qanastek/EMEA-V3 huggingface dataset:
The risk-benefit profile for romiplostim has not been established in MDS or other non-ITP patient populations.
Il- profil ta ’ riskju - benefiċċju għal romiplostim ma kienx stabbilit f’ MDS jew f’ popolazzjonijiet oħra ta ’ pazjenti li m’ għandhomx ITP.
In a single-arm, open-label clinical study of treatment with romiplostim in patients with MDS, there were reported cases of progression to acute myeloid leukaemia (AML), however this is an expected clinical outcome of MDS and the relationship to romiplostim treatment is unclear.
Fi studju kliniku open- label bi grupp wieħed, ta ’ kura b’ romiplostim f’ pazjenti b’ MDS, kienu rrapportati każijiet ta ’ żvilupp ta ’ lewkimja mijelojda akuta (AML), madankollu dan huwa riżultat kliniku mistenni ta ’ MDS u r- rabta mal- kura ta ’ romiplostim mhix ċara.
In addition, cases of transient blast cell increases were observed in this study.
Barra minn hekk, f’ dan l- istudju kienu osservati każijiet ta ’ żjidiet temporanji ta ’ ċelluli blastiċi.
The transient blast cell increases were reversible upon discontinuation of romiplostim.
Dawn iż- żjidiet temporanji ta ’ ċelluli blastiċi kienu riversibbli mal- waqfien ta ’ romiplostim.
Therefore this observation is inconsistent with progression to AML.
Għalhekk din l - osservazzjoni mhix konsistenti ma ’ żvilupp ta ’ AML.
It is not possible to distinguish leukaemic blasts from normal blasts.
Mhux possibbli li tiddistingwi blasti lewkimiċi minn blasti normali.
Loss of response to romiplostim
Telf ta ’ rispons għal romiplostim
A loss of response or failure to maintain a platelet response with romiplostim treatment within the recommended dosing range should prompt a search for causative factors, including immunogenicity (see section 4.8) and increased bone marrow reticulin (see above).
Telf ta ’ rispons jew falliment li jinżamm rispons tal- plejtlits b’ kura ta ’ romiplostim fil- firxa ta ’ dożaġġ irrakkomandat għandu jwassal għal tfittxija għall- fatturi li qed jikkawżaw dan, inkluż immunoġeniċità (ara sezzjoni 4. 8) u żjieda fir- retikulin tal- mudullun tal- għadam (ara fuq).
Effects of romiplostim on red and white blood cells
Effetti ta ’ romiplostim fuq ċelluli ħomor u bojod tad- demm
Alterations in red (decrease) and white (increase) blood cell parameters have been observed in non- clinical toxicology studies (rat and monkey) but not in ITP patients.
Fi studji mhux kliniċi dwar it- tossiċità (far u xadina) kienu osservati bidliet fil- parametri taċ- ċelluli ħomor (tnaqqis) u bojod (żjieda) tad- demm, iżda dan ma kienx osservat f’ pazjenti b’ ITP.
Monitoring of these parameters should be considered in patients treated with romiplostim.
Għandha tiġi kkunsidrata sorveljanza ta ’ dawn il- parametri f’ pazjenti kkurati b’ romiplostim.
The potential interactions of romiplostim with co- administered drugs due to binding to plasma proteins remain unknown.
L- interazzjonijiet potenzjali ta ’ romiplostim ma ’ mediċini mogħtija fl - istess waqt minħabba rbit mal- proteini fil- plażma għadhom mhux magħrufa.
Medicinal products used in the treatment of ITP in combination with romiplostim in clinical studies included corticosteroids, danazol, and/ or azathioprine, intravenous immunoglobulin (IVIG), and anti-D immunoglobulin.
Prodotti mediċinali wżati fil- kura ta ’ ITP f’ taħlita ma ’ romiplostim fl- istudji kliniċi jinkludu kortikosterojdi, danazol, u/ jew azathioprine, immunoglobulin mogħti fil- vini (IVIG), u immunoglobulin anti- D.
Platelet counts should be monitored when combining romiplostim with other medicinal products for the treatment of ITP in order to avoid platelet counts outside of the recommended range (see section 4.2).
L- għadd tal- plejtlits għandu jiġi ssorveljat meta romiplostim jitħallat ma ’ prodotti mediċinali oħra wżati fil- kura ta ’ ITP sabiex jiġi evitat għadd ta ’ plejtlits barra mill- firxa rrakkomandata (ara sezzjoni 4. 2).
Corticosteroids, danazol, and azathioprine use may be reduced or discontinued when given in combination with romiplostim (see section 5.1).
L- użu ta ’ kortikosterojdi, danazol, u azathioprine jista ’ jiġi mnaqqas jew imwaqqaf meta dawn jingħataw flimkien ma ’ romiplostim (ara sezzjoni 5. 1).
Platelet counts should be monitored when reducing or discontinuing other ITP treatments in order to avoid platelet counts below the recommended range (see section 4.2).
L- għadd tal- plejtlits għandu jiġi ssorveljat meta jitnaqqsu jew jitwaqqfu terapiji oħra għall- ITP sabiex jiġi evitat għadd tal- plejtlits taħt il- firxa rrakkomandata (ara sezzjoni 4. 2).
For romiplostim no clinical data on exposed pregnancies are available.
Għal romiplostim m’ hemmx tagħrif kliniku dwar l- użu waqt it- tqala.
Studies in animals have shown reproductive toxicity, such as transplacental passage and increased foetal platelet counts in rats (see section 5.3).
Studji fuq bhejjem urew ħsara fuq is- sistema riproduttiva, bħal passaġġ mill- plaċenta u żjieda fl- għadd ta ’ plejtlits tal- fetu fil- firien (ara sezzjoni 5. 3).
Romiplostim should not be used during pregnancy unless clearly necessary.
Romiplostim m’ għandux jintuża waqt it- tqala jekk m’ hemmx bżonn ċar.
There are no data on excretion of romiplostim in human milk.
M’ hemmx tagħrif dwar l- eskrezzjoni ta ’ romiplostim fil- ħalib tal- omm.
However, excretion is likely and a risk to the suckling child cannot be excluded.
Madankollu, eskrezzjoni hija probabbli u ma jistax jiġi eskluż riskju għat- tarbija li qed terda ’.
5 A decision on whether to continue/ discontinue breast-feeding or to continue/ discontinue therapy with romiplostim should be made taking into account the benefit of breast-feeding to the child and the benefit of romiplostim therapy to the woman.
Deċiżjoni dwar jekk għandux jitkompla/ jitwaqqaf it- treddigħ jew titkompla/ titwaqqaf it- terapija b’ romiplostim għandha tittieħed billi tikkonsidra l- benefiċċju tat- treddigħ għat- tarbija u l- benefiċċju ta ’ terapija b’ romiplostim għall- omm.
However, patients should be informed that in clinical trials mild to moderate, transient bouts of dizziness were experienced by some patients, which may affect the ability to drive or use machines.
Madankollu, l- pazjenti għandhom jiġu nfurmati li fil- provi kliniċi xi pazjenti kellhom esperjenza ta ’ episodji temporanji ta ’ sturdament ta ’ natura ħafifa sa moderata, li tista ’ taffettwa l- ħila biex issuq jew tħaddem magni.
Based on an analysis of all adult ITP patients receiving romiplostim in 4 controlled and 5 uncontrolled clinical studies, the overall subject incidence of all adverse events for romiplostim-treated subjects was 91.5% (248/ 271).
Ibbażat fuq analiżi tal- pazjenti adulti b’ ITP kollha li ngħataw romiplostim f’ 4 studji kliniċi kkontrollati u 5 mhux ikkontrollati, l- inċidenza globali fl- individwi ta ’ l- effetti avversi kollha għall - individwi kkurati b’ romiplostim kienet 91. 5% (248/ 271).
The mean duration of exposure to romiplostim in this study population was 50 weeks.
It- tul medju ta ’ espożizzjoni għal romiplostim f’ din il- popolazzjoni fl- istudju kien 50 ġimgħa.
The adverse events listed in the table below are those deemed treatment related by investigators and which occur at a > 1% incidence (n = 271).
L- avvenimenti avversi mniżżla fit- tabella hawn taħt huma dawk meqjusa mill- investigaturi bħala relatati mal- kura u li jseħħu b’ inċidenza ta ’ > 1% (n = 271).
Frequencies are defined as:
Il- frekwenzi huma definiti bħala:
Very common (≥ 1/ 10) and Common (≥ 1/ 100 to < 1/ 10).
Komuni ħafna (≥ 1/ 10) u Komuni (≥ 1/ 100 sa < 1/ 10).
Within each MedDRA system organ class and frequency grouping, undesirable effects are presented in order of decreasing incidence.
F’ kull sistema tal- klassifika tal- organi MedDRA u sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa huma mniżżla skond l- inċidenza tagħhom, bl- aktar komuni jitniżżlu l- ewwel.
MedDRA system organ class Blood and lymphatic system disorders Psychiatric disorders
Sistema tal- klassifika tal - organi MedDRA
Common Bone marrow disorder* Thrombocytopenia* Insomnia
Disturb tal- mudullun tal- għadam * Tromboċitopenija * Insomnja
Dizziness Paraesthesia Migraine
Sturdament Parasteżija Emigranja
Vascular disorders Respiratory, thoracic and mediastinal disorders
Disturbi vaskulari Disturbi respiratorji, toraċiċi u medjastinali
Flushing Pulmonary embolism*
Fwawar Emboliżmu pulmonari *
Nausea Diarrhoea Abdominal pain Dyspepsia Constipation
Tqalligħ Dijarea Uġigħ addominali Dispepsja Stitikezza
Pruritis Ecchymosis Rash
Ħakk Ekimosi Raxx
6 MedDRA system organ class General disorders and administration site conditions
6 Sistema tal- klassifika tal - organi MedDRA
Common Fatigue Injection site bruising Injection site pain Oedema peripheral Influenza like illness Pain Asthenia Pyrexia Chills Injection site haematoma Injection site swelling
Għeja Tbenġil fil- lok ta ’ l- injezzjoni Uġigħ fil- lok ta ’ l- injezzjoni Edima periferali Marda li tixbaħ lill- influwenza Uġigħ Astenja Deni Sirda Ematoma fil- lok ta ’ l- injezzjoni Nefħa fil- lok ta ’ l- injezzjoni
Injury, poisoning and procedural complications * see section 4.4
Korriment, avvelenament u komplikazzjonijiet ta ’ xi proċedura * ara sezzjoni 4. 4
In addition the events listed below have been deemed to be related to romiplostim treatment.
Barra dawn, l- avvenimenti mniżżla taħt kienu meqjusa bħala relatati ma ’ kura b’ romiplostim.
Thrombocytosis
Tromboċitosi
Based on an analysis of all adult ITP patients receiving romiplostim in 4 controlled and 5 uncontrolled clinical studies, 3 events of thrombocytosis were reported, n = 271.
Ibbażat fuq analiżi tal- pazjenti adulti b’ ITP kollha li ngħataw romiplostim f’ 4 studji kliniċi kkontrollati u 5 mhux ikkontrollati, kienu rrapporati 3 każi ta ’ tromboċitosi, n = 271.
No clinical sequelae were reported in association with the elevated platelet counts in any of the 3 subjects.
Fl- ebda mit- 3 individwi ma kien hemm effetti kliniċi rrapportati assoċjati ma ’ l- għadd ta ’ plejtlits elevat.
Thrombocytopenia after cessation of treatment
Tromboċitopenija wara waqfien tal- kura
Based on an analysis of all adult ITP patients receiving romiplostim in 4 controlled and 5 uncontrolled clinical studies, 4 events of thrombocytopenia after cessation of treatment were reported, n = 271 (see section 4.4).
Ibbażat fuq analiżi tal- pazjenti adulti b’ ITP kollha li rċevew romiplostim f’ 4 studji kliniċi kkontrollati u 5 mhux ikkontrollati, ġew irrapportati 4 avvenimenti ta ’ tromboċitopenija wara waqfien tal- kura, n = 271 (ara sezzjoni 4. 4).
In clinical studies, romiplostim treatment was discontinued in 4 of the 271 patients because of bone marrow reticulin deposition.
Fi studji kliniċi, kura b’ romiplostim twaqqfet f’ 4 mill- 271 pazjent minħabba depożizzjoni ta ’ reticulin fil- mudullun tal- għadam.
In 6 additional patients reticulin was observed upon bone marrow biopsy (see section 4.4).
F’ 6 pazjenti oħra reticulin kien osservat wara bijopsija tal- mudullun tal - għadam (ara sezzjoni 4. 4).
In clinical studies, antibodies to romiplostim were examined.
Fi studji kliniċi, kienu eżaminati antikorpi għal romiplostim.
Of the 271 adult ITP patients receiving romiplostim in the ITP clinical programme one patient developed antibodies capable of neutralising the activity of romiplostim but these antibodies did not cross react with endogenous TPO.
Mill- 271 pazjenti adulti b’ ITP li rċevew romiplostim fil- programm kliniku ta ’ ITP, pazjent wieħed żviluppa antikorpi li kapaċi jinnewtralizzaw l- attività ta ’ romiplostim iżda dawn l- antikorpi ma kellhomx reazzjoni ma ’ TPO endoġenu.
Approximately 4 months later, the patient tested negative for neutralising antibodies to romiplostim.
Madwar 4 xhur wara, il- pazjent ittestja negattiv għall- antikorpi newtralizzanti għal romiplostim.
As with all therapeutic proteins, there is a potential for immunogenicity.
Kif jista’ jiġri bil- proteini terapewtiċi kollha, hemm potenzjal għall- immunoġeniċità.
If formation of neutralising antibodies is suspected, contact the local representative of the Marketing Authorisation Holder (see section 6 of the Package Leaflet) for antibody testing.
Jekk ikun hemm suspett ta ’ formazzjoni ta ’ antikorpi newtralizzanti, ikkunttatja lir- rappreżentant lokali tad- Detentur ta ’ l- Awtorizzazzjoni għat- tqegħid fis- Suq (ara sezzjoni 6 tal- Fuljett ta ’ Tagħrif) biex isir it- test ta ’ l - antikorpi.
In early clinical studies, the maximum dose of romiplostim was 30 µg/ kg.
Fi studji kliniċi tal- bidu, id- doża massima ta ’ romiplostim kienet 30 µg/ kg.
This was later reduced to 10 µg/ kg due to lack of additional clinical benefit of doses above this level.
Wara, din tnaqqset għal 10 µg/ kg minħabba nuqqas ta ’ benefiċċju addizzjonali kliniku b’ dożi ’ l fuq minn dan il- livell.
No adverse effects were seen in rats given a single dose of 1000 μ g/ kg or in monkeys after repeated administration of romiplostim at 500 µg/ kg (100 or 50 times the maximum clinical dose of 10 µg/ kg, respectively).
Ma dehru l- ebda effetti avversi f’ firien li ngħataw doża waħda ta ’ 1000 μg/ kg jew f’ xadini wara għoti ripetut ta ’ romiplostim b’ dożi ta ’ 500 µg/ kg (100 darba jew 50 darba d- doża massima klinika ta ’ 10 µg/ kg, rispettivament).
7 In the event of overdose, platelet counts may increase above the normal range.
F’ każ ta ’ doża eċċessiva, l- għadd ta ’ plejtlits jista ’ jiżdied ’ l fuq mill- firxa normali.
Platelet counts should be monitored and appropriate treatment should be given (see section 4.2).
L- għadd ta ’ plejtlits għandu jiġi ssorveljat u għandha tingħata kura xierqa (ara sezzjoni 4. 2).
Antihemorrhagics, ATC code:
Sustanzi kontra l- emorraġija, Kodiċi ATC:
Romiplostim is an Fc-peptide fusion protein (peptibody) that signals and activates intracellular transcriptional pathways via the thrombopoietin (TPO) receptor (also known as cMpl) to increase platelet production.
Romiplostim huwa proteina Fc- peptide tal- irbit (peptibody) li jagħti sinjal u jattiva rotot ta ’ traskrizzjoni ġewwa ċ- ċelluli permezz tar- riċettur ta ’ thrombopoietin (TPO) (magħruf ukoll bħala cMpl) biex iżidu l- produzzjoni tal- plejtlits.
The peptibody molecule is comprised of a human immunoglobulin IgG1 Fc domain, with each single-chain subunit covalently linked at the C-terminus to a peptide chain containing 2 TPO receptor-binding domains.
Il- molekola peptibody hija magħmula minn unità ta ’ immunoglobulin IgG1 Fc uman, b’ kull sotto- unità ta ’ katina waħda mwaħħla b’ mod kovalenti ma ’ C - terminus tal- katina ta ’ peptide li fiha 2 unitajiet li jeħlu mar- riċettur ta ’ TPO.
Romiplostim has no amino acid sequence homology to endogenous TPO.
Romiplostim m’ għandux omoloġija ta ’ sekwenza ta ’ aċidi amminiċi għal TPO endoġenu.
In pre-clinical and clinical studies no anti-romiplostim antibodies cross reacted with endogenous TPO.
Fi studji pre - kliniċi u kliniċi l- ebda antikorp kontra romiplostim ma rreaġixxa ma ’ TPO endoġenu.
The safety and efficacy of romiplostim have been evaluated for up to 3 years of continuous treatment.
Is- sigurtà u l- effikaċja ta ’ romiplostim kienu evalwati sa 3 snin ta ’ kura kontinwa.
In clinical studies, treatment with romiplostim resulted in dose-dependent increases in platelet count.
Fi studji kliniċi, kura b’ romiplostim wasslet għal żjieda dipendenti mid- doża fl- għadd tal- plejtlits.
Time to reach the maximum effect on platelet count is approximately 10-14 days, and is independent of the dose.
Il- ħin sabiex jintlaħaq l- effett massimu fuq l- għadd tal- plejtlits huwa ta ’ madwar 10 sa 14- il ġurnata, u huwa indipendenti mid- doża.
After a single subcutaneous dose of 1 to 10 µg/ kg romiplostim in ITP patients, the peak platelet count was 1.3 to 14.9 times greater than the baseline platelet count over a 2 to 3 week period and the response was variable among patients.
Wara doża waħda taħt il- ġilda ta ’ 1 µg/ kg sa 10 µg/ kg ta ’ romiplostim f’ pazjenti b’ ITP, l- ogħla għadd tal- plejtlits kien 1. 3 sa 14. 9 darbiet akbar mill- għadd tal- plejtlits fil - linja bażi fuq perijodu ta ’ ġimagħtejn sa 3 ġimgħat u r- rispons kien ivarja fost il- pazjenti.
The platelet counts of ITP patients who received 6 weekly doses of 1 or 3 µg/ kg of romiplostim were within the range of 50 to 450 x 109/ l for most patients.
L- għadd tal - plejtlits ta ’ pazjenti b’ ITP li rċevew 6 dożi darba fil- ġimgħa ta ’ 1 µg/ kg jew 3 µg/ kg ta ’ romiplostim kienu fil- firxa ta ’ 50 sa 450 x 109/ l għall- biċċa l- kbira tal- pazjenti.
Of the 271 patients who received romiplostim in ITP clinical studies, 55 (20%) were age 65 and over, and 27 (10%) were 75 and over.
Mill- 271 pazjent li rċevew romiplostim fl- istudji kliniċi dwar ITP, 55 (20%) kellhom 65 sena jew aktar, u 27 (10%) kellhom 75 sena jew aktar.
No overall differences in safety or efficacy have been observed between older and younger patients in the placebo-controlled studies.
Ma kienet osservata l- ebda differenza globali fis- sigurtà jew l- effikaċja bejn pazjenti akbar u iżgħar fl- istudji kkontrollati bil- plaċebo.
Results from pivotal placebo-controlled studies
Riżultati minn studji pivitali kkontrollati bil- plaċebo
The safety and efficacy of romiplostim was evaluated in two placebo-controlled, double-blind studies in adults with ITP who had completed at least one treatment prior to study entry and are representative of the entire spectrum of such ITP patients.
Is- sigurtà u l- effikaċja ta ’ romiplostim kienet evalwata f’ żewġ studji double- blind ikkontrollati bil - plaċebo f’ adulti b’ ITP li kienu temmew għall- inqas kura waħda qabel ma daħlu fl- istudju u huma rappreżentattivi tal- firxa kollha ta ’ pazjenti bħal dawn b’ ITP.
Study S1 (212) evaluated patients who were non-splenectomised and had an inadequate response or were intolerant to prior therapies.
Studju S1 (212) evalwa pazjenti li ma tneħħitilhomx il- milsa u li kellhom rispons mhux adegwat jew kienu intolleranti għal terapiji ta ’ qabel.
Patients had been diagnosed with ITP for approximately 2 years at the time of study entry.
Meta daħlu fl- istudju l- pazjenti kienu ilhom dijanjosati b’ ITP għal madwar sentejn.
Patients had a median of 3 (range, 1 to 7) treatments for ITP prior to study entry.
Qabel daħlu fl- istudju l- pazjenti kellhom medjan ta ’ 3 (firxa, 1 sa 7) trattamenti għall- ITP.
Prior treatments included corticosteroids (90% of all patients), immunoglobulins (76%), rituximab (29%), cytotoxic therapies (21%), danazol (11%), and azathioprine (5%).
Kura minn qabel kienet tinkludi kortikosterojdi (90% tal- pazjenti kollha), immunoglobulini (76%), rituximab (29%), terapiji ċitotossiċi (21%), danazol (11%), u azathioprine (5%).
Patients had a median platelet count of 19 x 109/ l at study entry.
Meta daħlu fl- istudju l- pazjenti kellhom medjan ta ’ l- għadd tal- plejtlits ta ’ 19 x 109/ l.
Study S2 (105) evaluated patients who were splenectomised and continued to have thrombocytopenia.
Studju S2 (105) evalwa pazjenti li kellhom tneħħija tal- milsa u komplew ikollhom tromboċitopenija.
Patients had been diagnosed with ITP for approximately 8 years at the time of study entry.
Qabel daħlu fl -
In addition to a splenectomy, patients had a median of 6 (range, 3 to 10) treatments for ITP prior to study entry.
8 istudju, barra minn tneħħija tal- milsa, l- pazjenti kellhom medjan ta ’ 6 (firxa, 3 sa 10) trattamenti għall - ITP.
Prior treatments included corticosteroids (98% of all patients), immunoglobulins (97%), rituximab (71%), danazol (37%), cytotoxic therapies (68%), and azathioprine (24%).
Kura minn qabel kienet tinkludi kortikosterojdi (98% tal- pazjenti kollha), immunoglobulini (97%), rituximab (71%), danazol (37%), terapiji ċitotossiċi (68%), u azathioprine (24%).
Patients had a median platelet count of 14 x 109/ l at study entry.
Meta daħlu fl- istudju l- pazjenti kellhom medjan ta ’ l- għadd tal- plejtlits ta ’ 14 x 109/ l.
Both studies were similarly designed.
Iż- żewġ studji kienu ddisinjati b’ mod simili.
Patients (≥ 18 years) were randomised in a 2:1 ratio to receive a starting dose of romiplostim 1 µg/ kg or placebo.
Il- pazjenti (≥ 18 sena) kienu randomised f’ proporzjon ta ’ 2: 1 biex jingħataw doża tal- bidu ta ’ romiplostim ta ’ 1 µg/ kg jew plaċebo.
Patients received single subcutaneous weekly injections for 24 weeks.
Il- pażjenti rċevew injezzjonijiet taħt il- ġilda darba fil- ġimgħa għal 24 ġimgħa.
Doses were adjusted to maintain (50 to 200 x 109/ l) platelet counts.
Id- dożi kienu aġġustati biex jistabilizzaw l- għadd tal- plejtlits (50 sa 200 x 109/ l).
In both studies, efficacy was determined by an increase in the proportion of patients who achieved a durable
Fiż- żewġ studji, l- effikaċja kienet determinata minn żjieda fil - proporzjon ta ’ pazjenti li laħqu rispons tal- plejtlets dejjiemi.
The median average weekly dose for splenectomised patients was 3 µg/ kg and for non-splenectomised patients was 2 µg/ kg.
Il- medjan tad- doża medja ta ’ kull ġimgħa għall- pazjenti li tneħħitilhom il- milsa kienet 3 µg/ kg u għall- pazjenti li ma tneħħitilhomx il- milsa kienet 2 µg/ kg.
A significantly higher proportion of patients receiving romiplostim achieved a durable platelet response compared to patients receiving placebo in both studies.
Fiż- żewġ studji, proporzjon sinifikattivament ogħla ta ’ pazjenti li rċevew romiplostim laħqu rispons tal- plejtlits li jibqa ’, meta mqabbel ma ’ pazjenti li rċevew plaċebo.
Following the first 4-weeks of study romiplostim maintained platelet counts ≥ 50 x 109/ l in between 50% to 70% of patients during the 6 month treatment period in the placebo-controlled studies.
Wara l- ewwel 4 ġimgħat ta ’ studju romiplostim żamm l- għadd tal- plejtlits ≥ 50 x 109/ l f’ bejn 50% sa 70% tal- pazjenti waqt il- perijodu ta ’ kura ta ’ 6 xhur fl- istudji kkontrollati bil- plaċebo.
In the placebo group, 0% to 7% of patients were able achieve a platelet count response during the 6 months of treatment.
Fil- grupp tal- plaċebo, 0% sa 7% tal- pazjenti kienu kapaċi jilħqu rispons ta ’ l- għadd tal- plejtlits waqt is- 6 xhur ta ’ kura.
A summary of the key efficacy endpoints is presented below.
Sommarju tal- miri mportanti ta ’ l- effikaċja huwa miġbur hawn taħt.
Summary of key efficacy results from placebo-controlled studies
Sommarju tar- riżultati mportanti ta ’ l- effikaċja mill- istudji kkontrollati bil- plaċebo
Combined
Studji 1 & 2
non-splenectomised patients
tneħħitilhomx il- milsa
splenectomised patients
tneħħitilhom il- milsa
studies 1 & 2
romiplosti m
No.
Plaċebo
(%) patients with
Numru (%) ta ’
durable platelet responsea
pazjenti b’ rispons tal - plejtlits li jduma
1 (5%) 16 (38%) 0 (0%) 41 (50%)
16 (38%) 0 (0%)
(24%, 54%)
(24%, (0%,
(38%, 61%)
(38%,
(0%, 13%)
(0%,
0.0013
0. 0013
(%) patients with overall platelet responseb
Numru (%) ta ’ pazjenti b’ rispons globali tal- plejtlits b
(2%, 20%)
20%)
< 0.0001 < 0.0001
< 0. 0001 < 0. 0001
Mean no. weeks with platelet responsec
Medja ta ’ numru ta ’ ġimgħat b’ rispons tal - plejtlitsc
(SD) p-value
(SD) valur p
7.9 < 0.0001
7. 9 < 0. 0001
(%) patients requiring rescue therapiesd
Numru (%) ta ’ pazjenti li kellhom bżonn terapiji ta ’ salvataġġd
0.001
0. 001
0.0175
0. 0175
splenectomised patients
pazjenti li ma pazjenti li
studies 1 & 2
ikkombinati
(%) patients with durable
Numru (%) ta ’ pazjenti b’ rispons tal -
romiplostim (n = 41)
tneħħitilhomx il- milsa
Placebo (n = 42)
tneħħitilhom il- milsa
platelet response with stable dosee
plejtlits li jdum b’ doża stabblie
21 (51%)
21 (51%) 0 (0%)
0 (0%) 13 (31%) 0 (0%) 34 (41%)
13 (31%) 0 (0%)
(35%, 67%)
(0%, (35%, 67%) 16%)
(0%, 16%) (18%, 47%) (0%, 16%) (30%, 52%)
(18%, (0%, 47%) 16%)
0.0046
0. 0046
Durable platelet response was defined as weekly platelet count ≥ 50 x 109/ l for 6 or more times for study weeks 18-25 in the absence of rescue therapies any time during the treatment period. b Overall platelet response is defined as achieving durable or transient platelet responses.
Rispons tal- plejtlits li jdum kien definit bħala għadd tal- plejtlits ta ’ kull ġimgħa ta ’ ≥ 50 x 109/ l għal 6 darbiet jew aktar għall- ġimgħat ta ’ studju 18- 25 fin- nuqqas ta ’ terapiji ta ’ salvataġġ f’ xi ħin waqt il - perijodu ta ’ kura. b Rispons globali tal- plejtlits huwa definit bħala li jintlaħaq rispons tal- plejtlits li jdum jew temporanju.
Transient platelet response was defined as weekly platelet count ≥ 50 x 109/ l for 4 or more times during study weeks 2-25 but without durable platelet response.
Rispons temporanju tal- plejtlits kien definit bħala għadd tal- plejtlits ta ’ kull ġimgħa ta ’ ≥ 50 x 109/ l għal 4 darbiet jew aktar waqt ġimgħat 2- 25 ta ’ l- istudju iżda mingħajr rispons tal- plejtlits li jdum.
Patient may not have a weekly response within 8 weeks after receiving any rescue medicinal products. c Number of weeks with platelet response is defined as number of weeks with platelet counts ≥ 50 x 109/ l during study weeks 2-25.
Il- pazjent jista ’ ma jkollux rispons kull ġimgħa fi 8 ġimgħat wara li jirċievi xi prodotti mediċinali ta ’ salvataġġ. c Numru ta ’ ġimgħat b’ rispons tal- plejtlits huwa definit bħala n- numru ta ’ ġimgħat b’ għadd tal - plejtlits ta ’ ≥ 50 x 109/ l waqt ġimgħat 2- 25 ta ’ l- istudju.
Patient may not have a weekly response within 8 weeks after receiving any rescue medicinal products. d Rescue therapies defined as any therapy administered to raise platelet counts.
Il- pazjent jista ’ ma jkollux rispons kull ġimgħa fi 8 ġimgħat wara li jirċievi xi prodotti mediċinali ta ’ salvataġġ. d Terapiji ta ’ salvataġġ huma definiti bħala kull terapija mogħtija biex tgħolli l- għadd tal- plejtlits.
Patients requiring rescue medicinal products were not considered for durable platelet response.
Pazjenti li kellhom bżonn prodotti mediċinali ta 'salvataġġ ma kienux ikkunsidrati għar- rispons tal - plejtlits li jibqa ’.
Rescue therapies allowed in the study were IVIG, platelet transfusions, anti-D immunoglobulin, and corticosteroids. e Stable dose defined as dose maintained within ± 1 µg/ kg during the last 8 weeks of treatment.
Terapiji ta ’ salvataġġ permessi fl- istudju kienu IVIG, trasfużjonijiet tal- plejtlits, immunoglobulin anti- D, u kortikosterojdi e Doża stabbli hija definita bħala d- doża miżmuma f’ ± 1 µg/ kg waqt l- aħħar 8 ġimgħat ta ’ kura
Reduction in permitted concurrent ITP medical therapies
Tnaqqis fit- terapiji mediċi ta ’ ITP permessi fl- istess waqt
In both placebo-controlled, double-blind studies, patients already receiving ITP medical therapies at a constant dosing schedule were allowed to continue receiving these medical treatments throughout the study (corticosteroids, danazol and/ or azathioprine).
Fiż- żewġ studji double- blind u kkontrollati bil- plaċebo, il- pazjenti li diġà kienu qed jirċievu terapiji mediċinali ta ’ ITP fi programm kostanti ta ’ dożaġġ tħallew jibqgħu jirċievu dawn it- trattamenti mediċinali matul l- istudju (kortikosterojdi, danazol u/ jew azathioprine).
Twenty-one non-splenectomised and 18 splenectomised patients received on-study ITP medical treatments (primarily corticosteroids) at the start of study.
Fil- bidu ta ’ l- istudju, wieħed u għoxrin pazjent li ma tneħħitilhomx il- milsa u 18 li tneħħitilhom il- milsa rċevew trattamenti mediċinali ta ’ ITP waqt l- istudju (primarjament kortikosterojdi).
All (100%) splenectomised patients who were receiving romiplostim were able to reduce the dose by more than 25% or discontinue the concurrent ITP medical therapies by the end of the treatment period compared to 17% of placebo treated patients.
Il- pazjenti kollha (100%) li tneħħitilhom il- milsa li kienu qed jirċievu romiplostim kienu kapaċi jnaqqsu d- doża b’ aktar minn 25% jew iwaqqfu it- terapiji mediċinali ta ’ ITP fl- istess waqt sat- tmiem tal- perijodu ta ’ kura meta mqabbel ma ’ 17% tal- pazjenti kkurati bil- plaċebo.
Seventy-three percent of non-splenectomised patients receiving romiplostim were able to reduce the dose by more than 25% or discontinue concurrent ITP medical therapies by the end of the study compared to 50% of placebo treated patients (see section 4.5).
Tlieta u sebgħin fil- mija tal- pazjenti li ma tneħħitilhomx il - milsa li kienu qed jirċievu romiplostim kienu kapaċi jnaqqsu d- doża b’ aktar minn 25% jew iwaqqfu it - terapiji mediċinali ta ’ ITP fl- istess waqt sat- tmiem ta ’ l- istudju meta mqabbel ma ’ 50% tal- pazjenti kkurati bil- plaċebo (ara sezzjoni 4. 5).
Bleeding events
Avvenimenti ta ’ fsada
Across the entire ITP clinical programme an inverse relationship between bleeding events and platelet counts was observed.
Tul il- programm kliniku kollu ta ’ ITP kienet osservata relazzjoni inversa bejn l- avvenimenti ta ’ fsada u l- għadd tal- plejtlits.
All clinically significant (≥ grade 3) bleeding events occurred at platelet counts < 30 x 109/ l.
L- avvenimenti ta ’ fsada ta ’ sinifikanza klinika (≥ grad 3) kollha seħħew meta l - għadd tal- plejtlits kien ta ’ < 30 x 109/ l.
All bleeding events ≥ grade 2 occurred at platelet counts < 50 x 109/ l.
L- avvenimenti ta ’ fsada kollha ta ’ ≥ grad 2 seħħew b’ għadd tal- plejtlits ta ’ < 50 x 109/ l.
No statistically significant differences in the overall incidence of bleeding events were observed between Nplate and placebo treated patients.
Ma kienet osservata l- ebda differenza statistikament sinifikanti fl - inċidenza globali ta ’ avvenimenti ta ’ fsada bejn pazjenti kkurati b’ Nplate u dawk bil- plaċebo.
In the two placebo-controlled studies, 9 patients reported a bleeding event that was considered serious (5 [6.0%] romiplostim, 4 [9.8%] placebo; Odds Ratio [romiplostim/ placebo] = 0.59; 95% CI = (0.15, 2.31)).
Fiż- żewġ studji kkontrollati bil- plaċebo, 9 pazjenti rrapportaw avveniment ta ’ fsada li kien ikkunsidrat serju (5 [6. 0%] b’ romiplostim, 4 [9. 8%] bi plaċebo; Proporzjon ta ’ probabbiltà [romiplostim/ plaċebo] = 0. 59; 95% CI = (0. 15, 2. 31)).
Bleeding events that were grade 2 or higher were reported by 15% of patients treated with romiplostim and 34% of patients treated with placebo (Odds Ratio; [romiplostim/ placebo] = 0.35; 95% CI = (0.14, 0.85)).
Avvenimenti ta ’ fsada li kienu ta ’ grad 2 jew aktar kienu rrapportati minn 15% tal- pazjenti kkurati b’ romiplostim u minn 34% tal- pazjenti kkurati bil- plaċebo (Proporzjon ta ’ probabbiltà; [romiplostim/ plaċebo] = 0. 35; 95% CI = (0. 14, 0. 85)).
10 5.2 Pharmacokinetic properties
10 Il- farmakokinetika ta ’ romiplostim involviet dispożizzjoni medjata mit- targit, li preżumibbilment hija medjata minn riċetturi ta ’ TPO fuq plejtlits u ċelluli oħra ta ’ nisel trombopoetiku bħal megakarjoċiti.
After subcutaneous administration of 3 to 15 μ g/ kg romiplostim, maximum romiplostim serum levels in ITP patients were obtained after 7-50 hours (median 14 hours).
Wara għoti taħt il- ġilda ta ’ 3 μg/ kg sa 15 μg/ kg ta ’ romiplostim, l- livelli massimi ta ’ romiplostim fis - serum f’ pazjenti b’ ITP intlaħqu wara 7 - 50 siegħa (medjan 14- il siegħa).
The serum concentrations varied among patients and did not correlate with the dose administered.
Il- konċentrazzjonijiet fis - serum varjaw fost il- pazjenti u ma kkorrelawx mad- doża mogħtija.
Romiplostim serum levels appear inversely related to platelet counts.
Livelli ta ’ romiplostim fis- serum jidhru li huma relatati b’ mod invers ma ’ l- għadd tal- plejtlits.
The volume of distribution of romiplostim following intravenous administration of romiplostim decreased nonlinearly from 122, 78.8, to 48.2 ml/ kg for intravenous doses of 0.3, 1.0 and 10 μ g/ kg, respectively in healthy subjects.
Il- volum ta ’ distribuzzjoni ta ’ romiplostim mogħti ġol- vini naqas b’ mod mhux lineari minn 122, 78. 8, għal 48. 2 ml/ kg għall- dożi ġol- vini ta ’ 0. 3, 1. 0 u 10 μg/ kg, rispettivament, f’ individwi b’ saħħithom.
This non-linear decrease in volume of distribution is in line with the (megakaryocyte and platelet) target-mediated binding of romiplostim, which may be saturated at the higher doses applied.
Dan it- tnaqqis mhux lineari fil- volum ta ’ distribuzzjoni, huwa konsistenti mat- twaħħil ta ’ romiplostim medjat mit- targit (megakarjoċiti u plejtlit), li jista ’ jkun saturat fl- ogħla dożi mogħtija.
Elimination half-life of romiplostim in ITP patients ranged from 1 to 34 days (median, 3.5 days).
Il- half- life ta ’ l- eliminazzjoni ta ’ romiplostim f’ pazjenti b’ ITP varjat minn ġurnata sa 34 ġurnata (medjan, 3. 5 ijiem).
The elimination of serum romiplostim is in part dependent on the TPO receptor on platelets.
L- eliminazzjoni ta ’ romiplostim mis- serum hija dipendenti parzjalment fuq ir - riċettur ta ’ TPO fuq il- plejtlits.
As a result for a given dose, patients with high platelet counts are associated with low serum concentrations and vice versa.
Bħala riżulat ta ’ doża mogħtija, pazjenti b’ għadd tal- plejtlits għoli huma assoċjati ma ’ konċentrazzjonijiet baxxi fis- serum u viċi versa.
In another ITP clinical study, no accumulation in serum concentrations was observed after 6 weekly doses of romiplostim (3 μ g/ kg).
Fi studju kliniku ieħor dwar ITP, ma kienet osservata l- ebda akkumulazzjoni fil- konċentrazzjonijiet fis- serum wara 6 dożi ta ’ kull ġimgħa ta ’ romiplostim (3 μg/ kg).
Special patient populations
Popolazzjonijiet speċjali ta 'pazjenti
Pharmacokinetics of romiplostim in patients with renal and hepatic impairment has not been investigated.
Il- farmakokinetika ta ’ romiplostim f’ pazjenti b’ indeboliment tal- kliewi u tal- fwied ma ġietx investigata.
Romiplostim pharmacokinetics appear not affected by age, weight and gender to a clinically significant extent.
Il- farmakokinetika ta ’ romiplostim tidher li mhix affettwata minn età, piż u sess b’ mod klinikament sinifikanti.
Multiple dose romiplostim toxicology studies were conducted in rats for 4 weeks and in monkeys for up to 6 months.
Saru studji dwar it- tossikoloġija b’ dożi multipli ta ’ romiplostim f’ firien għal 4 ġimgħat u fix- xadini għal tul sa 6 xhur.
In general, effects observed during these studies were related to the thrombopoietic activity of romiplostim and were similar regardless of study duration.
Ġeneralment, l- effetti osservati waqt dawn l- istudji kienu relatati ma ’ l- attività trombopoetika ta ’ romiplostim u kienu simili irrispettivament mit- tul ta 'l- istudju.
Injection site reactions were also related to romiplostim administration.
Reazzjonijiet fis- sit ta ’ l- injezzjoni wkoll kienu relatati ma ’ l- għoti ta ’ romiplostim.
Myelofibrosis has been observed in the bone marrow of rats at all tested dose levels.
Majelofibrożi kienet osservata fil - mudullun tal- għadam ta ’ firien fil- livelli kollha ta ’ dożi ittestjati.
In these studies, myelofibrosis was not observed in animals after a 4-week post- treatment recovery period, indicating reversibility.
F’ dawn l- istudji, majelofibrożi ma kienetx osservata fl- annimali wara perijodu ta ’ rkupru ta ’ wara l- kura ta ’ 4 ġimgħat, jiġifieri dan jindika li l- effett huwa riversibbli.
In 1-month rat and monkey toxicology studies, a mild decrease in red blood cell count, haematocrit and haemoglobin was observed.
Fi studji ta ’ xahar dwar it- tossikoloġija fil- firien u xadini, kien osservat tnaqqis ħafif fl- għadd ta ’ ċelluli ħomor tad- demm, fl- ematokrit u fl- emoglobina.
There was also a stimulatory effect on leukocyte production, as peripheral blood counts for neutrophils, lymphocytes, monocytes, and eosinophils were mildly increased.
Kien hemm ukoll effett stimulanti fuq il - produzzjoni tal- lewkoċiti, peress li fid- demm fil- periferiji l- għadd ta ’ newtrofili, limfoċiti, monoċiti u esinofili kien kemm xejn miżjud.
In the longer duration chronic monkey study, there was no effect on the erythroid and leukocytic lineages when romiplostim was administered for 6 months where the administration of romiplostim was decreased from thrice weekly to once weekly.
Fl- istudju kroniku fuq perijodu itwal fix- xadini, ma kien hemm l - ebda effett fuq ir- razez eritrojdi u lewkoċitiċi meta romiplostim ingħata għal 6 xhur fejn l- għoti ta ’ romiplostim tnaqqas minn tliet darbiet fil- ġimgħa għal darba fil- ġimgħa.
Additionally, in the phase 3 pivotal studies, romiplostim did not affect the red blood cell and white blood cells lineages relative to placebo treated subjects.
Barra minn hekk, fl- istudji bażiċi ta ’ fażi 3, romiplostim ma kellux effett fuq ir- razez ta ’ ċelluli ħomor tad- demm u ċelluli bojod tad- demm meta mqabbel ma ’ pazjenti kkurati bil- plaċebo.
Due to the formation of neutralising antibodies pharmacodynamic effects of romiplostim in rats were often decreasing at prolonged duration of administration.
Minħabba l- formazzjoni ta ’ antikorpi newtralizzanti l- effetti farmakodinamiċi ta ’ romiplostim fil- firien ħafna drabi kienu qed jonqsu meta jingħata għal tul ta ’ żmien.
Toxicokinetic studies showed no interaction of the antibodies with the measured concentrations.
Studji tossikokinetiċi ma wrew l- ebda interazzjoni ta ’ l- antikorpi bil- konċentrazzjonijiet imkejla.
Although high doses were tested in the animal studies, due to differences between the laboratory species and humans with regard to the sensitivity for
Għalkemm fl- studji fuq l- annimali kienu ttestjati b’ dożi għolja, minħabba d- differenzi bejn l- ispeċi tal- laboratorju u l- bnedmin rigward is -
11 the pharmacodynamic effect of romiplostim and the effect of neutralising antibodies, safety margins cannot be reliably estimated.
11 sensittività għall- effett farmakodinamiku ta ’ romiplostim u l- effett ta 'antikorpi newtralizzanti, marġini ta ’ sigurtà ma jistgħux jiġu stmati b’ mod ċert.
The carcinogenic potential of romiplostim has not been evaluated.
Il- potenzjal karċinoġeniku ta ’ romiplostim ma ġiex evalwat.
Therefore, the risk of potential carcinogenicity of romiplostim in humans remains unknown.
Għalhekk, ir- riskju ta ’ potenzjal karċinoġeniku ta ’ romiplostim fil- bnedmin jibqa ’ mhux magħruf.
Reproductive toxicology:
Effett tossiku fuq is- sistema riproduttiva:
In all developmental studies neutralising antibodies were formed, which may have inhibited romiplostim effects.
Fl- istudji kollha ta ’ l- iżvilupp kienu ffurmati antikorpi newtralizzanti li setgħu jinibixxu l- effetti ta ’ romiplostim.
In embryo-foetal development studies in mice and rats, reductions in maternal body weight were found only in mice.
Fi studji dwar l- iżvilupp ta ’ l- embrijo- fetu fil- ġrieden u l- firien, tnaqqis fil- piż tal- ġisem ta ’ l- omm kien osservat biss fil- ġrieden.
In mice there was evidence of increased post- implantation loss.
Fil- ġrieden kien hemm evidenza ta ’ żjieda fit- telf ta ’ wara l- impjant tal- embriju.
In a prenatal and postnatal development study in rats an increase of the duration of gestation and a slight increase in the incidence of peri-natal pup mortality was found.
Fi studju dwar l- iżvilupp ta ’ qabel u wara t- twelid fil- firien, instabet żjieda fit- tul tat- tqala u żjieda ħafifa fl- inċidenza tal- mewt tal- frieħ qabel it- twelid.
Romiplostim is known to cross the placental barrier in rats and may be transmitted from the mother to the developing foetus and stimulate foetal platelet production.
Romiplostim huwa magħruf li jgħaddi mill- barriera tal- plaċenta fil- firien u jista ’ jiġi trasferit mill- omm għall- fetu li qed jiżviluppa u jistimula l- produzzjoni tal- plejtlits fil- fetu.
Romiplostim had no observed effect on the fertility of rats.
Romiplostim m’ għandux effett osservat fuq il- fertilità tal- firien.
Mannitol (E421) Sucrose L-histidine Hydrochloric acid (for pH adjustment) Polysorbate 20
Mannitol (E421) Sucrose L- histidine Hydrochloric acid (għall- aġġustament tal- pH) Polysorbate 20
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products, except those mentioned in section 6.6.
Minħabba li ma sarux studji li juru liema huma l- prodotti li ma jaqblux miegħu, dan il- prodott mediċinali m’ għandux jitħallat ma ’ prodotti mediċinali oħrajn, ħlief dawk imsemmija f’ sezzjoni 6. 6.
Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C and for 24 hours at 2°C – 8°C, when protected from light and kept in the original vial.
Stabbiltà kimika u fiżika waqt l- użu kienet murija għal 24 siegħa f’ 25°C u għal 24 siegħa f’ 2°C – 8°C, meta protett mid- dawl u miżmum fil- kunjett oriġinali.
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 25°C or 24 hours in a refrigerator (2°C – 8°C), protected from light.
Jekk ma jintużax minnufih il- perijodu u l- kondizzjonijiet ta ’ ħażna qabel l- użu huma r- responsabbiltà ta ’ min qed jagħmel użu minnu u normalment m’ humiex aktar minn 24 siegħa f’ 25°C jew 24 siegħa fi friġġ (2°C – 8°C), meta protett mid- dawl.
Store in the original carton in order to protect from light.
Aħżen fil- pakkett oriġinali sabiex tilqa ’ mid- dawl.
5 ml vial (type 1 clear glass) with a stopper (chlorobutyl rubber), seal (aluminium) and a flip-off cap (polypropylene).
Kunjett ta ’ 5 ml (ħġieġ ċar tat- tip I) b’ tapp (lastku chlorobutyl), siġill (aluminju), u għatu flip- off (polypropylene).
Carton containing 1 or 4 vials of 250 µg of romiplostim.
12 Kartuna fiha kunjett wieħed jew 4 kunjetti ta ’ 250 µg romiplostim.
12 Not all pack sizes may be marketed.
Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali.
Nplate is a sterile but unpreserved product and is intended for single use only.
Nplate huwa prodott sterili iżda mhux ippreservat u huwa maħsub għall- użu ta ’ darba biss.
Nplate should be reconstituted in accordance with good aseptic practice.
Nplate għandu jiġi rrikostitwit skond prattika asettika tajba.
Nplate 250 micrograms powder for solution for injection should be reconstituted with 0.72 ml sterile water for injections, yielding a deliverable volume of 0.5 ml.
Nplate 250 mikrogramma trab għal soluzzjoni għall- injezzjoni għandu jiġi rrikostitwit b’ 0. 72 ml ilma għall- injezzjoni sterili, li jirriżulta f’ volum li jista ’ jingħata ta ’ 0. 5 ml.
An additional overfill is included in each vial to ensure that 250 µg of romiplostim can be delivered.
Kull kunjett fih spażju żejjed li jista ’ jimtela sabiex jiġi żgurat li jista ’ jingħata 250 µg ta ’ romiplostim.
Sodium chloride solutions or bacteriostatic water should not be used when reconstituting the medicinal product.
Soluzzjonijiet ta ’ sodium chloride jew ilma batterjostatiku m’ għandhomx jintużaw biex jiġi rrikostitwit il- prodott mediċinali.
Water for injections should be injected into the vial.
Ilma għall- injezzjonijiet għandu jiġi njettat ġol- kunjett.
The vial contents may be swirled gently and inverted during dissolution.
Il- kontenut tal- kunjett jista ’ jitħallat bil- mod u jinqaleb ta ’ taħt fuq waqt id- dissoluzzjoni.
The vial should not be shaken or vigorously agitated.
Il- kunjett m’ għandux jitħawwad jew jiċċaqlaq b’ mod vigoruż.
Generally, dissolution of Nplate takes less than 2 minutes.
Ġeneralment, id- dissoluzzjoni ta ’ Nplate tieħu inqas minn żewġ minuti.
Visually inspect the solution for particulate matter and discolouration before administration.
Qabel l- għoti ifli s - soluzzjoni viżwalment għal xi frak u bidla fil- kulur.
The reconstituted solution should be clear and colourless and should not be administered if particulate matter and/ or discolouration are observed.
Is- soluzzjoni rrikostitwita għandha tkun ċara u bla kulur u m’ għandhiex tingħata jekk ikun osservat xi frak u/ jew bidla fil- kulur.
For the storage condition of the reconstituted product see section 6.3.
Għall- kundizzjonijiet ta ’ ħażna tal- prodott irrikostitwit ara sezzjoni 6. 3.
4 February 2009
4 ta ’ Frar 2009
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/.
Informazzjoni ddettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il- Mediċini (EMEA) http: // www. emea. europa. eu /.
Nplate 500 micrograms powder for solution for injection
Nplate 500 mikrogramma trab għal soluzzjoni għall- injezzjoni.
Each vial contains 500 µg of romiplostim.
Kull kunjett fih 500 µg ta ’ romiplostim.
After reconstitution, a deliverable volume of 1 ml solution contains 500 µg of romiplostim (500 µg/ ml).
Wara r- rikostituzzjoni, volum li jista ’ jingħata ta ’ 1 ml ta ’ soluzzjoni fih 500 µg ta ’ romiplostim (500 µg/ ml).
An additional overfill is included in each vial to ensure that 500 µg of romiplostim can be delivered.
Spazju żejjed li jista ’ jintela huwa inkluż f’ kull kunjett sabiex jiġi żgurat li tista ’ tingħata 500 µg ta ’ romiplostim.
Volume to administer:
14 Volum li għandu jingħata:
14 *Actual body weight at initiation of treatment should always be used when calculating dose of romiplostim.
* Meta tiġi kkalkulata d- doża ta ’ romiplostim, għandu dejjem jiġi wżat il- piż attwali tal- pazjent fil- bidu tal- kura.
Elderly patients (≥ 65 years)
15 Pazjenti anzjani (≥ 65 sena)
15 Children and adolescents (< 18 years)
Tfal u adoloxxenti (< 18- il sena)
Thrombotic/ thromboembolic complications
16 Komplikazzjonijiet trombotiċi/ tromboemboliċi
16 Progression of existing haematopoietic malignancies or Myelodysplastic Syndromes (MDS)
Progressjoni ta ’ tumuri malinni ematopojetiċi eżistenti jew Sindromi Mijelodisplastiċi (MDS)
4.6 Pregnancy and lactation
17 4. 6 Tqala u treddigħ
17 A decision on whether to continue/ discontinue breast-feeding or to continue/ discontinue therapy with romiplostim should be made taking into account the benefit of breast-feeding to the child and the benefit of romiplostim therapy to the woman.
Deċiżjoni dwar jekk għandux jitkompla/ jitwaqqaf it- treddigħ jew titkompla/ titwaqqaf it- terapija b’ romiplostim għandha tittieħed billi tikkonsidra l- benefiċċju tat- treddigħ għat- tarbija u l- benefiċċju ta ’ terapija b’ romiplostim għall- omm.
Musculoskeletal and connective tissue disorders
18 Sistema tal- klassifika tal - organi MedDRA
Arthralgia Myalgia Pain in extremity Muscle spasm Back pain Bone pain
Disturbi muskolu- skeltrali u tal - connective tissue
18 MedDRA system organ class General disorders and administration site conditions
Artralġja Majalġja Uġigħ fl- estremitajiet Spażmu fil- muskoli Uġigħ fid- dahar Uġigħ fl- għadam
Very common
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata
4.9 Overdose
19 4. 9 Doża eċċessiva
19 In the event of overdose, platelet counts may increase above the normal range.
F’ każ ta ’ doża eċċessiva, l- għadd ta ’ plejtlits jista ’ jiżdied ’ l fuq mill- firxa normali.
In addition to a splenectomy, patients had a median of 6 (range, 3 to 10) treatments for ITP prior to study entry.
20 istudju, barra minn tneħħija tal- milsa, l- pazjenti kellhom medjan ta ’ 6 (firxa, 3 sa 10) trattamenti għall - ITP.
22 5.2 Pharmacokinetic properties
22 Il- farmakokinetika ta ’ romiplostim involviet dispożizzjoni medjata mit- targit, li preżumibbilment hija medjata minn riċetturi ta ’ TPO fuq plejtlits u ċelluli oħra ta ’ nisel trombopoetiku bħal megakarjoċiti.
23 the pharmacodynamic effect of romiplostim and the effect of neutralising antibodies, safety margins cannot be reliably estimated.
23 sensittività għall- effett farmakodinamiku ta ’ romiplostim u l- effett ta 'antikorpi newtralizzanti, marġini ta ’ sigurtà ma jistgħux jiġu stmati b’ mod ċert.
Carton containing 1 or 4 vials of 500 µg of romiplostim.
24 Kartuna fiha kunjett wieħed jew 4 ta ’ 500 µg romiplostim.
24 Not all pack sizes may be marketed.
Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali.
Nplate 500 micrograms powder for solution for injection should be reconstituted with 1.2 ml sterile water for injections, yielding a deliverable volume of 1 ml.
Nplate 500 mikrogramma trab għal soluzzjoni għall- injezzjoni għandu jiġi rikostitwit b’ 1. 2 ml ilma għall- injezzjonijiet sterili, li jirriżulta f’ volum li jista ’ jingħata ta ’ 1 ml.
An additional overfill is included in each vial to ensure that 500 µg of romiplostim can be delivered.
Kull kunjett fih spażju żejjed li jista ’ jimtela sabiex jiġi żgurat li jista ’ jingħata 500 µg ta ’ romiplostim.
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