qanastek/EMEA-V3 huggingface dataset:
Significantly associated with Betaferon treatment for patients with first event suggestive of MS, p < 0.05 * Significantly associated with Betaferon treatment for RRMS, p < 0.05 ° Significantly associated with Betaferon treatment for SPMS, p < 0.05 § Injection site reaction (various kinds) comprises all adverse events occurring at the injection site, i. e. the following terms: injection site hemorrhage, injection site hypersensitivity, injection site inflammation, injection site mass, injection site necrosis, injection site pain, injection site reaction, injection site edema, and injection site atrophy & “ Flu-like symptom complex ” denotes flu syndrome and/ or a combination of at least two AEs from fever, chills, myalgia, malaise, sweating. # During the third year of the BENEFIT study, no change of the known risk profile of Betaferon was observed.
Assoċjat b’ mod sinifikattiv ma ’ kura b’ Betaferon għal pazjenti bl- ewwel avveniment li jissuġġerixxi sklerożi multipla, p < 0. 05 * Assoċjati b’ mod sinifikattiv ma ’ kura b’ Betaferon għal RRMS, p < 0. 05 ° Assoċjati b’ mod sinifikattiv ma ’ kura b’ Betaferon għal SPMS, p < 0. 05 § Reazzjoni fil- lok ta ’ l- injezzjoni (diversi tipi) tinkludi l- avvenimenti avversi kollha li jseħħu fil- lok ta l - injezzjoni, i. e. it- termini li ġejjin: emorraġija fil- lok ta ’ l- injezzjoni, sensittività eċċessiva fil- lok ta ’ l - injezzjoni, massa fil- lok ta ’ l- injezzjoni, nekrosi fil- lok ta ’ l- injezzjoni, uġigħ fil- lok ta ’ l- injezzjoni, reazzjoni fil- lok ta ’ l- injezzjoni, edima fil- lok ta ’ l- injezzjoni, u atrofija fil- lok ta ’ l- injezzjoni & “ Kumpless ta ’ sintomi li jixbħu lill- influwenza ” jindika s- sindrome ta ’ l- influwenza u/ jew taħlita ta ’ mill - anqas żewġ reazzjonijiet avversi minn deni, kesħa, mijalġja, telqa u għaraq. # Waqt it- tielet sena ta ’ l- istudju BENEFIT, ma kien osservat l- ebda tibdil fil- profil ta ’ riskji magħrufa ta ’ Betaferon.
The most appropriate MedDRA term is used to describe a certain reaction and its synonyms and related conditions.
L- aktar terminu xieraq ta ’ MedRA huwa wżat biex jiddeskrivi ċertu reazzjoni u s- sintomi tagħha u kundizzjonijiet relatati.
10 Table 2 (reporting rates (very common ≥ 1/ 10, common ≥ 1/ 100 to < 1/ 10, uncommon ≥ 1/ 1,000 to < 1/ 100, rare ≥ 1/ 10,000 to < 1/ 1,000, very rare < 1/ 10,000) based on spontaneous adverse drug reaction reports).
10 Tabella 2 (rati bbażati fuq rapporti spontanji ta ’ reazzjonijiet avversi tal- mediċina (komuni ħafna ≥ 1/ 10, komuni ≥ 1/ 100 sa < 1/ 10, mhux komuni ≥ 1/ 1, 000 sa < 1/ 100, rari ≥ 1/ 10, 000 sa < 1/ 1, 000 u rari ħafna < 1/ 10, 000)
System Organ Class
Sistema tal - Klassifika tal -
Uncommon ≥ 1/ 1,000 to < 1/ 100
Komuni ≥ 1/ 100 sa
Rare ≥ 1/ 10,000 to < 1/ 1,000
Mhux komuni ≥ 1/ 1, 000 sa
Blood and lymphatic system disorders
Rari ≥ 1/ 10, 000 sa
Lymphadenopathy
Organi
Psychiatric disorders
< 1/ 10
Convulsion
< 1/ 100
Cardiac disorders
< 1/ 1, 000
Cardiomyopathy, Tachycardia, Palpitation
Limfadenopatija Anemija, Disturbi tad - Tromboċitopenija, demm u tas - Lewkopenija sistema limfatika Reazzjonijiet Disturbi fis - anafilattiċi sistema immuni Ipertirojdiżmu, Disturbi fis - Ipotirojdiżmu, sistema Disturb tat- tirojde endokrinarja Żjieda fit - Disturbi fil - trigliċeridi fid - metaboliżmu u demm nutrizzjoni Anoressija Disturbi
Vascular disorders
Depressjoni (ara
Hypertension
Konfużjoni,
Respiratrory, thoracic and mediastinal disorders
psikjatriċi Disturbi fis - sistema nervuża Disturbi fil- qalb Disturbi vaskulari Disturbi respiratorji, toraċiċi u medjastinali
Gastrointestinal disorders
wkoll sezzjoni 4. 4) Pressjoni baxxa
Vomiting, Nausea
Ansjetà, Nuqqas ta ’ stabbilità emozzjonali, Attentat ta ’ suwiċidju (ara wkoll sezzjoni 4. 4) Aċċessjoni Kardjomijopatija, Takikardija, Palpitazzjoni Bronkospażmu, Qtugħ ta ’ nifs
Pancreatitis
Disturbi gastro - intestinali Disturbi fil- fwied u fil- marrara Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Disturbi muskolu- skeltrali u tal- connective tissue
Alanine amino- transferase increased, Aspartate amino- transferase increased
Rimettar, Tqalligħ Alanine amino - transferase miżjud, Aspartate amino - transferase miżjud Urtikarja, Raxx, Ħakk, Alopeċja Uġigħ fil- muskoli, Ipertonija
Blood bilirubin increased, Gamma-glutamyl- transferase increased, Hepatitis
Pankreatite Bilirubin fid- demm miżjud, Gamma- glutamyl - transferase miżjud, Epatite Bidla fil- kulur tal - ġilda
Skin and subcutaneous tissue disorders
11 Rari Mhux komuni Sistema tal -
Urticaria, Rash, Pruritus, Alopecia
Komuni ħafna
Skin discolouration
Komuni
Myalgia, Hypertonia
≥ 1/ 1, 000 sa
Menstrual disorder
≥ 1/ 10, 000 sa
11 System Organ Class
Klassifika tal -
Common ≥ 1/ 100 to < 1/ 10
≥ 1/ 100 sa
General disorders and administration site conditions
Disturb fil - Disturbi fis - sistema riproduttiva u fis - sider
Flu-like symptoms*, Chills*, Fever *, Injection site reaction*, Injection site inflammation*, Injection site pain
Sintomi jixbħu lill -
Injection site necrosis*
Nekrożi fil- lok ta ’
Chest pain, Malaise, Sweating
Uġigħ fis- sider,
Investigations
l- injezzjoni *
Weight decrease
Telqa, Għaraq Tnaqqis fil- piż
* frequencies based on clinical trials
* frekwenza msejsa fuq provi kliniċi
Interferon beta-1b has been given without serious adverse events compromising vital functions to adult cancer patients at individual doses as high as 5,500 microgram (176 million IU) intravenously three times a week.
Interferon beta- 1b ingħata mingħajr avvenimenti avversi serji li jikkompromettu funzjonijiet vitali, lill - pazjenti adulti bil- kanċer f’ dożi individwali għolja sa 5, 500 mikrogramma (176 miljun IU) mogħtija fil- vina, tliet darbiet fil- ġimgħa.
Cytokines, Interferons, ATC Code:
Ċitokini, Interferoni, Kodiċi ATC:
Three major classes of interferons have been identified: alpha, beta, and gamma.
Kienu identifikati tliet klassijiet prinċipali ta ’ interferoni: alfa, beta, u gamma.
Interferon alpha, interferon beta, and interferon gamma have overlapping yet distinct biologic activities.
Interferon alfa, interferon beta u interferon gamma għandhom karatteristiċi bijoloġiċi komuni iżda distinti.
The activities of interferon beta-1b are species-restricted and therefore, the most pertinent pharmacological information on interferon beta-1b is derived from studies of human cells in culture or in human in vivo studies.
L- attivitajiet ta ’ interferon beta- 1b huma limitati għal l - ispeċi, u għalhekk, l- aktar informazzjoni farmakoloġika rilevanti dwar interferon beta- 1b ġej minn studji ta ’ ċelluli umani f’ koltura jew minn studji in vivo fil- bniedem.
Interferon beta-1b has been shown to possess both antiviral and immunoregulatory activities.
Interferon beta- 1b intwera li għandu kemm azzjonijiet kontra il- virus kif ukoll azzjonijiet immuno - regulatorji.
The mechanisms by which interferon beta-1b exerts its actions in multiple sclerosis are not clearly understood.
Il- mekkaniżmi li bihom interferon beta- 1b jeffettwa l- isklerożi multipla għadhom mhumiex mifhuma sew.
However, it is known that the biologic response-modifying properties of interferon beta-1b are mediated through its interactions with specific cell receptors found on the surface of human cells.
Madankollu, hu magħruf li l- karatteristiċi bijoloġiċi ta ’ interferon beta- 1b, li jimmodifika r- rispons, iseħħu permezz ta ’ l- interazzjoni tiegħu ma ’ riċevituri speċifiċi li jinsabu fuq is - superfiċje taċ- ċelluli tal- bniedem.
The binding of interferon beta-1b to these receptors induces the expression of a number of gene products that are believed to be the mediators of the biological actions of interferon beta-1b.
L- irbit ta ’ interferon beta- 1b ma ’ dawn ir- riċevituri jwassal għall - ħelisen ta ’ numru ta ’ prodotti ġenetiċi li huma meqjusa bħala medjaturi ta ’ l- azzjonijiet bijoloġiċi ta ’ interferon beta- 1b.
A number of these products have been measured in the serum and cellular fractions of blood collected from patients treated with interferon beta-1b.
Numru minn dawn il- prodotti ġew imkejla fis- serum u fi frazzjonijiet ċellulari ta ’
12 Clinical trials:
12 demm, miġbura minn pazjenti kkurati b’ interferon beta- 1b.
One controlled clinical trial with Betaferon in patients with relapsing remitting multiple sclerosis and able to walk unaided (baseline EDSS 0 to 5.5) was performed.
Sar studju kliniku ikkontrollat b’ Betaferon f’ pazjenti bi sklerożi multipla li tirkadi u tbatti, u li setgħu jimxu mingħajr għajnuna (linja bażi ta ’ EDSS 0 sa 5. 5).
Patients receiving Betaferon showed a reduction in frequency (30%) and severity of clinical relapses, as well as the number of hospitalisations due to disease.
Pazjenti li ħadu Betaferon kellhom tnaqqis fil - frekwenza (30%) u fis- severità ta ’ l- irkadar kliniku, kif ukoll tnaqqis fin- numru ta ’ drabi li kellhom jittieħdu l- isptar minħabba l- marda.
Furthermore, there was a prolongation of the relapse-free interval.
Minnbarra dan, l- intervall mingħajr episodji ta ’ rkadar kien miżjud.
There is no evidence of an effect of Betaferon on the duration of relapses or on symptoms in between relapses, and no significant effect was seen on the progression of the disease in relapsing remitting multiple sclerosis.
Ma kienx hemm evidenza ta ’ effett ta ’ Betaferon fuq it- tul ta ’ kemm idum l- irkadar jew fuq is- sintomi li nħassu bejn l- irkadar, u ma kien osservat l- ebda effett sinnifikattiv fuq il- progressjoni tal- marda ta ’ sklerożi multipla li tirkadi u tbatti.
Two controlled clinical trials with Betaferon involving a total of 1657 patients with secondary progressive multiple sclerosis (baseline EDSS 3 to 6.5, i. e. patients were able to walk) were performed.
Saru żewġ studji kliniċi kkontrollati b’ Betaferon li fihom kien hemm total ta ’ 1657 pazjent bi sklerożi multipla progressiva sekondarja (linja bażi ta ’ EDSS 3 sa 6. 5, i. e. il- pazjenti setgħu jimxu).
The two studies showed inconsistent results for the primary endpoint time to confirmed progression, representing delay of disability progression:
Iż- żewġ studji wrew riżultati mhux konsistenti għall- ħin li għadda sabiex tkun ikkonfermata progressjoni tal- marda, li jirrapreżentaw itardjar fil- progressjoni ta ’ diżabilità.
One of the two studies demonstrated a statistically significant delay in the time to disability progression (Hazard Ratio = 0.69, 95% confidence interval (0.55, 0.86), p=0.0010, corresponding to a 31% risk reduction due to Betaferon) and in the time to becoming wheelchair bound (Hazard Ratio = 0.61, 95% confidence interval (0.44, 0.85), p=0.0036, corresponding to a 39% risk reduction due to Betaferon) in patients who received Betaferon.
Wieħed minn dawn iż- żewġ studji wera ittardjar statistikament sinifikanti fiż- żmien sal- progressjoni tad- diżabilità (Proporzjon ta ’ Periklu = 0. 69, 95% intervall ta ’ kunfidenza (0. 55, 0. 86), p=0. 0010, ekwivalenti għal tnaqqis ta ’ 31% fir- riskju minħabba Betaferon) u fiż- żmien li wieħed jieħu biex ikollu bżonn siġġu tar- roti (Proporzjon ta ’ Periklu = 0. 61, 95% intervall ta ’ kunfidenza (0. 44, 0. 85), p=0. 0036, ekwivalenti għal tnaqqis ta ’ 39% fir- riskju minħabba Betaferon) f’ pazjenti li rċevew Betaferon.
This effect continued over the observation period of up to 33 months.
Dan l- effett kompla tul il- perijodu ta ’ osservazzjoni sa ’ 33 xahar.
The treatment effect occurred in patients at all levels of disability investigated and independent of relapse activity.
L- effett tal- kura seħħ f’ pazjenti f’ kull livell ta ’ diżabilità investigati u kien indipendenti mill- irkadar.
In the second trial of Betaferon in secondary progressive multiple sclerosis, no delay in the time to disability progression was observed.
Fit- tieni prova ta ’ l- użu ta ’ Betaferon fi sklerożi multipla progressiva sekondarja ma kienx osservat ittardjar fiż- żmien sal- progressjoni tad- diżabilità.
There is evidence that the patients included in this study had overall less active disease than in the other study in secondary progressive multiple sclerosis.
Hemm evidenza li l- pazjenti ta ’ dan l- istudju kellhom marda anqas attiva meta mqabbla ma ’ l- istudju l- ieħor bi sklerożi multipla progressiva sekondarja.
In retrospective meta-analyses including the data of both studies, an overall treatment effect was found which was statistically significant (p=0.0076; 8 million IU Betaferon versus all placebo patients).
F’ meta- analiżi retrospettiva li tinkludi tagħrif miż- żewġ studji, instab effett globali tal- kura li kien statistikament sinifikanti (p=0. 0076; 8 miljun IU Betaferon kontra l- pazjenti kollha tal- plaċebo).
Retrospective analyses in subgroups showed that a treatment effect on disability progression is most likely in patients with active disease before treatment commences (Hazard Ratio 0.72, 95% confidence interval (0.59, 0.88), p=0.0011, corresponding to a 28% risk reduction due to Betaferon in patients with relapses or pronounced EDSS progression, 8 million IU Betaferon versus all placebo patients).
Analiżi retrospettiva f’ sottogruppi wriet li l- effett tal- kura fuq il- progressjoni tad- diżabilità hi l- aktar probabbli f’ pazjenti bil- marda attiva qabel il- bidu tal- kura (Proporzjon ta ’ Periklu 0. 72, 95% intervall ta ’ kunfidenza (0. 59, 0. 88), p=0. 0011, ekwivalenti għal tnaqqis ta ’ 28% fir- riskju minħabba Betaferon f’ pazjenti b’ irkadar jew bi progressjoni prominenti fl- EDSS, 8 miljun IU Betaferon kontra il- pazjenti kollha tal- plaċebo).
From these retrospective subgroup analyses there was evidence to suggest that relapses as well as pronounced EDSS progression (EDSS > 1 point or > 0.5 point for EDSS > =6 in the previous two years) can help to identify patients with active disease.
Minn dawn l- analiżi retrospettivi ta ’ sottogruppi, kien hemm evidenza li tagħti x’ tifhem li rkadar kif ukoll progressjoni prominenti fl- EDSS (EDSS > 1 punt jew > 0. 5 punt għal EDSS > =6 fis- sentejn ta ’ qabel) jistgħu jgħinu biex jidentifikaw pazjenti li għandhom marda attiva.
In both trials secondary progressive multiple sclerosis patients receiving Betaferon showed a reduction in frequency (30%) of clinical relapses.
Fiż- żewġ provi l- pazjenti bi sklerożi multipla progressiva sekondarja li ħadu Betaferon, kellhom tnaqqis fil- frekwenza (30%) ta ’ episodji ta ’ rkadar kliniku.
There is no evidence of Betaferon having an effect on the duration of relapses.
M’ hemmx evidenza li Betaferon għandu xi effett fuq it- tul ta ’ żmien ta ’ l- irkadar.
Single clinical event suggestive of MS:
Avveniment kliniku wieħed li jissuġġerixxi MS:
One controlled clinical trial with Betaferon was performed in patients with a single clinical event and MRI features suggestive of multiple sclerosis (at least two clinically silent lesions on the T2-weighted MRI).
Saret prova klinika waħda kkontrollata b’ Betaferon f’ pazjenti b’ avveniment kliniku wieħed u karatteristiċi ta ’ l- MRI li jissuġġerixxu sklerożi multipla (mill- inqas żewġ leżjonijiet mingħajr sintomi kliniċi fuq T2- weighted MRI).
Patients with monofocal or multifocal onset of the disease were included (i. e. patients with clinical evidence for a single or at least two lesions, respectively, of the central nervous system).
Kwalunkwe marda oħra minbarra sklerożi multipla li
Any disease other than multiple sclerosis that could better explain signs and symptoms of the patient had to be excluded.
13 setgħet tispjega aħjar is- sinjali u s- sintomi tal- pazjent kellha tiġi eskluża.
This study consisted of two phases, a placebo-controlled phase followed by a pre-planned follow-up phase.
Dan l- istudju kien jikkonsisti f’ żewġ fażijiet, fażi kkontrollata bil- plaċebo segwita minn fażi ta ’ visti ta ’ wara ppjanata minn qabel.
The placebo-controlled phase lasted for 2 years or until the patient developed clinically definite multiple sclerosis (CDMS), whichever came first.
Il- fażi kkontrollata bil- plaċebo damet sentejn jew sakemm il- pazjent żviluppa sklerożi multipla definita klinikament (CDMS), skond liema ġiet l- ewwel.
After the placebo-controlled phase, patient entered a pre-planned follow-up phase with Betaferon to evaluate the effects of immediate versus delayed start of Betaferon-treatment, comparing patients initially randomized to Betaferon ("immediate treatment group") or to placebo ("delayed treatment group").
Wara l- fażi kkontrollata bil- plaċebo, l- pazjent daħal fil- fażi ta ’ visti ta ’ wara ppjanata minn qabel b’ Betaferon biex jiġu stmati l- effetti ta ’ bidu immedjat kontra bidu ittardjat ta ’ kura b’ Betaferon, li qabbel pazjenti li fil- bidu kienu randomised għal Betaferon ("grupp ta ’ kura immedjata") jew għall- plaċebo ("grupp ta ’ kura ittardjata").
Patients and investigators remained blinded to the initial treatment allocation.
Il- pazjenti u l- investigaturi ma kienux jafu x’ kienet il- kura tal- bidu.
13 In the placebo-controlled phase, Betaferon delayed the progression from the first clinical event to clinically definite multiple sclerosis (CDMS) in a statistically significant and clinically meaningful manner, corresponding to a risk reduction of 47% (Hazard Ratio = 0.53, 95% confidence interval (0.39, 0.73), p < 0.0001).
0. 73), p < 0. 0001).
Within the study period of two years, CDMS occurred in 45% of the placebo group compared to 28% of the Betaferon group (Kaplan-Meier estimates).
Matul il- perijodu ta ’ l- istudju ta ’ sentejn, CDMS seħħet f’ 45% tal - grupp ta ’ plaċebo, meta mqabbel ma ’ 28% tal- grupp ta ’ Betaferon (stimi Kaplan- Meier).
Betaferon prolonged the time to CDMS by 363 days, from 255 days in the placebo group to 618 days in the Betaferon group (based on the 25th percentiles).
Betaferon tawwal iż- żmien sa CDMS b’ 363 jum, minn 255 jum fil- grupp tal- plaċebo għal 618- il jum fil- grupp ta ’ Betaferon (ibbażat fuq il- 25 perċentili).
This treatment effect was still evident after the additional year of follow-up at which stage the risk reduction was 41% (Hazard Ratio = 0.59, 95% confidence interval (0.42, 0.83), p = 0.0011). Within the study period of three years, CDMS occurred in 51% of the delayed treatment group compared to 37% of the immediate treatment group (Kaplan-Meier estimates).
Fil- perijodu ta ’ studju ta ’ tliet snin, CDMS seħħet f’ 51% fil- grupp ta ’ kura ittardjata meta mqabbel ma ’ 37% fil- grupp ta ’ kura immedjata (estimi Kaplan- Meier).
The persistence of the treatment effect was observed although the majority of patients from the placebo-group was treated with Betaferon in the third year of the study.
Il- persistenza ta ’ l- effett tal- kura kienet osservata għalkemm il- maġġoranza tal - pazjenti mill- grupp tal- plaċebo kienu kkurati b’ Betaferon fit- tielet sena ta ’ l- istudju.
The robustness of the treatment effect was also shown by the delay of progression to multiple sclerosis according to the McDonald criteria.
Is- saħħa ta ’ l- effett tal- kura kienet murija wkoll mid- dewmien tal- progressjoni għal sklerożi multipla skond il- kriterji ta ’ McDonald.
In two years, the risk in the placebo group was 85% and 69% in the Betaferon group (Hazard Ratio = 0.57, 95% confidence interval (0.46, 0.71), p < 0.00001).
F’ sentejn, ir- riskju tal- grupp tal- plaċebo kien ta ’ 85% u 69% fil- grupp ta ’ Betaferon (Proporzjon ta ’ Periklu = 0. 57, 95% intervall ta ’ kunfidenza (0. 46, 0. 71), p < 0. 0001).
After 3 years, a pre-planned interim analysis showed EDSS progression (confirmed increase in EDSS of greater than or equal 1.0 compared to baseline) occurred in 24% of the patients in the delayed treatment group compared to 16% in the immediate treatment group [Hazard ratio=0.6, 95% confidence interval (0.39, 0.92), p=0.022].
Wara 3 snin, analiżi interim ippjanata minn qabel uriet li progressjoni fl- EDSS (żjieda ikkonfermata fl - EDSS ta ’ 1. 0 jew aktar meta mqabbel mal- linja bażi) seħħet f’ 24% tal- pazjenti fil- grupp ta ’ kura ittardjata meta mqabbel ma ’ 16% fil- grupp ta ’ kura immedjata [Proporzjon ta ’ perilku=0. 6, 95% intervall ta ’ kunfidenza (0. 39, 0. 92), p=0. 022].
There is no evidence for benefit in terms of confirmed disability progression in the majority of patients receiving'immediate 'treatment.
M’ hemmx evidenza ta ’ benefiċċju f’ termini ta ’ progressjoni kkonfermata tad- diżabilità fil- maġġoranza tal- pazjenti li rċevew kura ‘ immedjata ’.
Follow-up of patients is continuing in order to provide additional data.
Visti ta ’ wara tal- pazjenti għadhom għaddejjin sabiex jiġi pprovdut tagħrif addizzjonali.
No benefit, attributable to Betaferon, in quality of life (as measured by FAMS - Functional Assessment of MS:
Ma deher l- ebda benefiċċju, attribwit lil Betaferon, fil- kwalità tal- ħajja (kif mkejjel mill- FAMS – Valutazzjoni Funzjonali ta ’ MS:
Treatment Outcomes Index) was seen.
Indiċi tar- Riżultat tal- Kura).
Subgroup analyses according to baseline factors demonstrated evidence of efficacy in all subgroups evaluated.
Analiżi ta ’ sottogruppi skond fatturi tal- linja bażi ta ’ referenza wrew evidenza ta ’ effikaċja fis - sottogruppi evalwati kollha.
Significant effects were also obtained in patients with less disseminated and less active disease at the time of the first event, the risk in two years for progression to CDMS in patients with monofocal onset was 47% for placebo and 24% for Betaferon, without gadolinium (Gd-) enhancement 41% and 20%, with less than 9 T2 lesions 39% and 18%.
Effetti sinifikanti kienu wkoll miksuba f’ pazjenti b’ marda anqas mifruxa u anqas attiva fiż- żmien ta ’ l- ewwel avveniment, ir- riskju f’ sentejn ta ’ progressjoni għal CDMS f’ pazjenti b’ bidu monofokali kien ta ’ 47% għal plaċebo u 24% għal Betaferon, mingħajr titjib b’ gadolinium (Gd -) 41% u 20%, b’ inqas minn 9 leżjonijiet T2 39% u 18%.
Further subgroup analyses indicated a high risk for progression to CDMS within 2 years in monofocal patients with at least 9 T2- lesions (55% risk for placebo, 26% for Betaferon) or Gd-enhancement (63% versus 33%).
Aktar analiżi ta ’ sottogruppi ndikat riskju għoli ta ’ progressjoni għal CDMS fi żmien sentejn f’ pazjenti monofokali b’ ta ’ l- inqas 9 leżjonijiet T2 (riskju ta ’ 55% għal plaċebo, 26% għal Betaferon) jew titjib b’ Gd (63% kontra 33%).
In multifocal patients, the risk for CDMS was independent from MRI findings at baseline, indicating a high risk for CDMS because of the dissemination of the disease based on clinical findings.
F’ pazjenti multifokali r- riskju għal CDMS kien indipendenti mir- riżultati tal- MRI fil- linja bażi, li jindika riskju għoli għal CDMS minħabba l- firxa tal- marda skond riżultati kliniċi.
However, the long-term impact of early treatment with Betaferon is unknown even in these high risk subgroups as this study was mainly designed to assess the time to CDMS rather than the long term evolution of the disease.
Madankollu, l - impatt fuq perijodu ta ’ żmien twil ta ’ kura bikrija b’ Betaferon mhux magħruf f’ dawn is- sottogruppi ta ’ riskju għoli peress li dan l- istudju kien maħsub primarjament biex jiġi stmat iż- żmien sa CDMS u mhux l- iżvilupp fit- tul tal- marda.
Furthermore, for the time being there is no well established definition of a high risk patient, although a more conservative approach is to accept at least nine T2 hyperintense lesions on the initial scan and at least one new T2 or one new Gd-enhancing lesion on a follow-up scan taken at least 1 month after the initial scan.
Barra dan, għall- perijodu attwali għad m’ hemmx definizzjoni stabbilita tajjeb ta ’ pazjent li għandu riskju għoli, għalkemm mod konservattiv huwa li wieħed għandu jaċċetta ta ’ l- inqas disa ’ leżjonijiet T2 ipertensivi fuq l- ewwel scan u ta ’ l- inqas T2 waħda ġdida jew leżjoni waħda mtejba b’ Gd ġdida fuq scan ta ’ wara meħuda mill- inqas xahar wara l- ewwel scan.
In any case, treatment should only be considered for patients classified as high risk.
Fi kwalunkwe każ, il- kura għandha tiġi kkunsidrata biss għal pazjenti klassifikati bħala riskju għoli.
Therapy with Betaferon was well accepted in the study of patients with a single clinical event as indicated by a high rate of trial completion (92.8% in the Betaferon group).
It- terapija b’ Betaferon kienet aċċettata tajjeb fl- istudju ta ’ pazjenti b’ avveniment kliniku wieħed kif indikat mir- rata għolja ta ’ dawk li temmew il- prova (92. 8% fil- grupp ta ’ Betaferon).
To increase tolerability of Betaferon in the study of patients with a first clinical event, a dose titration was applied and non- steroidal anti-inflammatory drugs were administered at start of therapy.
Biex tiżdied it - tollerabilità ta ’ Betaferon fl- istudju ta ’ pazjenti bl- ewwel avveniment kliniku, kienet applikata titrazzjoni tad- doża u fil- bidu tat- terapija ngħataw mediċini anti- infjammatorji mhux sterojdi.
Moreover, an autoinjector was used by the majority of patients throughout the study.
Flimkien ma ’ dan, matul l- istudju ntuża awto- injettatur mill- maġġoranza tal- pazjenti.
RR-MS, SP-MS and single clinical event suggestive of MS:
14 RR- MS, SP- MS u avveniment kliniku wieħed li jissuġġerixxi MS:
Betaferon was effective in all multiple sclerosis studies to reduce disease activity (acute inflammation in the central nervous system and permanent tissue alterations) as measured by magnetic resonance imaging (MRI).
Betaferon kien effettiv biex inaqqas l- attività tal- marda fl- istudji kollha dwar sklerożi multipla (infjammazzjoni akuta fis- sistema nervuża ċentrali u bidla permanenti fit- tessuti) kif imkejjel b’ magnetic resonance imaging (MRI).
The relation of multiple sclerosis disease activity as measured by MRI and clinical outcome is currently not fully understood.
Ir- relazzjoni ta ’ l- attività tal- marda ta ’ l- isklerożi multipla kif imkejla bl- MRI u r- riżultat kliniku, għad mhux mifhuma tajjeb.
Betaferon serum levels were followed in patients and volunteers by means of a not completely specific bioassay.
Il- livelli ta ’ Betaferon fis- serum kienu studjati f’ pazjenti u voluntiera permezz ta ’ bioassay li mhux speċifiku kompletament.
Maximum serum levels of about 40 IU/ ml were found 1-8 hours after subcutaneous injection of 500 microgram (16.0 million IU) interferon beta-1b.
L- ogħla livelli fis- serum ta ’ madwar 40 IU/ ml instabu 1 sa 8 sigħat wara injezzjoni minn taħt il- ġilda ta ’ 500 mikrogramma (16. 0 miljun IU) interferon beta- 1b.
From various studies mean clearance rates and half-lives of disposition phases from serum were estimated to be at most 30 ml·min-1·kg-1 and 5 hours, respectively.
Minn diversi studji kien stmat li r- rata medja tat- tneħħija u l- half lives tal- fażijiet ta ’ dispożizzjoni fis- serum, ma kienux aktar minn 30 ml· min- 1· kg- 1 u 5- sigħat, rispettivament.
Betaferon injections given every other day do not lead to serum level increases, and the pharmacokinetics does not seem to change during therapy.
Injezzjonijiet ta ’ Betaferon mogħtija ġurnata iva u oħra le ma jwasslux għall- żjidiet fil- livelli fis- serum, u l- farmakokinetika ma jidhirx li tinbidel waqt it- terapija.
The absolute bioavailability of subcutaneously administered interferon beta-1b was approximately 50%.
Il- bijodisponibiltà assoluta ta ’ interferon beta- 1b mogħti minn taħt il- ġilda kienet madwar 50%.
As rodents do not react to human interferon beta, repeated dose studies were carried out with rhesus monkeys.
Peress li l- firien ma jkollhomx reazzjoni għal interferon beta uman, saru studji b’ dozi ripetuti fuq xadini rhesus.
Transitory hyperthermia was observed, as well as a significant rise in lymphocytes and a significant decrease in thrombocytes and segmented neutrophils.
Kienet osservata ipertermija transitorja, kif ukoll żjieda sostanzjali fil- limfoċiti u tnaqqis sinifikanti fit- tromboċiti u fin- newtrofili segmentati.
No long-term studies have been conducted.
Ma sarux studji għal tul ta ’ żmien.
Reproduction studies with rhesus monkeys revealed maternal toxicity and an increased rate of abortion, resulting in prenatal mortality.
Studji dwar ir- riproduzzjoni fuq xadini rhesus urew tossiċità fl- omm u żjieda fir- rata ta ’ korrimenti, li wasslet għall- mewt qabel it- twelid.
No malformations have been observed in the surviving animals.
Ma dehrux malformazzjonijiet fl - annimali li għexu.
No investigations on fertility have been conducted.
Ma sarux studji dwar il- fertilità.
No influence on the monkey oestrous cycle has been observed.
Ma kien osservat l- ebda effett fuq iċ- ċiklu sesswali tax- xadini.
Experience with other interferons suggest a potential for impairment of male and female fertility.
Esperjenza b’ interferoni oħrajn tissuġġerixxi potenzjal ta ’ indeboliment fil- fertilità maskili u femminili.
In one single genotoxicity study (Ames test), no mutagenic effect has been observed.
Fi studju wieħed dwar l- effett tossiku fuq il- ġeni (test ta ’ Ames), ma kien osservat l- ebda effett mutaġeniku.
Carcinogenicity studies have not been performed.
Ma sarux studji dwar riskju ta ’ kanċer.
An in vitro cell transformation test gave no indication of tumorigenic potential.
Test in vitro dwar it- trasformazzjoni taċ- ċelluli ma ndikax potenzjal tumoriġeniku.
6.1 List of excipients:
6. 1 Lista ta ’ sustanzi mhux attivi:
Vial (with powder for solution and injection):
Kunjett (bi trab għal soluzzjoni għall- injezzjoni):
Human albumin Mannitol
Albumina umana Mannitol
Sodium Chloride, Water for injections.
Solvent (soluzzjoni ta ’ sodium chloride 5. 4mg/ ml (0. 54% w/ v)) Sodium Chloride Ilma għall- injezzjonijiet.
After reconstitution an immediate use is recommended.
Wara li jiġi rikostitwit huwa rrakkomandat użu immedjat.
However, the in-use stability has been demonstrated for 3 hours at 2-8 °C.
Madankollu, stabbiltà waqt l- użu intweriet għal tliet sigħat f’ temperatura ta ’ 2- 8 °C.
For storage conditions of the reconstituted product see section 6.3.
Għall- kundizzjonijiet ta ’ ħażna tal- prodott mediċinali rikostitwit, ara sezzjoni 6. 3.
Vial (with powder for solution for injection):
Kunjett (bi trab għal soluzzjoni għall- injezzjoni):
3 ml clear vial (type I glass) with a butyl rubber stopper (type I) and aluminium overseal and
Kunjett ċar ta ’ 3 ml (ħġieġ tip I) b’ tapp tal- lasktu butyl (tip I) u b’ siġill fuq kollox ta ’ l- aluminiju.
Solvent (with sodium chloride solution 5.4 mg/ ml (0.54%):
Solvent (b’ soluzzjoni ta ’ sodium chloride ta ’ 5. 4mg/ ml (0. 54%)):
1.2 ml pre-filled syringe (type I glass) with 1.2 ml solvent.
Siringa mimlija għal lest ta ’ 1. 2ml (ħġieġ tip I) b’ 1. 2ml ta ’ solvent.
- 5 vials with powder and 5 pre-filled syringes with solvent, or
- 5 kunjetti bit- trab u 5 siringi mimlija għal- lest bis- solvent, jew
- 15 vials with powder and 15 pre-filled syringes with solvent.
- 15- il kunjett bit- trab u 15- il siringa mimlija għal- lest bis- solvent.
• Reconstitution:
• Rikostituzzjoni:
To reconstitute lyophilised interferon beta-1b for injection, use the pre-filled syringe with solvent provided and a needle to inject the 1.2 ml of the solvent (sodium chloride solution, 5.4 mg/ ml (0.54% w/ v)) into the Betaferon vial.
Sabiex tirrikostitwixxi interferon beta- 1b lajofiliżat għall- injezzjoni, uża s- siringa mimlija għal- lest bis - solvent ipprovduta u labra biex tinjetta 1. 2 ml tas- solvent (soluzzjoni ta ’ sodium chloride, 5. 4mg/ ml (0. 54% w/ v)) fil- kunjett ta ’ Betaferon.
Dissolve the powder completely without shaking.
Dewweb it- trab kompletament mingħajr ma ’ tħawwad.
After reconstitution, draw 1.0 ml from the vial into the syringe for the administration of 250 micrograms Betaferon.
Wara r- rikostituzzjoni, iġbed 1. 0ml mill- kunjett għal ġos- siringa għall- għoti ta ’ 250 mikrogramma ta ’ Betaferon.
• Inspection prior to use
• Spezzjoni qabel l- użu
Inspect the reconstituted product visually before use.
Ifli l- prodott rikostitwit qabel ma tużah.
The reconstituted product is colourless to light yellow and slightly opalescent to opalescent.
Il- prodott rikostitwit huwa bla kulur sa isfar ċar u kemmxejn opalexxenti sa opalexxenti.
Discard the product before use if it contains particulate matter or is discoloured.
Armi l- prodott qabel l- użu jekk ikun fih xi frak jew jekk jibdel il- kulur.
• Disposal
• Rimi
MARKETING AUTHORISATION NUMBERS
IN- NUMRI TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
30 November 1995 Date of last renewal:
30 ta ’ Novembru, 1995 Data ta ’ l- aħħar tiġdid:
31 January 2006
31 ta ’ Jannar, 2006
The titration period may be adjusted, if any significant adverse reaction occurs.
18 jiġi aġġustat.
A titration pack composed of four triple packs is available for the titration period and the patient ’ s initial treatment with Betaferon.
Hemm disponibbli pakkett ta ’ titrazzjoni magħmul minn erba ’ pakketti tripli għall- perijodu ta ’ titrazzjoni u l- perijodu tal- bidu ta ’ kura b’ Betaferon tal- pazjent.
This package meets the patient ’ s needs for the first 12 injections.
Dan il- pakkett fih dak kollu li l- pazjent għandu bżonn għall- ewwel 12- il injezzjoni.
The triple packs are highlighted in different colours (see section 6.5).
Il- pakketti tripli huma mmarkati b’ kuluri differenti (ara sezzjoni 6. 5).
187.5 microgram
187. 5 Mikrogrammi
19, 21, 23 et seqq.
19, 21, 23 et seqq.
250 microgram
250 mikrogramma
19 Gastrointestinal disorders
19 Disturbi fis- sistema nervuża
Betaferon should be administered with caution to patients with previous or current depressive disorders, in particular to those with antecedents of suicidal ideation (see section 4.3).
Betaferon għandu jingħata b’ attenzjoni lil pazjenti li kellhom jew għandhom disturbi depressivi, b’ mod partikolari dawk bi ħsibijiet ta ’ suwiċidju (ara sezzjoni 4. 3).
Depression and suicidal ideation are known to occur in increased frequency in the multiple sclerosis population and in association with interferon use.
Depressjoni u ħsibijiet ta ’ suwiċidju huwa magħruf li jseħħu bi frekwenza akbar fil- popolazzjoni bi sklerosi multipla u f’ assoċjazzjoni ma ’ l- użu ta ’ interferon.
Patients treated with Betaferon should be advised to immediately report any symptoms of depression and/ or suicidal ideation to their prescribing physician.
Pazjenti kkurati b’ Betaferon għandhom jingħataw parir biex jirrapportaw sintomi ta ’ depressjoni u/ jew ta ’ ħsibijiet ta ’ suwiċidju lit- tabib tagħhom minnufih.
In the absence of clinical evidence for liver damage and after normalisation of liver enzymes a reintroduction of therapy could be considered with appropriate follow-up of hepatic functions.
Għandu jkun hemm attenzjoni u sorveljanza mill- qrib għandha tiġi kkunsidrata meta Interferon beta jingħata lil pazjenti b’ insuffiċjenza severa tal- kliewi.
20 Renal and urinary disorders
20 Disturbi fil- qalb
Caution should be used and close monitoring considered when administering Interferon beta to patients with severe renal failure.
Għandu jintuża b’ attenzjoni ukoll f’ pazjenti li jbatu minn disturbi fil- qalb eżistenti minn qabel.
It should also be used with caution in patients who suffer from pre-existing cardiac disorders, Patients with pre-existing significant cardiac disease, such as congestive heart failure, coronary artery disease or arrhythmia, should be monitored for worsening of their cardiac condition, particularly during initiation of treatment with Betaferon.
Pazjenti li għandhom mard tal- qalb sinifikanti eżistenti minn qabel, bħal insuffiċjenza tal- qalb konġestiva, mard ta ’ l- arterji koronarji jew arritmija, għandhom jiġu sorveljati għall- aggravar tal- kundizzjoni kardijaka tagħhom, b’ mod partikolari waqt il- bidu tal- kura b’ Betaferon.
While Betaferon does not have any known direct-acting cardiac toxicity, symptoms of the flu-like syndrome associated with beta interferons may prove stressful to patients with pre-existing significant cardiac disease.
Waqt li Betaferon mhux magħruf li għandu xi tossiċità kardijaka li taġixxi direttament, sintomi tas - sindrome li tixbaħ lill- influwenza assoċjati ma ’ interferoni beta jistgħu jkunu ta ’ stress għall- pazjenti b’ mard tal- qalb sinifikanti li kien jeżisti minn qabel.
During the postmarketing period very rare reports have been received of worsening of cardiac status in patients with pre-existing significant cardiac disease temporarily associated with the initiation of Betaferon therapy.
Waqt il- perijodu ta ’ wara t- tqegħid fis- suq waslu rapporti rari ħafna ta ’ aggravar fl- istat kardijaku ta ’ pazjenti b’ mard tal- qalb sinifikanti li kien jeżisti minn qabel, temporanjament assoċjat ma ’ bidu ta ’ terapija b’ Betaferon.
− use an aseptic injection technique − rotate the injection sites with each dose.
− jużaw teknika ta ’ injezzjoni mhux settika − jibdlu l- lok ta ’ injezzjoni ma ’ kull doża
21 In the different controlled clinical trials, between 23% and 41% of the patients developed serum interferon beta-1b neutralising activity confirmed by at least two consecutive positive titres; of these patients, between 43% and 55% converted to a stable antibody negative status (based on two consecutive negative titres) during the subsequent observational period of the respective study.
Fil- provi kliniċi kkontrollati differenti, bejn 23% u 41% tal- pazjenti żviluppaw attività newtralizzanti għal interferon beta 1- b fis- serum li kienet ikkonfermata b’ minn ta ’ l- anqas żewġ titri konsekuttivi pożittivi; minn dawn il- pazjenti, bejn 43% u 55% qalbu għal stat negattiv ta ’ anti- korpi stabbli (skond żewġ titri negattivi konsekuttivi) matul il- perijodu ta ’ osservazzjoni sussegwenti ta ’ l- istudju rispettiv.
The development of neutralising activity is associated with a reduction in clinical efficacy only with regard to relapse activity.
21 L- iżvilupp ta ’ attività li tinnewtralizza hija assoċjata ma ’ tnaqqis fl- effikaċja klinika biss fil- qasam ma ’ l- attivita ta ’ rkadar.
In the study of patients with a single clinical event suggestive of multiple sclerosis, neutralising activity measured every 6 months was observed at least once in 32% (88) of the patients treated immediately with Betaferon; of these, 47% (41) returned to negative status over a 3 year period.
Fl- istudju ta ’ pazjenti b’ avveniment kliniku wieħed li jissuġġerixxi sklerożi multipla, l- attività newtralizzanti li kienet imkejla kull 6 xhur kienet osservata ta ’ l- inqas darba f’ 32% (88) tal- pazjenti kkurati mmedjatament b’ Betaferon; minn dawn, 47% (41) marru lura għal stat negattiv fuq perijodu ta ’ 3 snin.
22 • Women of child-bearing potential
• Nisa li jistgħu joħorġu tqal
If the patient becomes pregnant or plans to become pregnant while taking Betaferon, she should be informed of the potential hazards and discontinuation of therapy should be considered (see section 5.3).
F’ pazjenti b’ rata għolja ta ’
In patients with a high relapse rate before treatment started, the risk of a severe relapse following discontinuation of Betaferon in the event of pregnancy should be weighed against a possible increased risk of spontaneous abortion.
22 rkadar qabel inbdiet il- kura, ir- riskju ta ’ rkadar serju wara l- waqfien ta ’ Betaferon f’ każ ta ’ tqala għandu jitqies kontra l- possibbiltà ta ’ riskju ogħla ta ’ korriment spontanju
• Lactation
• Treddigħ
23 Table 1 (adverse events and laboratory abnormalities with incidence rates ≥ 10% and the respective percentages under placebo; significantly associated side effects < 10%).
23 Tabella 1 (avvenimenti avversi u anormalitajiet tal- laboratorju li seħħew b’ rata ta ’ ≥ 10% u l - perċentwali rispettivi għall- plaċebo; effetti sekondarji assoċjati b’ mod sinnifikattiv < 10%)
General disorders and administration site conditions Injection site reaction Λ § (various kinds) * °
Disturbi ġenerali u kundizzjonijiet ta ’ mnejn jingħata
52% (11%)
25 Sklerożi Multipla li Sklerożi Multipla Sistema tal- Klassifika
78% (20%)
Avveniment
89% (37%)
Sklerożi
85% (37%)
Progressiva
Injection site necrosis * ° & Λ
Tirkadi u Tbatti
1% (0%)
tal- Organi
5% (0%)
Wieħed li
5% (0%)
Sekondarja
Flu-like symptoms *° Fever Λ * °
jissuġġerixxi
61% (40%) 40% (13%)
(Studju fl -
43% (33%) 29% (24%)
Avveniment Avvers
52% (48%) 59% (41%)
Sklerożi
25 SystemOrganClass
Sekondarja
Single Event suggestive of
u Amerika ta ’ Fuq)
Secondary Secondary Progressive Progressive
Multipla
Relapsing Remitting
(Studju
Adverse Event and Laboratory Abnormalities
(BENEFIT) # Anormalitajiet tal- Laboratorju
Pain Chest pain ° Peripheral edema Asthenia * Chills Λ * ° Sweating * Malaise * × Laboratory abnormality Λ
Deni Λ * ° Uġigħ Uġigħ fis- sider ° Edima periferali Astenja * Kesħa Λ * ° Għaraq * Telqa *
26 Table 2 (reporting rates (very common ≥ 1/ 10, common ≥ 1/ 100 to < 1/ 10, uncommon ≥ 1/ 1,000 to < 1/ 100, rare ≥ 1/ 10,000 to < 1/ 1,000, very rare < 1/ 10,000) based on spontaneous adverse drug reaction reports).
26 Tabella 2 (rati bbażati fuq rapporti spontanji ta ’ reazzjonijiet avversi tal- mediċina (komuni ħafna ≥ 1/ 10, komuni ≥ 1/ 100 sa < 1/ 10, mhux komuni ≥ 1/ 1, 000 sa < 1/ 100, rari ≥ 1/ 10, 000 sa < 1/ 1, 000 u rari ħafna < 1/ 10, 000)
Skin and subcutaneous tissue disorders
27 Rari Mhux komuni Sistema tal -
27 System Organ Class
Klassifika tal -
28 Clinical trials:
28 demm, miġbura minn pazjenti kkurati b’ interferon beta- 1b.
Any disease other than multiple sclerosis that could better explain signs and symptoms of the patient had to be excluded.
29 setgħet tispjega aħjar is- sinjali u s- sintomi tal- pazjent kellha tiġi eskluża.
29 In the placebo-controlled phase, Betaferon delayed the progression from the first clinical event to clinically definite multiple sclerosis (CDMS) in a statistically significant and clinically meaningful manner, corresponding to a risk reduction of 47% (Hazard Ratio = 0.53, 95% confidence interval (0.39, 0.73), p < 0.0001).
0. 73), p < 0. 0001).
RR-MS, SP-MS and single clinical event suggestive of MS:
30 RR- MS, SP- MS u avveniment kliniku wieħed li jissuġġerixxi MS:
30 5.2 Pharmacokinetic properties
5. 2 Tagħrif farmakokinetiku
31 6.4 Special precautions for storage
6. 4 Prekawzjonijiet speċjali għall- ħażna
2.25 ml pre-filled syringe (type I glass) with 1.2 ml solvent.
Siringa mimlija għal lest ta ’ 2. 25 ml (ħġieġ tip I) b’ 1. 2ml ta ’ solvent.
Pack sizes − Pack with 5 single packs, each containing 1 vial with powder, 1 pre-filled syringe with solvent, 1 vial adapter with needle, 2 alcohol wipes or − Pack with 15 single packs, each containing 1 vial with powder, 1 pre-filled syringe with solvent, 1 vial adapter with needle, 2 alcohol wipes or − 3-month pack with 3x15 single packs, each containing 1 vial with powder, 1 pre-filled syringe with solvent, 1 vial adapter with needle, 2 alcohol wipes or − 3-month pack with 3x14 single packs, each containing 1 vial with powder, 1 pre-filled syringe with solvent, 1 vial adapter with needle, 2 alcohol wipes or − Titration pack for dose titration with 4 differently coloured and numbered triple packs:
Daqsijiet tal- pakkett: _ Pakkett b’ 5 pakketti singoli, kull wieħed fih kunjett bit- trab, siringa mimlija għal- lest bis - solvent, adattatur tal- kunjett b’ labra, 2 imsielaħ ta ’ l- alkoħol jew − Pakkett bi 15- il pakkett singolu, kull wieħed fih kunjett bit- trab, siringa mimlija għal- lest bis - solvent, adattatur tal- kunjett b’ labra, 2 imsielaħ ta ’ l- alkoħol jew − Pakkett għal 3 xhur bi 3x15- il pakkett singolu li kull wieħed fih kunjett 1 bit- trab, siringa mimlija għal- lest bis- solvent, adattatur tal- kunjett b’ labra, 2 imsielaħ ta ’ l- alkoħol jew − Pakkett għal 3 xhur bi 3x14- il pakkett singolu li kull wieħed fih kunjett 1 bit- trab, siringa mimlija għal- lest bis- solvent, adattatur tal- kunjett b’ labra, 2 imsielaħ ta ’ l- alkoħol jew − Pakkett ta ’ titrazzjoni għal titrazzjoni tad- doża b’ 4 pakketti tripli ta ’ kuluri u b’ numri differenti:
- yellow, with the number “ 1” (treatment days 1, 3 and 5; 0.25- ml syringe marking),
- isfar, bin- numru “ 1 ” (ġranet ta ’ kura 1, 3 u 5; siringa b’ marka f’ 0. 25 - ml),
- red, with number “ 2” (treatment days 7, 9 and 11; 0.5- ml syringe marking)
- aħmar, bin- numru “ 2 ” (ġranet ta ’ kura 7, 9 u 11; siringa b’ marka f’ 0. 5 - ml)
- green, with number “ 3” (treatment days 13, 15 and 17; 0.75- ml syringe marking)
- aħdar, bin- numru “ 3 ” (ġranet ta ’ kura 13, 15 u 17; siringa b’ marka f’ 0. 75 - ml)
- blue, with number “ 4” (treatment days 19, 21 and 23; 0.25, 0.5, 0.75 and 1-ml syringe
- blu, bin- numru “ 4 ” (ġranet ta ’ kura 19, 21 u 23; siringa b’ marka f’ 0. 25, 0. 5, 0. 75 u 1- ml)
marking) Each triple pack contains 3 vials with powder, 3 pre-filled syringes with solvent, 3 vial adapters with pre-attached needle and 6 alcohol wipes for skin and vial cleaning.
− Kull pakkett triplu fih 3 kunjetti bi trab, 3 siringi mimlija għall- lest b’ solvent, 3 adatturi għall - kunjett b’ labra mwaħħla minn qabel u 6 imsielaħ ta ’ l- alkoħol biex tnaddaf il- ġilda u l- kunjett.
To reconstitute lyophilised interferon beta-1b for injection, connect the vial adapter with attached needle on the vial.
Sabiex tirrikostitwixxi interferon beta- 1b lajofiliżat għall- injezzjoni, qabbad l- adattatur tal- kunjett bil - labra mwaħħla mal- kunjett.
Connect the pre-filled syringe with solvent to the vial adapter and inject the 1.2 ml of the solvent (sodium chloride solution, 5.4 mg/ ml (0.54% w/ v)) into the Betaferon vial.
Qabbad is- siringa mimlija għal- lest bis- solvent ma ’ l- adattaur tal- kunjett u injetta 1. 2 ml tas- solvent (soluzzjoni ta ’ sodium chloride, 5. 4mg/ ml (0. 54% w/ v)) fil- kunjett ta ’ Betaferon.
Betaferon may also be administered with a suitable autoinjector.
Għat- titrazzjoni tad- doża fil- bidu tal- kura iġbed il- volum rispettiv kif imniżżel f’ sezzjoni 4. 2 Pożoloġija u metodu ta ’ kif għandu jingħata.
The reconstituted product is colourless to light yellow and slightly opalescent to opalescent.
Qabel ma ’ tieħu l- injezzjoni, aqla ’ l- kunjett bl- adattaur tal- kunjett minn mas- siringa mimlija għal- lest.
Discard the product before use if it contains particulate matter or is discoloured.
Betaferon jista ’ jingħata wkoll b’ awto- injettatur xieraq.
32 • Disposal
32 • Spezzjoni qabel l- użu
Any unused product or waste material should be disposed of in accordance with local requirements.
Il- prodott rikostitwit huwa bla kulur sa isfar ċar u kemmxejn opalexxenti sa opalexxenti.
MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
MANIFATTURI TAS- SUSTANZA BIJOLOĠIKA ATTIVA U DETENTUR TA ’ L- AWTORIZZAZZJONI TAL- MANIFATTURA RESPONSABBLI GĦALL- ĦRUĠ TAL- LOTT B.
Boehringer Ingelheim Austria, Dr. -Boehringer-Gasse 5-11, A-1121 Vienna, Austria
Boehringer Ingelheim Awstrija, Dr. - Boehringer- Gasse 5- 11, A- 1121 Vienna, l- Awstrija
5650 Hollis Street, Emeryville, CA 94608, USA
5650 Hollis Street, Emeryville, CA 94608, L- Istati Uniti
Bayer Schering Pharma AG D-13342 Berlin Germany
Isem u indirizz tal- manifattur responsabbli għall- ħruġ tal- lott Bayer Schering Pharma AG D- 13342 Berlin Il- Ġermanja
35 ANNEX III
35 ANNEX III
37 PARTICULARS TO APPEAR ON THE OUTER PACKAGING (15 VIALs / 15 PRE-FILLED SYRINGES)
37 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA (15- IL KUNJETT / 15- IL SIRINGA MIMLIJA GĦAL- LEST)
1 ml contains250 microgram (8 million IU) Interferon beta-1b when reconstituted.
1 ml fih 250 mikrogramma (8 miljun IU) Interferon beta- 1b meta rikostitwit.
15 vials with powder and 15 pre-filled syringes with solvent:
15- il kunjett bi trab u 15- il siringa mimlija għal- lest b’ solvent:
After reconstitution 1 ml contains 250 microgram (8 million IU)Interferon beta-1b*
Wara r- rikostituzzjoni 1ml fih 250 mikrogramma (8 miljun IU) ta ’ Interferon beta- 1b *
1 pre-filled syringe with 1.2 ml solvent for reconstitution contains: sodium chloride solution 5.4 mg/ ml.
Siringa waħda mimlija għal- lest b’ 1. 2ml ta ’ solvent għar- rikostituzzjoni fiha: soluzzjoni ta ’ sodium chloride ta ’ 5. 4mg/ ml.
Multipack comprising 15 single packs, each containing:
Multipakk li jikkonsisti minn 15- il pakkett singolu, li kull wieħed fih:
After reconstitution 1 ml contains 250 microgram (8 million IU) Interferon beta-1b*.
Wara r- rikostituzzjoni 1ml fih 250 mikrogramma (8 miljun IU) ta ’ Interferon beta- 1b *.
1 pre-filled syringe with 1.2 ml solvent for reconstitution contains sodium chloride solution 5.4 mg/ ml.
Siringa waħda mimlija għal- lest b’ 1. 2ml ta ’ solvent għar- rikostituzzjoni fiha: soluzzjoni ta ’ sodium chloride ta ’ 5. 4mg/ ml.
For subcutaneous injection after reconstitution with 1.2 ml of solvent.
Għall- injezzjoni minn taħt il- ġilda wara rikostituzzjoni b’ 1. 2ml ta ’ solvent.
41 PARTICULARS TO APPEAR ON THE OUTER PACKAGING (5 VIALs / 5 PRE-FILLED SYRINGES (1.2 ml))
41 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA (5 KUNJETTI / 5 SIRINGI MIMLIJA GĦAL- LEST (1. 2ml))
5 vials with powder and 5 pre-filled syringes with solvent
5 kunjetti bi trab u 5 siringi mimlija għal- lest b’ solvent:
1 vial with powder for solution for injection contains 300 microgram (9.6 million IU).
Kunjett wieħed (bi trab għal soluzzjoni għall- injezzjoni fih 300 mikrogramma (9. 6 miljun IU).