qanastek/EMEA-V3 huggingface dataset:
Thyroid dysfunction most often presenting as hypothyroidism or hyperthyroidism
Disfunzjoni tat - tirojde l- iktar bħala ipotirojdiżmu jew ipertirojdiżmu
Depression, insomnia
Depressjoni, insomnia
Suicide attempt
Attentat ta ’ suwiċidju
Seizures
Seizures
Diarrhoea, vomiting, nausea
Dijarea, rimettar, nawsea.
Pruritus, rash, erythematous rash, maculo-papular rash
ħakk, raxx, raxx erythematus, raxx makulari bl- infafet
Musculoskeletal and connective tissue disorders
6 Sistema tal- klassifika tal- organi
Myalgia, arthralgia
Komuni ħafna
General disorders and administration site conditions
Komuni
Injection site inflammation, injection site reaction, influenza-like symptoms
Mhux komuni
Injection site pain, fatigue, rigors, fever
Mhux magħrufa *
Injection site necrosis, injection site mass
Disturbi muskolu - skeletrali u tal - connective tissue
Investigations
majalġja, artralġja
Asymptomatic transaminase increase
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata
Respiratory, thoracic and mediastinal disorders
Infjammazjoni fis - sit ta ’ injezzjoni, reazzjoni fis- sit ta ’ injezzjoni, sintomi bħal ta ’ l- influenza
Dyspnoea
Uġigħ fis- sit ta ’ injezzjoni, g] eja, tertir, deni
Immune system disorders Vascular disorders
Nekrozi fis- sit ta ’ injezzjoni, massa fis- sit ta ’ injezzjoni
Anaphylactic reactions Thromboembolic events
Investigazzjonijiet Disturbi respiratorji, toraċiċi u medjastinali Disturbi fis- sistema immuni Disturbi vaskulari Disturbi fil- fwied u fil - marrara
Hepatobiliary disorders
żdieda asimtomatika tat - transaminase
Hepatitis with or without icterus
Qtugħ ta ’ nifs Reazzjonijiet anafilattiċi eventi tromboemboliċi Epatite b’ ikterus jew migħajr
6 *Adverse reactions identified during post marketing surveillance (frequency not known)
* Effetti mhux mixtieqa identifikati matul studju wara l- bejgħ (frekwenza mhux magħrufa):
Interferon beta has a potential for causing severe liver injury.
Interferon beta għandu l- potenzjal li joħloq periklu għall- fwied.
The mechanism for the rare symptomatic hepatic dysfunction is not known.
Il- mekkaniżmu għall- funzjoni ħażina epatika rari mhux magħruf.
The majority of the cases of severe liver injury occurred within the first six months of treatment.
Il- maġġoranza tal- każi ta ’ ħsara tal- fwied dehret fl- ewwel sitt xhur tal - kura.
No specific risk factors have been identified.
L- ebda fatturi ta ’ riskji speċifiċi ma ġew identifikati.
Treatment with Rebif should be stopped if icterus or other clinical symptoms of liver dysfunction appear (see section 4.4).
Il- kura b’ Rebif għandu titwaqqaf jekk ikterus jew sintomi oħra ta ’ funzjoni ħazina tal- fwied jinħassu (ara Sezzjoni 4. 4)
The administration of interferons has been associated with anorexia, dizziness, anxiety, arythmias, vasodilation and palpitation, menorrhagia and metrorrhagia.
It- teħid ta ’ interferons ġie assoċjat ma ’ anoressja, sturdament, anzjetà, arythmias, twessigħ ta ’ l- arterji u taħbit qawwi tal- qalb, menorraġja u metrorraġja.
An increased formation of auto-antibodies may occur during treatment with interferon beta.
Formazzjoni għola ta ’ awtoantikorpi tista ’ tidher matul il- kura bl- interferon beta.
In case of overdose, patients should be hospitalised for observation and appropriate supportive treatment should be given.
F’ każ ta ’ doża eċċessiva, il- pazjenti għandhom jittieħdu l- isptar għal osservazzjoni u l- kura meħtieġa għandha tingħata.
Immunostimulants, Interferons, ATC code:
Immunostimulanti, Interferons, Kodiċi ATC:
L03AB07.
LO3AB07.
Interferons (IFNs) are a group of endogenous glycoproteins endowed with immunomodulatory, antiviral and antiproliferative properties.
Interferons (IFNs) huma grupp ta ’ glikoproteini endoġeni li għandhom effetti immunodulatorji, kontra l- viruses u antiproliferattivi.
Rebif (interferon beta-1a) shares the same amino acid sequence with endogenous human interferon beta.
Rebif (interferon beta- 1a) jaqsam l- istess sekwenza amino aċida ma ’ interferon beta uman endoġenu.
It is produced in mammalian cells (Chinese hamster ovary) and is therefore glycosylated like the natural protein.
Jiġi prodotti fiċ- ċelluli mammaljani (ovarju tal- ħamster Ċiniż) u hu għalhekk glikosilizzat bħal proteina naturali.
The precise mechanism of action of Rebif in multiple sclerosis is still under investigation.
Il- mekkaniżmu prċiż ta ’ azzjoni ta ’ Rebif fl- isklerożi multipla għadu qiegħed jiġi studjat.
The safety and efficacy of Rebif has been evaluated in patients with relapsing-remitting multiple sclerosis at doses ranging from 11 to 44 micrograms (3-12 million IU), administered subcutaneously three times per week.
7 Is- sigurtà u l- effikaċja ta ’ Rebif ġiet ippruvata f’ pazjenti li jbatu minn attakki ripetuti ta ’ sklerożi multipla f’ dożi li jvarjaw minn 11 sa 44 mikrogramma (3- 12 – il miljun IU), mogħtija minn taħt il - ġilda tliet darbiet fil- ġimgħa.
At licensed posology, Rebif 22 micrograms has been demonstrated to decrease the incidence (approximately 30% over 2 years) and severity of clinical relapses in patients with at least 2 exacerbations in the previous 2 years and with an EDSS of 0-5.0 at entry.
F’ posoloġija liċenzjata, Rebif 22 mikrogramma instab li jnaqqas l - inċidenza (bejn wieħed u ieħor bi 30% fi żmien sentejn) u s- severità ta ’ attakki ripetuti f’ pazjienti bi tnejn jew iżjed exaserbazzjonijiet fis- sentejn ta ’ qabel u bi EDSS ta ’ 0- 5. 0 meta beda l- kura.
The proportion of patients with disability progression, as defined by at least one point increase in EDSS confirmed three months later, was reduced from 39% (placebo) to 30% (Rebif 22 micrograms).
Il - proporzjon ta ’ pazjenti bi progressjoni ta ’ diżabilità, hekk kif definiti b’ mill- anqas punt aktar żieda fl - EDSS konfermat tliet xhur wara, naqas minn 39% (placebo) sa 27% (Rebif 22 mikrogramma).
Over 4 years, the reduction in the mean exacerbation rate was 22% in patients treated with Rebif 22 micrograms, and 29% in patients treated with Rebif 44 micrograms group compared with a group of patients treated with placebo for 2 years and then either Rebif 22 or Rebif 44 micrograms for 2 years.
Fi żmien erba ’ snin, in- nuqqas tar- rata bejn wieħed u ieħor ta ’ iggravar kienet 22% f’ pazjenti kkurati b’ Rebif 22 mikrogramma, u 29% f’ pazjenti kkurati b’ Rebif 44 mikrogramma kkomparati ma ’ grupp ta ’ pazjenti ikkurati bi plaċebo għal sentejn u mbagħad jew b’ Rebif 22 jew b’ Rebif 44 mikrogramma għal sentejn.
In a 3-year study in patients with secondary progressive multiple sclerosis (EDSS 3-6.5) with evidence of clinical progression in the preceding two years and who had not experienced relapses in the preceding 8 weeks, Rebif had no significant effect on progression of disability, but relapse rate was reduced by approximately 30%.
Fi studju ta ’ tliet snin f’ pazjenti li jbatu minn sklerożi multipla sekondarja progressiva (EDSS 3- 6. 5) b’ evidenza ta ’ progress kliniku fis- sentejn ta ’ qabel u li ma kellhomx relaps fit- tmien ġimgħat ta ’ qabel, Rebif ma kellu l- ebda effett sinjifikattiv fuq il- progress tad- diżabilità, iżda r- rata ta ’ attakki ripetuti tnaqqset bi 30%.
If the patient population was divided into 2 subgroups (those with and those without relapses in the 2-year period prior to study entry), there was no effect on disability in patients without relapses, but in patients with relapses, the proportion with progression in disability at the end of the study was reduced from 70% (placebo) to 57% (Rebif 22 micrograms and 44 micrograms combined).
Jekk il- popolazzjoni tal- pazjenti kienet maqsuma f’ żewġ gruppi (dawk b’ attakki ripetuti matul il- perjodu ta ’ sentejn qabel ma daħlu għall- istudju u dawk mingħajr), ma kien hemm l- ebda effett fuq pazjenti li ma kellhomx attakki ripetuti, iżda f’ pazjenti li kellhom attakki ripetuti, il- proporzjon mal- progress fid- diżabilità fl- aħħar ta ’ l- istudju naqas minn 70% (plaċebo) sa ’ 57% (Rebif 22 mikrogrammi u 44 mikrogrammi flimkien).
These results obtained in a subgroup of patients a posteriori should be interpreted cautiously.
Dawn ir- riżultati miksuba fi grupp ta ’ pazjenti a posteriori għandhom ikunu interpretati bil- qies.
Rebif has not yet been investigated in patients with primary progressive multiple sclerosis, and should not be used in such patients.
Rebif s’ issa ma kienx studjat f’ pazjenti li jbatu minn sklerożi multipla progressiva primarja, u m’ għandux jintuża fuq dawn il- pazjenti.
In healthy volunteers after intravenous administration, interferon beta-1a exhibits a sharp multi-exponential decline, with serum levels proportional to the dose.
F’ persuni f’ saħħithom wara għoti mill- vina, interferon beta- 1a juri nuqqas serju multi esponenzjali, b’ livelli ta ’ serum proporzjonali għad- doża.
The initial half-life is in the order of minutes and the terminal half-life is several hours, with the possible presence of a deep compartment.
L- ewwel half- life tidher f’ ħin ta ’ minuti u l- aħħar half- life hi ta ’ diversi sigħat, bil- possibilità ta ’ preżenza ta ’ kompartiment fil- fond.
When administered by the subcutaneous or intramuscular routes, serum levels of interferon beta remain low, but are still measurable up to 12 to 24 hours post-dose.
Meta mogħtija minn taħt il - ġilda jew mill- muskolu, il- livelli ta ’ serum ta ’ interferon beta jibqgħu baxxi, iżda jibqgħu jitkejlu minn 12 sa ’ 24 siegħa wara d- doża.
Subcutaneous and intramuscular administrations of Rebif produce equivalent exposure to interferon beta.
Għoti ta ’ Rebif minn taħt il- ġilda jew mill- muskolu għandhom l- istess espożizzjoni għall- interferon beta.
Following a single 60 microgram dose, the maximum peak concentration, as measured by immunoassay, is around 6 to 10 IU/ ml, occurring on average around 3 hours after the dose.
Wara doża waħda ta ’ 60 mikrogrammi, il- quċċata ta ’ konċentrazzjoni massima, hekk kif imkejla f’ test ta ’ immunità, hi ta ’ madwar 6 sa 10 IU/ ml, li tidher is- soltu madwar tliet sigħat wara d- doża.
After subcutaneous administration at the same dose repeated every 48 hours for 4 doses, a moderate accumulation occurs (about 2.5 x for AUC).
Wara għoti minn taħt il- ġilda ta ’ l- istess doża ripetuta kull 48 siegħa għal 4 dożi, tidher akkumulazzjoni moderata (madwar 2. 5 x għal AUC).
Regardless of the route of dosing, pronounced pharmacodynamic changes are associated with the administration of Rebif.
Ikun xi jkun il- metodu kif tingħata d- doża, bidliet farmakodinamiċi kbar huma assoċjati mat- teħid ta ’ Rebif.
After a single dose, intracellular and serum activity of 2-5A synthetase and serum concentrations of beta-2 microglobulin and neopterin increase within 24 hours, and start to decline within 2 days.
Wara doża waħda, attività intraċellulari u tas- serum ta ’ 2- 5 A sintetaċi u konċentrazzjonijiet tas - serum ta ’ beta- 2 mikroglobulina u neopterina jogħlew fi żmien 24 siegħa, u jibdew jonqsu fi żmien jumejn.
Intramuscular and subcutaneous administrations produce fully superimposable responses.
Teħid minn taħt il- ġilda u mill- muskolu jipproduċi l- istess effetti.
After repeated subcutaneous administration every 48 hours for 4 doses, these biological responses remain elevated, with no signs of tolerance development.
Wara teħid ripetut minn taħt il- ġilda kull 48 siegħa għal 4 dożi, dawn ir- risposti bioloġiċi jibqgħu għoljin, mingħajr l- ebda sinjal ta ’ żvilupp ta ’ tolleranza.
Interferon beta-1a is mainly metabolised and excreted by the liver and the kidneys.
Interferon beta- 1a hu metabolizzat u mormi mill- fwied u l- kliewi.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated-dose toxicity, and genotoxicity.
Informazzjoni mhux klinika, magħmula fuq studji konvenzjonali ta ’ sigurtà farmakoloġika, effett tossiku minn dożi ripetuti, effett tossiku fuq il- ġeni.
Rebif has not been investigated for carcinogenicity.
Rebif ma kienx studjat għal karċinoġeniċità.
A study on embryo/ foetal toxicity in monkeys showed no evidence of reproductive disturbances.
Studju ta ’ tossiċità fuq l- embriju/ il- fetu fix- xadini ma weriex evidenza ta ’ probemi ta ’ riproduttività.
Based on observations with other alpha and beta interferons, an increased risk of abortions cannot be excluded.
Ibbażat fuq osservazzjonijiet b’ interferons alfa u beta oħrajn, riskju għola ta ’ kurramenti ma jistax jiġi eskluż.
No information is available on the effects of the interferon beta-1a on male fertility.
L- ebda informazzjoni ma tinstab fuq l- effetti ta ’ interferon beta- 1a fuq il- fertilità maskili.
Mannitol Poloxamer 188 L-methionine Benzyl alcohol Sodium acetate Acetic acid for pH adjustment Sodium hydroxide for pH adjustment Water for injections
Mannitol Poloxamer 188 L- methionine Benzyl alkohol Sodju aċetate Aċidu aċitiku għal aġġustament tal- pH Idrossidu tas- sodju għal aġġustament tal- pH Ilma għall- injezzjonijiet
Store in a refrigerator (2°C – 8°C) away from the cooling element.
Aħżen fi friġġ (2°C – 8°C), tħallix qrib il- freezer.
One ml type 1glass syringe, with a stainless steel needle, containing 0.5 ml solution.
Siringa waħda ta ’ 1ml tal- ħġieġ tat- tipI, b’ labra magħmulha minn azzar li ma jittebbax, bi 0. 5ml ta ’ soluzzjoni.
Rebif 22 micrograms is available as a package of 1, 3 or 12 syringes.
Rebif 22 mikrogramma jinstab f’ pakketti ta ’ 1, 3 u 12 siringi.
The solution for injection in a pre-filled syringe is ready for use.
It- taħlita għall- injezzjoni hija f’ siringa mimlija lesta għall- użu.
It may also be administered with a suitable auto-injector.
Tista ’ tingħata wkoll permezz ta ’ awtoinjettur apposta.
Only clear to opalescent solution without particles should be used and without visible signs of deterioration.
Tista tintuża biss soluzzjoni li hija ċara għal opalexxenti mingħajr frak u mingħajr sinjali visibbli ta ’ deterjorament.
Serono Europe Limited 56, Marsh Wall London E14 9TP United Kingdom
Serono Europe Limited 56, Marsh Wall London E14 9TP Ir- Renju Unit
Date of first authorization:
Data ta ’ l- ewwel awtoriazzazzjoni:
4th May 1998 Date of first renewal:
4 Mejju 1998 Data ta ’ l- ewwel tigdid:
4th May 2003 Date of latest renewal:
Data ta ’ l- aħħar tiġdid ta ’ l- awtorizzazzjoni:
20th May 2008
20 ta ’ Mejju 2008
Rebif 44 micrograms solution for injection in pre-filled syringe
Rebif 44 mikrogrammi – soluzzjoni għall- injezzjoni b’ siringa mimlija għal- lest
Each pre-filled syringe (0.5 ml) contains 44 micrograms (12 MIU*) of interferon beta-1a**.
Kull siringa mimlija lesta (0. 5 ml) fiha 22 mikrogrammi (6 MIU *) ta ’ interferon beta- 1a **.
* Million International Units, measured by cytopathic effect (CPE) bioassay against the in house IFN beta-1a standard which is calibrated against the current international NIH standard (GB-23-902-531). ** produced in Chinese hamster ovary Cells (CHO-K1) by recombinant DNA technology.
* Miljun Unità Internazzjonali meqjus permezz ta ’ test tal- effett kitopatiku (EKP) mqabbel ma ’ l - istandard IFN beta- 1a li jsir fil- fabbrika li jinstab wara li jitqabbel ma ’ l- istandard kurrenti internazzjonali NIH (GB- 23- 902- 531). ** magħmulin fiċ- Ċelluli ta ’ l- ovarju tal- ħamster Ċiniz (CHO- K1) li għandhom materjal ġenetiku mibdul.
Efficacy has not been demonstrated in patients with secondary progressive multiple sclerosis without ongoing relapsing activity (see section 5.1).
(ara sezzjoni 5. 1).
Method of administration Prior to injection and for an additional 24 hours after each injection, an antipyretic analgesic is advised to decrease flu-like symptoms associated with Rebif administration.
11 Qabel l- injezzjoni u għal 24- il siegħa wara kull injezzjoni, huwa rakkomandat li jingħata analġesiku li huwa ukoll kontra d- deni sabiex jitnaqqsu is- sintomi li jixbħu l- influenza li huma assoċjati ma ’ l - amministrazzjoni ta ’ Rebif.
10 At the present time, it is not known for how long patients should be treated.
S’ issa għadu mhux magħruf għal kemm tul ta ’ żmien il- pazjenti għandhom ikunu ikkurati.
It is recommended that patients should be evaluated at least every second year in the 4-year period after initiation of treatment with Rebif and a decision for longer term treatment should then be made on an individual basis by the treating
Hu rakkomandat li l- pazjenti għandhom ikunu eżaminati mill- anqas matul it- tieni sena tal- perjodu ta ’ erba ’ snin wara li tkun inbdiet il- kura b’ Rebif u d- deċiżjoni sabiex titkompla l- kura għandha ssir fuq bażi individwali mit- tabib li jikkura.
However, limited published data suggest that the safety profile in adolescents from 12 to 16 years of age receiving Rebif 22 micrograms subcutaneous three times per week is similar to that seen in adults.
Iżda, inforamazzjoni limitata li ġie ippublikat juri li l- profil tas- sigurta ’ fl- adolexxenti ta ’ l- eta ’ ta ’ bejn 12 u 16- il sena li ħadu Rebif 22 mikrogrammi taħt il- ġilda tliet darbiet fil- ġimgħa kien simli bħal dak fl- adulti.
• Initiation of treatment in pregnancy (see section 4.6). • Hypersensitivity to natural or recombinant interferon-β, or to any excipients. • Current severe depression and/ or suicidal ideation (see sections 4.4 and 4.8).
• Inizjazzjoni tal- kura fin- nisa tqal (ara sezzjoni 4. 6). • Ipersensibilita ’ għal interferon beta naturali jew rikombinat, jew xi sustanzi mhux attivi. • Depressjoni u/ jew b’ ideat ta ’ suwiċidju (ara sezzjonijiet 4. 4 u 4. 8).
Symptoms of the flu-like syndrome associated with interferon beta-1a therapy may prove stressful to patients with cardiac conditions.
Sintomi ta ’ sindromu li jixbah lill- influwenza assoċjati mat- terapija bl - interferon beta- 1a jistgħu jkunu ta ’ stress fuq pazjenti li jbatu bil- qalb.
If the patient experiences any break in the skin, which may be associated with swelling or drainage of fluid from the injection site, the patient should be advised to consult with their physician before continuing injections with Rebif.
12 Jekk fil- pazjent jidher xi qsim fil- ġilda, li jista ’ jkun assoċjat ma ’ nefħa jew telf ta ’ likwidu mis- sit ta ’ l- injezzjoni, il- pazjent għandu jkun mgħarraf sabiex jikkonsulta mat- tabib qabel ikompli l - injezzjonijiet b’ Rebif.
11 In clinical trials with Rebif, asymptomatic elevations of hepatic transaminases (particularly alanine aminotransferase (ALT)) were common and 1-3% of patients developed elevations of hepatic transaminases above 5 times the upper limit of normal (ULN).
Fi provi kliniċi b’ Rebif, elevazzjonijiet mingħajr sintomi ta ’ transminases epatika (b’ mod partikolari ALT) kienu komuni u bejn 1 u 3% tal- pazjenti żviluppaw elevazzjoni ta ’ transminases epatika aktar minn 5 darbiet l- għola limitu normali (ULN- upper limit of normal).
Treatment with Rebif should be stopped if icterus or other clinical symptoms of liver dysfunction appear (see section 4.8).
Il- kura b’ Rebif għandha titwaqqaf jekk jidhru ikterus jew sintomi oħra kliniċi ta ’ funzjoni ħażina tal - fwied (ara sezzjoni 4. 8).
These should be more frequent when initiating Rebif 44 micrograms.
Għaldaqstant, flimkien ma ’ testijiet tal- laboratorju ġeneralment mitluba sabiex tinstab l- isklerożi multipla fuq il- pazjenti, u flimkien ma ’ testijiet ta ’ enżimi tal- fwied, l- għadd komplut u differenzjat ta ’ ċelluli tad- demm u l - għadd ta ’ platelets huma wkoll rakkomandati ta’ spis (1, 3 u 6 xur) wara l- introduzzjoni tal- kura ta ’ Rebif u imbagħad perjodikament jekk ma hemx sintomi kliniċi.
Clinical data suggest that after 24 to 48 months of treatment with Rebif 44 micrograms, approximately 13 to 14% of patients develop persistent serum antibodies to interferon beta-1a.
Informazzjoni klinika tissuġġerixxi li wara 24 sa 28 xhar ta ’ kura b’ Rebif 22 mikrogramma, madwar 24% tal- pazjenti jiżviluppaw antikorpi persistenti fis serum għal interferon beta- 1a.
The use of various assays to detect serum antibodies and differing definitions of antibody positivity limits the ability to compare antigenicity among different products.
L- użu ta ’ testijiet varji sabiex jinstabu l- antikorpi tas- serum u sabiex tinsab id- differenza ta ’ definizzjonijiet ta ’ posittivita ’ ta ’ antikorpi tillimita l- abilità li tiġi kkumparata l- anti[ ġniċita ’ bejn prodotti differenti.
4.5 Interaction with other medicinal products and other forms of interaction
13 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
No interaction studies have been performed with interferon beta-1a in humans.
Ma sarux studji dwar l- effett ta ’ mediċini jew ta ’ affarijiet oħra fuq l- effett farmaċewtiku ta ’ interferon beta- 1a fil- bnedmin.
12 medicinal products that have a narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance, e. g. antiepileptics and some classes of antidepressants.
Għandha ssir attenzjoni meta jingħata Rebif flimkien ma ’ prodotti mediċinali oħra li għandhom indiċi terapewtiku qasir u li jiddependu ħafna fuq is- sistema hepatic cytochrome P450 sabiex jitnaddfu eż: anti- epilettiċi u xi tipi ta ’ antidipressivi.
The interaction of Rebif with corticosteroids or adrenocorticotropic hormone (ACTH) has not been studied systematically.
L- effetti ta ’ Rebif flimkien ma ’ corticosteroids jew l- ormon adrenokortikotropiku (ACTH) ma ġewx studjati sistematikament.
Therefore initiation of treatment is contraindicated during pregnancy (see section 4.3).
Għalhekk l- inizjazzjoni tal- kura muwiex indikat waqt it- tqala (ara sezzjoni 4. 3).
In patients with a high relapse rate before treatment has started, the risk of a severe relapse following discontinuation of Rebif in the event of pregnancy should be weighed against a possible increased risk of spontaneous abortion.
F’ pazjienti bi rata għolja ta ’ marda li tirkadi qabel li nbeda l- kura, huwa importanti li wieħed jeżaminah ir- riskju ta ’ relapse severa wara li jitwaqqaf Rebif f’ kaz ta ’ tqala, kontra possibilta ’ ta ’ riskju akbar ta ’ abbort spontanju.
Approximately 70% of patients treated with Rebif can expect to experience the typical interferon flu-like syndrome within the first six months after starting treatment.
Dawn is- sintomi bħal ta ’ l- influenza huma aktar prominenti fil - bidu tal- kura u jitnaqqsu fil- frekwenza meta il- kura titkompla. Madwar 70% tal- pazjenti kkurati b’ Rebif jistgħu jistennew li jħossu s- sindromu li jixbah lill- influwenza fl- ewwel sitt xhur wara li jibew il- kura.
The adverse reactions reported below are classified according to frequency of occurrence as follows:
14 L- effetti mhux mixtieqa li jissemmew hawn taħt huma klassifikati skond il- frekwenza ta ’ kif jidhru kif ġej:
Very Common Common Uncommon Rare Very rare
Komuni ħafna Komuni Mhux komuni Rari Rari ħafna Mhux magħrufa
≥ 1/ 10 ≥ 1/ 100 to < 1/ 10 ≥ 1/ 1,000 to < 1/ 100 ≥ 1/ 10,000 to < 1/ 1,000 < 1/ 10,000
≥ 1/ 10 ≥1/ 100 sa < 1/ 10 ≥1/ 1, 000 sa < 1/ 100 ≥1/ 10, 000 sa < 1/ 1, 000 < 1/ 10, 000 Ma tistax tittieħed stima mid - dejta disponibbli
13 The data presented is obtained from pooled clinical studies in multiple sclerosis (placebo=824 patients; Rebif 22 micrograms three times per week (TIW)=398 patients; Rebif 44 micrograms TIW=727 patients) and shows the frequency of adverse reactions observed at six months (excess over placebo).
L- informazzjoni ppreżentata hi miksuba minn studji kliniċi fi sklerożi multipla (plaċebo=824 pazjienti; Rebif 22 mikrogrammi TIW=398 pazjienti; Rebif 44 mikrogrammi tlitt darbiet fil- ġimgħa (TIW) =727 pazjienti) u turi l- frekwenza ta ’ l- effetti mhux mixtieqa f’ sitt xhur (żieda fuq plaċebo).
Angioedema, urticaria, erythema multiforme, erythema multiforme-like skin reactions, Stevens-Johnson syndrome, hair loss
anġjoedema, urtikarja, eritema multiformi, reazzjonijiet tal - ġilda li jixbhu lill - eritema multiformi, sindromu Stevens - Johnson, twaqqigħ tax- xagħar
Myalgia, arthralgia
Majalġja, artralġja
General disorders and administration site conditions
15
Injection site inflammation, injection site reaction, influenza-like symptoms
Sistema tal- klassifika tal- organi
Injection site pain, fatigue, rigors, fever
Komuni ħafna
Injection site necrosis, injection site mass
Mhux komuni
Investigations
Mhux magħrufa *
Asymptomatic transaminase increase
Disturbi ġenerali u
Respiratory, thoracic and mediastinal disorders
Infjammazjoni fis -
Dyspnoea
Uġigħ fis- sit
Immune system disorders
Nekrozi fis- sit ta ’
Anaphylactic reactions
kondizzjonijiet ta '
14 System Organ Class Vascular disorders
ta ’ injezzjoni, ta ’ injezzjoni,
Very common
injezzjoni, massa
Common
mnejn jingħata
Uncommon
għeja, tertir, deni
Not known* Thromboembolic events
fis- sit ta ’ injezzjoni
Hepatitis with or without icterus
Qtugħ ta ’ nifs Reazzjonijiet anafilattiċi Eventi tromboemboliċi Epatite b’ ikterus jew migħajr
*Adverse reactions identified during post marketing surveillance (frequency not known)
* Effetti mhux mixtieqa identifikati matul studju wara l- bejgħ (frekwenza mhux magħrufa):
Treatment with Rebif should be stopped if icterus or other clinical symptoms of liver dysfunction appear (see section 4.4).
Il- kura b’ Rebif għandu titwaqqaf jekk ikterus jew sintomi oħra ta ’ funzjoni ħazina tal- fwied jinħassu (ara sezzjoni 4. 4)
In case of overdose, patients should be hospitalised for observation and appropriate supportive treatment should be given.
F’ każ ta ’ doża eċċessiva, il- pazjenti għandhom jittieħdu l- isptar għal osservazzjoni u l- kura meħtieġa għandhau tingħata.
Immunostimulants, Interferons, ATC code:
Immunostimulanti, interferon, Kodiċi ATC:
Rebif (interferon beta-1a) shares the same amino acid sequence with endogenous human interferon beta.
Rebif (interferon beta- 1a) jaqsam l- istess sekwenza nattiva amino aċida ma ’ interferon beta uman endoġenu.
The precise mechanism of action of Rebif in multiple sclerosis is still under investigation.
Il- mekkaniżmu preċiż ta ’ azzjoni ta ’ Rebif fl- isklerożi multipla għadu qiegħed jiġi studjat.
The safety and efficacy of Rebif has been evaluated in patients with relapsing-remitting multiple sclerosis at doses ranging from 11 to 44 micrograms (3-12 million IU), administered subcutaneously three times per week.
Is- sigurtà u l- effikaċja ta ’ Rebif ġiet ippruvata f’ pazjenti li jbatu minn attakki ripetuti ta ’ sklerożi multipla f’ dożi li jvarjaw minn 11 sa 44 mikrogramma (3- 12 – il miljun IU), mogħtija minn taħt il - ġilda tliet darbiet fil- ġimgħa.
At licensed posology, Rebif 44 micrograms has been demonstrated to decrease the incidence (approximately 30% over 2 years) and severity of clinical relapses in patients with at least 2 exacerbations in the previous 2 years and with an EDSS of 0-5.0 at entry.
F’ posoloġija liċenzjata, Rebif 22 mikrogramma instab li jnaqqas l - inċidenza (bejn wieħed u ieħor bi 30% fi żmien sentejn) u s- severità ta ’ attakki ripetuti f’ pazjienti bi
The proportion of patients with disability progression, as defined by at least one point increase in EDSS confirmed three months later, was reduced from 39% (placebo) to 27% (Rebif 44 micrograms).
Il - proporzjon ta ’ pazjenti bi progressjoni ta ’ diżabilità, hekk kif definiti b’ mill- anqas punt aktar żieda fl - EDSS konfermat tliet xhur wara, naqas minn 39% (plaċebo) sa 27% (Rebif 22 mikrogramma).
Over 4 years, the reduction in the mean exacerbation rate was 22% in patients treated with Rebif 22 micrograms, and 29% in patients treated with Rebif 44 micrograms group compared with a group of patients treated with placebo for 2 years and then either Rebif 22 or Rebif 44 micrograms for 2 years.
Fi żmien erba ’ snin, in- nuqqas tar- rata bejn wieħed u ieħor ta ’ iggravar kienet 22% f’ pazjenti kkurati b’ Rebif 22 mikrogramma, u 29% f’ pazjenti kkurati b’ Rebif 44 mikrogramma kkomparati ma ’ grupp ta ’ pazjenti kkurati bi plaċebo għal sentejn u mbagħad jew b’ Rebif 22 jew b’ Rebif 44 mikrogramma għal sentejn.
If the patient population was divided into 2 subgroups (those with and those without relapses in the 2-year period prior to study entry), there was no effect on disability in patients without relapses, but in patients with relapses, the proportion with progression in disability at the end of the study was reduced from 70% (placebo) to 57% (Rebif 22 micrograms and
Jekk il- popolazzjoni tal- pazjenti kienet maqsuma f’ żewġ gruppi (dawk b’ attakki ripetuti matul il- perjodu ta ’ sentejn qabel ma daħlu għall- istudju u dawk mingħajr), ma kien hemm l- ebda effett fuq pazjenti li ma kellhomx attakki ripetuti, iżda f’ pazjenti li kellhom attakki ripetuti, il- proporzjon mal- progress fid- diżabilità fl- aħħar ta ’ l- istudju naqas minn 70% (plaċebo) sa ’ 57% (Rebif 22 mikrogrammi u 44 mikrogrammi flimkien).
Rebif has not yet been investigated in patients with primary progressive multiple sclerosis, and should not be used in such patients.
Rebif s’ issa ma kienx studjat f’ pazjenti li jbatu minn sklerożi multipla progressiva primarja, u m’ g] andux jintuża fuq dawn il- pazjenti.
In healthy volunteers after intravenous administration, interferon beta-1a exhibits a sharp multi- exponential decline, with serum levels proportional to the dose.
F’ persuni f’ saħħithom wara g] oti mill- vina, interferon beta- 1a juri nuqqas serju multi esponenzjali, b’ livelli ta ’ serum proporzjonali għad- doża.
No information is available on the effects of the interferon beta-1a on male fertility.
L- ebda informazzjoni ma tinstab fuq l- effetti ta ’ interferon beta – 1a fuq il- fertilità maskili.
One ml type 1 glass syringe, with a stainless steel needle, containing 0.5 ml solution.
Siringa waħda ta ’ 1ml tal- ħġieġ tat- tipI, b’ labra magħmulha minn azzar li ma jittebbax, bi 0. 5ml ta ’ soluzzjoni.
Rebif 44 micrograms is available as a package of 1, 3 or 12 syringes.
Rebif 44 mikrogramma jinstab f’ pakketti ta ’ 1, 3 u 12 siringi..
Rebif 8.8 micrograms solution for injection in pre-filled syringe Rebif 22 micrograms solution for injection in pre-filled syringe
Rebif 8. 8 mikrogrammi – soluzzjoni għall- injezzjoni b’ siringa mimlija għal- lest Rebif 22 mikrogrammi – soluzzjoni għall- injezzjoni b’ siringa mimlija għal- lest
Each pre-filled syringe (0.2 ml) contains 8.8 micrograms (2.4 MIU*) of interferon beta-1a**.
Kull siringa mimlija lesta (0. 2 ml) fiha 8. 8 mikrogrammi (2. 4 MIU *) ta ’ interferon beta- 1a **.
*Million International Units, measured by cytopathic effect (CPE) bioassay against the in-house IFN beta-1a standard which is calibrated against the current international NIH standard (GB-23-902-531). ** produced in Chinese hamster ovary Cells (CHO-K1) by recombinant DNA technology.
* Miljun Unità Internazzjonali meqjus permezz ta ’ test tal- effett kitopatiku (EKP) mqabbel ma ’ l - istandard IFN beta- 1a li jsir fil- fabbrika li jinstab wara li jitqabbel ma ’ l- istandard kurrenti internazzjonali NIH (GB- 23- 902- 531). ** magħmulin fiċ- Ċelluli ta ’ l- ovarji tal- hamster Ċiniz (CHO- K1) li għandhom materjal ġenetiku mibdul.
1.0 mg benzyl alcohol For a full list of excipients, see section 6.1.
1. 0 mg benzyl alkohol Għal- lista kompleta ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
* Million International Units, measured by cytopathic effect (CPE) bioassay against the in-house IFN beta-1a standard which is calibrated against the current international NIH standard (GB-23-902-531). ** produced in Chinese hamster ovary Cells (CHO-K1) by recombinant DNA technology.
* Miljun Unità Internazzjonali meqjus permezz ta ’ test tal- effett kitopatiku (EKP) mqabbel ma ’ l - istandard IFN beta- 1a li jsir fil- fabbrika li jinstab wara li jitqabbel ma ’ l- istandard kurrenti internazzjonali NIH (GB- 23- 902- 531). ** magħmulin fiċ- Ċelluli ta ’ l- ovarji tal- hamster Ċiniz (CHO- K1) li għandhom materjal ġenetiku mibdul.
In clinical trials, this was characterised by two or more acute exacerbations in the previous two years (see section 5.1).
Fi studji kliniċi, dan ġie karaterizzat bħala ripetizzjoni ta ’ 2 każi jew aktar fl- aħħar sentejn (ara sezzjoni 5. 1).
Efficacy has not been demonstrated in patients with secondary progressive multiple sclerosis without ongoing relapse activity (See section 5.1).
(ara sezzjoni 5. 1).
The Rebif initiation package corresponds to the patient needs for the first month of treatment.
Il- pakkett għall- ewwel fażi tal- kura ta ’ Rebif jikkorrispondi għall- ħtiġiet tal- pazjent għall- ewwel xahar ta ’ kura.
Thereafter, 22 micrograms be administered
Għal pazjenti li jkunu qegħdin jibdew il- kura b’ Rebif, id- doża għandha tiżdied gradwalment sabiex tkun tista ’ tiżviluppa takifilassi u b’ hekk jitnaqqsu r- reazzjonijiet avversi, huwa rakkomandat li 8. 8mg jingħataw b’ injezzjoni taħt il- ġilda tlett darbiet fil- ġingħa waqt l- ewwel ġimgħatejn ta ’ terapija.
18 by subcutaneous injection three times per week in weeks 3 and 4, and the total of the 44 micrograms strength be administered from the fifth week onwards.
20 Wara, 22 mikrogrammi jingħataw b’ injezzjoni taħt il- ġilda tlett darbiet fil- ġimgħa f’ ġimgħat 3 u 4 u t - total ta ’ 44 mikrogrammi doża sħiħa jingħata mill- 5 ġimgħa ‘ l quddiem.
Method of administration Prior to injection and for an additional 24 hours after each injection, an antipyretic analgesic is advised to decrease flu-like symptoms associated with Rebif administration.
Kif Jingħata Qabel l- injezzjoni u għal 24- il siegħa wara kull injezzjoni, huwa rakkomandat li jingħata analġesiku li huwa ukoll kontra d- deni sabiex jitnaqqsu is- sintomi li jixbħu l- influenza li huma assoċjati ma ’ l - amministrazzjoni ta ’ Rebif.
At the present time, it is not known for how long patients should be treated.
S’ issa għadu mhux magħruf għal kemm tul ta ’ żmien il- pazjenti għandhom ikunu ikkurati.
These symptoms tend to be most prominent at the initiation of therapy and decrease in frequency and severity with continued treatment.
Dawn is- sintomi l- aktar jidhru malli jinbeda t- te] id tat- terapija u jonqsu fil- frekwenza u s- severita ’ meta titkompla l- kura.
Depression and suicidal ideation are known to occur in increased frequency in the multiple sclerosis population and in association with interferon use.
Id- dipressjoni u l- idea ta ’ suwiċidju huma magħrufa li jinstabu b’ rata aktar g] olja f’ persuni li jbatu minn sklerożi multipla kif ukoll f’ persuni li jużaw l- interferon.
The procedure for the self-administration by the patient should be reviewed periodically especially if injection site reactions have occurred.
21 Il- proċedura għat- teħid mill- pazjent stess għandha tkun eżaminata mill- ġdid kull tant żmien speċjalment jekk reazzjonijiet fejn ikunu saru l- injezzjonijiet ikunu dehru.
19 If the patient experiences any break in the skin, which may be associated with swelling or drainage of fluid from the injection site, the patient should be advised to consult with their physician before continuing injections with Rebif.
Jekk fil- pazjent jidher xi qsim fil- ġilda, li jista ’ jkun assoċjat ma ’ nefħa jew telf ta ’ likwidu mis- sit ta ’ l- injezzjoni, il- pazjent għandu jkun mgħarraf sabiex jikkonsulta mat- tabib qabel ikompli l - injezzjonijiet b’ Rebif.
In clinical trials with Rebif, asymptomatic elevations of hepatic transaminases (particularly alanine aminotransferase (ALT)) were common and 1-3% of patients developed elevations of hepatic transaminases above 5 times the upper limit of normal (ULN).
Fi provi kliniċi b’ Rebif, elevazzjonijiet mingħajr sintomi ta ’ transminases epatika (b’ mod partikolari ALT) kienu komuni u bejn 1 u 3% tal- pazjenti żviluppaw elevazzjoni ta ’ transminases epatika aktar minn 5 darbiet l- għola limitu normali (ULN- upper limit of normal).
No specific risk factors have been identified.
L- ebda fatturi ta ’ riskju ma ġewx identifikati.
If a patient responds poorly to therapy with Rebif, and has neutralising antibodies, the treating physician should reassess the benefit/ risk ratio of continued Rebif therapy.
Jekk pazjent jkollu rispons fqir għat- terapija b’ Rebif, u għandu antikorpi newtralizzanti, it- tabib li jikkurah għandu jerġa ’ jeżamina mill- ġdid ir- rata benefċċju/ riskju tat- tkomplija tat- terapija b’ Rebif.
This medicinal product contains 1.0 mg benzyl alcohol per dose of 0.2 ml and 2.5 mg benzyl alcohol per dose of 0.5 ml.
22 Dan il- prodott mediċinali fih 1. 0 mg ta ’ benzyl alkohol f’ kull doża ta ’ 0. 2 ml u 2. 5 mg ta ’ benzyl alkohol f’ kull doża ta ’ 0. 5 ml.
May cause toxic reactions and anaphylactoid reactions in infants and children up to 3 years old.
Jista ’ jikkawża reazzjonijiet tossiċi u reazzjonijiet anafilattojdi fit- trabi u fi tfal sa l- età ta ’ 3 snin.
20 4.5 Interaction with other medicinal products and other forms of interaction
4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
Caution should be exercised when administering Rebif in combination with medicinal products that have a narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance, e. g. antiepileptics and some classes of antidepressants.
Għandha ssir attenzjoni meta jingħata Rebif flimkien ma ’ prodotti mediċinali oħra li għandhom indiċi terapewtiku qasir u li jiddependu ħafna fuq is- sistema hepatic cytochrome P450 sabiex jitnaddfu eż: anti- epilettiċi u xi tipi ta ’ antidipressivi.
Therefore initiation of treatment is contraindicated during pregnancy (see section 4.3).
Informazzjoni li hemm jindika li jista ’ jkun hemm riskju akbar ta ’ abbort spontanju. Għalhekk, l- inizjazzjoni tal- kura muwiex indikat waqt it- tqala (ara sezzjoni 4. 3).
Because of the potential for serious adverse reactions in breast-fed infants, a decision should be made either to discontinue nursing or to discontinue Rebif therapy.
Minħabba l- potenzjal ta ’ effetti serji negattivi fuq trabi li jerdgħu, deċiżjoni għandha tittieħed jekk jitwaqqafx it- treddiegħ jew inkella t- terapija b’ Rebif.
21 The adverse reactions reported below are classified according to frequency of occurrence as follows:
23 L- effetti mhux mixtieqa li jissemmew hawn taħt huma klassifikati skond il- frekwenza ta ’ kif jidhru kif ġej:
Very Common Common Uncommon Rare Very rare
Komuni ħafna Komuni Mhux komuni Rari Rari ħafna
≥ 1/ 10 ≥ 1/ 100 to < 1/ 10 ≥ 1/ 1,000 to < 1/ 100 ≥ 1/ 10,000 to < 1/ 1,000 < 1/ 10,000
≥1/ 10 ≥1/ 100 sa < 1/ 10 ≥1/ 1, 000 sa < 1/ 100 ≥1/ 10, 000 sa < 1 / 1, 000 < 1/ 10, 000
Cannot be estimated from the available data
Ma tistax tittieħed stima mid -
The data presented is obtained from pooled clinical studies in multiple sclerosis (placebo=824 patients; Rebif 22 micrograms three times per week (TIW)=398 patients; Rebif 44 micrograms TIW=727 patients) and shows the frequency of adverse reactions observed at six months (excess over placebo).
L- informazzjoni ppreżentata hi miksuba minn studji kliniċi fi sklerożi multipla (plaċebo=824 pazjienti; Rebif 22 mikrogrammi tlitt darbiet fil- ġimgħa (TIW) =398 pazjienti; Rebif 44 mikrogrammi TIW=727 pazjienti) u turi l- frekwenza ta ’ l- effetti mhux mixtieqa f’ sitt xhur (żieda fuq plaċebo).
Thyroid dysfunction most often presenting as hypothyroidism or hyperthyroidism
Disfunzjoni tat - tirojde l- iktar bħala ipotirojdiżmu jew ipertirojidiżmu
22 System Organ Class General disorders and administration site conditions
24
Very common Injection site inflammation, injection site reaction, influenza-like symptoms
Sistema tal- klassifika tal- organi
Common Injection site pain, fatigue, rigors, fever
Komuni ħafna
Uncommon Injection site necrosis, injection site mass
Komuni
Not known*
Mhux komuni
Dyspnoea
Uġigħ fis- sit ta ’ injezzjoni, għeja, tertir, deni
Treatment with Rebif should be stopped if icterus or other clinical symptoms of liver dysfunction appear (see section 4.4).
Il- kura b’ Rebif għandha titwaqqaf jekk ikterus jew sintomi oħra ta ’ funzjoni ħazina tal- fwied jinħassu (ara Sezzjoni 4. 4)
L03AB07.
LO3AB07
At licensed posology, Rebif 22 micrograms has been demonstrated to decrease the incidence (approximately 30% over 2 years) and severity of clinical relapses in patients with at
F’ posoloġija liċenzjata, Rebif 22 mikrogramma instab li jnaqqas l - inċidenza (bejn wieħed u ieħor bi 30% fi żmien sentejn) u s- severità ta ’ attakki ripetuti f’ pazjienti bi
23 least 2 exacerbations in the previous 2 years and with an EDSS of 0-5.0 at entry.
25 tnejn jew iżjed exaserbazzjonijiet fis- sentejn ta ’ qabel u bi EDSS ta ’ 0- 5. 0 meta beda l- kura.
The proportion of patients with disability progression, as defined by at least one point increase in EDSS confirmed three months later, was reduced from 39% (placebo) to 30% (Rebif 22 micrograms).
Il - proporzjoni ta ’ pazjenti bi progressjoni ta ’ diżabilità, hekk kif definiti b’ mill- anqas punt aktar żieda fl - EDSS konfermat tliet xhur wara, naqas minn 39% (plaċebo) sa 27% (Rebif 22 mikrogramma).
In healthy volunteers after intravenous administration, interferon beta-1a exhibits a sharp multi- exponential decline, with serum levels proportional to the dose.
F’ persuni f’ saħħithom wara għoti mill- vina, interferon beta- 1a juri nuqqas serju multi esponenzjali, b’ livelli ta ’ serum proporzjonali għad- doża.
When administered by the subcutaneous or intramuscular routes, serum levels of interferon beta remain low, but are still measurable up to 12 to 24 hours post-dose.
Meta mog] tija minn ta] t il - [ilda jew mill- muskolu, il- livelli ta ’ serum ta ’ interferon beta jibqgħu baxxi, iżda jibqgħu jitkejlu minn 12 sa ’ 24 siegħa wara d- doża.
24 6.
26 6.
For patients initiating treatment with Rebif, Rebif 8.8 micrograms and Rebif 22 micrograms are available in an initiation pack composed of 6 individual doses of a 1 ml type 1 glass syringe with a stainless steel needle containing 0.2 ml of Rebif 8.8 micrograms solution for injection and 6 individual doses of a 1 ml type 1 glass syringe with a stainless steel needle containing 0.5 ml of Rebif 22 micrograms solution for injection.
Għal pazjienti li se jibdew il- kura ta ’ Rebif, Rebif 8. 8 mikrogrammi u Rebif 22 mikrogrammi huwa disponibbli bħala pakkett apposta għal dan bi 6 dożi individwali ta ’ ta’ siringa ta 1ml tal- ħġieġ tat- tip I b’ labra ta ’ azzar li ma jittebbax li fiha 0. 2ml ta Rebif 8. 8 mikrogrammi soluzzjoni għall- injezzjoni (0. 2ml) u 6 dożi individwali ta ’ siringa ta 1ml tal- ħġieġ tat- tip I b’ labra ta ’ azzar li ma jittebbax li fiha 0. 5ml Rebif 22 mikrogrammi, soluzzjoni għall- injezzjoni
This package corresponds to the patient needs for the first month of therapy.
Dan il- pakkett jikkorrispondi għall- ħtiġijiet tal- pazjent għall- ewwel xahar ta ’ terapija.
4th May 2003 Date of latest renewal:
4 Mejju 2003 Data ta ’ l- aħħar tiġdid ta ’ l- awtorizzazzjoni:
Rebif 22 micrograms/ 0.5 ml solution for injection in cartridge
Rebif 22 mikrogrammi/ 0. 5 ml soluzzjoni għall- injezzjoni fi skartoċċ
Each pre-filled cartridge contains 66 micrograms (18 MIU*) of interferon beta-1a** in 1.5 ml solution, corresponding to 44 micrograms/ ml.
Kull skartoċċ mimli għal- lest fih 66 mikrogrammi (18- il MIU *) ta ’ interferon beta- 1a ** f’ soluzzjoni ta ’ 1. 5 ml, li jikkorrispondu għal 44 mikrogrammi/ ml.
Excipient:7.5 mg benzyl alcohol For a full list of excipients, see section 6.1.
Għal- lista kompleta ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
Solution for injection in cartridge.
Soluzzjoni għall- injezzjoni fi skartoċċ.
Clear to opalescent solution, with pH 3.7 to 4.1 and osmolarity 250 to 450 mOsm/ l.
Soluzzjoni ċara għal opalexxenti b’ pH ta ’ 3. 7 sa 4. 1 u osmolarità ta ’ 250 sa 450 mOsm/ l.
When first starting treatment with Rebif, the dose should be gradually escalated in order to allow tachyphylaxis to develop thus reducing adverse reactions.
Għal pazjenti li jkunu qegħdin jibdew il- kura b’ Rebif, id- doża għandha tiżdied gradwalment sabiex tkun tista ’ tiżviluppa takifilassi u b’ hekk jitnaqqsu r- reazzjonijiet avversi.
Method of Administration Rebif solution for injection in cartridge is intended for multidose use and should only be used with the RebiSmart autoinjector device following adequate training of the patient and/ or carer.
Kif Jingħata Rebif soluzzjoni għall- injezzjoni fi skartoċċ b’ ħafna dożi hija intenzjonata għall- użu biss mal- apparat awtoinjettatur ta ’ RebiSmart wara taħriġ adegwat tal- pazjent u/ jew min ikun jieħu ħsiebu.
For administration, the instructions provided in the package leaflet and in the instruction manual provided with the RebiSmart autoinjector device should be followed.
Għall- għoti, l- istruzzjonijiet li hemm fil- fuljett ta ’ tagħrif u fil- manwal ta ’ istruzzjonijiet li jiġi pprovdut mal- apparat awtoinjettatur ta ’ RebiSmart għandhom jiġu segwiti.
Prior to injection and for an additional 24 hours after each injection, an antipyretic analgesic is advised to decrease flu-like symptoms associated with Rebif administration.
29 Qabel l- injezzjoni u għal 24- il siegħa wara kull injezzjoni, huwa rakkomandat li jingħata analġesiku li huwa ukoll kontra d- deni sabiex jitnaqqsu is- sintomi li jixbħu l- influenza li huma assoċjati ma ’ l- amministrazzjoni ta ’ Rebif.
27 At the present time, it is not known for how long patients should be treated.
S’ issa għadu mhux magħruf għal kemm tul ta ’ żmien il- pazjenti għandhom ikunu ikkurati.
28 In clinical trials with Rebif, asymptomatic elevations of hepatic transaminases (particularly alanine aminotransferase (ALT)) were common and 1-3% of patients developed elevations of hepatic transaminases above 5 times the upper limit of normal (ULN).
Fi provi kliniċi b’ Rebif, elevazzjonijiet mingħajr sintomi ta ’ transminases epatika (b’ mod partikolari ALT) kienu komuni u bejn 1 u 3% tal- pazjenti żviluppaw elevazzjoni ta ’ transminases epatika aktar minn 5 darbiet l- għola limitu normali (ULN- upper limit of normal).
This medicinal product contains 2.5 mg benzyl alcohol per dose of 0.5 ml.
Dan il- prodott mediċinali fih 2. 5 mg ta ’ benzyl alkohol f’ kull doża ta ’ 0. 5 ml.
4.5 Interaction with other medicinal products and other forms of interaction
31 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
29 medicinal products that have a narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance, e. g. antiepileptics and some classes of antidepressants.
Għandha ssir attenzjoni meta jingħata Rebif flimkien ma ’ prodotti mediċinali oħra li għandhom indiċi terapewtiku qasir u li jiddependu] afna fuq is- sistema hepatic cytochrome P450 sabiex jitnaddfu eż:. anti- epilettiċi u xi tipi ta ’ antidipressivi.
The adverse reactions reported below are classified according to frequency of occurrence as follows:
32 L- effetti mhux mixtieqa li jissemmew hawn taħt huma klassifikati skond il- frekwenza ta ’ kif jidhru kif ġej:
≥ 1/ 10 ≥ 1/ 100 to < 1/ 10 ≥ 1/ 1,000 to < 1/ 100 ≥ 1/ 10,000 to < 1/ 1,000 < 1/ 10,000
≥ 1/ 10 ≥1/ 100 sa < 1/ 10 ≥1/ 1, 000 sa < 1/ 100 ≥1/ 10, 000 sa < 1/ 1, 000 1/ 1, 000 < 1/ 10, 000 Ma tistax tittieħed stima mid- dejta disponibbli
30 The data presented is obtained from pooled clinical studies in multiple sclerosis (placebo=824 patients; Rebif 22 micrograms three times per week (TIW)=398 patients; Rebif 44 micrograms TIW=727 patients) and shows the frequency of adverse reactions observed at six months (excess over placebo).
L- informazzjoni ppreżentata hi miksuba minn studji kliniċi fi sklerożi multipla (plaċebo=824 pazjienti; Rebif 22 mikrogrammi tlitt darbiet fil- ġimgħa (TIW) =398 pazjienti; Rebif 44 mikrogrammi TIW=727 pazjienti) u turi l- frekwenza ta ’ l- effetti mhux mixtieqa f’ sitt xhur (żieda fuq plaċebo).
*Not known Injection site infections, including cellulitis
Infezzjonijiet fis - sit ta l- injezzjoni, inkluż ċellulitis
Musculoskeletal and connective tissue disorders
33 Sistema tal- klassifika tal- organi
System Organ Class Hepatobiliary disorders
żdieda asimtomatika tat - transaminase
*Not known Hepatitis with or without icterus
Qtugħ ta ’ nifs Reazzjonijiet anafilattiċi eventi tromboemboliċi Epatite b’ ikterus jew migħajr
Immunostimulants, Interferon, ATC code:
Immunostimulanti, Interferons, Kodiċi ATC:
The safety and efficacy of Rebif has been evaluated in patients with relapsing-remitting multiple sclerosis at doses ranging from 11 to 44 micrograms (3-12 million IU), administered subcutaneously three times per week.
34 Is- sigurtà u l- effikaċja ta ’ Rebif ġiet ippruvata f’ pazjenti li jbatu minn attakki ripetuti ta ’ sklerożi multipla f’ dożi li jvarjaw minn 11 sa 44 mikrogramma (3- 12 – il miljun IU), mogħtija minn taħt il - ġilda tliet darbiet fil- ġimgħa.
32 Rebif has not yet been investigated in patients with primary progressive multiple sclerosis, and should not be used in such patients.
Rebif s’ issa ma kienx studjat f’ pazjenti li jbatu minn sklerożi multipla progressiva primarja, u m’ għandux jintuża fuq dawn il- pazjenti.
After first injection use within 28 days.
Wara l- ewwel injezzjoni uża fi żmien 28 jum.