizumab 4 mg/ kg plus DMARD (p < 0.0001).
16% rispettivament) f’ pazjenti li rċevew tocilizumab 8 mg/ kg flimkien ma ’ DMARD mill- pazjenti li rċevew tocilizumab 4 mg/ kg flimkien ma ’ DMARD (p < 0. 0001).
Table 2.
11 Tabella 2.
ACR responses in placebo-/ MTX-/ DMARDs-controlled studies (% patients)
Reazzjonijiet ACR fi studji kkontrollati minn plaċebo/ MTX/ DMARD (% ta ’ pazjenti)
Study I
Studju I
Study II
Studju II
Study III
Studju III
Study IV
Studju IV
Study V
Studju V
TCZ MTX TCZ
Ġimgħa
8 mg/ kg
TCZ MTX 8 mg / kg
mg/ kg MTX
PBO MTX
MTX
+
70%** *
70% * **
44%**
44% * *
28%**
28% * *
TCZ - Tocilizumab MTX - Methotrexate PBO - Placebo DMARD - Disease modifying anti-rheumatic drug * - p < 0.05, TCZ vs.
TCZ - Tocilizumab MTX - Methotrexate PBO - Plaċebo DMARD - Mediċina kontrar- rewmatiżmu li timmodifika l- marda * - p < 0. 05, TCZ vs.
PBO + MTX/ DMARD ** - p < 0.01, TCZ vs.
PBO + MTX/ DMARD ** - p < 0. 01, TCZ vs.
PBO + MTX/ DMARD *** - p < 0.0001, TCZ vs.
PBO + MTX/ DMARD *** - p < 0. 0001, TCZ vs.
Radiographic response In Study II, in patients with an inadequate response to MTX, inhibition of structural joint damage was assessed radiographically and expressed as change in modified Sharp score and its components, the erosion score and joint space narrowing score.
Fi Studju II, f’ pazjenti li ma rrispondewx tajjeb għal MTX, ġie stmat b’ mod radjografiku l- impediment ta ’ ħsara strutturali fil- ġog u ġie espress bħala bidla fil- punteġġ Sharp immodifikat u l- komponenti tiegħu, il- punteġġ ta ’ tagħwir u l- punteġġ ta ’ djuq fl- ispazju tal- ġog.
Inhibition of joint structural damage was shown with significantly less radiographic progression in patients receiving tocilizumab compared to control (Table 3).
L- impediment ta ’ ħsara strutturali fil- ġog intwera bi progressjoni radjografika sinifikament anqas f’ pazjenti li rċevew tocilizumab meta mqabbel mal- kontroll (Tabella 3).
Radiographic mean changes over 52 weeks in Study II
Bidliet medji radjografiċi fuq medda ta ’ 52 ġimgħa fi Studju II
(+ TCZ from week 24) Total Sharp-Genant score Erosion score
(+ TCZ
= 393 1.13 0.71
mill- 24 ġimgħa) N = 393
JSN score PBO MTX TCZ JSN
Punteġġ Sharp- Genant Totali
- Placebo - Methotrexate - Tocilizumab - Joint space narrowing
Punteġġ ta ’ tagħwir Punteġġ JSN PBO - Plaċebo MTX - Methotrexate TCZ - Tocilizumab
0.42
0. 71 0. 42
0.12**
0. 17 * 0. 12 **
PBO
JSN - Djuq fl- ispazju tal- ġog * - p≤0. 0001, TCZ vs.
** - p < 0.005, TCZ vs.
PBO + MTX ** - p < 0. 005, TCZ vs.
Health-related and quality of life outcomes Tocilizumab-treated patients reported an improvement in all patient-reported outcomes (Health Assessment Questionnaire Disability Index - HAQ-DI), Short Form-36 and Functional Assessment of Chronic Illness Therapy questionnaires.
Effetti relatati mas- saħħa u l- kwalità ta ’ ħajja Pazjenti kkurati b’ tocilizumab irrapportaw titjib fl- effetti kollha rrapportati mill- pazjenti (Indiċi ta ’ Diżabilità ibbażat fuq Kwestjonarju ta ’ Valutazzjoni tas- Saħħa - HAQ- DI), Short Form- 36 u kwestjonarji tal- Valutazzjoni Funzjonali ta ’ Terapija għal Mard Kroniku.
Statistically significant improvements in HAQ-DI scores were observed in patients treated with RoActemra compared with patients treated with DMARDs.
Titjib statistikament sinifikanti fil- punteġġi ta ’ HAQ- DI kienu osservati f’ pazjenti kkurati b’ RoActemra meta mqabbel ma ’ pazjenti kkurati b’ DMARDs.
Haemoglobin levels Statistically significant improvements in haemoglobin levels were observed with tocilizumab compared with DMARDs (p < 0.0001) at week 24.
12 Livelli ta ’ emoglobina Titjib statistikament sinifikanti fil- livelli ta ’ emoglobina ġew osservati b’ tocilizumab meta mqabbel ma ’ DMARDs (p < 0. 0001) fl- 24 ġimgħa.
Mean haemoglobin levels increased by week 2 and remained within normal range through to week 24.
Il- livelli medji ta ’ emoglobina żdiedu mat- 2 ġimgħa u baqgħu fil- parametri normali sal- 24 ġimgħa.
The pharmacokinetics of tocilizumab were determined using a population pharmacokinetic analysis on a database composed of 1,793 RA patients treated with a one-hour infusion of 4 and 8 mg/ kg tocilizumab every 4 weeks for 24 weeks.
Il- farmakokinetika ta ’ tocilizumab ġiet iddeterminata bl- użu ta ’ analiżi tal- farmakokinetika tal - popolazzjoni minn tagħrif miġbur minn 1, 793 pazjent b’ RA kkurati b’ infużjoni ta ’ siegħa ta ’ 4 u 8 mg/ kg tocilizumab kull erba ’ ġimgħat għal 24 ġimgħa.
The following parameters (predicted mean ± SD) were estimated for a dose of 8 mg/ kg tocilizumab given every 4 weeks: steady-state area under curve (AUC) = 35000 ± 15500 h µg/ ml, trough concentration (Cmin) = 9.74 ± 10.5 μ g/ ml and maximum concentration (Cmax) = 183 ± 85.6 µg/ ml, and. the accumulation ratios for AUC and Cmax were small, 1.22 and 1.06, respectively.
Il- parametri li ġejjin (medja imbassra ± SD) kienu stmati għal doża ta ’ 8 mg/ kg tocilizumab mogħtija kull erba ’ ġimgħat: l- erja taħt il- kurva (AUC) fi stat fiss = 35000 ± 15500 h · µg/ ml, l- inqas konċentrazzjoni (Cmin) = 9. 74 ± 10. 5 μg/ ml u l- ogħla konċentrazzjoni (Cmax) = 183 ± 85. 6 µg/ ml u l - proporzjonijiet ta 'akkumulazzjoni għal AUC u Cmax kienu żgħar, 1. 22 u 1. 06, rispettivament.
The accumulation ratio was higher for Cmin (2.35), which was expected based on the non-linear clearance contribution at lower concentrations.
Il - proporzjon ta ’ akkumulazzjoni kien ogħla għal Cmin (2. 35), li kien mistenni fuq il- bażi tal - kontribuzzjoni tat- tneħħija mhux lineari f’ konċentrazzjonijiet aktar baxxi.
Steady-state was reached following the first administration for Cmax and after 8 and 20 weeks for AUC and Cmin, respectively.
Intlaħaq stat fiss wara l - ewwel teħid għal Cmax u wara 8 u 20 ġimgħa għall- AUC u Cmin, rispettivament.
Distribution In RA patients the central volume of distribution was 3.5 l, the peripheral volume of distribution was 2.9 l resulting in a volume of distribution at steady state of 6.4 l.
Distribuzzjoni F’ pazjenti b’ RA, il- volum ta ’ distribuzzjoni ċentrali kien ta ’ 3. 5 l, il- volum ta ’ distribuzzjoni periferali kien ta ’ 2. 9 l li rriżulta f’ volum ta ’ distribuzzjoni fi stat fiss ta ’ 6. 4 l.
Elimination Following intravenous administration, tocilizumab undergoes biphasic elimination from the circulation.
Eliminazzjoni Wara għoti fil- vini, tocilizumab jgħaddi minn eliminazzjoni ta ’ żewġ fażijiet miċ- ċirkolazzjoni.
The total clearance of tocilizumab was concentration-dependent and is the sum of the linear and non-linear clearance.
It - tneħħija totali ta ’ tocilizumab kienet dipendenti fuq il- konċentrazzjoni u hija s- somma tat- tneħħija lineari u mhux lineari.
The linear clearance was estimated as a parameter in the population pharmacokinetic analysis and was 12.5 ml/ h.
It- tneħħija lineari kienet stmata bħala parametru fl- analiżi tal- farmakokinetika tal- popolazzjoni u kienet 12. 5 ml/ siegħa.
The concentration-dependent non-linear clearance plays a major role at low tocilizumab concentrations.
It- tneħħija mhux lineari dipendenti fuq il- konċentrazzjoni għandha rwol importanti f’ konċentrazzjonijiet baxxi ta ’ tocilizumab.
Once the non-linear clearance pathway is saturated, at higher tocilizumab concentrations, clearance is mainly determined by the linear clearance.
Ladarba s- sensiela ta ’ reazzjonijiet tat- tneħħija mhux lineari tilħaq is- saturazzjoni, f’ konċentrazzjonijiet ogħla ta ’ tocilizumab, it- tneħħija tiġi ddeterminata l- aktar mit- tneħħija lineari.
The t1/ 2 of tocilizumab was concentration-dependent.
It- t1/ 2 ta ’ tocilizumab kienet dipendenti fuq il- konċentrazzjoni.
At steady-state following a dose of 8 mg/ kg every 4 weeks, the effective t1/ 2 decreased with decreasing concentrations within a dosing interval from 14 days to 8 days.
Fi stat fiss, wara doża ta ’ 8 mg/ kg kull 4 ġimgħat, it- t1/ 2 effettiv naqas mat- tnaqqis fil- konċentrazzjonijiet waqt intervall fid- doża minn 14- il ġurnata għal 8 ijiem.
Linearity Pharmacokinetic parameters of tocilizumab did not change with time.
Linearità Il- parametri farmakokinetiċi ta ’ tocilizumab ma nbidlux maż- żmien.
Cmax increased
Għad- dożi ta ’ 4 u 8 mg/ kg kull 4 ġimgħat kienet osservata żjieda aktar minn proporzjonali mad- doża fl- AUC u Cmin.
12 dose-proportionally.
Cmax żdiedet b’ mod proporzjonali mad- doża.
At steady-state, predicted AUC and Cmin were 2.7 and 6.5 fold higher at 8 mg/ kg as compared to 4 mg/ kg, respectively.
Fi stat fiss, l- AUC u Cmin imbassra kienu 2. 7 u 6. 5 drabi ogħla rispettivament bi 8 mg/ kg meta mqabbel ma ’ 4 mg/ kg.
Special populations Renal impairment:
Popolazzjonijiet speċjali Indeboliment tal- kliewi:
No formal study of the effect of renal impairment on the pharmacokinetics of tocilizumab has been conducted.
Ma sar l- ebda studju formali dwar l- effett ta ’ indeboliment tal- kliewi fuq il - farmakokinetika ta ’ tocilizumab.
Most of the patients in the population pharmacokinetic analysis had normal renal function or mild renal impairment.
Il- maġġoranza tal- pazjenti fl- analiżi tal- farmakokinetika tal - popolazzjoni kellhom funzjoni tal- kliewi normali jew indeboliment tal- kliewi ħafif.
Mild renal impairment (creatinine clearance based on Cockcroft-Gault < 80 ml/ min and ≥ 50 ml/ min) did not impact the pharmacokinetics of tocilizumab.
L- indeboliment tal- kliewi ħafif (tneħħija ta ’ krejatinina bbażata fuq Cockcroft- Gault < 80 ml/ min u ≥ 50 ml/ min) ma ħalliex effett kbir fuq il- farmakokinetika ta ’ tocilizumab.
No formal study of the effect of hepatic impairment on the pharmacokinetics of tocilizumab has been conducted.
Ma sar l- ebda studju formali dwar l- effett ta ’ indeboliment tal- fwied fuq il- farmakokinetika ta ’ tocilizumab.
Age, gender and ethnicity:
Età, sess u razza:
Population pharmacokinetic analyses in adult RA patients, showed that age, gender and ethnic origin did not affect the pharmacokinetics of tocilizumab.
Analiżi tal- farmakokinetika tal- popolazzjoni f’ pazjenti adulti b’ RA wriet li l- età, is- sess u l- oriġini etnika ma affettwawx il- farmakokinetika ta ’ tocilizumab.
5.3 Preclinical safety data
13 5. 3 Tagħrif prekliniku dwar is- sigurtà tal- mediċina
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity.
Tagħrif li mhux kliniku, bbażat fuq studji konvenzjonali ta ’ sigurtà farmakoloġika, effett tossiku minn dożi ripetuti u ġenotossiċità, ma juri l- ebda periklu speċjali għall- bnedmin.
Carcinogenicity and fertility studies were not performed with tocilizumab due to the lack of appropriate models for an antibody with no reactivity to rodent IL-6 receptors.
Ma sarux studji b’ tocilizumab dwar il- karċinoġeniċità u l- fertilità minħabba n- nuqqas ta ’ mudelli adattati għal antikorp mingħajr reattività għal riċetturi ta ’ IL- 6 fl- annimali gerriema.
Available non-clinical data demonstrated the effect of IL-6 on malignant progression and apoptosis resistance to various cancer types.
Tagħrif mhux kliniku wera l- effett ta ’ IL- 6 fuq il- progressjoni ta ’ tumuri malinni u reżistenza ta ’ apoptosi għal tipi varji ta ’ kanċer.
This data does not suggest a relevant risk for cancer initiation and progression under tocilizumab treatment.
Dan it- tagħrif ma jimplikax riskju rilevanti għal bidu u progressjoni ta ’ kanċer taħt kura b’ tocilizumab.
Additionally, proliferative lesions were not observed in a 6-month chronic toxicity study in cynomolgus monkeys or in IL-6 deficient mice.
Barra minn hekk, fi studju dwar it- tossiċità kronika li dam 6 xhur ma ġewx osservati leżjonijiet li jiżdiedu f’ xadini tat- tip cynomolgus u fi ġrieden b’ defiċjenza ta ’ IL- 6.
Available non-clinical data do not suggest an effect on fertility under tocilizumab treatment.
Tagħrif mhux kliniku disponibbli ma jimplikax effett fuq il- fertilità taħt kura b’ tocilizumab.
Effects on endocrine active and reproductive system organs were not observed in a chronic cynomolgus monkey toxicity study and reproductive performance was not affected in IL-6 deficient mice.
Ma ġewx osservati effetti fuq l- organi tas- sistema riproduttiva u f’ dawk b’ attività endokrina fi studju ta ’ tossiċità kronika f’ xadini tat- tip cynomolgus u l- kapaċità riproduttiva ma ġietx affettwata fi ġrieden mingħajr IL- 6.
Tocilizumab administered to cynomolgus monkeys during early gestation, was observed to have no direct or indirect harmful effect on pregnancy or embryonal-foetal development.
Ġie osservat li tocilizumab li ngħata lil xadini tat- tip cynomolgus kmieni fit- tqala ma kellu l- ebda effett detrimentali, la dirett u lanqas indirett, fuq it- tqala jew fuq l- iżvilupp tal- embriju- fetu.
However, a slight increase in abortion/ embryonal-foetal death was observed with high systemic exposure (> 100 x human exposure) in the 50 mg/ kg/ day high-dose group compared to placebo and other low-dose groups.
Madankollu, ġiet osservata żjieda żgħira fl- abort/ mewt tal- embriju- fetu b’ espożizzjoni sistemika għolja (> 100 x l- espożizzjoni umana) fil- grupp ta ’ doża għolja ta ’ 50 mg/ kg/ jum meta mqabbel ma ’ plaċebo u gruppi oħra ta ’ doża baxxa.
Although IL-6 does not seem to be a critical cytokine for foetal growth or the immunological control of the maternal/ foetal interface, a relation of this finding to tocilizumab cannot be excluded.
Għalkemm IL- 6 ma jidhirx li huwa ċitokin kritiku għall- iżvilupp tal- fetu jew fil- kontroll immunoloġiku bejn l- omm u l- fetu, ir- relazzjoni ta ’ din l- osservazzjoni fil - konfront ta ’ tocilizumab ma tistax tiġi eskluża.
Sucrose Polysorbate 80 Disodium phosphate dodecahydrate Sodium dihydrogen phosphate dihydrate Water for injections
Sucrose Polysorbate 80 Disodium phosphate dodecahydrate Sodium dihydrogen phosphate dihydrate Ilma għall- injezzjonijiet
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
Dan il- prodott mediċinali m’ għandux jitħallat ma ’ prodotti mediċinali oħra ħlief dawk imsemmija f’ sezzjoni 6. 6.
Diluted product:
Prodott dilwit:
After dilution, the prepared solution for infusion is physically and chemically stable in sodium chloride 9 mg/ ml (0.9%) solution for injection at 30ºC for 24 hours.
Wara d- dilwazzjoni, is- soluzzjoni għall- infużjoni lesta hija stabbli fiżikament u kimikament f’ soluzzjoni għall- injezzjoni ta ’ sodium chloride 9 mg/ ml (0. 9%) f’ temperatura ta ’ 30°C għal 24 siegħa.
From a microbiological point of view, the prepared solution for infusion should be used immediately.
Mil- lat mikrobijoloġiku, is- soluzzjoni għall- infużjoni lesta għandha tintuża immedjatament.
If not used immediately, in use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C– 8°C, unless dilution has taken place in controlled and validated aseptic conditions.
Jekk ma tintużax immedjatament, iż- żmien ta ’ ħażna waqt l- użu u l- kundizzjonijiet qabel l- użu jaqgħu taħt ir - risponsabilità ta ’ min qed jagħmel użu mill- prodott u normalment ma jkunux iżjed minn 24 siegħa f’ temperatura ta ’ bejn 2°C - 8°C sakemm id- dilwazzjoni ma tkunx saret f’ kundizzjonijiet asettiċi kkontrollati u validati.
RoActemra is supplied as a sterile concentrate that does not contain preservatives.
RoActemra huwa disponibbli bħala konċentrat sterili li ma fihx preservattivi.
Store vials in a refrigerator (2°C– 8°C).
Aħżen il- kunjetti fi friġġ (2°C – 8°C).
Keep the vial(s) in the outer carton in order to protect from light.
Żomm il- kunjett( i) fil- kartuna ta ’ barra sabiex tilqa ’ mid- dawl.
For storage conditions of the diluted medicinal product see section 6.3.
Għall- kundizzjonijiet ta ’ ħażna tal- prodott mediċinali dilwit, ara sezzjoni 6. 3.
RoActemra is supplied in a vial (type I glass) with a stopper (butyl rubber) containing 4 ml, 10 ml or 20 ml concentrate.
RoActemra huwa disponibbli f’ kunjett (ħġieġ tat- tip I) b’ tapp (tal- lastku butyl) li fih 4 ml, 10 ml jew 20 ml ta ’ konċentrat.
Pack sizes of 1 and 4 vials.
Daqsijiet tal- pakkett ta ’ kunjett wieħed u 4 kunjetti.
Instructions for dilution prior to administration Parenteral medicinal products should be inspected visually for particulate matter or discoloration prior to administration.
Istruzzjonijiet għad- dilwazzjoni qabel l- għoti Prodotti mediċinali parenterali għandhom jiġu spezzjonati viżwalment għall- frak jew bidla fil- kulur qabel l- għoti.
Only solutions which are clear to opalescent, colourless to pale yellow and free of visible particles should be diluted
Għandhom jiġu dilwiti biss solużżjonijiet li huma ċari sa opalaxxenti, bla kulur sa isfar ċar u li m’ għandhomx frak viżibbli.
Withdraw a volume of sterile, non-pyrogenic sodium chloride 9 mg/ ml (0.9%) solution for injection from a 100 ml infusion bag, equal to the volume of RoActemra concentrate required for the patients dose, under aseptic conditions.
Taħt kundizzjonijiet asettiċi iġbed volum ta ’ soluzzjoni għall- injezzjoni sterili u mhux piroġenika ta ’ sodium chloride 9 mg/ ml (0. 9%) minn borża għall- infużjoni ta ’ 100 ml, daqs il- volum ta ’ konċentrat ta ’ RoActemra meħtieġ għad- doża tal- pazjent.
The required amount of RoActemra concentrate (0.4 ml/ kg) should be withdrawn from the vial and placed in the 100 ml infusion bag.
Dan għandu jkun volum finali ta ’ 100 ml.
To mix the solution, gently invert the infusion bag to avoid foaming.
Biex tħallat is- soluzzjoni, dawwar il- borża ta ’ l- infużjoni ta ’ taħt fuq bil - mod sabiex tevita li jkun hemm xi rawgħa.
RoActemra is for single-use only.
RoActemra huwa għall- użu ta ’ darba biss.
16-3 Kiyohara Kogyodanchi Utsunomiya City Tochigi, 321-3231 Japan
16- 3 Kiyohara Kogyodanchi Utsunomiya City Tochigi, 321- 3231 Ġappun
Roche Pharma AG Emil-Barell-Strasse 1 D-79639 Grenzach-Wyhlen Germany
1 D- 79639 Grenzach- Wyhlen Il- Ġermanja
Physician Information Pack Nurse Information Pack Patient Information Pack
Pakkett ta ’ Informazzjoni għat- Tabib Pakkett ta ’ Informazzjoni għall- infermier Pakkett ta ’ Informazzjoni għall- Pazjent
The Physician Information pack should contain the following key elements: • The Summary of Product Characteristics • Dose calculation, preparation of infusion and infusion rate • Risk of serious infections o The product should not be given to patients with active or suspected infection o The product may lessen signs and symptoms of acute infection delaying the diagnosis • Serious infusion reaction and their management • Serious hypersensitivity reactions and their management • Risk of gastrointestinal perforations especially in patients with history of diverticulitis or intestinal ulcerations • Reporting of serious adverse drug reactions • The Patient Information Packs (to be given to patients by healthcare professionals)
Il- Pakkett ta ’ Informazzjoni għat- Tabib għandu jkun fih il- punti prinċipali li ġejjin: • Is- Sommarju tal- Karatteristiċi tal- Prodott • Kalkulazzjoni tad- doża, preparazzjoni ta ’ l- infużjoni u r- rata ta ’ l- infużjoni • Riskju ta ’ infezzjonijiet serji o Il- prodott m’ għandux jingħata lill- pazjenti b’ infezzjoni attiva jew b’ suspett ta ’ infezzjoni o Il- prodott jista ’ jnaqqas is- sinjali u s- sintomi ta ’ infezzjoni akuta u jittardja d- dijanjosi • Reazzjonijiet għall- infużjoni serji u l- immaniġjar tagħhom • Reazzjonijiet ta ’ sensittività eċċessiva serji u l- immaniġjar tagħhom • Riskju ta ’ perforazzjoni gastro- intestinali speċjalment f’ pazjenti b’ passat ta ’ divertikulite jew ulċerazzjoni intestinali • Rapport ta ’ reazzjonijiet avversi serji tal- mediċina • Il- Pakketti ta ’ Informazzjoni għall- Pazjent (sabiex jingħataw lill- pazjenti minn professjonisti fil- qasam tas- saħħa)
The Nurse Information Pack should contain the following key elements: • Prevention of medical errors and infusion reactions o Preparation of infusion o Infusion rate
18 Il- Pakkett ta ’ Informazzjoni għan- Ners għandu jkun fih il- punti prinċipali li ġejjin: • Prevenzjoni ta ’ żbalji mediċi u reazzjonijiet għall- infużjoni o Preparazzjoni ta ’ l- infużjoni o Rata ta ’ l- infużjoni • Sorveljanza tal- pazjent għal reazzjonijiet għall- infużjoni • Rapport ta ’ reazzjonijiet avversi serji tal- mediċina
The Patient Information Pack should contain the following key elements: • Patient Information Leaflet • Patient Alert Card
Il- Pakkett ta ’ Informazzjoni għall- infermier għandu jkun fih il- punti prinċipali li ġejjin: • Fuljett ta ’ Tagħrif għall- Pazjent • Biljett ta ’ Twissija għall- Pazjent
Pharmacovigilance system The MAH must ensure that the system of pharmacovigilance, as described in version 3.3 presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market.
Sistema ta ’ Farmokoviġilanza Id- Detentur ta ’ L- Awtorizzazzjoni għat- Tqegħid fis- Suq għandu jiżgura li s- sistema ta ’ farmakoviġilanza, kif deskritt f’ verżjoni 3. 3 ippreżentata f ’ Modulu 1. 8. 1 ta ’ l- Applikazzjoni għall - Awtorizzazzjoni għat- Tqegħid fis- Suq, hija f’ postha u qed tiffunzjona qabel u waqt li l- prodott jitqiegħed fis- suq.
Risk Management plan The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 3 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.
Pjan għall- Immanniġġjar ta ’ Riskji Id- Detentur ta ’ L- Awtorizzazzjoni għat- Tqegħid fis- Suq jwiegħed li jwettaq l- istudji u l- attivitajiet ta ’ farmakoviġilanza oħrajn dettaljati fil- Pjan ta ’ Farmakoviġilanza kif miftiehem f’ verżjoni 3. 0 tal- Pjan għall- Immaniġġjar ta ’ Riskji (RMP) ippreżentat f’ Modulu 1. 8. 2 ta ’ l- Applikazzjoni għal - Awtorizzazzjoni għat- Tqegħid fis- Suq u kull aġġornament sussegwenti ta ’ RMP miftiehem miċ - CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR).
Skond il- Linji Gwida ta ’ CHMP dwar is- Sistemi ta ’ Mmaniġġjar ta ’ Riskji għall- prodotti mediċinali għall- użu fil- bniedem, l- RMP aġġornat għandu jiġi pprovdut fl- istess żmien mar- Rapport Perjodiku ta ’ Aġġornament dwar is- Sigurtà (PSUR) ta ’ wara.
In addition, an updated RMP should be submitted • When new information is received that may impact on the current Safety Specification, Pharmacovigilance Plan or risk minimisation activities • Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being reached • At the request of the EMEA
Barra minn hekk, għandu jiġi ppreżentat RMP aġġornat • Meta tinkiseb informazzjoni ġdida li jista ’ jkollha effett fuq l- Ispeċifikazzjonijiet ta ’ Sigurtà kurrenti, Pjan ta ’ Farmakoviġilanza jew attivitajiet li jnaqqsu r- riskju • Fi żmien 60 ġurnata wara li tintlaħaq mira ta ’ importanza (farmakoviġilanza jew tnaqqis ta ’ riskju) • Mat- talba ta ’ l- EMEA
20 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
TIKKETTA
RoActemra 20 mg/ml concentrate for solution for infusion Tocilizumab
RoActemra 20 mg/ ml konċentrat għal soluzzjoni għall- infużjoni Tocilizumab
1 vial contains 80 mg tocilizumab.
Kunjett fih 80 mg ta ’ tocilizumab.
Polysorbate 80, sucrose, disodium phosphate dodecahydrate, sodium dihydrogen phosphate dihydrate and water for injections.
Polysorbate 80, sucrose, disodium phosphate dodecahydrate, sodium dihydrogen phosphate dihydrate u ilma għall- injezzjonijiet.
Concentrate for solution for infusion 80 mg/4 ml 1 vial of 4 ml 4 vials of 4 ml
Konċentrat għal soluzzjoni għall- infużjoni 80 mg/ 4 ml Kunjett ta ’ 4 ml 4 kunjetti ta ’ 4 ml
For intravenous infusion after dilution The diluted product should be used immediately Read the package leaflet before use
Għall- infużjoni fil- vini wara d- dilwazzjoni Il- prodott dilwit għandu jintuża immedjatament Aqra l- fuljett ta ’ tagħrif qabel l- użu
Store in a refrigerator Do not freeze Keep the vial in the outer carton in order to protect from light
Aħżen fi friġġ Tagħmlux fil- friża Żomm il- kunjett fil- kartuna ta ’ barra sabiex tipproteġih mid- dawl
GENERAL CLASSIFICATION FOR SUPPLY
KLASSIFIKAZZJONI ĠENERALI TA ’ KIF JIĠI PROVDUT
INFORMATION IN BRAILLE
TAGĦRIF BIL- BRAILLE
1 vial contains 200 mg tocilizumab.
Kunjett fih 200 mg ta ’ tocilizumab.
Concentrate for solution for infusion 200 mg/10 ml 1 vial of 10 ml 4 vials of 10 ml
Konċentrat għal soluzzjoni għall- infużjoni 200 mg/ 10 ml Kunjett ta ’ 10 ml 4 kunjetti ta ’ 10 ml
Store in a refrigerator Do not freeze Keep the vial in the outer carton, in order to protect from light
Aħżen fi friġġ Tagħmlux fil- friża Żomm il- kunjett fil- kartuna ta ’ barra sabiex tipproteġih mid- dawl
1 vial contains 400 mg tocilizumab.
Kunjett fih 400 mg ta ’ tocilizumab.
Concentrate for solution for infusion 400 mg/20 ml 1 vial of 20 ml 4 vials of 20 ml
Konċentrat għal soluzzjoni għall- infużjoni 400 mg/ 20 ml Kunjett ta ’ 20 ml 4 kunjetti ta ’ 20 ml
26 MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
27 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ IL- PAKKETTI Ż- ŻGĦAR EWLENIN
RoActemra 20 mg/ml sterile concentrate Tocilizumab IV
RoActemra 20 mg/ ml konċentrat sterili Tocilizumab IV
IV infusion
Infużjoni IV
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
IL- KONTENUTI SKOND IL- PIŻ, VOLUM, JEW PARTI INDIVIDWALI
EXP IRY DATE
DATA TA ’ SKADENZA
RoActemra Patient Alert Card
Biljett ta ’ Twissija għall- Pazjent dwar RoActemra
Complications of Diverticulitis
Komplikazzjonijiet tad- Divertikulite Pazjenti li jieħdu RoActemra jistgħu
This patient alert card contains important safety Patients using RoActemra may develop information that you need to be aware of before complications of diverticulitis which can and
Dan
during treatment with RoActemra.
il- biljett ta ’ twissija għall- pazjent fih
serious if not treated.
jiżviluppaw komplikazzjonijiet
•
tad -
Show this card to any doctor involved in your care.
tagħrif importanti dwar is- sigurtà li għandek tkun konxju dwaru qabel u waqt il- kura b’ RoActemra.
- Seek medical attention immediately if you develop stomach pain, colic, or
divertikulite li jekk ma jiġux ikkurati jistgħu jsiru serji. - Fittex attenzjoni medika immedjatament
Read the RoActemra package leaflet for more information.
Infezzjonijiet
notice blood in your stools.
jekk ikollok uġigħ fl- istonku, kolika jew jekk tinnota xi demm mal- ippurgar tiegħek.
Dates of RoActemra Treatment:
Dati tal- Kura b’ RoActemra:
Infections Start:
Bidu:
RoActemra increases the risk of getting infections which can become serious if not
RoActemra jżid ir- riskju li jkollok infezzjonijiet li jistgħu jsiru serji jekk ma jiġux
treated. - -You should not be treated with RoActemra if you have a severe infection.
ikkurati. - Jekk għandek infezzjoni severa m’ għandekx tiġi kkurat/ a b’ RoActemra. - Qabel il- kura b’ RoActemra suppost tkun
Most recent: ______________________
L- aktar reċenti: ______________________
- You should have been screened for tuberculosis prior to treatment with RoActemra - Talk to your doctor about any
ġejt eżaminat biex wieħed jara jekk għandekx it- tuberkulożi. - Qabel ma tibda l- kura b’ RoActemra tkellem mat- tabib tiegħek dwar xi tilqim
• Please make sure you also have a list of all your other medicines with you at any visit to a healthcare professional.
• Jekk jogħġbok aċċerta ruħek li kull darba li tara tabib iġorr miegħek lista ta ’ kull mediċina li qiegħed/ qiegħda tieħu.
vaccinations you may need before you start treatment with RoActemra - If you have an infection of any kind (even a head cold) at the time of your next treatment, the infusion should be
li jista ’ jkollok bżonn. - Jekk meta tmur għat- trattament li jmiss ikollok xi infezzjoni (anki flissjoni), l - infużjoni għandha tiġi posposta għal
Patient’s Name: __________________ Doctor’s Name: __________________ Doctor’s Phone: __________________
Isem il- Pazjent: __________________ Isem it- Tabib: __________________ Telefown tat- Tabib: __________________
delayed until you are feeling better - Seek medical attention immediately if you develop symptoms such as fever, persistent cough, weight loss, throat pain or soreness, wheezing, red or swollen skin blisters, tears, wounds, severe weakness or tiredness.
meta tkun qed tħossok aħjar. - Fittex immedjatament attenzjoni medika jekk ikollok sintomi bħal deni, sogħla persistenti, telf ta ’ piż, uġigħ jew tisliħ fil- griżmejn, tħarħir, infafet ħomor jew minfuħin fuq il- ġilda, dmugħ, feriti, għeja jew debbulizza kbira.