qanastek/EMEA-V3 huggingface dataset:
Following booster vaccination with tetanus toxoid (recall antigen), the ability to mount an immune response to the tetanus toxoid was preserved in those patients undergoing Raptiva therapy.
Wara tilqima rafforzanti tat- toxoid tat- tetanu (recall antiġen), il- kapaċita ’ sabiex tibni risposta immuna għal din it- toxoid tat- tetanu kienet preservata f’ dawk il- pazjienti taħt kura ma ’ Raptiva.
After 35 days of treatment with Raptiva, the proportion of subjects treated with efalizumab with positive skin test reactions to Candida was significantly reduced compared with the placebo group.
Wara 35 tjiem ta ’ kura ma ’ Raptiva, dawk il- pazjienti ttratati ma ’ efalizumab li kellhom test tal- ġilda positiva għal Candida kienet fhem imnaqqsa meta kkomparata mal- grupp li kienu fuq plaċebo.
Antibody response to an experimental neo-antigen (∅ X174) was reduced during Raptiva therapy, but began to normalize 6 weeks after discontinuation of Raptiva therapy and did not demonstrate tolerance induction.
Ir- risposta ta ’ l- antikorpi għal antiġen ġdida taħt l- esperiment (∅X174) kienet imnaqqsa waqt il- kura ma ’ Raptiva, iżda sar normali 6 ġimgħat wara li twaqqaf Raptiva u ma wriex tolerance indcution.
A pneumococcal vaccine administered 6 weeks after discontinuation of Raptiva yielded normal results.
Tilqima tal- pnemuococcal li ngħata 6 ġimgħat wara li twqqaf ir- Raptiva tagħ rizultati normali.
Neo-vaccinations given during treatment with Raptiva may induce antibody levels lower than non-treated subjects, but the clinical significance of this is unknown.
Tilqima ġodda li jingħatgħu waqt kura ma ’ Raptiva jistgħu jinduċu livelli ta ’ antikorpi li jkunu inqas minn dawk il- pazjienti li mhumiex qeg] din jie] du l- kura, izda is- sinifikant kliniku ta ’ dan mhuwiex magħruf.
Patients should not receive live and live-attenuated vaccines during Raptiva treatment.
Pazjienti ma jistgħux jingħtagħ tilqima tat- tipi live u live- attentuated waqt il- kura ma ’ Raptiva.
(See section 4.4).
(ara sezzjoni 4. 4).
Given the mechanism of action of efalizumab, its effects on the immune system may be potentiated by systemic immunosuppressives commonly used for the treatment of psoriasis (see section 4.4).
Minħabba l- mod ta ’ kif jaħdem efalizumab, l- effetti tiegħu fuq is- sistema immune jista ’ jiġi potenzjat minn immunosuppressives sistemiċċ, li jintuzaw ta ’ spiss għal- kura ta ’ psorjażi (ara sezzjoni 4. 4).
Raptiva has been used in combination with topical corticosteroids in psoriasis patients without any untoward effects nor with any observable significant beneficial effect of the combination therapy above monotherapy with efalizumab.
Raptiva ġie użat ma ’ corticosterojdi topiċi f’ pazjienti b’ psorjażi mingħajr effetti mhux mixtieqa magħrufin u ukoll ma kienx hemm effett benefiċjail ta ’ sinjifikanza bl- użu ikkombinat fuq l- użu singolari ma ’ efalizumab.
Pregnancy In general, immunoglobulins are known to cross the placental barrier.
Tqala Ġeneralment, l- immunoglobulini huma magħrufa li jaqsmu l- plaċenta.
There are no adequate data from the use of efalizumab in pregnant women.
Ma hemx informazzjoni adegwata fuq l- użu ta efalizumab fin- nisa tqala.
Animal studies indicate an impairment of the immune function of the offspring (see section 5.3).
Studji li saru fl- annimali juru li jkun hemm indeboliment tal- funzjoni immuna taz- zgħar (ara sezzjoni 5. 3).
Pregnant women should not be treated with Raptiva.
Nisa tqala ma jistgħux jieħdu l- kura ta ’ Raptiva.
Women of childbearing potential have to use appropriate contraception during treatment.
Nisa ta ’ l- eta ’ li jitgħhu jkollhom it- tfal jridu jużaw mod appropriat ta ’ kontraċezzjoni waqt il- kura.
Lactation Excretion of efalizumab in human milk has not been investigated, however immunoglobulins are expected to be excreted in human milk.
5 Eskrezzjoni ta ’ efalizumab fil- ħalib uman ma ġiex studjat, pero immunoglobulini huma mistennija li jiġu eskrezzjati fil- ħalib uman.
Moreover, an antibody analogue of efalizumab was shown to be excreted in milk of mice.
Fuq min hekk, analogu ta ’ l- antikorpu ta ’ efalizumab wera li jiġi eskrezzjat fil- ħalib tal- ġrieden.
Women should not breastfeed during treatment with Raptiva.
In- nisa ma jistgħawx jreddgħu waqt il- kura ma ’ Raptiva.
Based on the pharmacological mechanism of action of efalizumab, the use of Raptiva is not expected to affect patient’ s ability to drive and use machines.
Bazat fuq il- mod farmakoloġiku ta ’ kif jaħdem efalizumab, l- użu ta ’ Raptiva mhuwiex mistenni li jkollu effett fuq il- ħila tal- pazjient biex issuq u jħaddem magni.
The most frequent symptomatic adverse drug reactions (ADRs) observed during Raptiva therapy were mild to moderate dose-related acute flu-like symptoms including headache, fever, chills, nausea and 5 myalgia.
Ir- reazzjonijiet avversi tal- mediċina illi ġew osservati l- iktar spiss huma ħafif- moderat simptomi bħal ta ’ l- influenza, li huma akuti u doża- relatata, inkluż uġigħ ta ras, deni, sirdat, nawsea u majalġja.
In large placebo-controlled clinical studies, these reactions were observed in approximately 41% of Raptiva-treated patients and 24% in placebo-treated patients over 12 weeks of treatment.
F’ studji kliniċi kbar, kontrollati minn plaċebo, dawn ir- reazzjonijiet ġew osservati f’ approssimattiv ta ’ 41% ta ’ pazjienti fuq Raptiva u 24% ta ’ pazjienti fuq plaċebo, li ħadu l- kura fuq 12 ġimgħat.
After initiation of therapy, these reactions were generally less frequent and occurred at similar rates to that seen in the placebo group from the third and subsequent weekly injections.
Wara l - bidu tal- kura, dawn ir- reazzjonijiet kienu ġeneralment inqas frekwenti u ġrew fl- istess rata ta ’ dawk li raw fil- grupp tal- plaċebo mitt- tielet injezzjoni u dawk ta wara.
Antibodies to efalizumab were detected in only 6% of patients.
Antikorpi għal efalizumab instabu f’ 6% biss ta ’ pazjienti.
In this small number of patients no differences were observed in pharmacokinetics, pharmacodynamics, clinically noteworthy adverse events or clinical efficacy.
F’ dan in- numru zgħar ta ’ pazjienti ma ġew osservati l- ebda differenzi fil - farmakokinetiku, farmakodinamiku, effetti mhux mixtieqa ta ’ sinjifikanza klinika, jew effikaċja.
Adverse events (Preferred Terms) in the overall population studied clinically with Raptiva are listed below by frequency of occurrence and by MedDRA System Organ Class.
Effetti avversi fuq il- populazzjoni ġenerali li fuqu ġie studjat Raptiva, huma mmniżżla taħt, f’ ordni ta ’ frekwenża u mil MedDRA System Organ Class.
System Organ Class
Komuni Komuni
Very
Mhux
Common
Rari
Uncommon
Rari] afna
Very rare
(> 1/ 100,
Not known
(> 1/ 10, 00
Infections and infestations
(< 1/ 10, 000)
common (> 1/ 10)
(> 1/ 10)
(> 1/ 100 < 1/ 10)
< 1/ 10)
(> 1/ 1,000, < 1/ 100)
< 1/ 100)
(< 1/ 10,000)
< 1/ 1, 000)
Aseptic meningitis*, Severe infections*, JC virus infection resulting in progressive multifocal leukoencephalopathy*
Meninġite assetika *, infezzjonijiet severi *, Infezzjoni tal - JC virus riżultanti f' lewkoenkefa lopatija progressiva multifokali *
Blood and the lymphatic system disorders
Disturbi tad - demm u tas -
Leuko- cytosis and lympho- cytosis
Lewkoċit osi u limfoċitos
Thrombo- cytopenia
Tromboċito penja
Immune mediated haemolytic anaemia*
Immune mediated
Immune system disorders
sistema Disturbi fis - sistema immuni
Hyper- sensitivity reactions
Reazzjoniji et ta ipersensitti vita ’
Nervous system disorders Respiratory, thoracic and mediastinal disorders
haemolytic anaemia *
Facial palsy (Bell’ s palsy)
Paralazi tal -
Inflammatory polyradiculo- neuropathy* Interstitial pneumonitis*
Inflamma -
Skin and subcutaneous tissue disorders
sistema nervuża
Psoriasis
wiċċ
Urticaria
(Bell’ s Palsy)
Erythema multiforme*
polyradiculo neuropathy *
Musculoskeletal and connective tissue disorders
6 Interstitial Disturbi pneumonitis respiratorji, * toraċiċi u medjastinali Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Disturbi muskolu - skeltrali u tal - connective tissue
Arthralgia Arthritis / Psoriatic arthritis (exacerbation/ flare)
Psorjażi Artralġja artrite / artrite psorjażi (issir għar)
General disorders and administration site conditions
Erythema multiforme *
Flu-like symptoms including fever, headaches, chills, nausea and myalgia
Disturbi ġenerali
Back pain, Asthenia
u kondizzjonijiet
Injection site reactions
et fis- sit ta ’
Investigations
ta 'mnejn jingħata
Elevation of alkaline Phosphatase, Elevation of ALT
influenza, inkluż deni, uġigħ ta ’ ras, sirdat, nawsea u majalġja.
6
l- injezzjoni
* Events identified during postmarketing surveillance
Elevazzjoni Investigazzjoniji ta ’ alkaline et phosphates u ALT * Ġrajjiet li seħħew waqt surveljanza wara li l- prodott kien fuq is- suq
The safety profile in the target population as defined in section 4.1 is similar to the safety profile in the overall population treated during clinical development of Raptiva as presented above.
Il- profil tas- sigurta ’ fil- populazzjoni targit, kif inhu definit f’ sezzjoni 4. 1 huwa simili għal profil tas - sigurta fil- populazzjoni ġenerali li ħadu l- kura waqt l- izvilupp kliniku ta ’ Raptiva kif inhu presentat hawn fuq.
Additional Information
Aktar Informazzjoni
Analysis following long-term use in a cohort of 339 patients with moderate to severe psoriasis receiving Raptiva 1 mg/ kg/ week, of which 166 patients have been treated for more than 2 years and up to 3 years, did not show any noteworthy differences in frequency of adverse events as compared to 12 weeks of exposure to Raptiva.
Espozizzjoni fit - tul Analiżi li seħħ wara l- użu fit- tul f’ grupp ta ’ 339 pazjienti b’ psorjażi moderat - sever li rrċevew Raptiva 1mg/ kg/ week, minn liema 166 pazjienti kienu taħt il- kura għal aktar minn sentejn sa tlett snin, ma wrex xi differenżi partikolari fil- frekwenza ta ’ effetti avversi, meta jiġi kkomparat ma ’ 12- il ġimgħa ta ’ esponiment għal Raptiva.
Leucocytosis and lymphocytosis: in large placebo-controlled and in long-term clinical studies, between 40 and 50% of patients developed sustained asymptomatic lymphocytosis during Raptiva therapy.
Fi studji kliniċi kbar ikkontrollati minn plaċebo u fit- tul taz- żmien, bejn 40 u 50% ta ’ pazjienti zviluppaw limfoċitosi minn simpotmi sostnat, waqt kura ma ’ Raptiva.
All values were between 2.5 fold and 3.5 fold the ULN (Upper Limit of Normal).
Il- valuri kollha kienu bejn 2. 5 u 3. 5- il darba il- fuq minn ULN (Upper Limit of Normal).
Lymphocyte count returned to baseline after therapy discontinuation.
L- ammont ta limfoċiti reġa ’ għall- linea ta basi wara li twaqqaf il- kura.
Slight elevation in absolute neutrophil count and eosinophil count were observed but in a smaller proportion of patients.
Ġie osservat elevazzjoni zgħira fl- ammont totali tal - newtrofils u esenofils, iżda f’ poporzjoni iżgħar ta ’ pazjienti.
In the combined safety database of 3291 Raptiva-treated patients at the time of approval, there were nine occurrences (0.3%) of thrombocytopenia with less than 52,000 cells per μ l reported.
F’ database ikkombinat tas- sigurta ’ ta ’ 3291 pazjienti taħt il- kura b’ Raptiva fiz- żmien ta l’ approvazzjoni, kien hemm 9 ġrajjiet ta tromboċitopenja ma ’ inqas minn 52, 000 ċelluli/ μl irraportat.
Four of these patients had clinical signs of thrombocytopenia.
Erbgħa minn dawn il- pazjienti kellhom sinjali kliniċi ta ’ tromboċitopenja.
Based on available platelet count measurements, the onset of platelet decline was between 8 and 12 weeks after the first dose of Raptiva in 5 patients, but occurred later in the other patients.
Ibbasat fuq il- misuri li kien hemm fuq l- ammont ta ’ plajtlits, l- inzul tal- plajtlits beda ’ bejn 8 u 12- il ġimgħa wara l- ewwel doża ta ’ Raptiva f’ ħames pazjienti, iżda seħħ aktar tard fil- pazjienti l- oħra.
In one patient, thrombocytopenia occurred 3 weeks after treatment discontinuation.
F’ pazjient wieħed tromboċitopenja seħħ tlett ġimgħat wara li twaqqaf il- kura.
Over long term treatment up to 3 years, a small and gradual decrease in mean platelet counts within the normal range was observed.
Ġie osservat li wara kura għal tul taz- żmien sa tlett snin, kien hemm tnaqqis gradwali tal- medja tal- għadd tal- plaitlits sa normali.
Psoriasis:
7 Psorjażi:
In the first 12 weeks of placebo-controlled studies, the rate of psoriasis adverse events was 3.2% in the Raptiva-treated patients and 1.4% in the placebo-treated patients.
Fl- ewwel 12- il ġimgħa ta ’ studji kontrollati minn plaċebo, ir- rata ta effetti mhux mixtieqa ta ’ psorjażi kien 3. 2% f’ dawk il- pazjienti taħt il- kura ma ’ Raptiva u 1. 4% fil- pazjienti kkurati minn plaċebo.
Among 3291 patients in the combined safety database, 39 patients presented an erythrodermic or pustular psoriasis (1.2%).
Fost it- 3291 pazjienti fid- database ikkombinat tas- sigurta ’, 39 pazjienti kellhom erythrodermic jew pusutalar psorjażi (1. 2%).
Seventeen of these events occurred after discontinuation of Raptiva, while 22 occurred during treatment.
Sbatax minn dawn il- ġrajjiet seħħew wara li twaqqaf Raptiva, waqt li 22 seħħew waqt il- kura.
In the cases occurring during treatment, most of these events (16/ 22) occurred in patients presenting no response to Raptiva.
F’ dawk il- każijiet li seħħew waqt il- kura, l- iktar minnhom (16/ 22) seħħew f’ dawk il- pazjienti li ma kellhomx risposta għal Raptiva.
Cases occurring after discontinuation were observed both in patients responding or not responding to Raptiva treatment.
Kazijiet li seħħew wara it- twaqqif kienu osservati kemm fil- pazjienti li kellhom risposta għal kura ma ’ Raptiva, kemm f’ dawk li ma kellhomx.
Arthritis / Psoriatic arthritis:
Artrite / Artrite Psorjażi:
In the first 12 weeks of placebo-controlled studies, arthritis and exacerbation or flare of arthritis were observed in 1.8% of Raptiva-treated patients and placebo-treated patients.
Fl- ewwel 12- il ġimgħa ta ’ l- istudji kontrollati minn plaċebo, artrite u artrite li ssir għar kien osservat fi 1. 8% ta ’ pazienti taħt il- kura ta ’ Raptiva u taħt il- kura ta ’ plaċebo.
In these studies, the incidence of other types of arthritis-related adverse events were similar between the Raptiva and placebo groups.
F’ dawn is- studji, ir- rata ta tipi oħra ta ’ effetti mhux mixtieqa li għandhom x’ jaqsmu ma ’ l- artrite kien simili bejn il- grupp ta ’ Raptiva u dak ta ’ plaċebo.
Flu-like symptoms:
Simptomi bħal l- influenza:
In large placebo-controlled clinical studies, approximately 20% of patients in excess of placebo reported flu-like symptoms including headaches, chills, fever, nausea and myalgia.
Fi studji kliniċi kbar ikkontrollati minn plaċebo, madwar 20% ta pazjienti iktar minn plaċebo rrapurtaw simptomi bħal ta ’ l- influenza inkluż uġigħ ta ’ ras, sirdat, deni, nawsea u mjalġja.
The percentage of patients reporting flu-like symptoms was greatest with the first injection and decreased by more than 50% with the second injection.
Il - perċentaġġ ta pazjienti li rrapurtaw simptomi bħal ta ’ l- influenza kien l- akbar ma ’ l- ewwel injezzjoni, u naqqas iktar minn 50% mat- tieni injezzjoni.
These symptoms diminished thereafter to a percentage comparable to that of patients treated with placebo.
Dawn is- simptomi naqqsu wara dan, għal perċentaġġ li huwa komparabbli għal pazjienti ikkurati minn plaċebo.
Headache was the most frequent of the flu-like symptoms.
Uġigħ ta ’ ras kien l- iktar frekwenti minn dawn is- simptomi.
None of those events was serious and less than 5% were considered severe.
L- ebda minn dawn il- ġrajjiet kien serji w inqas minn 5% kienu kkonsidrati severi.
Overall less than 1% of patients discontinued therapy because of acute flu-like symptoms.
Fuq kollox, inqas minn 1% ta pazjienti waqqaf il- kura minħabba simptomi.
Hypersensitivity and allergic disorders:
Ipersensitivita u dizordni allerġiċi:
In large placebo-controlled clinical studies, the percentage of patients experiencing an adverse event suggestive of hypersensitivity, including urticaria, rash and allergic reactions was slightly higher in the Raptiva group (8%) than in the placebo group (7%).
Fi studji kliniċi kbar ikkontrollati minn plaċebo, il- perċentaġġ ta ’ pazjienti li kellhom esperjenza ta xi effett avvers ta ’ ipersensitivita ’ inkluz l- urtikarja, raxx u reazzjonijiet allerġiċi kien xi ftit għola fil - grupp ta Raptiva (8%) milli fil- grupp ta plaċebo (7%).
Over long term treatment, the frequency of hypersensitivity-related adverse events did not increase.
F’ kura għal tul ta ’ żmien, il - frekwenza ta effetti avversi minħabba ipersensitivita ma żdietx.
7 Elevation of alkaline phosphatase:
Elevazzjoni ta ’ alkaline phosphatase:
In large placebo-controlled clinical studies approximately 4.5% of patients developed sustained elevation of alkaline phosphatase throughout Raptiva therapy compared to 1% in placebo patients.
Fi studji kliniċi kbar ikkontrollati minn plaċebo madwar 4. 5% ta pazjienti sviluppaw elevazzjoni sostenuta ta alkaline phosphatase waqt it- tul tal- kura ma ’ Raptiva, ikkomparat minn 1% fil- pazjienti fuq plaċebo.
All values were between 1.5 fold and 3 fold the ULN, and returned to baseline levels after therapy discontinuation.
Il- valuri kollha kienu bejn 1. 5 and 3 il- darba l- ULN, and reġgħaw għall- linea ta basi wara t- twaqqif tal- kura.
Elevation of ALT:
Elevazzjoni ta ’ ALT:
About 5.7% of patients developed elevation in ALT during Raptiva therapy compared to 3.5% in placebo.
Madwar 5. 7% ta pazjienti sviluppaw elevazzjoni ta ALT waqt il- kura ma ’ Raptiva, meta dan jiġi ikkomparat ma ’ dawk fuq plaċebo.
All occurrences were asymptomatic and values above 2.5 fold ULN were not more frequent in the Raptiva group than in the placebo group.
Il- ġrajjiet kollha kienu mingħajr simptomi u l- valuri l- fuq minn 2. 5 il- darba ULN ma kienux aktar frekwenti fil- grupp ta ’ Raptiva milli fil- grupp ta ’ plaċebo.
All values returned to baseline levels upon therapy discontinuation.
Il- valuri kollha reġgħaw għall- linea ta basi wara t- twaqqif tal- kura.
Other therapies that alter T-lymphocyte function have been associated with increased risk of developing serious infections.
Terapiji oħrajn li għandhom effett fuq il- funzjoni ta ’ limfoċiti T, ġew assoċjati ma ’ riskju akbar għal l - izvilupp ta ’ infezzonijiet serji.
In placebo controlled clinical trials, infection rates in Raptiva-treated patients was approximately 27.3% versus 24.0% in placebo-treated patients.
Fi studji kliniċi kkontrollati minn plaċebo, ir- rata ta infezzjonijiet f’ pazjienti taħt il- kura ta ’ Raptiva kien madwar 27. 3% kontra 24. 0% f’ pazjienti fuq plaċebo.
As regards serious infections, the overall incidence in both controlled and uncontrolled studies of up to 12 weeks was 2.8 per 100 patient-years for Raptiva-treated patients compared with 1.4 per 100 patient-years for placebo-treated patients.
Fi populazzjoni targit studjat fl- istudju IMP24011, ir- rata ta infezzjoni f’ pazjienti taħt il- kura ta ’ Raptiva kien madwar 25. 7% knotra 22. 3% f’ pazjienti fuq plaċebo., F’ każijiet ta ’ infezzjonijiet serji, fuq kollox, fi studji kontrollati kif ukoll dawk li ma kienux kontrollati, sa 12- il sena, kien 2. 8 / 100 patient - years għal dawk il- pazjienti fuq Raptiva, ikkomparat ma ’ 1. 4/ 100 patient- years għal pazjienti fuq plaċebo.
The most frequent serious infections were pneumonia, cellulitis, infections not otherwise specified and sepsis.
L- infezzjonijiet l- aktar serji li ġrew l- iktar spiss kienu pnewmonja, cellulitis, infezzjonijiet mhux speċifiċi u sepsi.
Over long term treatment, the incidence of serious infection was 1.8 per 100 patient years (see section 4.).
F’ kura għal tul ta żmien, l’ inċidenza ta; infezzjoni serja kien ta 1. 8/ 100 patient - years( ara sezzjoni 4. 4).
JC virus infection resulting in PML has been reported in post-marketing surveillance in a patient with psoriasis receiving Raptiva (see section 4.4).
Infezzjoni tal- JC virus riżultanti fil- PML ġiet irrapurtata waqt sorveljanza wara t- tqegħid fis- suq, f' pazjenti li jsofru bil- psorijasi u li kienu qed jieħdu r- Raptiva (ara sezzjoni 4. 4).
Class adverse reactions
8 Reazzjonijiet avversi tal- klassi
Neoplasms benign and malignant:
Neoplasims benign u malignant:
A higher rate of malignancies has been associated with therapies affecting the immune system.
Rata għola ta malinni ġie assoċjat ma ’ terapiji li għandhom effett fuq is- sistema immuni.
In placebo controlled clinical trials, the overall incidences of malignancy (the majority of which were non-melanoma skin cancers) were similar in Raptiva-treated patients and in placebo-treated patients.
Fi studji kliniċi kontrollati minn plaċebo, fuq kollox, ir- rata ta ’ malinni (il- maġorita ’ ta min kienu non - melanoma kanċer tal- ġilda) kienu simili f’ pazjienti fuq Raptiva u pazjienti fuq plaċebo.
In addition, the incidences of specific tumours in Raptiva patients were in line with those observed in control psoriasis populations.
Iktar minn hekk, il- ġrajja ta ’ tumuri speċifiċi f’ pazjienti fuq Raptiva kienu fl- istess linea ma ’ dawk osservati f’ populazzjonijiet psorjażi kkontrollati.
0.9 per 100 patient-years, short term and long term treatment, respectively) (See section 4.4).
Maż- żmien, ma kien ebda evidenza ta riskju żejjed ta ’ xi malinn partikulari, ħlief l- eċċeżżjoni ta ’ ċanċer tal- ġilda li mhuwiex melanoma (0. 3 vs 0. 9 / patient years, kura għal żmien qasir u żmien twil, respettivament) (ara sezzjoni 4. 4).
Inflammatory polyradiculoneuropathy:
Inflammatory polyradiculoneuropathy:
Isolated cases have been observed during post-marketing surveillance.
Kazijiet isolati ġew osservati waqt sorvelljanza wara li l- prodott tpoġġa fuq is- suq.
In a clinical study, where subjects were exposed to higher doses of efalizumab (up to 10 mg/ kg intravenous), one subject receiving 3 mg/ kg intravenous dose experienced hypertension, chills, and fever on the day of study drug dosing, which required hospitalization.
Fi studju kliniku, fejn is- suġġetti kienu esposti għad- doza għola ta ’ efalizumab (sa ’ 10mg/ kg ġol vina), suġġet wieħed li rrċieva doza ta ’ 3mg/ kg fil- vina, esperjienza ipertensjoni, sirdat u deni fil- ġurnata tad - doza tal- droga għall- istudju, li kellhu bżonn li jidħol l- isptar.
Another subject who received 10 mg/ kg intravenous dose experienced severe vomiting following administration of efalizumab, which also required hospitalization.
Suġġett ieħor li rrċieva doża ta ’ 10mg/ kg ġol vina esperjienza rrimettar severa wara l- amministrazzjoni ta ’ efalizumab, li wkoll kellu bżonn li jidħol l- isptar.
Both occurrences fully resolved without any sequelae.
It- tnejn li huma fiequ mingħajr konsegwenzi.
Doses up to 4 mg/ kg/ week subcutaneously for 10 weeks have been administered without any toxic effect.
Dożi sa 4mg/ kg/ ġimgħa taħt il- ġilda ngħataw għal 10 ġimgħat mingħajr effetti tossiċi.
There is no known antidote to Raptiva or any specific treatment for Raptiva overdose other than withholding treatment and patient observation.
Ma hemx mediċina magħrufa li għandha effett sabiex tikkanċella l- effett ta ’ Raptiva, jew xi kura speċifika għal doża eċċessiva ta ’ Raptiva.
In case of overdose, it is recommended that the patient be monitored under close medical care and appropriate symptomatic treatment instituted immediately.
F’ kaz ta ’ doża eċċessiva, huwa rrakomandat li l- pazjient jiġi osservat taħt kura mill- qrib u jingħata kura sistemika addattata immedjatament.
Pharmacotherapeutic group: selective immunosuppressive agents, ATC code:
Kategorija farmakoterapewtika: selective immunosuppressive agents, Kodiċi ATC code:
L04AA21
LO4AA21
Mechanism of action Efalizumab is a recombinant humanized monoclonal antibody that binds specifically to the CD11a subunit of LFA-1 (lymphocyte function-associated antigen-1), a leukocyte cell surface protein.
Mod ta ’ kif jaħdem Efalizumab huwa monoclonal antikorpu umanizzat rikombinat li jorbot speċifikament mas- subunit CD11a ta ’ LFA- 1 (lymphocyte function- associated antigen- 1), proteina li tinsab fuq il- wiċċ taċ- ċellula lewkoċita.
By this mechanism, efalizumab inhibits the binding of LFA-1 to ICAM-1, which interferes with T lymphocytes adhesion to other cell types.
B’ dan il- mekkanizmu, efalizumab jipprevjieni ir- rabta ta ’ LFA- 1 ma ’ ICAM- 1, li jinterferi mat - tkaħħil ta ’ T - limfoċiti ma ’ tipi ta ’ ċelluli oħrajn.
LFA-1 is present on activated T lymphocytes, and ICAM-1 is up-regulated on endothelial cells and keratinocytes in psoriasis plaques.
LFA- 1 huwa presenti fuq T- limfoċiti, u ICAM- 1 huwa jiżdied fuq iċ- ċelluli endothelial u keratinoċiti fi plakki ta ’ psorjażi.
By preventing LFA-1/ ICAM binding, efalizumab may alleviate signs and symptoms of psoriasis by inhibiting several stages in the immunologic cascade.
Meta jiġi pprevenut ir- rabta LFA- 1/ ICAM, efalizumab jista ’ jonqos is- sinjali u s- simptomi ta ’ psorjażi billi jipprevieni ċerti passi fil- cascade immunoloġika.
Pharmacodynamic effects In studies using an initial dose of 0.7 mg/ kg followed by 11 weekly doses of 1.0 mg/ kg, efalizumab maximally reduced expression of CD11a on circulating T lymphocytes to approximately 15-30% of pre-dose baseline values and saturated CD11a to < 5% of baseline available CD11a binding sites.
Effetti farmakodinamiċi Fi studji, fejn intuża doża iniżjali ta ’ 0. 7mg/ kg, issegwit minn 11- il ġimgħa ta ’ doża kull ġimgħa ta ’ 1. 0% mg/ kg, efalizumab naqqas, b’ effett massimu, l- espressjoni ta ’ CD11a fuq T- limfoċiti fiċ - ċirkulazzjoni, għal madwar 15- 30% tal- valuri tal- linea basi qabel id- doża u CD11a ssaturat għal < 5% tal- linea basi li hemm CD11a siti għar- rabta.
The full effect was seen 24 to 48 hours after the first dose, and was maintained between weekly doses.
L- effett komplut inara 24- 48- il sigħa wara l- ewwel doża, u kien mantenut bejn doża li ngħataw kull ġimgħa.
Within 5 to 8 weeks following the 12th and final dose of efalizumab administered at 1.0 mg/ kg/ wk, CD11a levels returned to within a range of ±25% of baseline values.
Fi 5- 8 ġimgħat wara it- 12 ‘ l- doża and l- aħħar doża ta efalizumab amministrat ta ’ 1. 0mg/ kg/ ġimgħa, il- livelli ta ’ CD11a reġgħu ritornaw fil- firxa ta ’ ±25% tal- valuri tal- linea basi.
Another pharmacodynamic marker, consistent with the mechanism of action of efalizumab, was the increase in the absolute counts of circulating leukocytes observed during efalizumab treatment.
9 Marker ieħor farmakodinamiku, li huwa konsistenti mal- mod ta ’ kif jaħdem efalizumab, kien iz- zieda fin- numri assoluti tal- lewkoċiti fiċ- ċirkulazzjoni li ġie osservat waqt il- kura ma ’ Raptiva.
Increased absolute counts were apparent within 24 hours of the first dose, remained elevated with weekly dosing, and returned to baseline after treatment cessation.
Zieda fin - numri assoluti deher fi 24- il sigħa wara l- ewwel doża, baqa ’ elevat ma ’ doża ta ’ kull ġimgħa, u reġa ’ għal- linea ta ’ basi wara li twaqqaf il- kura.
The largest increase occurred in the absolute count of circulating lymphocytes.
L- akbar zieda ġara fin- numri assoluti tal- lewkoċiti fiċ - ċirkulazzjoni.
In clinical trials, mean lymphocyte counts approximately doubled relative to baseline in subjects receiving 1.0 mg/ kg/ wk of Raptiva.
Fi studji kliniċi, in- numru medja tal- limfoċiti sar madwar doppju tal- linea ta ’ basi, f’ dawk is- suġġetti li rrċevew 1. 0mg/ kg/ ġimgħa ta ’ Raptiva.
The increase included CD4 T-lymphocytes, CD8 T-lymphocytes, B-lymphocytes, and natural killer (NK) cells, although NK cells and CD4 cells increased less relative to other cell types.
Iz- zieda tinkludi CD4 T- limfoċiti, CD8 T - limfoċiti, B- limf006ċiti u ċelluli natural killer (NK), anke jekk iċ- ċelluli NK u CD4 zdiedu inqas, meta kkomparat ma ’ ċelluli ta tipi oħrajn.
At a dose of 1.0 mg/ kg/ wk subcutaneous efalizumab, lymphocyte levels returned to within 10% of baseline by 8 weeks post last dose.
B’ doża ta ’ 1. 0mg/ kg/ ġimgħa efalizumab li jingħata taħt il- ġilda, il- livelli tal- limfoċiti reġa ’ nizel għal 10% tal- linea basi sat- 8 ġimgħa wara l- aħħar doża.
Clinical efficacy The efficacy of Raptiva versus other systemic therapies in patients with moderate to severe psoriasis has not been evaluated in studies directly comparing Raptiva with other systemic therapies.
Effikaċja klinika L- effikaċja ta ’ Raptiva kontra terapiji sistemiċi oħrajn f’ pazjienti b’ psorjażi moderata – severa, għadu ma ġiex evaluat fi studji li jikkomparaw direttament Raptiva ma ’ terapiji sistemiċi oħrajn.
The present results of Raptiva versus placebo over 12 weeks of treatment with different populations indicate a PASI 75 response to Raptiva in 22% to 39% of patients (see Table 2).
Ir- riżultati t’ issa ta ’ Raptiva kontra plaċebo f’ 12- il ġimgħa ta kura f’ populazzjonijiet differenti juru PASI 75 respons għal Raptiva f’ 22% sa 39% ta pazjienti (ara Medja 2).
Based on the clinical development data generated (see Table 1) and long-term experience, Raptiva is recommended for use in patients as defined in section 4.1.
Ibbasat fuq l- nformazzjoni ta ’ l - izvilupp kliniku li tħarreġ (ara Medja 1) u esperjienza ta ’ żmien twil, Raptiva huwa rrakomandat għall- użu f’ pazjienti kif inhu definit fi sezzjoni 4. 1.
Failure on prior systemic therapies is defined as insufficient response (PASI < 50 or PGA less than good), or worsening of disease in patients while on treatment, and who were adequately dosed for a sufficiently long duration to assess response with at least each of the 3 major systemic therapies as available.
Fallament fuq terapji sistemiċi li ntużaw qabel, huwa definit bħala risposta insuffiċenti (PASI < 50 jew PGA inqas minn tajjeb) jew pazjienti li l- marda tagħhom jsir iktar għar waqt il- kura, u li rrċevew doża mhux adegwata għal żmien twil suffiċenti sabiex wieħed jeżamina risposta, b’ kull minn tlett terpaiji sistemiċi kif inhu disponibbli.
The safety and efficacy of Raptiva in moderate to severe plaque psoriasis patients has been demonstrated in five randomized, double-blind, placebo-controlled trials at the recommended dose (n=1742).
(n= 1742).
There are no comparative data with Raptiva versus other systemic psoriasis therapies.
Ma hemx informazzjoni li tikkompara Raptiva ma ’ terapiji sistemiċi oħra għal psorjażi.
The largest study IMP24011 (n=793) included patients (n=526) who were not controlled by, contraindicated to, or intolerant to two or more systemic therapies as judged from the patients’ histories of psoriasis treatment.
L- akbar studju IMP24011 (n=793) inklu\ a pazjienti (n=526) li ma kienux kontrollati minn, ma kienux kontra- indikati għal, jew intoleranti għal tnejn jew aktar terapji sistemiċi kif inhu ġġudikat mill- passat tal- kura għal psorjażi tal- pazjienti.
In all studies, the primary endpoint was the proportion of patients with a ≥ 75% improvement in the Psoriasis Area and Severity Index score (a PASI 75 response) relative to baseline when assessed one week after a 12-week treatment course.
Fl- istudji kollha, il- puntu ta ’ l- aħħar primarja kien il- proporzjoni ta ’ pazjienti bi titjieba ta ’ ≥ 75% fil Psoriasis Area and Severity Index score (PASI 75 risposta), relattata mal- linea ta ’ basi, meta ġie ezaminat ġimgħa wara kors ta ’ kura ta ’ 12- il ġimgħa.
Secondary endpoints included the proportion of subjects who achieved a rating of Minimal or Clear on a static global assessment by the physician, the Overall Lesion Severity (OLS), the proportion of patients with a ≥ 50% improvement in 9 PASI score (a PASI 50 response) relative to baseline after 12 weeks of treatment, the time-course of mean PASI percentage improvement from baseline, improvement in the Dermatology Life Quality Index (DLQI), Psoriasis Symptom Assessment (PSA), the Physician’ s Global Assessment (PGA) of change, change in the PASI thickness component, and change in the body surface area affected.
Punti ta ’ l- aħħar secondarji kienu l- proporzjoni ta suġġetti li kellhom rata ta Minimal jew Clear fuq static global assessment min l- ispeċjalist, il Overall Lesion Severity (OLS), il- proporzjoni ta ’ pazjienti bi titjieba ta ’ ≥ 50% fil - PASI score (PASI 50 risposta) relattata mal- linea ta ’ basi wara 12- il ġimgħa ta ’ kura, it- tul tal - kors tal- medja titjieba ta ’ PASI perċentaġġ mil- linea ta ’ basi, titjieba fil - Dermatology Life Quality Index (DLQI), Psoriasis Symptom Assessment (PSA), Physician’ s Global Assessment (PGA) ta ’ kambju, kambju fil- ħxuna tal - komponiment ta ’ PASI, u bidla fil- partijiet tal- ġisem li huma affetwati.
In all five studies, patients randomized to the Raptiva group achieved statistically significantly better responses than placebo on the primary endpoint.
Fil - ħames studji, pazjienti li kienu fil - grupp ta ’ Raptiva għal adoċċ, kellhom risposti statistikament sinikanti aħjar minn plaċebo għal puntu ta ’ l- aħħar primarja.
The same results were confirmed in patients that were unsuitable for other systemic therapies (see Table 1 below).
((ara Mejda 1 taħt).
Table 1 Primary Endpoint:
10 Mejda 1 Puntu ta ’ l- a]] ar Primarja:
Proportion of Subjects with ≥ 75% improvement in PASI after 12 weeks of Treatment (PASI 75) Efalizumab a
Proporzjoni ta ’ Pazjienti bi titjieba ta ’ ≥75% improvement fi PASI wara 12- il ġimgħa ta ’ kura (PASI 75) Efalizumab a
Patient population IMP24011
Populazzjoni ta ’ Pazjienti IMP24011
1.0 mg/ kg/ wk
1. 0 mg/ kg/ wk
Treatment Effect [95% CI]
Effett tal - Kura [95% CI]
All patients
Pazjienti Kollha
Patients who are not controlled by,
Pazjienti li ma kienux ikkontrollati ma, li
contraindicated to, or intolerant to two or more systemic therapies *
setgħu jieħdu, jew kienu intolleranti għal tnejn jew aktar kuri sistemiċi * a
(n=342) b
(n=342)
p-values compared efalizumab with placebo using logistic regression including baseline PASI score, prior treatment for psoriasis and geographical region as covariates. b p < 0.001. * As judged from the patients’ histories of psoriasis treatments
p- values ikkomparaw efalizumab ma ’ plaċebo bl- użu ta ’ logistic regression, inkluz linea ta ’ basi PASI score, kura li ntuża qabel għal psorjażi, u reġjun ġeografiku bħal covariates. b p < 0. 001. kif kien iġġudikat mill- passat tal- pazjienti tal- kuri għal psorjażi *
In all five studies, patients randomized to the Raptiva dose group achieved statistically significantly better responses than placebo on the primary endpoint (PASI 75 response) (see Table 2 below) and on all the secondary efficacy endpoints.
Fil - ħames studji, pazjienti li kienu fil - grupp ta ’ Raptiva għal adoċċ, kellhom risposti statistikament sinifikanti aħjar minn plaċebo għal puntu ta ’ l- aħħar primarja (PASI 75 risposta) (ara Mejda 2 taħt) u fuq il- punti ta ’ l- aħħar sekondarji kollha.
Table 2 Primary Endpoint:
Mejda 2 Puntu ta ’ l- aħħar Primarja:
Proportion of Subjects with ≥ 75% improvement in PASI after 12 weeks of Treatment (PASI 75)
Proporzjoni ta ’ Pazjienti bi titjieba ta ’ ≥75% improvement fi PASI wara 12- il ġimgħa ta ’ kura (PASI 75)
1.0 mg/ kg/ wk Treatment Effect [95% CI]
1. 0 mg/ kg/ wk Effett tal- Kura [95% CI]
10 a IMP24011: p-values compared efalizumab with placebo using logistic regression including baseline PASI score, prior treatment for psoriasis and geographical region as covariates.
IMP24011: p- values ikkomparaw efalizumab ma ’ plaċebo bl- użu ta ’ logistic regression, inkluz linea ta ’ basi PASI score, kura li ntuża qabel għal psorjażi, u reġjun ġeografiku
Other studies: p-values compared each efalizumab group with placebo using Fisher’ s exact test within each study. b p < 0.001.
bħal covariates. efalizumab group with within each study. p < 0. 001.
The efalizumab used in the study is the Genentech manufactured product
L- efalizumab użat fl- istudju huwa l- prodott manifatturat minn Genentech
Time to relapse (≥ 50% loss of improvement) was evaluated in Study ACD2058g and IMP 24011 for patients who were classified as responders (≥ 75% improvement on PASI) after 12 weeks of treatment.
Iż- żmien sakemm terġa toħroġ il- marda (≥50% nuqqas ta ’ miljorament) kien evaluat fl- Istudju ACD2058g u IMP 24011 għal pazjienti li ġew ikklassifikati bħal responders (≥ 75% miljorament fuq il PASI) wara 12- il ġimgħa ta ’ kura.
The median time to relapse among PASI responders ranged from 58 to 74 days following the last Raptiva dose in the initial treatment period.
Iż- żmien medju sakemm terġa toħroġ il- marda fost il - PASI responders kien bejn 58 – 74 – il ġurnata wara l- aħħar doża ta ’ Raptiva, fil- perijodu iniziali tal- kura.
In study IMP24011, approximately half of the patients (46.8%) who were partial responders (50% to 74% improvement on PASI, similar to PGA good) after 12 weeks of Raptiva treatment achieved a PASI 75 response at week 24.
Fl- istudju IMP24011, madwar nofs mil pazjienti (46. 8%) li kienu responders parzjali (50% sa 74%
Long-term treatment:
Kura għal żmien twil:
Data from extended treatment (more than 12 weeks) have been obtained from 4311 patients in open label uncontrolled studies.
Informazzjoni taż- żmien twil (iktar minn 12 ġimgħat) kienu kisbien minn 4311 pażjienti f’ istudju ‘ open label ’ mhux ikkontrollat.
Over 600 patients have been treated for more than 1 year including 166 patients treated for more than 2 years and up to 3 years.
Aktar minn 600 pażjienti kienu taħt il- kura għal minn sena inklużi 166 pażjienti ikkurati għal aktar minn 2 snin sa 3 snin.
Approximately half of the patients treated for more than 1 year were PASI 75 responders (when all dropouts were considered as non-responders).
Madwar nofs il- pazjienti taħt il- kura għal aktar minn sena kienu PASI 75 responders (meta dawk kollha li twaqqfu kienu ikkonsidrati bħala non - responders).
After subcutaneous administration of efalizumab peak plasma concentrations are reached after 1- 2 days.
Wara l- ammistrazzjoni taħt il- ġilda ta ’ efalizumab l- ogħla konċentrazzjonijiet tal- plażma seħħew wara 1- 2 ġurnata.
Comparison with intravenous data indicated an average bioavailability of about 50% at the recommended dose level of 1.0 mg/ kg/ wk subcutaneous.
Meta wieħed jikkompara dan ma ’ l- informazzjoni ta ’ meta jingħata ġol - vina, hemm biodisponibilta ’ medja ta ’ 50% meta jingħata id- doża rrakkomandata ta ’ 1. 0mg/ kg/ ġimgħa taħt il - ġilda.
Steady state was achieved at week 4.
Livell fiss intlaħaq fl- 4 ġimgħa.
At the 1 mg/ kg/ wk dose level (with an initial dose of 0.7 mg/ kg the first week), mean efalizumab plasma trough values were 11.1±7.9 µg/ ml.
Fil- livell ta ’ 1mg/ kg/ ġimgħa (b’ doża iniziali ta ’ 0. 7mg/ kg l- ewwel ġimgħa), il- valuri medji l- aktar baxxi ta ’ efalizumab fil- plażma kienu 11. 1±7. 9 µg/ ml.
Measurements of volume of distribution of the central compartment after single intravenous doses were 110 ml/ kg at dose 0.03 mg/ kg and 58 ml/ kg at dose 10 mg/ kg.
Miżuri tal - volum tad- distribuzzjoni tal- kompartiment ċentrali wara dożi singolari fil- vina kienu 110mg/ kg fi doża ta ’ 0. 03mg/ kg u 58ml/ kg fi doża ta ’ 10mg/ kg.
The metabolism of efalizumab is through internalisation followed by intracellular degradation as a consequence of either binding to cell surface CD11a or through endocytosis.
Il- metaboliżmu ta ’ efalizumab huwa permess ta ’ internalisation issegwit minn intracellular degradation bħala konsegwenza jew ta ’ rabta ma ’ wiċċ tal- ċellula CD11a jew ta ’ endoċitosi.
The expected degradation products are small peptides and individual amino acids which are eliminated by glomerular filtration.
Il- prodotti li huma mistennin wara d- degradazzjoni huma peptidi żgħar u amino aċidi individuali li jiġu eliminati permess ta ’ filtrazzjoni glomerulari.
Cytochrome P450 enzymes as well as conjugation reactions are not involved in the metabolism of efalizumab.
L- enżimi Cytochrom P450, kif ukoll reazzjonijiet ta ’ konġugazzjoni mhumiex involuti fil- metaboliżmu ta ’ efalizumab.
Efalizumab is cleared by nonlinear saturable elimination (dose dependent).
Efalizumab jiġi eliminat permezz ta ’ nonlinear saturable elimination (doża- dipendenti).
Mean steady state clearance is 24 ml/ kg/ day (range 5-76 ml/ kg/ day) at 1 mg/ kg/ week subcutaneous.
Il- valur medju ta ’ l- eliminazzjoni fiss huwa 24ml. kg/ ġurnata (firxa ta ’ 5- 76 ml/ kg/ ġurnata) għal 1mg/ kg/ ġimgħa doża taħt il- ġilda.
The elimination half-life was about 5.5-10.5 days at 1 mg/ kg/ week subcutaneous.
Il half- life tal- eliminazzjoni kien ta ’ madwar 5. 5- 10. 5 ġranet għal doża ta ’ 1mg/ kg/ ġimgħa.
Tend at steady state is 25 days (range 13-35 days).
Tend fi fiss huwa 25 ġurnata (firxa ta ’ 13- 35 ġranet).
Weight is the most significant covariate affecting efalizumab clearance.
Il- piż huwa il- varjanti l- aktar sinjifikanti li jaffetwa l- eliminazzjoni ta ’ efalizumab.
Non-linearity:
Non- linearity:
Efalizumab shows dose-dependent nonlinear pharmacokinetics which can be explained by its saturable specific binding to cell surface receptors CD11a.
Efalizumab juri farmakokinetika li hija nonlinear, doża- dipendenti li jista ’ jiġi mifthemi mir- rabta spe1ifika saturata ma ’ riċetturi fil- wiċċ taċ- ċelluli CD11a.
It appeared that the receptor mediated clearance of efalizumab was saturated when plasma efalizumab concentrations were above 1 μ g/ ml.
Ġie osservat li l- eliminazzjoni ta ’ efalizumab li hu medjat minn riċetturi kien saturat meta il- konċentrazzjonijiet ta ’ efalizumab ġol plażma kienu ‘ l fuq minn 1 μg/ ml.
Through population pharmacokinetic analysis, weight was found to affect efalizumab clearance.
Minn analażi farmakokinetiċi ta ’ populazzjoni, instab li l- piż jaffatwa l- eliminazzjoni ta ’ efalizumab.
Covariates as baseline PASI, baseline lymphocyte count and age had modest effects on clearance;
Varjanti bħal linea ta ’ basi PASI, linea ta ’ basi ta ’ l- ammont ta ’ limfoċiti w eta ’ kellhom effett moderata fuq l- eliminazzjoni; is- sess u l- oriġini etniku ma kellhomx effett.
The pharmacokinetics of efalizumab in paediatric patients have not been studied.
Il- farmakokinetika ta ’ efalizumab f’ pazjienti pediatrika ma ġewx issudjati.
The effect of renal or hepatic impairment on the pharmacokinetics of efalizumab has not been studied.
L- effett ta ’ indeboliment ta ’ fwied jew kliewi fuq il- farmakokinetika ta ’ efalizumab ma ġiex issudjat.
Antibodies to efalizumab were detected in only 6% of patients evaluated.
Anitkorpji għal efalizumab kienu skopruti biss f’ 6% ta ’ pazjienti evaluatati.
In this small number of patients no differences were observed in either pharmacodynamic or pharmacokinetic parameters.
F’ dan in- numru iżgħar ta ’ pazjienti ma ġewx osservati xi differenżi la fil- parametri farmakodinamiċi jew farmaokokientiċi.
Efalizumab does not cross-react with CD11a from species other than humans and chimpanzees.
Efalizumab ma jagħmilx cross- reaction ma CD11a minn species oħrajn barra minn umani u ċimpanzi.
Therefore, conventional non-clinical safety data with the medicinal product are limited and do not allow for a comprehensive safety assessment.
12 ma jitħalliex għal eżami tas- sigurta komrensiva.
Inhibitory effects were observed on the humoral and T-cell dependent immune responses.
Effetti ħabitarji kienu osservati fuq ir- rispoti immuni li huma dipendenti fuq ċelluli- T u humoral.
In pups of mice treated with an antibody analogue of efalizumab, a decrease in T-cell dependent immunity was observed up to at least 11 weeks of age.
Fiż- żgħar ta ’ ġrieden li ħadu analogu ta ’ l- antikorpju ta ’ efalizumab, kien osservat nuqqas ta ’ l- immunita ’ taċ- ċelluli T- dipendenti, sa minn l- inqas 11- il ġimgħa t’ eta ’.
Only at 25 weeks of age was this decrease no longer significant.
Dan in- nuqqas ma kienx sinjifikanti biss fi 25 ġimgħat t’ eta ’.
Otherwise, the effects observed in non-clinical studies could be related to the pharmacology of efalizumab.
Inkella, l- effetti osservati fi studji mhux kliniċi jistgħu jkunu rrelatati mal- farmakoloġija ta ’ efalizumab.
No lymphomas were observed following 6 months treatment with an antibody analogue of efalizumab in a 6 months study with p53 +/ + wild type mice.
Ma kienux osservati limfomas 6 xhur wara kura ma analogu ta ’ l- antikorpju ta ’ efalizumab fi studju ta ’ 6 xhur ma ’ p53+/ + wild type ġrieden.
No teratogenic effects were seen in mice during organogenesis.
Ma kienux osservati effetti teratoġeniċi fil- ġrieden waqt organoġenesi.
Polysorbate 20 Histidine Histidine hydrochloride monohydrate Sucrose
Trab għal soluzzjoni għall- injezzjoni Polisorbat 20 Histidine Hisitidine hydrochloride monohydrate Sukrożju
Water for injections
Ilma għal injezzjoni
4 years.
4 snin
After reconstitution, an immediate use is recommended (see also section 6.4).
Wara rikostituzzjoni, l- użu mmedjat huwa rrakomandat (ara sezzjoni 6. 4).
From a microbiological point of view, the product should be used immediately after first opening and reconstitution.
Mill- lat mikrobiolo[ iku, il- prodott irid jintuża immedjatament wara li jinfetaħ għall- ewwel darba u jiġi rrikonstitwit.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.
Jekk ma jintużax immedjatament, iż- żmien ta ’ in- use storage u kondizzjonijiet qabel l - użu huma r- responsabilita ’ ta ’ dak li qed jużah u normalment dan ma jkunx aktar minn 24 sigħat f’ temperatura ta ’ 2°C - 8°C, sakemm ir- rikostituzzjoni ma sarx taħt kondizzjonijiet kontrollati u asettiċi.
Physico-chemical stability of the reconstituted product has been shown for 24 hours at 2°C to 8°C.
L- istabilta ’ fisjo- kimika tal- prodott rikostitut kien dimostrat għal 24 sigħat f’ temperatura ta ’ 2°C - 8°C.
Colourless type I glass vial with a butyl rubber stopper, and aluminium seal fitted with a flip-off plastic cap.
Vjala tal- ħġieġ (tip 1) bla kulur magħluqa b’ tappijiet tal - butil ipproteġuti b' siġill ta ’ l- aluminju u tappijiet li jfaqqaw f' posthom.
Type I glass pre-filled syringe.
Siringa lesta għal l- użu tal- ħġieġ tat- tip 1.
Raptiva is available in:
13 Raptiva huwa disponibbli fi:
Packs of 1 vial of powder, 1 pre-filled syringe of solvent, 1 EasyMIX adapter for reconstitution and 1 needle for injection.
Pakketti ta ’ vjala waħda ta ’ trab, siringa mimlija lesta għal l- użu ta ’ solvent, EasyMIX adaptor għal rikostituzzjoni, u labra għall- injezzjoni.
Packs of 4 vials of powder, 4 pre-filled syringes of solvent, 4 EasyMIX adapters for reconstitution and 4 needles for injection.
Pakketti ta ’ 4 vjali ta ’ trab, 4 siringi mimlijien lesti għal l- użu ta ’ solvent, 4 EasyMIX adaptors għal rikostituzzjoni, u 4 labar għall- injezzjoni.
Packs of 12 vials of powder, 12 pre-filled syringes of solvent, 12 EasyMIX adapters for reconstitution and 12 needles for injection.
Pakketti ta ’ 12 vjali ta ’ trab, 12 siringi mimlijien lesti għal l- użu ta ’ solvent, 12 EasyMIX adaptors għal rikostituzzjoni, u 12 labar għall- injezzjoni
Raptiva is for single use only.
Raptiva huwa għall- użu singolari biss.
One vial of Raptiva should be reconstituted with the solvent before use.
Vjala waħda ta ’ Raptiva jrid jiġi rrkositut mas- solvent qabel l- użu.
Reconstitution of the single- use vial with 1.3 ml of the supplied water for injections yields approximately 1.5 ml of solution to deliver 100 mg per 1 ml of Raptiva.
Rikostituzzjoni tal- vjala ta ’ użu singolari ma ’ 1. 3ml ta ’ l- ilma għal injezzjoni li huwa xxuplit, jagħti madwar 1. 5ml ta ’ soluzzjoni sabiex jagħti 100mg/ 1ml ta ’ Raptiva.
The maximum retrievable dose is 125 mg per 1.25 ml of Raptiva.
Id- doża massima li tista ’ tittiħed huwa 125mg għal kull 1. 25ml ta ’ raptiva.
The solution should reconstitute in not more than 5 minutes.
Is- soluzzjoni suppost jkun rikostitut f’ mhux aktar minn 5 minuti.
The reconstituted solution is a clear to slightly opalescent, colourless to pale yellow solution, and should not be administered if it contains particles or is not clear.
Is- soluzzjoni rrikostitut huwa ċar għal xi ftit opalexenti, soluzzjoni mingħajr kulur għal isfar ċar, u ma jistgħax jiġi amministrat jekk ikun fih biċċiet jew ma jkunx ċar
Detailed instructions for use are provided in the package leaflet.
Informazzjoni għall- użu f’ aktar dettal tinsab fil fuljett ta ’ tagħrif.
20 September 2004
20 Settembru 2004
MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
MANIFATTUR( I) TAS- SUSTANZA BIJOLOĠIKA ATTIVA U DETENTUR( I) TA ’ L- AWTORIZZAZZJONI TAL - MANIFATTURA RESPONSABBLI GĦALL- HRUĠ TAL - LOTT
15 A MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
MANIFATTUR( I) TAS- SUSTANZA BIJOLOĠIKA ATTIVA U DETENTUR (I) TA ’ L - AWTORIZZAZZJONI TAL- MANIFATTURA RESPONSABBLI GĦALL- HRUĠ TAL - LOTT
Merck Serono S. p. A.
Merck Serono S. pA.
Einaudi 11, 00012 Guidonia Montecelio (Rome) Italy
Einaudi 11, 00012 Guidonia Montecelio (Rome) Italy