qanastek/EMEA-V3 huggingface dataset:
The efficacy and safety of Zavesca has not been specifically evaluated in patients with severe Gaucher disease.
L- effikaċja u s- sigurtà ta ’ Zavesca ma ġewx evalwati speċifikatament f’ pazjenti bil- marda ta ’ Gaucher li tkun severa.
Approximately 38% of patients in clinical trials in type 1 Gaucher disease, and 58% of patients in a clinical trial in Niemann-Pick type C disease reported tremor on treatment.
Madwar 38% tal- pazjenti fil- provi kliniċi bil- marda ta ’ Gaucher ta ’ tip 1, u 58% tal- pazjenti fi prova klinika bil- marda ta ’ Niemann- Pick ta ’ tip Ċ irrappurtaw li qabdithom rogħda meta ħadu l- kura.
In type 1 Gaucher disease, these tremors were described as an exaggerated physiological tremor of the hands.
Fil - marda ta ’ Gaucher ta ’ tip 1, din ir- rogħda kienet deskritta bħala rogħda fiżjoloġika esaġerata fl- idejn.
Tremor usually began within the first month, and in many cases resolved during treatment after between 1 and 3 months.
Ir- rogħda s- soltu tibda matul l- ewwel xahar tal- kura, u f’ ħafna każijiet din tgħib wara bejn xahar u 3 xhur.
Dose reduction may ameliorate the tremor, usually within days, but discontinuation of treatment may sometimes be required.
It- tnaqqis fid- doża jista ’ jnaqqas ir- rogħda, normalment fi ftit jiem, iżda xi kultant jista ’ jkun hemm il- bżonn li l- kura titwaqqaf.
Regular monitoring of vitamin B12 level is recommended because of the high prevalence of vitamin B12 deficiency in patients with type 1 Gaucher disease.
Monitoraġġ regolari tal- livelli tal- vitamina B12 hu rrakkomandat minħabba l- prevalenza qawwija ta ’ defiċjenza ta ’ vitamina B12 f’ pazjenti bil- marda ta ’ Gaucher ta ’ tip 1.
Peripheral B
3 Każijiet ta ’ newropatija periferali kienu rrappurtati f’ pazjenti kkurati b’ Zavesca li kellhom jew ma kellhomx kundizzjonijiet oħrajn fl- istess ħin, bħal defiċjenza ta ’ vitamina BB12 u gammopatija monoklonali.
neuropathy seems to be more common in patients with type 1 Gaucher disease compared to the general population.
Meta mqabbel mal- popolazzjoni ġenerali, newropatija periferali tidher li hija aktar komuni f’ pazjenti bil- marda ta ’ Gaucher ta ’ tip 1.
All patients should undergo baseline and repeat neurological evaluation.
Il- pazjenti kollha għandha ssirilhom evalwazzjoni newroloġika fil- linja bażi u ripetuta.
Patients who develop symptoms such as numbness and tingling should have a careful re-assessment of risk-benefit.
Pazjenti li jiżviluppaw sintomi bħal tmewwit jew tnemnim għandha ssirilhom evalwazzjoni bir- reqqa dwar jekk ir- riskji humiex iktar meta mqabbla mal - benefiċċji.
Gastrointestinal events, mainly diarrhoea, have been observed in more than 80% of patients, either at the outset of treatment or intermittently during treatment (see section 4.8).
Avvenimenti gastro- intestinali, prinċipalment dijarea, kienu osservati f’ aktar minn 80% tal- pazjenti, jew fil- bidu tal- kura jew b’ mod intermittenti waqt il- kura (ara sezzjoni 4. 8).
The mechanism is probably inhibition of disaccharidases in the gastrointestinal tract.
Il- mekkaniżmu huwa probabbilment l- inibizzjoni ta ’ disaccharidases fl- apparat gastro- intestinali.
The majority of cases are mild and are expected to resolve spontaneously on therapy.
Il- maġġoranza tal- każijiet huma ħfief u huma mistennija li jfiequ spontanjament mal- kura.
In clinical practice, diarrhoea has been observed to respond to diet modification (reduction of lactose and other carbohydrate intake), to taking Zavesca away from meals, and/ or to anti-diarrhoeal medicinal products such as loperamide.
Fil- prattika klinika, kien osservat li d- dijarea rrispondiet għall- modifikazzjoni fid- dieta (tnaqqis fil- lactose u fit- teħid ta ’ karboidrati oħra), għat- teħid ta ’ Zavesca l- bogħod mill- ikliet, u/ jew għal prodotti mediċinali kontra d- dijarea bħal loperamide.
In some patients, temporary dose reduction may be necessary.
F’ xi pazjenti, jista ’ jkun neċessarju tnaqqis temporanju fid- doża.
Patients with chronic diarrhoea or other persistent gastrointestinal events that do not respond to these interventions should be investigated according to clinical practice.
Pazjenti b’ dijarea kronika jew b’ episodji gastro- intestinali persistenti li ma jirrispondux għal dawn l- interventi għandhom jiġu nvestigati skond il- prattika klinika.
Zavesca has not been evaluated in patients with a history of significant gastrointestinal disease, including inflammatory bowel disease.
Zavesca ma ġiex studjat f’ pazjenti b’ passat ta ’ mard gastro- intestinali sinifikanti, inkluż il- marda ta ’ nfjammazzjoni tal- musrana.
Male patients should maintain reliable contraceptive methods while taking Zavesca.
Il- pazjenti rġiel għandhom jibqgħu jużaw metodi ta ’ kontraċezzjoni affidabbli waqt li jkunu qed jieħdu Zavesca.
Studies in the rat have shown that miglustat adversely affects spermatogenesis and sperm parameters, and reduces fertility (see sections 4.6 and 5.3).
Studji fil- firien urew li miglustat jaffettwa b’ mod negattiv il- produzzjoni ta ’ l- isperma, il- parametri ta ’ l- isperma u jnaqqas il- fertilità (ara sezzjonijiet 4. 6 u 5. 3).
Until further information is available, before seeking to conceive, male patients should cease Zavesca and maintain reliable contraceptive methods for a further 3 months.
Sakemm ikun hemm iktar informazzjoni, huwa rrakkomandat li qabel ma jiddeċiedu li jkollhom it- tfal, pazjenti rġiel m’ għandhomx jieħdu Zavesca u jkomplu jużaw metodi ta ’ kontraċezzjoni affidabbli għal tliet xhur oħra.
Due to limited experience, Zavesca should be used with caution in patients with renal or hepatic impairment.
Minħabba esperjenza limitata, Zavesca għandu jintuża b’ attenzjoni f’ pazjenti b’ indeboliment tal- kliewi jew tal- fwied.
There is a close relationship between renal function and clearance of miglustat, and exposure of miglustat is markedly increased in patients with severe renal impairment (see section 5.2).
Hemm relazzjoni mill- qrib bejn il- funzjoni tal- kliewi u t- tneħħija ta ’ miglustat, u l- espożizzjoni ta ’ miglustat tiżdied ħafna f’ pazjenti b’ indeboliment serju tal- kliewi (ara sezzjoni 5. 2).
At present, there is insufficient clinical experience in these patients to provide dosing recommendations.
Fil- preżent, m’ hemmx biżżejjed esperjenza klinika f’ dawn il- pazjenti biex jingħataw rakkomandazzjonijiet dwar id- dożaġġ.
Use of Zavesca in patients with severe renal impairment (creatinine clearance < 30 ml/ min/ 1.73 m2) is not recommended.
L- użu ta ’ Zavesca f’ pazjenti b’ indeboliment kbir tal- kliewi (b’ rata ta ’ tneħħija tal- krejatinina ta ’ < 30 ml/ min/ 1. 73 m2) mhux irrakkomandat.
Niemann-Pick type C disease
Marda ta ’ Niemann- Pick ta ’ tip Ċ
The benefit of treatment with Zavesca for neurological manifestations in patients with Niemann-Pick type C disease should be evaluated on a regular basis, e. g. every 6 months; continuation of therapy should be re-appraised after at least 1 year of treatment with Zavesca.
Il- benefiċċju ta ’ kura b’ Zavesca għall- manifestazzjonijiet newroloġiċi f’ pazjenti li għandhom il- marda ta ’ Niemann- Pick ta ’ tip Ċ għandu jiġi ivvalutat fuq bażi regolari, eż. kull 6 xhur; jekk għandhiex titkompla it- terapija għandu jiġi ivvalutat mill- ġdid wara mill- inqas sena ta ’ kura b’ Zavesca.
Reduced growth has been reported in some paediatric patients with Niemann-Pick type C disease in the early phase of treatment with miglustat where the initial reduced weight gain may be accompanied or followed by reduced height gain.
Fil- fażi bikrija ta ’ kura b’ miglustat, kien irrappurtat tnaqqis fit- tkabbir f’ xi pazjenti pedjatriċi bil - marda ta ’ Niemann- Pick ta ’ tip Ċ, fejn iż- żjieda imnaqqsa fil- piż inizjali tista ’ tkun akkompanjata jew segwita minn żjieda imnaqqsa fit- tul.
Growth should be monitored in paediatric and adolescent patients during treatment with Zavesca; the benefit/ risk balance should be re-assessed on an individual basis for continuation of therapy.
It- tkabbir għandu jiġi sorveljat f’ pazjenti pedjatriċi u adoloxxenti waqt kura b’ Zavesca; il- bilanċ tal- benefiċċju/ riskju għandu jerġa jiġi vvalutat fuq bażi individwali għall- kontinwazzjoni tat- terapija.
Mild reductions in platelet counts without association to bleeding were observed in some patients with Niemann-Pick type C disease treated with Zavesca.
F’ xi pazjenti bil- marda ta ’ Niemann- Pick ta ’ tip Ċ kkurati b’ Zavesca kien osservat tnaqqis ħafif fl - għadd ta ’ plejtlits mingħajr assoċjazzjoni ma ’ fsada.
In patients included in the clinical trial, 40%-50% of patients had platelet counts below the lower limit of normal at baseline.
Fil- pazjenti inklużi fil- prova klinika, 40% - 50% tal- pazjenti kellhom għadd ta ’ plejtlits taħt l- inqas limitu tan- normal fil- linja bażi.
Monitoring of platelet counts is recommended in these patients.
F’ dawn il- pazjenti hija rrakkomandata sorveljanza ta ’ l- għadd tal- plejtlits.
Limited data suggest that co-administration of Zavesca and Cerezyme in patients with type 1 Gaucher disease may result in decreased exposure to miglustat (approximate reductions of 22% in Cmax and 14% in AUC were observed in a small parallel-group study).
Tagħrif limitat jissuġġerrixxi li l- użu ta ’ Zavesca flimkien ma ’ Cerezyme f’ pazjenti bil- marda ta ’ Gaucher ta ’ tip 1 jista ’ jirriżulta fi tnaqqis ta ’ l- espożizzjoni għal miglustat (tnaqqis ta ’ madwar 22% fis - Cmax u tnaqqis ta ’ madwar 14% fl- AUC kien osservat fi studju żgħir ta ’ gruppi paralleli).
This study also indicated that Zavesca has no or limited effect on the pharmacokinetics of Cerezyme.
Dan l - istudju indika wkoll li Zavesca m’ għandux effett jew għandu effett limitat fuq il- farmakokinetiċi ta ’ Cerezyme.
4 There are no adequate data from the use of miglustat in pregnant women.
M’ hemmx tagħrif biżżejjed dwar l- użu ta ’ miglustat f’ nisa tqal.
Studies in animals have shown reproductive toxicity, including dystocia (see section 5.3).
Studji fuq l- annimali wrew tossiċità riproduttiva, li tinkludi diffikultà waqt it- twelid (ara sezzjoni 5. 3).
Miglustat crosses the placenta and should not be used during pregnancy.
Miglustat jgħaddi mill- plaċenta u m’ għandux jintuża waqt it- tqala.
Contraceptive measures should be used by women of childbearing potential.
In- nisa li jistgħu joħorgu tqal għandhom jużaw miżuri ta ’ kontraċezzjoni.
It is not known if miglustat is secreted in breast milk.
Mhux magħruf jekk miglustat jiġix imnixxi fil- ħalib tas- sider.
Zavesca should not be used during breast-feeding.
Zavesca m’ għandux jintuża waqt it - treddigħ.
Male patients should maintain reliable contraceptive methods while taking Zavesca and for 3 months after finishing treatment (see sections 4.4 and 5.3)
Pazjenti rġiel għandhom jibqgħu jużaw metodu ta ’ kontraċezzjoni affidabbli waqt it- teħid ta ’ Zavesca u għal tliet xhur wara li tintemm il- kura (ara sezzjonijiet 4. 4 u 5. 3).
No studies on the effects of Zavesca on the ability to drive or use machines have been performed.
Ma sarux studji dwar l- effetti ta ’ Zavesca fuq il- ħila biex issuq jew tħaddem magni.
However, dizziness has been reported as a very common adverse event, and patients suffering from dizziness should not drive or operate machinery.
Madankollu, sturdament kien irrapportat bħala effett avvers komuni ħafna, u pazjenti li jbatu minn sturdament m’ għandhomx isuqu jew iħaddmu magni.
In nine clinical trials in different indications 206 patients were treated with Zavesca at dosages of 50- 200 mg t. i. d. for an average duration of 2.2 years.
F’ disa ’ provi kliniċi dwar indikazzjonijiet differenti, 206 pazjent kienu kkurati b’ Zavesca b’ dożaġġ ta ’ 50- 200 mg t. i. d. għal tul medju ta ’ 2. 2 snin.
Of these patients, 90 had type 1 Gaucher disease, and 40 had Niemann-Pick type C disease.
Minn dawn il- pazjenti, 90 kellhom il- marda ta ’ Gaucher ta ’ tip 1, u 40 kellhom il- marda ta ’ Niemann- Pick ta ’ tip Ċ.
Adverse reactions were generally of mild to moderate severity and occurred with similar frequency across indications and dosages tested.
Ir- reazzjonijiet avversi ġeneralment kienu ħfief sa moderati fis- severità tagħhom u seħħew bi frekwenza simili fl- indikazzjonijiet u d- dożaġġi eżaminati kollha.
The most common adverse reactions were gastrointestinal, with diarrhoea and other abdominal complaints, and weight loss.
L- aktar reazzjonijiet avversi komuni kienu gastro- intestinali, b’ dijarea, u effetti addominali oħra, u tnaqqis fil- piż.
Adverse drug reactions, defined as treatment-emergent adverse events reported as related to treatment by the investigator and occurring in > 1% of patients, are listed in the table below by body system and frequency (very common: ≥ 1/ 10, common: ≥ 1/ 100 < 1/ 10).
Reazzjonijiet avversi tal- mediċina, definiti bħala avvenimenti avversi li seħħew mal- kura, rrapportati bħala relatati mal- kura mill- investigatur u li seħħew f ’ > 1% tal- pazjenti, huma mniżżlin fit- tabella taħt skond is- sistema tal- ġisem u skond il- frekwenza (komuni ħafna: ≥1/ 10, komuni: ≥1/ 100, < 1/ 10).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
L- effetti li huma l- aktar serji għandhom jitniżżlu l- ewwel, segwiti minn dawk anqas serji.
Metabolism and Nutrition Disorders Very common Common
Disturbi fil- Metaboliżmu u n- Nutrizzjoni Komuni ħafna Komuni
Weight loss Anorexia, decreased appetite
Tnaqqis fil- piż Anoreksja, tnaqqis fl- aptit
Insomnia, libido decreased
Nuqqas ta ’ rqad, tnaqqis fil- libido
Nervous System Disorders Very common Common
Disturbi fis- Sistema Nervuża Komuni ħafna Komuni
Tremor, Peripheral neuropathy, headache, paraesthesia, dizziness, ataxia, hypoaesthesia
Tregħid Newropatija periferali, uġigħ ta ’ ras, parasteżija, sturdament, ataxja, ipoestesija
Gastrointestinal Disorders Very common Common
Disturbi Gastro- intestinali Komuni ħafna Komuni
Diarrhoea, flatulence, abdominal pain Nausea, vomiting, abdominal distension/ discomfort, constipation, dyspepsia
Dijarea, gass, uġigħ addominali Tqalligħ, rimettar, nefħa/ skomdu addominali, stitikezza, dispepsja
Musculoskeletal and connective tissue disorders Common
Disturbi muskolu- skeltrali u tal- connective tissue 5 Komuni
Investigations
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata Komuni:
Fatigue, asthenia
Għeja, astenja
5
Investigazzjonijiet
Nerve conduction studies abnormal,
Studji ta ’ trasmissjoni tan- nervaturi mhux normali,
Weight loss has been observed in approximately 60% of patients.
Kien osservat tnaqqis fil- piż f’ madwar 60% tal- pazjenti.
The greatest effect was at 12 months, with a mean weight loss of 6– 7% of body weight, with a subsequent tendency for an increase in weight towards the baseline value.
L- ikbar effett kien wara 12- il xahar, bi tnaqqis medju fil- piż tal- ġisem ta ’ 6– 7%, b’ tendenza sussegwenti għal żjieda fil- piż lejn il- valur tal- linja bażi.
Zavesca has been studied in indications where certain events reported as adverse drug reactions, such as neurological symptoms/ signs and thrombocytopenia could also be due to the underlying conditions.
Zavesca kien studjat f’ indikazzjonijiet fejn ċertu avvenimenti rrapportati bħala ADRs, bħal sintomi/ sinjali newroloġiċi u tromboċitopenja jista ’ jkunu kkawżata wkoll mill- marda li ġa hemm.
Isolated cases of cognitive dysfunction have been reported during clinical trials of Zavesca in type 1 Gaucher disease.
Każijiet iżolati ta ’ disfunzjoni konjittiva kienu rrapportati waqt il- provi kliniċi ta ’ Zavesca fil- marda ta ’ Gaucher ta ’ tip 1.
A causal relationship to Zavesca has not been established.
Ma ġietx stabbilita relazzjoni kawżali għal Zavesca.
No acute symptoms of overdose have been identified.
L- ebda sintomi akuti ta ’ doża eċċessiva ma kienu identifikati.
Zavesca has been administered at doses of up to 3000 mg/ day for up to six months in HIV positive patients during clinical trials.
Matul l- istudji kliniċi, Zavesca ngħata f’ dożi sa 3000 mg/ kuljum sa sitt xhur f’ pazjenti li huma pożittivi għall- HIV.
Adverse events observed included granulocytopenia, dizziness and paraesthesia.
Avvenimenti avversi osservati kienu jinkludu granuloċitopenja, sturdament u parasteżija.
Leukopenia and neutropenia have also been observed in a similar group of patients receiving 800 mg/ day or higher dose.
Lewkopenja u newtropenja kienu osservati wkoll fi grupp simili ta ’ pazjenti li ngħataw doża ta ’ 800 mg/ kuljum jew iktar.
1 Pharmacodynamic properties
5. 1 Tagħrif farmakodinamiku
Other alimentary tract and metabolism products, ATC Code:
Kodiċi ATC:
This means that due to the rarity of the disease it has not been possible to obtain complete information on this medicinal product.
Dan ifisser li minħabba r- rarità tal- marda ma kienx possibbli li tinkiseb informazzjoni kompleta dwar dan il- prodott mediċinali.
The European Medicines Agency (EMEA) will review any new information, which may become available every year and this SPC will be updated as necessary.
L- Aġenzija Ewropeja dwar il- Mediċini (EMEA) ser tirrevedi kull informazzjoni ġdida li tista ’ ssir disponibbli kull sena u ser taġġorna dan is- Sommarju tal- Karatteristiċi tal- Prodott, skond il - bżonn.
Type 1 Gaucher disease
Marda ta ’ Gaucher ta ’ Tip 1
Gaucher disease is an inherited metabolic disorder caused by a failure to degrade glucosylceramide resulting in lysosomal storage of this material and widespread pathology.
Il- marda ta ’ Gaucher hi marda metabolika li tintiret ġenetikament li hi kkawżata min- nuqqas fil- kapaċità tal- ġisem biex ikisser il- glucosylceramide, li jirriżulta fil- ħżin ta ’ lysosomal ta ’ dan il- materjal u f’ patoloġija mifruxa.
Miglustat is an inhibitor of glucosylceramide synthase, the enzyme responsible for the first step in the synthesis of most glycolipids.
Miglustat hu impeditur ta ’ glycosylceramide synthase, l- enzima responsabbli għall- ewwel pass tas- sintesi ta ’ ħafna mill- glycolipids.
In vitro, glucosylceramide synthase is inhibited by miglustat with an IC50 of 20-37 µM.
In vitro, glucosylceramide synthase huwa inibit minn miglustat b’ IC50 ta ’ 20- 37 µM.
In addition, inhibitory action on a non-lysosomal glycosylceramidase has been demonstrated experimentally in vitro The inhibitory action on glucosylceramide synthase forms the rationale for substrate reduction therapy in Gaucher disease.
L- azzjoni ta ’ inibizzjoni fuq glucosylceramide synthase hi r- raġuni għat- terapija tat- tnaqqis tas- sottostrat (substrate reduction therapy) fil- marda ta ’ Gaucher.
The pivotal trial of Zavesca was conducted in patients unable or unwilling to receive ERT.
L- istudju importanti ħafna dwar Zavesca sar f’ pazjenti li ma setgħux jew li ma riedux jieħdu l- ERT.
Reasons for not receiving ERT included the burden of intravenous infusions and difficulties in venous access.
Ir- raġunijiet li ma ntużatx l- ERT kienu jinkludu l- iskumdità ta ’ l- infużjoni minn ġol- vini u d - diffikultajiet ta ’ l- aċċess għall- vini.
Twenty-eight patients with mild to moderate type 1 Gaucher disease were enrolled in this 12-month non-comparative study, and 22 patients completed the study.
Tmienja u għoxrin pazjent li kellhom il- marda ta ’ Gaucher ta ’ tip 1 li kienet minn ħafifa sa moderata, kienu rreġistrati f’ dan l- istudju mhux komparattiv li dam 12- il xahar, u 22 pazjent temmew l- istudju.
At 12 months, there was a mean reduction in liver organ volume of 12.1% and a mean reduction in spleen volume of 19.0%.
Wara 12- il xahar, kien hemm tnaqqis medju fil- volum ta ’ l - 6 organu tal- fwied ta ’ 12. 1% u tnaqqis medju fil- volum tal- milsa ta ’ 19. 0%.
A mean increase in haemoglobin concentration of 0.26 g/ dl and a mean platelet count increase of 8.29 × 109/ l were observed.
Żjieda medja fil - konċentrazzjoni ta ’ l- emoglobina ta ’ 0. 26 g/ dl u żjieda medja fl- għadd tal- plejtlets ta ’ 8. 29 × 109/ l kienu osservati.
Eighteen patients then continued to receive Zavesca under an optional extended treatment protocol.
Tmintax- il pazjent imbagħad komplew jirċievu Zavesca taħt protokoll ta ’ kura estiż mhux tabilfors.
Clinical benefit has been assessed at 24 and 36 months in 13 patients.
Il- benefiċċju kliniku kien eżaminat wara 24 u 36 xahar fi 13- il pazjent.
After 3 years of continuous Zavesca treatment, mean reductions in liver and spleen organ volume were 17.5% and 29.6%, respectively.
Wara 3 snin ta ’ kura kontinwa b’ Zavesca, kien hemm tnaqqis medju fil- volum ta ’ l- organu tal- fwied u tal- milsa ta ’ 17. 5% u 29. 6%, rispettivament.
There was a mean increase of 22.2 × 109/ l in platelet count, and a mean increase of 0.95 g/ dl in haemoglobin concentration.
Kien hemm żjieda medja ta ’ 22. 2 × 109/ l fl- għadd tal- plejtlets u żjieda medja ta ’ 0. 95 g/ dl fil- konċentrazzjoni ta ’ l- emoglobina.
6 A second open, controlled study randomised 36 patients who had received a minimum of 2 years of treatment with ERT, into three treatment groups: continuation with Cerezyme, Cerezyme in combination with Zavesca, or switch to Zavesca.
Sar studju ieħor tat- tip open, controlled u randomised fejn 36 pazjent u li kienu rċivew kura bl- ERT għal mill- inqas sentejn, inqasmu fi tliet gruppi ta ’ kura: grupp li kompla l- kura bl- użu ta ’ Cerezyme, grupp ieħor li ngħata Cerezyme flimkien ma ’ Zavesca, u l- aħħar grupp li fih il- pazjenti qalbu l- kura għal Zavesca.
This study was conducted over a 6-month randomised comparison period followed by 18 months extension where all patients received Zavesca monotherapy.
Dan l- istudju twettaq fuq perjodu ta ’ paragun randomised ta ’ 6 xhur segwit minn estensjoni ta’ 18- il xahar fejn il- pazjenti kollha rċevew monoterapija ta ’ Zavesca.
In the first 6 months in patients who were switched to Zavesca, liver and spleen organ volumes and haemoglobin levels were unchanged.
F’ ewwel 6 xhur f’ pazjenti li qalbu għal Zavesca, il- volumi ta ’ l- organi tal- fwied u tal- milsa u l- livelli ta ’ emoglobina ma nbidlux.
In some patients there were reductions in platelet count and increases in chitotriosidase activity indicating that Zavesca monotherapy may not maintain the same control of disease activity in all patients.
F’ xi pazjenti, kien hemm tnaqqis fl- għadd tal- plejtlets u żjieda fl- attività tal - chitotriosidase li jindika li t- terapija b’ Zavesca tista 'ma żżommx l- istess kontroll ta ’ l- attività tal - marda fil- pazjenti kollha.
29 patients continued in the extension period.
29 pazjent komplew fil- perijodu ta ’ estensjoni.
When compared to the measurements at 6 months, disease control was unchanged after 18 and 24 months of Zavesca monotherapy (20 and 6 patients, respectively).
Meta mqabbel mar- riżultati wara 6 xhur, il- kontroll tal- marda baqa ’ ma nbidilx wara 18 u 24 xahar ta ’ monoterapija ta ’ Zavesca (20 u 6 pazjent, rispettivament).
No patient showed rapid deterioration of type 1 Gaucher disease following the switch to Zavesca monotherapy.
L- ebda pazjent ma wera deterjorazzjoni rapida tal- marda ta ’ Gaucher tat- tip 1 wara bidla għall- monoterapija ta ’ Zavesca.
A total daily dose of 300 mg Zavesca administered in three divided doses was used in the above two studies.
F’ dawn iż- żewg studji ntużat doża totali ta ’ 300 mg ta ’ Zavesca kuljum, maqsuma fi tliet dożi.
An additional monotherapy study was performed in 18 patients at a total daily dose of 150 mg, and results indicate reduced efficacy compared to a total daily dose of 300 mg.
Fi studju ieħor b’ terapija waħda, imwettaq fuq 18- il pazjent, ingħatat doża totali ta ’ 150 mg kuljum, u r - riżultati jindikaw tnaqqis fl- effikaċja meta mqabbla mad- doża ta ’ 300 mg.
Bone manifestations of type 1 Gaucher disease were evaluated in 3 open-label clinical studies in patients treated with miglustat 100 mg t. i. d. for up to 2 years (n = 72).
Manifestazzjonijiet fl- għadam tal- marda ta ’ Gaucher tat- tip 1 kienu evalwati fi 3 studji kliniċi open - label f’ pazjenti kkurati b’ miglustat 100 mg t. i. d. għal perijodu sa sentejn (n = 72).
In a pooled analysis of uncontrolled data, bone mineral density Z-scores at the lumbar spine and femoral neck increased by more than 0.1 units from baseline in 27 (57%) and 28 (65%) of the patients with longitudinal bone density measurements.
F’ analiżi miġbura ta ’ tagħrif mhux ikkontrollat, punteġġi Z tad- densità tal- minerali fl- għadam fl- ispina lombari u fl - għonq femorali żdiedu b’ aktar minn 0. 1 unità mil- linja bażi f’ 27 (57%) u 28 (65%) tal- pazjenti b’ qisien lonġitudinali tad- densità ta ’ l- għadam.
There were no events of bone crisis, avascular necrosis or fracture during the treatment period.
Ma kien hemm l- ebda avveniment ta ’ kriżi ta ’ l - għadam, nekrożi avaskulari jew ksur waqt il- perijodu ta ’ kura.
Niemann-Pick type C disease is a very rare, invariably progressive and eventually fatal neurodegenerative disorder characterised by impaired intracellular lipid trafficking.
Il- marda ta ’ Niemann- Pick ta ’ tip Ċ hija disturb newrodeġenerattiv rari ħafna, progressiv b’ mod kostanti u eventwalment fatali, ikkaratterizzat minn traffikar indebolit tal- lipidi fiċ- ċelluli.
The neurological manifestations are considered secondary to the abnormal accumulation of glycosphingolipids in neuronal and glial cells.
Il - manifestazzjonijet newroloġiċi huma kkunsidrati sekondarji għall- akkumulazzjoni mhux normali ta ’ glycosphingolipids fiċ- ċelluli newronali u glijali.
Data to support safety and efficacy of Zavesca in Niemann-Pick type C disease come from a prospective open-label clinical trial and a retrospective survey.
Tagħrif li jsostni s- sigurtà u l- effikaċja ta ’ Zavesca fil- marda ta ’ Niemann- Pick ta ’ tip Ċ ġej minn prova klinika open- label prospettiva u minn servej retrospettiv.
The clinical trial included 29 adult and juvenile patients in a 12-month controlled period, followed by extension therapy for an average total duration of 3.9 years and up to 5.6 years.
Il- prova klinika inkludiet 29 pazjent adult u minorenni f’ perijodu ikkontrollat ta ’ 12- il xahar, segwit minn estensjoni tat- terapija għal medja ta ’ tul totali ta ’ 3. 9 snin u sa 5. 6 snin.
In addition 12 paediatric patients were enrolled in an uncontrolled substudy for an overall average duration of 3.1 years and up to 4.4 years.
Barra dan, 12- il pazjent pedjatriku oħra ħadu sehem f’ sottostudju mhux ikkontrollat għal medja ta ’ tul totali ta ’ 3. 1 snin u sa 4. 4 snin.
Among the 41 patients enrolled in the trial 14 patients were treated with Zavesca for more than 3 years.
Fost il- 41 pazjent li ħadu sehem fil- prova 14- il pazjent kienu kkurati b’ Zavesca għal aktar minn 3 snin.
The survey included a case series of 66 patients treated with Zavesca outside of the clinical trial for a mean duration of 1.5 years.
Is- servej kien jinkludi serje ta ’ każijiet ta ’ 66 pazjent ikkurati b’ Zavesca barra mill- prova klinika għal medja ta ’ tul ta ’ żmien ta ’ 1. 5 snin.
Both data sets included paediatric, adolescent and adult patients with an age range of 1 year to 43 years.
Iż- żewġ settijiet ta ’ tagħrif kienu jinkludu pazjenti pedjatriċi, adoloxxenti u adulti ta ’ età li varjat minn sena sa 43 sena.
The usual dose of Zavesca in adult patients was 200 mg t. i. d., and was adjusted according to body surface area in paediatric patients.
Id- doża tas- soltu ta ’ Zavesca f’ pazjenti adulti kienet 200 mg t. i. d., u kienet aġġustata kif meħtieġ skond l- erja tas- superfiċje tal- ġisem f’ pazjenti pedjatriċi.
Overall the data show that treatment with Zavesca can reduce the progression of clinically relevant neurological symptoms in patients with Niemann-Pick type C disease.
Globalment it- tagħrif wera li kura b’ Zavesca tista ’ tnaqqas il- progressjoni tas- sintomi newroloġiċi klinikament rilevanti f’ pazjenti bil- marda ta ’ Niemann- Pick ta ’ tip Ċ.
The benefit of treatment with Zavesca for neurological manifestations in patients with Niemann-Pick type C disease should be evaluated on a regular basis, e. g. every 6 months; continuation of therapy should be re-appraised after at least 1 year of treatment with Zavesca, (see section 4.4).
Il- benefiċċju ta ’ kura b’ Zavesca għall- manifestazzjonijiet newroloġiċi f’ pazjenti bil- marda ta ’ Niemann- Pick ta ’ tip Ċ għandu jiġi evalwat fuq bażi regolari, eż. kull 6 xhur; jekk għandhiex titkompla it- terapija għandu jiġi ivvalutat mill- ġdid wara mill- inqas sena ta ’ kura b’ Zavesca, (ara sezzjoni 4. 4).
5.2 Pharmacokinetic properties
7 5. 2 Tagħrif farmakokinetiku
Pharmacokinetic parameters of miglustat were assessed in healthy subjects, in a small number of patients with type 1 Gaucher disease, Fabry disease, HIV-infected patients, and in adults, adolescents and children with Niemann-Pick type C disease or type 3 Gaucher disease.
Il- parametri farmakokinetiċi ta ’ miglustat kienu evalwati f’ individwi b’ saħħithom, fi grupp żgħir ta ’ pazjenti li kellhom il- marda ta ’ Gaucher ta ’ tip 1, il- marda ta ’ Fabry, pazjenti infetti bl- HIV, u f’ adulti adoloxxenti u tfal bil- marda ta ’ Niemann- Pick ta ’ tip Ċ jew il- marda ta ’ Gaucher ta ’ tip 3.
The kinetics of miglustat appear to be dose linear and time independent.
Il- kinetiċi ta ’ miglustat jidhru li huma lineari mad- doża u ma jiddipendux miż- żmien.
In healthy subjects miglustat is rapidly absorbed.
F’ indvidwi b’ saħħithom miglustat jiġi assorbit malajr.
Absolute bioavailability has not been determined.
Il- konċentrazzjonijiet massimi fil- plażma jintlaħqu madwar sagħtejn wara li tittieħed id- doża.
Concomitant administration of food decreases the rate of
Il- bijodisponibilità assoluta ta ’ Zavesca mhijiex magħrufa.
7 absorption (Cmax was decreased by 36% and tmax delayed 2 hours), but has no statistically significant effect on the extent of absorption of miglustat (AUC decreased by 14%).
Meta Zavesca jittieħed ma ’ l- ikel, ir- rata ta ’ l- assorbiment tonqos (Cmax naqset b’ 36% u tmax intlaħaq sagħtejn iktar tard min- normal), imma dan m’ għandu l- ebda effett statistikament sinifikanti fuq l - ammont ta ’ assorbiment ta ’ miglustat (AUC naqset b’ 14%).
The apparent volume of distribution of miglustat is 83 l.
Il- volum apparenti tad- distribuzzjoni ta ’ miglustat hu ta ’ 83 l.
Miglustat does not bind to plasma proteins.
Miglustat ma jeħilx mal- proteini tal - plażma.
Miglustat is mainly eliminated by renal excretion, with urinary recovery of unchanged drug accounting for 70-80% of the dose.
Fil- biċċa l- kbira miglustat huwa eliminat permezz ta ’ eskrezzjoni renali, b’ irkupru mill - awrina tal- mediċina mhux mibdula li jammonta għal 70- 80% tad- doża.
Apparent oral clearance (CL/ F) is 230 ± 39 ml/ min.
Ir- rata ta ’ tneħħija apparenti mill- ħalq (apparent oral clearance) (CL/ F) hi ta ’ 230 ± 39 ml/ min.
The average half-life is 6– 7 hours.
Il- medja tal- half- life hi ta ’ 6– 7 sigħat.
Following administration of a single dose of 100 mg 14C-miglustat to healthy volunteers, 83% of the radioactivity was recovered in urine and 12% in faeces.
Wara għoti ta ’ doża waħda ta ’ 100 mg 14C- miglustat lill- voluntiera b’ saħħithom, 83% tar- radjuattività kienet irkuprata fl- awrina u 12% fl- ippurgar.
Several metabolites were identified in urine and faeces.
Bosta metaboliti kienu identifikati fl- awrina u fl - ippurgar.
The most abundant metabolite in urine was miglustat glucuronide accounting for 5% of the dose.
L- aktar metabolit abbundanti fl- awrina kien miglustat glucuronide li jammonta għal 5% tad - doża.
The terminal half-life of radioactivity in plasma was 150 h suggesting the presence of one or more metabolites with very long half-life.
Il- half- life terminali tar- radjuattività fil- plażma kienet 150 h li tissuġġerixxi l- preżenza ta ’ metabolit wieħed jew aktar b’ half- life twila ħafna.
The metabolite accounting for this has not been identified, but may accumulate and reach concentrations exceeding those of miglustat at steady state.
Il- metabolit responsabbli għal dan għadu ma ġiex identifikat, iżda jista ’ jakkumula u jilħaq konċentrazzjonijiet li jaqbżu dawk ta ’ miglustat fi stat fiss.
The pharmacokinetics of miglustat is similar in adult type 1 Gaucher disease patients and Niemann-Pick type C disease patients when compared to healthy subjects.
Meta mqabbla ma ’ individwi b’ saħħithom, il- farmakokinetika ta ’ miglustat hija simili f’ pazjenti adulti bil- marda ta ’ Gaucher ta ’ tip 1 u pazjenti adulti bil- marda ta ’ Niemann- Pick ta ’ tip Ċ.
Pharmacokinetic data were obtained in paediatric patients with type 3 Gaucher disease aged 3 to 15 years, and patients with Niemann-Pick type C disease aged 5– 16 years.
Tagħrif farmakokinetiku kien miksub minn pazjenti pedjatriċi bil- marda ta ’ Gaucher ta ’ tip 3 b’ età minn 3 snin sa 15- il sena u minn pazjenti bil- marda ta ’ Niemann- Pick ta ’ tip Ċ b’ età minn 5 snin sa 16- il sena.
Dosing in children at 200 mg t. i. d. adjusted for body surface area resulted in Cmax and AUCτ values which were approximately two-fold those attained after 100 mg t. i. d. in type 1 Gaucher disease patients, consistent with the dose-linear pharmacokinetics of miglustat.
Dożaġġ fit- tfal b’ 200 mg t. i. d. aġġustat għall- erja tas- superfiċje tal- ġisem wassal għall- valuri ta ’ Cmax u AUCτ li kienu madwar darbtejn dawk miksuba wara 100 mg t. i. d. f’ pazjenti bil- marda ta ’ Gaucher ta ’ tip 1, konsistenti mal- farmakokinetika lineari mad- doża ta ’ miglustat.
At steady state, the concentration of miglustat in cerebrospinal fluid of six type 3 Gaucher disease patients was 31.4– 67.2% of that in plasma.
Fi stat stabbli, il - konċentrazzjoni ta ’ miglustat fil- fluwidu ċerebrospinali ta ’ sitt pazjenti bil- marda ta ’ Gaucher ta ’ tip 3 kienet 31. 4– 67. 2% ta ’ dik fil- plażma.
Limited data in patients with Fabry disease and impaired renal function showed that CL/ F decreases with decreasing renal function.
Tagħrif limitat dwar pazjenti li jbatu bil- marda ta ’ Fabry u b’ indeboliment tal- funzjoni tal- kliewi wera li s- CL/ F tonqos iktar ma tonqos il- funzjoni tal- kliewi.
While the numbers of subjects with mild and moderate renal impairment were very small, the data suggest an approximate decrease in CL/ F of 40% and 60% respectively, in mild and moderate renal impairment (see section 4.2).
Waqt li n- numru ta ’ individwi b’ indeboliment tal- kliewi minn ħafif sa moderat kien żgħir ħafna, t- tagħrif jindika tnaqqis fis- CL/ F ta ’ madwar 40% u 60%, rispettivament, f’ indeboliment tal- kliewi minn ħafif sa moderat (ara sezzjoni 4. 2).
Data in severe renal impairment are limited to two patients with creatinine clearance in the range 18 – 29 ml/ min and cannot be extrapolated below this range.
Tagħrif dwar indeboliment sever tal- kliewi hu limitat għal żewg pazjenti bir- rata ta ’ tneħħija tal- krejatinina ta ’ 18 – 29 ml/ min, u dan ma jistax ikun estrapolat taħt din il- medda.
These data suggest a decrease in CL/ F by at least 70% in patients with severe renal impairment.
Dan it- tagħrif jissuġġerixxi tnaqqis fis - CL/ F ta ’ mill- inqas 70% f’ pazjenti b’ indeboliment sever tal- kliewi.
Over the range of data available, no significant relationships or trends were noted between miglustat pharmacokinetic parameters and demographic variables (age, BMI, gender or race).
Mill- medda ta ’ tagħrif disponibbli, ma kienu osservati l- ebda relazzjonijiet jew tendenzi sinifikanti bejn il- parametri farmakokinetiċi ta ’ Miglustat u l- varjanti demografiċi (età, BMI, sess jew razza).
There are no pharmacokinetic data available in patients with liver impairment or in the elderly (> 70 years).
M’ hemm l- ebda tagħrif farmakokinetiku disponibbli f’ pazjenti b’ indeboliment tal- fwied jew fl- anzjani (> 70 sena).
The main effects common to all species were weight loss and diarrhoea, and, at higher doses, damage to the gastrointestinal mucosa (erosions and ulceration).
L- effetti prinċipali li dehru fl- ispeċi kollha kienu tnaqqis fil- piż tal- ġisem u dijarea u, bl- użu ta ’ dożi ogħla, ħsara tal- mukosa gastro- intestinali (tgħawwir u ulċeri).
Further effects seen in animals at doses that result in exposure levels similar to or moderately higher than the clinical exposure level were: changes in lymphoid organs in all species tested, transaminase changes, vacuolation of thyroid and pancreas, cataracts, nephropathy and myocardial changes in rats.
Effetti oħrajn li dehru fl- annimali b’ dożi li jirriżultaw f’ livelli ta ’ espożizzjoni simili għal jew moderatament ogħla mil- livelli ta ’ espożizzjoni kliniċi kienu: bidliet fl- organi tal- limfojde fl- ispeċi kollha ttestjati, bidliet fit- transaminase, 8 formazzjoni ta ’ spazji żgħar mimlijin bl- arja fit- tirojde u fil- frixa, katarretti, nefropatija u bidliet mijokardijaċi fil- firien.
These findings were considered to be secondary to debilitation.
Dawn ir- riżultati kienu kkunsidrati li seħħew bħala konsegwenza ta ’ l- indeboliment.
Administration of miglustat to male and female Sprague-Dawley rats by oral gavage for 2 years at dose levels of 30, 60 and 180 mg/ kg/ day resulted in an increased incidence of testicular interstitial cell (Leydig cell) hyperplasia and adenomas in male rats at all dose levels.
L- għoti ta ’ miglustat lill- firien Sprague- Dawley maskili u femminnili permezz ta ’ gavage orali għal sentejn f’ livelli ta ’ doża ta ’ 30, 60 u 180 mg/ kg/ kuljum wassal għal żjieda fl- inċidenza ta ’ iperplasja taċ- ċellola interstizjali testikolari (ċellola Leydig) u adenomi fil- firien maskili fil- livelli ta ’ dożaġġ kollha.
The systemic exposure at the lowest dose was below or comparable to that observed in humans (based on AUC0-∞) at the recommended human dose.
L- espożizzjoni sistemika fid- doża l- aktar baxxa kienet inqas jew komparabbli għal dik osservata fil- bnedmin (ibbażat fuq l- AUC0- ∞) fid- doża rrakkomandata għall- bnedmin.
A No Observed Effect Level (NOEL) was not established and the effect was not dose dependent.
Ma ntlaħaqx livell ta ’ l- Ebda Effett Osservat (NOEL) u l- effett ma kienx dipendenti mid- doża.
There was no drug-related increase in tumour incidence in male or female rats in any other organ.
Ma kienx hemm żjieda relatata mal- mediċina fl- inċidenza ta ’ tumur f’ firien maskili u femminnili fl- ebda organu ieħor.
Mechanistic studies revealed a rat specific mechanism which is considered to be of low relevance for humans.
Studji mekkanisti wrew mekkaniżmu speċifiku għall- firien li huwa kkunsidrat bħala ta ’ rilevanza baxxa għal bnedmin.
8 Administration of miglustat to male and female CD1 mice by oral gavage at dose levels of 210, 420 and 840/ 500 mg/ kg/ day (dose reduction after half a year) for 2 years resulted in an increased incidence of inflammatory and hyperplastic lesions in the large intestine in both sexes.
L- għotja ta ’ miglustat lill- ġrieden CD1 maskili u femminnili permezz ta ’ gavage orali f’ livelli ta ’ doża ta ’ 210, 420 u 840/ 500 mg/ kg/ kuljum (tnaqqis fid- doża wara nofs sena) għal sentejn wasslet għal żjieda fl- inċidenza ta ’ leżjonijiet infjammati u iperplastiċi fil- musrana l- kbira fiż- żewġ sessi.
Based on mg/ kg/ day and corrected for differences in faecal excretion, the doses corresponded to 8, 16 and 33/ 19 times the highest recommended human dose (200 mg t. i. d.).
Ibbażat fuq mg/ kg/ kuljum u kkoreġut għad- differenzi fit- tneħħija fl- ippurgar, id- dożi kkorrispondew għal 8, 16 u 33/ 19 darba l- ogħla doża rrakkomandata għall- bniedem (200 mg t. i. d.).
Carcinomas in the large intestine occurred occasionally at all doses with a statistically significant increase in the high dose group.
Kultant dehret karċinoma fil- musrana l- kbira bid- dożi kollha b’ żjieda statistikament sinifikanti fil- ġrupp bid- doża l- għolja.
A relevance of these findings to humans cannot be excluded.
Rilevanza ta ’ dawn is- sejbiet għall- bnedmin ma tistax tiġi eskluża.
There was no drug-related increase in tumour incidence in any other organ.
Ma kienx hemm inċidenza ta ’ żjieda fit- tumur relatata mal- mediċina fl- ebda organu ieħor.
Miglustat did not show any potential for mutagenic or clastogenic effects in the standard battery of genotoxicity tests.
Miglustat ma wera l- ebda potenzjal għal effetti mutaġeniċi jew klastoġeniċi fit- testijiet stàndard ta ’ ġenotossiċità.
Repeated-dose toxicity studies in rats showed effects on the seminiferous epithelium of the testes.
Studji dwar l- effett tossiku minn dożi ripetuti fil- firien juru effetti fuq l- epitelju seminiferu tat - testikoli.
Other studies revealed changes in sperm parameters (motility and morphology) consistent with an observed reduction in fertility.
Studji oħrajn urew bidliet fil- parametri ta ’ l- isperma (moviment u morfoloġija) li kienu konsistenti mat- tnaqqis fil- fertilità osservata.
These effects occurred at exposure levels similar to those in patients, but showed reversibility.
Dawn l- effetti seħħew ukoll f’ livelli ta ’ l- espożizzjoni simili għal dawk fil- pazjenti, imma li wrew li kienu riversibbli.
Miglustat affected embryo/ foetal survival in rats and rabbits, dystocia was reported, post-implantation losses were increased, and an increased incidence of vascular anomalies occurred in rabbits.
Miglustat affettwa s- sopravivenza ta ’ l- embriju u tal- fetu fil- firien u fil- fniek; ġew irrappurtati diffikultajiet waqt it- twelid; it- telf wara l - impjantazzjoni żdied, u żdiedet ukoll l- inċidenza ta ’ anomaliji vaskulari fil- fniek.
These effects may be partly related to maternal toxicity.
Dawn l- effetti jistgħu jkunu parzjalment marbuta ma ’ tossiċità ta ’ l- omm.
Changes in lactation were observed in female rats in a 1-year study.
Fi studju li dam sejjer sena, kienu osservati bidliet fit- treddigħ tal- firien nisa.
The mechanism for this effect is unknown.
Il- mekkaniżmu ta ’ dan l - effett mhux magħruf.
Sodium starch glycollate, Povidone (K30), Magnesium stearate.
Sodium starch glycollate, Povidone (K30), Magnesium stearate
Gelatin, Water, Titanium dioxide (E171).
Gelatin, Ilma, Titanium dioxide (E171).
Printing ink:
Linka tal- kitba:
Black iron oxide (E172) Shellac.
Black iron oxide (E172), Shellac.
6.4 Special precautions for storage
6. 4 Prekawzjkonijiet speċjali għall- ħażna
ACLAR/ ALU blister strips supplied as a box of 4 blister strips, each blister strip containing 21 capsules providing a total of 84 capsules.
Kull strixxa tal- folja fiha 21 kapsula għal total ta ’ 84 kapsula.
9 6.6 Special precautions for disposal
6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema
20 November 2002
20 ta ’ Novembru 2002
20 November 2007
20 ta ’ Novembru 2007
Name and address of the manufacturer responsible for batch release Actelion Pharmaceuticals Deutschland GmbH Basler Strasse 63-65 79100 Freiburg Germany
Actelion Pharmaceuticals Deutschland GmbH Basler Strasse 63- 65 79100 Freiburg Il- Ġermanja
Risk Management Plan The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 3 of the Risk Management Plan (RMP), dated 8 September 2008, presented in Module 1.8.2. of the Marketing Authorisation and any subsequent updates of the RMP agreed by the CHMP.
Pjan ta ’ Mmaniġġjar ta ’ Riskji Id- Detentur ta ’ L- Awtorizzazzjoni għat- Tqegħid fis- Suq jikkommetti ruħu li jwettaq l- istudji u l - attivitajiet ta ’ Farmakoviġilanza oħra kif dettaljati fil- Pjan ta ’ Farmakoviġilanza, kif miftiehem f’ verżjoni 3 tal- Pjan ta ’ Mmaniġġjar ta ’ Riskji (RMP), datat 8 ta ’ Settembru 2008, ippreżentat f’ Modulu 1. 8. 2 ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq u kull aġġornament sussegwenti ta ’ l- RMP miftieħem mis- CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR).
Skond il- linji gwida ta ’ CHMP dwar is- Sistemi għall- immanniġjar ta ’ Riskji għal prodotti mediċinali għall- użu mill- bniedem, l- RMP aġġornat għandu jiġi sottomess fl- istess żmien tar- Rapport Aggornat dwar is- Sigurtà Perjodiku (PSUR).
In addition, an updated RMP should be submitted • When new information is received that may impact on the current Safety Specification, Pharmacovigilance Plan or risk minimisation activities • Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being reached • At the request of the EMEA
Barra minn hekk RMP aġġornat għandu jiġi sottomess • Meta tinkiseb informazzjoni ġdida li jista ’ jkollha impatt fuq il- Pjan ta ’ Farmakoviġilanza Speċifiku dwar is- Sigurtà attwali jew attivitajiet ta ’ tnaqqis ta ’ riskji • Fi żmien 60 jum minn meta tintlaħaq mira mportanti (farmakoviġilanza jew tnaqqis ta ’ riskji) • Mat- talba ta ’ l- EMEA
The MAH will continue to submit yearly PSURs unless otherwise specified by the CHMP.
L- MAH se tissokta tissottometti PSUR kull sena sakemm ma jiġiex speċifikat mod ieħor mis- CHMP.
The Marketing Authorisation Holder shall complete the following programme of studies within the specified time frame, the results of which shall form the basis of the annual reassessment of the benefit/ risk profile.
Id- Detentur ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq għandu jtemm il- programm ta 'studji li ġejjin fiż- żmien speċifikat, u r- riżultati ta' dawn l- istudji għandhom iservu ta 'bażi għall- istima tal- profil bejn il- benefiċċju/ riskju li ssir kull sena.
Clinical aspects:
12 Aspetti kliniċi:
Actelion commits to continue the comprehensive Zavesca Post-Marketing Surveillance Plan (PMSP) in the EU, which will educate prescribers on the appropriate use of Zavesca and
Actelion tikkommetti ruħha li tkompli l- Pjan ta ’ Sorveljanza ta ’ wara t- Tqegħid fis- Suq ta ’ Zavesca (PMSP) fl- EU, li se jeduka lil minn jippreskrivi dwar l- użu xieraq ta ’ Zavesca u jitlob b’ mod attiv tagħrif dwar is- sigurtà mingħand numru kbir kemm jista ’ jkun ta ’ pazjenti li jirċievu Zavesca, biex tissupplimenta l- PSURs.
The PMSP, as previously submitted to and agreed by CHMP will continue to be implemented prior to launch of Zavesca in each Member State.
Il- PMSP, kif sottomess qabel lil, u maqbul mis- CHMP, se jkompli jkun implimentat qabel it- tnedija ta ’ Zavesca f’ kull Stat Membru.
Summary safety information gathered will be provided alongside the Annual Re-assessment/ PSURs.
Sommarju tat- tagħrif dwar is- sigurtà miġbur se jkun ipprovdut flimkien ma ’ l- Evalwazzjoni Annwali mill- Ġdid/ PSURs.
Actelion will ensure that a capture protocol is continued for all patients currently receiving Zavesca in the ongoing type 1 Gaucher disease clinical studies.
Actelion ser tiżgura li protokoll capture jitkompla għall- pazjenti kollha li bħalissa qed jirċievu Zavesca fl- istudji kliniċi li għadhom għaddejjin dwar il- marda ta ’ Gaucher ta ’ tip 1.
Continued safety and efficacy assessments will be included as well as further periodic neurological and neuropsychological evaluations.
Evalwazzjonijiet kontinwi dwar is- sigurtà u l- effikaċja se jkunu inklużi, kif ukoll evalwazzjonijiet perjodiċi ulterjuri newroloġiċi u newropsikoloġiċi.
This study is referenced as OGT 918-016.
Dan l- istudju hu riferut bħala OGT 918- 016.
The final study report will be provided to the CHMP upon completion.
Ir- rapport dwar l- istudju finali ser ikun ipprovdut lic- CHMP meta jitlesta.
Actelion will conduct an open-label study to provide safety and efficacy data for patients switched from Enzyme Replacement Therapy (ERT) to Zavesca.
Actelion se twettaq studju open- label biex tipprovdi tagħrif dwar is- sigurtà u l- effikaċja għall - pazjenti li jaqilbu mit- Terapija ta ’ Sostituzzjoni ta ’ l- Enżima (ERT) għal Zavesca.
This study is referenced as OGT 918-011.
Dan l- istudju hu riferut bħala OGT 918- 011.
Progress and recruitment updates will be provided alongside the Annual Re-assessment/ PSURs.
Aġġornamenti dwar l- progress u r- reklutaġġ se jkunu pprovduti flimkien ma ’ l- Evalwazzjoni Annwali mill- Ġdid/ PSURs.
The final study report will be provided to the CHMP upon completion.
Ir- rapport finali dwar l- istudju se jkun ipprovdut lic- CHMP meta jitlesta.
Actelion will conduct a natural history observational study of 100 patients with type 1 Gaucher disease taking the Scientific Advice provided in November 2003 into consideration.
Actelion ser twettaq studju ta ’ osservazzjoni ta ’ l- istorja naturali ta ’ 100 pazjent li għandhom il - marda ta ’ Gaucher ta ’ tip 1, filwaqt li tikkunsidra l- Parir Xjentifiku pprovdut f’ Novembru 2003.
The study will be conducted in conjunction with the European Working Group for Gaucher disease (EWGGD).
L- istudju se jitwettaq flimkien mal- European Working Group for Gaucher disease (EWGGD).
This study will aim to enhance the knowledge of the neurological aspects of type 1 Gaucher disease.
Dan l- istudju se jkollu l- għan li jkabbar l- għarfien dwar l- aspetti newroloġiċi tal- marda ta ’ Gaucher ta ’ tip 1.
Longitudinal data will then be gathered on the patient cohort over a 2-year period.
Wara se jinġabar tagħrif lonġitudinali fuq medda ta ’ sentejn minn pazjenti b’ karatteristiċi komuni.