qanastek/EMEA-V3 huggingface dataset:
Aldurazyme should not be used in people who may have a severe allergic reaction (anaphylactic reaction) to laronidase or any of the other ingredients.
Aldurazyme ma għandux jintuża f’ nies li jista ’ jkollhom reazzjoni allerġika severa (reazzjoni anafilattika) għal laronidase jew għal xi sustanza attiva oħra.
Why has Aldurazyme been approved?
Għaliex ġie approvat Aldurazyme?
The Committee for Medicinal Products for Human Use (CHMP) decided that Aldurazyme gives effective control of the symptoms of MPS I.
Il- Kumitat għall- Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) iddeċieda li Aldurazyme jagħti kontroll effettiv tas- sintomi ta ’ MPS I.
The Committee decided that Aldurazyme’ s benefits are greater than its risks for long-term enzyme replacement therapy in patients with a confirmed diagnosis of MPS I.
Il- Kumitat iddeċieda li l- benefiċċji ta ’ Aldurazyme huma akbar mir- riskji tiegħu għal terapija ta ’ sostituzzjoni ta ’ l- enzim fit- tul f’ pazjenti b’ dijanjożi konfermata ta ’ MPS I.
The Committee recommended that Aldurazyme be given marketing authorisation.
Il- Kumitat irrikmanda li Aldurazyme jingħata awtorizzazzjoni għat- tqegħid fis- suq.
Aldurazyme has been authorised under ‘ Exceptional Circumstances’.
Aldurazyme ġie awtorizzat taħt ‘ Ċirkustanzi ta ’ Eċċezzjoni ’.
This means that, because the disease is rare, it has not been possible to obtain complete information about Aldurazyme.
Dan ifisser li, minħabba li l- marda hija rari, mhuwiex possibbli li tinkiseb informazzjoni sħiħa dwar Aldurazyme.
Every year, the European Medicines Agency (EMEA) will review any new information that may become available and this summary will be updated as necessary.
Kull sena, l- Aġenzija Ewropea dwar il- Mediċini (EMEA) sejra tirrevedi kwalunkwe informazzjoni ġdida li tista ’ ssir disponibbli u dan is- sommarju se jiġi aġġornat bix- xieraq.
What information is still awaited for Aldurazyme?
X’ informazzjoni għadha mistennija għal Aldurazyme?
The company that makes Aldurazyme will monitor patients receiving Aldurazyme, looking at reactions to the infusion and the development of antibodies.
Sejrin jimmonitorjaw pazjenti, filwaqt li jħarsu lejn ir- reazzjonijiet għall- infużjoni u l- iżvilupp ta ’ antikorpi.
Other information about Aldurazyme:
Tagħrif ieħor dwar Aldurazyme:
The European Commission granted a marketing authorisation valid throughout the European Union for Aldurazyme to Genzyme Europe B. V. on 10 June 2003.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fis- suq valida madwar l- Unjoni Ewropea kollha għal Aldurazyme lil Genzyme Europe B. V. fl- 10 ta ’ Ġunju 2003.
The record of Aldurazyme’ s designation as an orphan medicine is available here The full EPAR for Aldurazyme can be found here.
L- EPAR sħiħ għal Aldurazyme jista ’ jinstab hawnhekk.
This summary was last updated in 12-2007.
Dan is- sommarju ġie aġġornat l- aħħar f’ 11- 2007.
Invented name
Mnejn jing ata
Pharmaceutical Form
Numru ta ’ l- EU
Packaging
Isem inventat
Package size
Qawwa
EU/ 1/ 03/ 253/ 001
G amla farma ewtika
Aldurazyme
Il- pakkett
Vial (glass)
(kon entrazzjoni)
5 ml (100 U/ ml)
Daqs tal- pakkett
Concentrate for solution for infusion
kon entrat g al soluzzjoni g all- infu joni kon entrat g al soluzzjoni g all- infu joni kon entrat g al soluzzjoni g all- infu joni
Vial (glass)
Minn ol- vina.
5 ml (100 U/ ml)
Minn ol- vina.
Intravenous use
Minn ol- vina.
Vial (glass)
Kunjett (ie) Kunjett (ie) Kunjett (ie)
25 vials
1 kunjett 10 kunjett 25 kunjett
Aldurazyme 100 U/ ml concentrate for solution for infusion
Aldurazyme 100 U/ ml konċentrat għal soluzzjoni għall- infużjoni.
1 ml contains 100 U (approximately 0.58 mg) of laronidase.
1 ml fih 100 U (madwar 0. 58 mg) ta ’ laronidase.
Each vial of 5 ml contains 500 U of laronidase.
Kull kunjett ta ’ 5 ml fih 500 U ta ’ laronidase.
The activity unit (U) is defined as the hydrolysis of one micromole of substrate (4-MUI) per minute.
L- unità ta ’ l- attività (U) hi definita bħala l- idrolisi ta ’ mikromol wieħed ta ’ substrat (4- MUI) kull minuta.
Laronidase is a recombinant form of human α -L-iduronidase and is produced by recombinant DNA technology using mammalian Chinese Hamster Ovary (CHO) cell culture.
Laronidase hu forma rikombinanti ta ’ α- L- glucosidase uman u hu magħmul minn teknoloġija tad- DNA rikombinanti bl- użu ta ’ koltura taċ- ċelluli mammiferi ta ’ l- Ovarji tal- Ħamster Ċiniż (CHO).
Each vial of 5 ml contains 1.29 mmol sodium.
Kull kunjett ta ’ 5 ml fih 1. 29 mmol ta ’ sodium
Concentrate for solution for infusion.
GĦAMLA FARMAĊEWTIKA Konċentrat għal soluzzjoni għall- infużjoni.
A clear to slightly opalescent, and colourless to pale yellow solution.
Soluzzjoni ċara sa kemm kemm opalexxenti, u bla kulur jew isfar ċar.
Aldurazyme is indicated for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Mucopolysaccharidosis I (MPS I; α -L-iduronidase deficiency) to treat the non- neurological manifestations of the disease (see section 5.1).
Aldurazyme hu indikat għal terapija fit- tul tas- sostituzzjoni ta ’ l- enzimi f’ pazjenti b’ dijanjosi kkonfermata ta ’ Mucopolysaccharidosis I (defiċjenza ta ’ MPS I; α- L- iduronidase) għall- kura ta ’ manifestazzjonijiet mhux newroloġiċi tal- marda (ara sezzjoni 5. 1).
Aldurazyme treatment should be supervised by a physician experienced in the management of patients with MPS I or other inherited metabolic diseases.
Il- kura b’ Aldurazyme għandha tkun issorveljata minn tabib b’ esperjenza fl- immaniġġjar ta ’ pazjenti bil- marda b’ MPS I jew b’ mard ieħor metaboliku li jintiret.
Administration of Aldurazyme should be carried out in an appropriate clinical setting where resuscitation equipment to manage medical emergencies would be readily available.
L- għoti ta ’ Aldurazyme għandu jsir fi sfond kliniku adattat fejn tagħmir tar- risuxitazzjoni għandu jkun disponibbli fil- pront, biex emerġenzi mediċi jkunu jistgħu jiġu mmaniġġjati.
The recommended dosage regimen of Aldurazyme is 100 U/ kg body weight administered once every week as an intravenous infusion.
Il- kors tad- dożaġġ rakkomandat ta ’ Aldurazyme hu ta ’ 100 U/ kg ta ’ piż tal- ġisem, mogħti darba kull ġimgħa bħala infużjoni ġol- vini.
The initial infusion rate of 2 U/ kg/ h may be incrementally increased every fifteen minutes, if tolerated, to a maximum of 43 U/ kg/ h.
Ir- rata inizjali ta ’ l- infużjoni ta ’ 2 U/ kg/ siegħa tista ’ tiżdied b’ mod inkrementali kull ħmistax- il minuta, jekk tkun ittollerata, sa massimu ta ’ 43 U/ kg/ siegħa.
The total volume of the administration should be delivered in approximately 3-4 hours.
Il- volum kollu ta ’ l- għoti għandu jingħata f’ madwar 3- 4 sigħat.
For information on pre-treatment, see section 4.4 and for further instructions, see section 6.6.
Għal tagħrif dwar il- kura ta ’ qabel, ara sezzjoni 4. 4, u għal aktar struzzjonijiet ara sezzjoni 6. 6.
The safety and efficacy of Aldurazyme in patients older than 65 years have not been established and no dosage regimen can be recommended in these patients.
Is- sigurtà u l- effikaċja ta ’ Aldurazyme f’ pazjenti li għandhom iktar minn 65 sena ma kinux stabbliti, u l- ebda kors ta ’ dożaġġ speċifiku ma jista ’ jkun rakkomandat għal dawn il- pazjenti.
The safety and efficacy of Aldurazyme in patients with renal or hepatic insufficiency have not been evaluated and no dosage regimen can be recommended in these patients.
Is- sigurtà u l- effikaċja ta ’ Aldurazyme f’ pazjenti b’ insuffiċjenza renali jew epatika ma kinux evalwati, u l- ebda kors ta ’ dożaġġ speċifiku ma jista ’ jkun rakkomandat għal dawn il- pazjenti.
Severe hypersensitivity (e. g. anaphylactic reaction) to the active substance or to any of the excipients (see sections 4.4 and 4.8).
4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu
Patients treated with Aldurazyme may develop infusion-associated reactions (IARs), defined as any related adverse event occurring during the infusion or until the end of the infusion day (see section 4.8).
Pazjenti kkurati b’ Aldurazyme jistgħu jiżviluppaw reazzjonijiet marbuta ma ’ l- infużjoni (IARs), definiti bħala kwalunkwe reazzjoni avversa marbuta ma ’ l- infużjoni li sseħħ matul l- infużjoni jew sat- tmiem tal- jum ta ’ l- infużjoni (ara sezzjoni 4. 8).
Some of these IARs may be severe (see below).
Xi wħud minn dawn l- IARs jistgħu jkunu severi (ara hawn taħt).
Patients treated with Aldurazyme should be closely monitored and all cases of infusion-associated reactions, delayed reactions and possible immunological reactions reported.
Il- pazjenti kkurati b’ Aldurazyme għandhom ikunu mmonitorjati mill- qrib, u l- każijiet kollha ta ’ reazzjonijiet marbuta ma ’ l- infużjoni, reazzjonijiet li jseħħu wara ċertu żmien u reazzjonijiet immunoloġiċi possibbli, għandhom ikunu rrappurtati.
Antibody status should be regularly monitored and reported.
L- istatus ta ’ l- antikorpi għandu jkun immonitorjat u rrappurtat regolarment.
Severe infusion associated reactions have been reported in patients with pre-existent severe underlying upper airway involvement and therefore specifically these patients should continue to be closely monitored and only be infused with Aldurazyme in an appropriate clinical setting where resuscitation equipment to manage medical emergencies would be readily available.
Reazzjonijiet severi marbuta ma ’ l - infużjoni kienu rrappurtati f’ pazjenti b’ disturb bażiku li kien jeżisti minn qabel fin- naħa ta ’ fuq tal- passaġġ tan- nifs, u għalhekk, dawn il- pazjenti għandhom speċifikament ikunu mmonitorjati mill- qrib, u jingħataw l- infużjoni b’ Aldurazyme biss fi sfond kliniku adattat, fejn tagħmir tar- risuxitazzjoni għandu jkun disponibbli fil- pront, biex emerġenzi mediċi jkunu jistgħu jiġu mmaniġġjati.
Patients with an acute underlying illness at the time of Aldurazyme infusion appear to be at greater risk for IARs.
Pazjenti b’ mard akut bażiku meta jingħataw l- infużjoni b’ Aldurazyme, jidher li jkunu f’ riskju akbar għal IARs.
Careful consideration should be given to the patient’ s clinical status prior to administration of Aldurazyme.
Għandha tingħata konsiderazzjoni kbira lill- istat kliniku tal- pazjent qabel l- għoti ta ’ Aldurazyme.
Based on the Phase 3 clinical trial, almost all patients are expected to develop IgG antibodies to laronidase, mostly within 3 months of initiation of treatment.
Ibbażat fuq il- prova klinika ta ’ Fażi 3, kważi il- pazjenti kollha huma mistennija li jiżviluppaw antikorpi IgG għal laronidase, l- aktar fi żmien 3 xhur tal- bidu tal- kura.
Patients who have developed antibodies or symptoms of IARs should be treated with caution when administering Aldurazyme (see sections 4.3 and 4.8).
Pazjenti li żviluppaw antikorpi jew sintomi ta ’ IARs għandhom ikunu kkurati bl- attenzjoni meta jingħata Aldurazyme (ara sezzjonijiet 4. 3 u 4. 8).
In clinical studies IARs were usually manageable by slowing the rate of infusion and by (pre-) treating the patient with antihistamines and/ or antipyretics (paracetamol or ibuprofen), thus enabling the patient to continue treatment.
Fi studji kliniċi l- IARs normalment kienu kkontrollati bit- tnaqqis tar- rata ta ’ l- infużjoni u bil- kura tal - pazjent minn qabel bl- antistamini u/ jew antipiretiċi (paracetamol jew ibuprofen), u dan għamilha possibbli li l- pazjent seta ’ jkompli jirċievi l- kura.
As there is little experience on resumption of treatment following prolonged interruption, use caution due to the theoretical increased risk of hypersensitivity reaction after treatment interruption.
Minħabba li hemm ftit esperjenza dwar il- bidu mill- ġdid tal- kura wara interruzzjoni fit- tul, oqgħod attent minħabba r- riskju ogħla teoretiku ta ’ reazzjoni minħabba sensittività eċċessiva wara l - interruzzjoni tal- kura.
With initial administration of Aldurazyme or upon re-administration following interruption of treatment, it is recommended that patients be administered pretreatment medicines(antihistamines and/ or antipyretics) approximately 60 minutes prior to the start of the infusion, to minimise the potential occurrence of IARs.
Meta Aldurazyme jingħata għall- ewwel darba jew meta jerġa ’ jibda jingħata wara interruzzjoni tal- kura, hu rakkomandat li l- pazjenti jingħataw mediċini ta ’ qabel il- kura (antistamini u/ jew antipiretiċi) madwar 60 minuta qabel il- bidu ta ’ l- infużjoni, biex l- okkorrenza potenzjali ta ’ IARs tkun imminimizzata.
If clinically indicated, administration of pretreatment medications with subsequent infusions of Aldurazyme should be considered.
Jekk ikun indikat klinikament, l- għoti ta ’ mediċini ta ’ qabel il- kura b’ infuzjonijiet sussegwenti ta ’ Aldurazyme għandu jkun ikkunsidrat.
In case of a mild or moderate IAR, treatment with antihistamines and paracetamol/ ibuprofen should be considered and/ or a reduction in the infusion rate to half the infusion rate at which the reaction occurred.
F’ każ ta ’ IAR ħafifa jew moderata, il- kura bl- antistamini u paracetamol/ ibuprofen u/ jew it- tnaqqis tar- rata ta ’ l- infużjoni bin- nofs tar- rata li fiha seħħet ir- reazzjoni, għandhom ikunu kkunsidrati.
In case of a single severe IAR, the infusion should be stopped until the symptoms are resolved and treatment with antihistamines and paracetamol/ ibuprofen should be considered.
Jekk ikun hemm każ wieħed ta ’ IAR severa, l- infuzjoni għandha titwaqqaf sakemm is- sintomi jfiequ u l- kura bl- antistamini u l- paracetamol/ ibuprofen għandha tkun ikkunsidrata.
The infusion can be restarted with a reduction of the infusion rate to 1/ 2 – 1/ 4 the rate of the infusion at which the reaction occurred.
L- infużjoni tista ’ terġa ’ tinbeda bi tnaqqis fir- rata ta ’ l- infużjoni għal 1/ 2 – 1/ 4 tar- rata li fiha seħħet ir- reazzjoni.
In case of a recurrent moderate IAR or re-challenge after a single severe IAR, pretreatment should be considered (antihistamines and paracetamol/ ibuprofen and/ or corticosteroids) and a reduction of the infusion rate to 1/ 2 – 1/ 4 the rate of the infusion at which the previous reaction occurred.
F’ każ ta ’ IAR rikorrenti moderata u jew re- challenge wara IAR severa waħda, għandu jkun ikkunsidrata li jingħataw mediċini ta ’ qabel il- kura (antistamini u paracetamol/ ibuprofen u/ jew kortikosterojdi), u tnaqqis fir- rata ta ’ l- infużjoni għal 1/ 2 – 1/ 4 tar- rata ta ’ l- infużjoni li fiha seħħet ir- reazzjoni ta ’ qabel.
As with any intravenous protein product, severe allergic-type hypersensitivity reactions are possible.
Bħal kull prodott tal- proteini li jingħata ġol- vini, reazzjonijiet ta ’ sensittività severi li jixbhu lill- allerġiji, huma possibbli.
If these reactions occur, immediate discontinuation of Aldurazyme is recommended and appropriate medical treatment should be initiated.
3 Jekk dawn ir- reazzjonijiet iseħħu, it- twaqqif immedjat ta ’ Aldrazyme hu rakkomandat, u għandha tinbeda kura medika adattata.
The current medical standards for emergency treatment are to be observed.
L- istandards mediċi kurrenti għal kura ta ’ emerġenza għandhom ikunu osservati.
3 This medicinal product contains sodium and is administered in 0.9% sodium chloride intravenous solution (see section 6.6).
Dan il- prodott mediċinali fih is- sodium u jingħata f’ soluzzjoni ta ’ 0. 9% sodium chloride ġol- vini (ara sezzjoni 6. 6).
To be taken into consideration by patients on a controlled sodium diet.
Dan għandu jkun ikkunsidrat minn pazjenti li qegħdin fuq dieta kkontrollata tas- sodium.
Based on its metabolism, laronidase is an unlikely candidate for Cytochrome P450 mediated interactions.
Ibbażat fuq il- metaboliżmu tiegħu, laronidase mhux mistenni li jkollu interazzjonijiet medjati permezz ta ’ Ċitokrom P450.
Aldurazyme should not be administered simultaneously with chloroquine or procaine due to a potential risk of interference with the intracellular uptake of laronidase.
Aldurazyme m’ għandux jingħata fl- istess ħin ma ’ chloroquine jew procaine minħabba li riskju potenzjali ta ’ interferenza fl- assorbiment intraċellulari ta ’ laronidase.
There are inadequate data on the use of Aldurazyme in pregnant women.
M’ hemmx tagħrif biżżejjed dwar l- użu ta ’ Aldurazyme f’ nisa tqal.
Animal studies do not indicate direct or indirect harmful effects on pregnancy, embryonal/ foetal development, parturition and postnatal development (see section 5.3).
Studji fuq il- bhejjem ma jurux effetti ħżiena diretti jew indiretti fuq it- tqala, fuq l- iżvilupp ta ’ l- embriju/ fetu, il- ħlas jew l- iżvilupp ta ’ wara t- twelid (ara sezzjoni 5. 3).
Therefore Aldurazyme should not be used during pregnancy unless clearly necessary.
Għalhekk Aldurazyme m’ għandux jintuża waqt it- tqala jekk m’ hemmx bżonn ċar.
Laronidase may be excreted in milk.
Laronidase jista ’ jitneħħa fil- ħalib.
Because there are no data available in neonates exposed to laronidase via breast milk, it is recommended to stop breast-feeding during Aldurazyme treatment.
Minħabba li m’ hemm l- ebda informazzjoni disponibbli dwar l - effett fuq trabi tat- twelid esposti għal laronidase permezz tal- ħalib tas- sider, hu rakkomandat li t - treddigħ jitwaqqaf waqt il- kura b’ Aldurazyme.
The majority of the related adverse events in the clinical trials were classified as infusion-associated reactions (IARs), experienced by 53% of the patients in the Phase 3 study (treated for up to 4 years) and 35% of the patients in the under 5 study (up to 1 year of treatment).
Il- maġġoranza ta ’ l- avvenimenti avversi relatati fil- provi kliniċi kienu kklassifikati bħala reazzjonijiet li kienu marbuta ma ’ l- infużjoni (IARs), li seħħew fi 53% tal- pazjenti fl- istudju ta ’ Fażi 3 (ikkurati sa perijodu ta ’ 4 snin) u 35% tal- pazjenti fil- kategorija ta ’ taħt il- 5 snin (sa perijodu ta ’ sena ta ’ kura).
Over time the number of these reactions decreased.
Matul iż- żmien, in- numru ta ’ dawn ir- reazzjonijiet naqas.
The majority of the IARs were mild or moderate in intensity.
Il- maġġoranza ta ’ l- IARs kienu ta ’ intensità ħafifa jew moderata.
The most frequent adverse drug reactions (ADRs) were: headache, nausea, abdominal pain, rash, arthralgia, backpain, pain at extremity, flushing, pyrexia, infusion site reactions, blood pressure increased, oxygen saturation decreased tachycardia and chills.
L- iktar reazzjonijiet avversi tal- mediċina (ADRs) frekwenti kienu: uġigħ ta ’ ras, nawseja, uġigħ addominali, raxx, artralġja, uġigħ fid- dahar, uġigħ fl- estremitajiet, fwawar, deni, reazzjonijiet fis- sit ta ’ l- infużjoni, żieda fil- pressjoni tad- demm, tnaqqis fis- saturazzjoni ta ’ l- ossiġnu, takikardija u tertir.
ADRs to Aldurazyme reported during the Phase 3 study and its extension in a total of 45 patients age 5 years and older and treated up to 4 years are listed below using the following categories of frequency: very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10).
ADRs għal Aldurazyme li kienu rrappurtati matul l- istudju ta ’ Fażi 3 u l- estensjoni tiegħu f’ total ta ’ 45 pazjent li kellhom 5 snin jew aktar, u li kienu kkurati sa perijodu ta ’ 4 snin, huma elenkati hawn taħt bl- użu tal- kategoriji tal- frekwenza li ġejjin: komuni ħafna (≥ 1/ 10); komuni (≥ 1/ 100 sa < 1/ 10).
Due to the small patient population, an ADR reported in a single patient is classified as common.
Minħabba l- popolazzjoni żgħira tal- pazjenti, ADR irrappurtata f’ pazjent wieħed hi kklassifikata bħala komuni.
System Organ Class
Sistema tal- Klassi ta ’ l- Organi
Preferred Term
Terminu Preferut
body temperature increased,
temperatura tal- ġisem li tiżdied
oxygen saturation decreased
tnaqqis fis- saturazzjoni ta ’ l- ossiġnu
Cardiac disorders
komuni
tachycardia
Disturbi fil- qalb
common
takikardija
Nervous system disorders
komuni
paraesthesia, dizziness,
komuni uġigħ ta ’ ras ħafna Disturbi fis- sistema nervuża
Respiratory, thoracic and mediastinal
parestesija, sturdament, problemi respiratorji, qtugħ ta ’ nifs,
disorders
komuni
nausea, abdominal pain
Disturbi
Skin and subcutaneous tissue disorders angioneurotic edema, swelling face,
respiratorji, toraċiċi u medjastinali Disturbi gastro- intestinali
urticaria, pruritus, cold sweat, alopecia, hyperhidrosis arthropathy, arthralgia, back pain,
sogħla tqalligħ, uġigħ addominali
Musculoskeletal and connective tissue ain extremity disorders
komuni komuni ħafna
common very common common
rimettar, dijarea raxx
General disorders and administration site
komuni komuni ħafna
conditions
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda edema anġjonewrotika, nefħa fil - komuni wiċċ, urtikarja, ħakk, għaraq kiesaħ, alopeċja, iperidrosi Disturbi muskolu- skeletrali u tal- connective tissue artropatija, artralġja, uġigħ fid - dahar, uġigħ fl- estremitajiet uġigħ muskoloskeletali fwawar Disturbi vaskulari pressjoni baxxa, sfurija, kesħa periferali deni, reazzjoni fil- post ta ’ l- injezzjoni Disturbi ġenerali u kundizzjonijiet ta ’ mnejn jingħata tertir, tħoss is- sħana, tħoss il- ksieħ, għeja kbira, mard qisu influwenza
system disorders
komuni ħafna komuni komuni ħafna komuni komuni ħafna komuni
anaphylactic reaction
Disturbi fis- sistema immuni: reazzjoni anafilattika Disturbi psikjatriċi nuqqas ta ’ kwiet f’ ġismek
Psychiatric disorders
komuni komuni
Most of the ADRs were mild to moderate in severity.
Il- biċċa l- kbira ta ’ l- ADRs kienu ta ’ intensità minn ħafifa sa moderata.
A single patient with pre-existing airway compromise developed a severe reaction three hours from the start of the infusion (at week 62 of treatment) consisting of urticaria and airway obstruction, requiring tracheostomy.
infużjoni (f’ ġimgħa 62 tal- kura) li kienet tikkonsisti f’ urtikarja u ostruzzjoni fil- pajp tan- nifs, li kienet teħtieġ trakeostomija.
This patient tested positive for IgE.
Dan il- pazjent kien pożittiv għal IgE.
Post-marketing experience of infusion associated reactions revealed reporting of pyrexia, chills and vomiting, mostly mild to moderate in intensity.
L- esperjenza ta ’ wara l- bejgħ ta ’ reazzjonijiet marbuta ma ’ l- infużjoni żvelat ir- rappurtaġġ ta ’ deni, tertir ta ’ bard u rimettar, li kienu l- aktar minn ħfief sa moderati fl- intensità.
Additionally, a few patients who had a prior history of severe MPS I- related upper airway and pulmonary involvement, experienced severe reactions including bronchospasm, respiratory arrest, and facial oedema (see section 4.4).
Flimkien ma ’ dan, ftit pazjenti li kellhom storja medika fil- passat ta ’ disturb fin- naħa ta ’ fuq tal- passaġġ tan- nifs u disurb pulmonari marbut ma ’ MPS I, kellhom reazzjonijiet severi li kienu jinkludu bronkospażmu, waqfien respiratorju, u edema tal- wiċċ (ara sezzjoni 4. 4).
Paediatric population ADRs to Aldurazyme reported during a Phase 2 study in a total of 20 patients, under 5 years of age and mainly of the severe phenotype, treated up to 12 months are listed below.
Popolazzjoni pedjatrika ADRs għal Aldurazyme li kienu rrappurtati matul studju ta ’ Fażi 2 f’ total ta ’ 20 pazjent li kellhom inqas minn 5 snin u li kienu primarjamet tal- fenotipsever, u li kienu kkurati sa perijodu ta ’ 12- il xahar, huma elenkati hawn taħt.
ADRs were all mild to moderate in severity.
L- ADRs kienu kollha ta ’ intensità minn ħafifa sa moderata.
Preferred term
Terminu preferut
Investigations
żieda fil- pressjoni tad - Komuni ħafna demm Investigazzjonijiet tnaqqis fis- saturazzjoni ta ’ Komuni ħafna l- ossiġnu
blood pressure increased
Disturbi fil- qalb
Very common
takikardija
Cardiac disorders
Komuni ħafna
oxygen
deni
Very common Very common
Komuni ħafna
pyrexia chills
mnejn jingħata
5 In a phase 4 study 33 MPS1 patients received 1 of 4 dose regimens:
Fi studju ta ’ fażi 4, 33 pazjent b’ MPS1 irċivew minn 1 sa 4 korsijiet ta ’ doża:
100 U/ Kg IV every week (recommended dose), 200 U/ Kg IV every week, 200 U/ Kg IV every 2 weeks or 300 U/ Kg IV every 2 weeks.
100 U/ Kg IV kull ġimgħa (doża rakkomandata), 200 U/ Kg IV kull ġimgħa, 200 U/ Kg IV kull ġimagħtejn jew 300 U/ Kg IV kull ġimagħtejn.
The recommended dose group had the fewest number of patients who experienced ADRs and IARs.
Il- grupp tad- doża rakkomandata kellu l- inqas numru ta ’ pazjenti li ġarrbu ADRs u IARs.
The type of IARs was similar to those seen in other clinical studies.
It- tip ta ’ IARs kienu simili għal dawk li kienu osservati fi studji kliniċi oħrajn.
Immunogenicity Almost all patients developed IgG antibodies to laronidase.
Immunoġeniċità Kważi l- pazjenti kollha żviluppaw antikorpi IgG għal laronidase.
Most patients seroconverted within 3 months of initiation of treatment; although seroconversion in patients under 5 years old with a more severe phenotype occurred mostly within 1 month (mean 26 days versus 45 days in patients 5 years and older).
Il- biċċa l- kbira tal- pazjenti kellhom serokonverżjoni fi żmien 3 xhur mill- bidu tal- kura; għalkemm is- serokonverżjoni f’ pazjenti taħt il- 5 snin b’ fenotip iktar sever seħħet l- aktar fi żmien xahar (medja ta ’ 26 jum kontra 45 jum f’ pazjenti li kellhom 5 snin jew aktar).
By the end of the Phase 3 study (or at time of early study withdrawal), 13/ 45 patients had no detectable antibodies by radioimmunoprecipitation (RIP) assay, including 3 patients that had never seroconverted.
Sat- tmiem ta ’ l- istudju ta ’ Fażi 3 (jew fiż- żmien li l- pazjent ħareġ kmieni mill- istudju), 13/ 45 pazjent ma kellhom l- ebda antikorpi li setgħu jkunu osservati permezz ta ’ l- assaġġ radioimmunoprecipitation (RIP), li kienu jinkludu 3 pazjenti li qatt ma kellhom serokonverżjoni.
Patients with absent to low antibody levels showed a robust reduction in urinary GAG level, whereas patients with high antibody titers showed variable reduction in urinary GAG.
Pazjenti li ma kellhomx antikorpi jew livelli baxxi ta ’ antikorpi wrew tnaqqis qawwi fil- livell ta ’ GAG fl- awrina, filwaqt li pazjenti b’ titers għoljin ta ’ antikorpi wrew tnaqqis varjabbli fil- livell ta ’ GAG fl - awrina.
The clinical significance of this finding is unknown since there were no consistent relationships between IgG antibody level and clinical efficacy endpoints.
Ir- rilevanza klinika ta ’ din is- sejba mhijiex magħrufa għax ma kien hemm l- ebda relazzjonijiet konsistenti bejn il- livell ta ’ l- antikorpi ta ’ IgG u riżultati aħħarin ta ’ l- effikaċja klinika.
In addition 60 patients in the Phase 2 and 3 studies were tested for in-vitro neutralising effects.
Flimkien ma ’ dan, 60 pazjent fl- istudji ta ’ Fażi 2 U 3 kienu ttestjati għal effetti li jinnewtralizzaw in vitro.
Four patients (three in the Phase 3 study and one in the Phase 2 study) showed marginal to low level in vitro inhibition of laronidase enzymatic activity, which did not appear to impact clinical efficacy and/ or urinary GAG reduction.
Erba ’ pazjenti (tlieta fl- istudju ta ’ Fażi 3 u wieħed fl- istudju ta ’ Fażi 2) urew inibizzjoni in vitro ta ’ attività enzimatika laronidase, li ma deherx li kellha impatt fuq l- effikaċja klinika u/ jew tnaqqis tal - GAG urinarju.
The presence of antibodies did not appear to be related to the incidence of IARs, although the onset of IARs typically coincided with the formation of IgG antibodies.
Il- preżenza ta ’ l- antikorpi ma tidhirx li hi marbuta ma ’ l- inċidenza ta ’ IARs, għalkemm il- bidu ta ’ IARs tipikament ikkoinċida mal- formazzjoni ta ’ antikorpi ta ’ IgG.
The occurrence of IgE antibodies was not fully explored.
L- okkorrenza ta ’ l- antikorpi IgE ma kinitx investigata għal kollox.
Enzymes, ATC code:
Enzimi, Kodiċi ATC:
Mucopolysaccharide storage disorders are caused by the deficiency of specific lysosomal enzymes required for the catabolism of glycosaminoglycans (GAGs).
Problemi tal- ħażna tal- mucopolysaccharide huma kkawżati mid- defiċjenza ta ’ enzimi lisosomali speċifiċi li huma meħtieġa għall- kataboliżmu ta ’ glycosaminoglycans (GAGs).
MPS I is a heterogeneous and multisystemic disorder characterised by the deficiency of α -L-iduronidase, a lysosomal hydrolase which catalyses the hydrolysis of terminal α -L-iduronic residues of dermatan sulfate and heparan sulfate.
MPS I hu disturb eteroġenu u multisistemiku li hu kkaratterizzat mid- defiċjenza ta ’ α- L- iduronidase, hydrolase lisosomali li jikkatalizza l- idrolisi ta ’ residwi α- L- iduronic terminali ta ’ dermatan sulfate u heparan sulfate.
Reduced or absent α -L-iduronidase activity results in the accumulation of the GAGs, dermatan sulfate and heparan sulfate in many cell types and tissues.
Attività mnaqqsa jew assenti ta ’ α- L- iduronidase tirriżulta fl- akkumulazzjoni tal- GAGs, dermatan sulfate u heparan sulfate f’ ħafna tipi ta ’ ċelluli u tessuti.
The rationale for enzyme replacement therapy is to restore a level of enzymatic activity sufficient to hydrolyse the accumulated substrate and to prevent further accumulation.
6 Ir- raġuni fundamentali tat- terapija tas- sostituzzjoni ta ’ l- enzimi hi biex treġġa ’ lura għan- normal livell ta ’ attività enzimatika li jkun suffiċjenti biex jidrolizza s- substrat akkumulat, u biex ma jħallix li ssir akkumulazzjoni addizzjonali.
After intravenous infusion, laronidase is rapidly removed from the circulation and taken up by cells into lysosomes, most likely via mannose-6 phosphate receptors.
Wara l- infużjoni fil- vini, laronidase jitneħħa malajr miċ- ċirkulazzjoni u jkun assorbit miċ- ċelluli fil- lisosomi, x’ aktarx permezz tar- riċetturi mannose- 6 phosphate.
Purified laronidase is a glycoprotein with a molecular weight of approximately 83 kD.
Laronidase ppurifikat hu glikoproteina b’ piż molekulari ta ’ madwar 83 kd.
Laronidase is comprised of 628 amino acids after cleavage of the N-terminus.
Laronidase jikkonsisti f’ 628 amino acids wara l- cleavage tat- terminus N.
The molecule contains 6 N-linked oligosaccharide modifications sites.
Il- molekula fiha 6 siti ta ’ modifikazzjonijiet N- linked ta ’ oligosaccharide.
Three clinical trials were performed with Aldurazyme to assess its efficacy and safety.
Saru tliet studji kliniċi b’ Aldurazyme biex jevalwaw l- effikaċja u s- sigurtà tiegħu.
One study mainly assessed the safety and
Studju kliniku kkonċentra primarjament fuq l- evalwazzjoni ta ’ l- effett ta ’ Aldurazyme fuq il- manifestazzjonijiet sistemiċi ta ’ MPS I bħal ħila batuta li wieħed jissaporti t- tbatija, mard restrittiv fil- pulmun, ostruzzjoni fin- naħa ta ’ fuq tal- pajp tan- nifs, tnaqqis fil- medda tal- moviment tal- ġogi, epatomegalija u indeboliment tal- vista.
6 pharmacokinetics of Aldurazyme in patients less than 5 years old, but some efficacy measurements were included as well.
Studju wieħed evalwa primarjament is- sigurtà u l- farmakokinetika ta ’ Aldurazyme f’ pazjenti li kellhom inqas minn 5 snin, iżda xi kejl ta ’ l- effikaċja kien inkluż ukoll.
The third study was conducted to evaluate the pharmacodynamics and safety of different dose regimens of Aldurazyme.
It - tielet studju sar biex jevalwa l- farmakodinamika u s- sigurtà ta ’ korsijiet ta ’ doża differenti ta ’ Aldurazyme.
To date there are no clinical data that demonstrate any benefit on the neurological manifestations of the disorder.
S’ issa m’ hemm l- ebda informazzjoni klinika li turi xi benefiċċju tal- manifestazzjonijiet newroloġiċi tad- disturb.
The safety and efficacy of Aldurazyme was assessed in a randomised, double-blind, placebo controlled, Phase 3 Study of 45 patients, ranging in age from 6 to 43 years.
Is- siġurtà u l- effikaċja ta ’ Aldurazyme kienu evalwati fi Studju ta ’ Fażi 3 li kien randomised, double- blind u kkontrollat bil- plaċebo li sar fuq 45 pazjent li kellhom minn 6 sa 43 sena.
Although patients representing the full range of the disease spectrum were enrolled, the majority of the patients were of the intermediate phenotype, with only one patient exhibiting the severe phenotype.
Għalkemm il- pazjenti li kienu jirrappreżentaw il- firxa sħiħa ta ’ l- ispektrum tal- marda kienu rreġistrati, il- maġġoranza tal- pazjenti kellhom il- fenotip intermedju, u pazjent wieħed biss kellu l- fenotip sever.
Patients were enrolled with a Forced Vital Capacity (FVC) less than 80% of the predicted value and had to be able to stand for 6 minutes and to walk 5 meters.
Il- pazjenti rreġistrati kellhom Forced Vital Capacity (FVC) ta ’ inqas minn 80% tal- valur imbassar, u kellhom ikunu kapaċi jibqgħu bilwieqfa għal 6 minuti u jimxu 5 metri.
Patients received either 100 U/ kg of Aldurazyme or placebo every week for a total of 26 weeks.
Il- pazjenti rċievew jew 100 U/ kg ta ’ Aldurazyme jew il- plaċebo kull ġimgħa għal total ta ’ 26 ġimgħa.
The primary efficacy endpoints were changes in percent of predicted normal FVC and absolute distance travelled in the six-minute walk test (6MWT).
Ir- riżultati aħħarin ta ’ l - effikaċja kienu tibdil fil- perċentwali tal- FVC normali imbassra u d- distanza assoluta li mxew fit- test tal- mixja ta ’ 6 minuti (6MWT).
All patients subsequently enrolled in an open label extension study where they all received 100 U/ kg of Aldurazyme every week for an additional 3.5 years (182 weeks).
Sussegwentement, il- pazjenti kollha rreġistraw fi studju ta ’ estensjoni open label fejn kollha ngħataw 100 U/ Kg ta ’ Aldurazyme kull ġimgħa għal 3. 5 snin addizzjonali (182 ġimgħa).
Following 26 weeks of therapy, Aldurazyme-treated patients showed improved respiratory function and walking ability as compared to placebo as indicated below.
Wara 26 ġimgħa ta ’ terapija, il- pazjenti li kienu kkurati b’ Aldurazyme wrew funzjoni respiratorja mtejba u kapaċità tal- mixi kif imqabbla mal- plaċebo kif indikat hawn taħt.
Phase 3, 26 weeks of treatment compared to placebo
Fażi 3, 26 ġimgħa ta ’ kura meta mqabbla mal- plaċebo
p value
valur p
Confidence interval (95%)
Intervall tal- kunfidenza (95%)
Percent Predicted
Perċentwali mbassar
mean
medja
FVC (percentage point)
FVC (punt perċentwali)
median
medjan
0.009
0. 009
0.9 - 8.6
0. 9 - 8. 6
38.1
38. 1
0.066
0. 066
-2.0 - 79.0
- 2. 0 - 79. 0
The open label extension study showed improvement and/ or maintenance of these effects up to 208 weeks in the Aldurazyme/ Aldurazyme group and 182 weeks in the Placebo/ Aldurazyme group as indicated in the table below.
L- istudju ta ’ estensjoni open label wera titjib u/ jew il- manteniment ta ’ dawn l- effetti sa 208 ġimgħat fil- grupp ta ’ Aldurazyme/ Aldurazyme u sa 182 ġimgħa fil- grupp tal- Plaċebo/ Aldurazyme kif indikat fit- tabella hawn taħt.
Mean change from pre-treatment baseline
Bidla medja jibdlu mil- linja bażi ta ’ qabel il- kura
Aldurazyme/ Aldurazyme At 208 weeks
Aldurazyme/ Aldurazyme Wara 208 ġimgħa
Placebo/ Aldurazyme At 182 weeks
Plaċebo/ Aldurazyme Wara 182 ġimgħa
Percent predicted FVC (%)1 6 MWT (meters) Apnea/ Hypopnea Index (AHI) Shoulder flexion Range Of Motion (degrees) CHAQ/ HAQ Disability Index 2
CHAQ/ HAQ Indiċi tad- Diżabilità
- 1.2 + 39.2 - 4.0 + 13.1 - 0.43
- 0. 43
- 3.3 + 19.4 - 4.8 + 18.3 - 0.26
- 0. 26
The decrease in percent predicted FVC is not clinically significant over this timeframe, and absolute lung volumes continued to increase commensurate with changes in height in growing paediatric patients.
It- tnaqqis fil- perċentwali mbassar tal- FVC mhuwiex klinikament sinifikanti fuq dan il- perijodu, u l - volumi assoluti tal- pulmun komplew jiżdiedu fi proporzjon mat- tibdil fit- tul f’ pazjenti pedjatriċi li kienu qed jikbru.
2 Both groups exceeded the minimal clinically important difference (-0.24)
2 Iż- żewġ gruppi qabżu d- differenza importanti klinikament minima (- 0. 24)
Of the 26 patients with abnormal liver volumes at pre-treatment baseline, 22 (85%) achieved a normal liver size by the end of the study.
Mis- 26 pazjenti b’ volumi anormali tal- fwied fil- linja ta ’ qabel il- kura, 22 (85%) kisbu daqs normali tal- fwied sat- tmiem ta ’ l- istudju.
There was a rapid reduction in the excretion of urinary GAG (µg/ mg creatinine) within the first 4 weeks, which was maintained through the remainder of the study.
Kien hemm tnaqqis mgħaġġel fit- tneħħija tal- GAG (µg/ mg krejatinina) fl- awrina fi żmien l- ewwel 4 ġimgħat, li kompla matul il- bqija ta ’ l- istudju.
Urinary GAG levels decreased by 77% and 66% in the Placebo/ Aldurazyme and Aldurazyme/ Aldurazyme groups, respectively; at the end of the study one-third of the patients (15 of 45) had reached normal urinary GAG levels.
Il- livelli ta ’ GAG fl- awrina naqsu b’ 77% u 66% fil- gruppi tal- Plaċebo/ Aldurazyme u Aldurazyme/ Aldurazyme, rispettivament; fit- tmiem ta ’ l- istudju, terz tal- pazjenti (15 minn 45) kienu laħqu livelli normali ta ’ GAG fl- awrina.
7 To address the heterogeneity in disease manifestation across patients, using a composite endpoint that summed up clinically significant changes across five efficacy variables (percent predicted normal FVC, 6MWT distance, shoulder flexion range of motion, AHI, and visual acuity) the global response was an improvement in 26 patients (58%), no change in 10 patients (22%), and a deterioration in 9 patients (20%).
Biex jindirizza l- eteroġeneità fil- manifestazzjoni tal- marda fil- pazjenti, bl- użu ta ’ riżultat aħħari kompost li kien juri t- total tal- bidliet klinikament sinifikanti ta ’ ħames fatturi varjabbli ta ’ l- effikaċja (perċentwali imbassra tal- FVC normali, distanza 6MWT, medda tal- moviment tal- liwi ta ’ l- ispallejn, AHI, u ċarezza tal- vista), ir- rispons globali kien titjib f’ 26 pazjent (58%), l- ebda bidla f’ 10 pazjenti (22%), u deterjorament f’ 9 pazjenti (20%).
A Phase 2 open-label, 1-year study was conducted that mainly assessed the safety and pharmacokinetics of Aldurazyme in 20 patients less than 5 years of age at the time of enrolment (16 patients with the severe phenotype and 4 with the intermediate phenotype).
Sar studju ta ’ sena ta ’ Fażi 2, open- label, li primarjament evalwa s- sigurtà u l- farmakokinetika ta ’ Aldurazyme f’ 20 pazjent li kellhom inqas minn 5 snin meta kienu rreġistrati fl- istudju (16- il pazjent b’ fenotip sever u 4 b’ fenotip intermedju).
The patients were scheduled to receive Aldurazyme 100 U/ kg weekly infusions for a total duration of 52 weeks.
Il- pazjenti kienu skedati biex jirċievu infużjonijiet ta ’ Aldurazyme 100 U/ kg kull ġimgħa għal tul ta ’ żmien totali ta ’ 52 ġimgħa.
Four patients underwent dosage increases to 200 U/ kg for the last 26 weeks because of elevated urinary GAG levels at Week 22.
Erba ’ pazjenti kellhom żidiet fid- dożaġġ għal 200 U/ kg fl- aħħar 26 ġimgħa minħabba livelli għoljin ta ’ GAG fl- awrina f’ Ġimgħa 22.
Eighteen patients completed the study.
Tmintax- il pazjent temmew l- istudju.
Aldurazyme was well tolerated at both dosages.
Aldurazyme kien ittollerat tajjeb meta ngħataw iż- żewġ dożaġġi.
The mean urinary GAG level declined by 50% at Week 13 and was reduced by 61% at the end of the study.
Il- medja tal- livell ta ’ GAG fl- awrina naqset b’ 50% f’ Ġimgħa 13 u tnaqqset b’ 61% fit- tmiem ta ’ l - istudju.
Upon study completion, all patients showed reductions in liver size and 50% (9/ 18) had normal liver size.
Meta l- istudju tlesta, il- pazjenti kollha wrew tnaqqis fid- daqs tal- fwied u 50% (9/ 18) minnhom kellhom daqs normali tal- fwied.
The proportion of patients with mild left ventricular hypertrophy decreased from 53% (10/ 19) to 17% (3/ 18), and mean left ventricular mass normalized for body surface area decreased by 0.9 Z-Score (n=17).
Il- proporzjon ta ’ pazjenti b’ ipertrofija ventrikulari ħafifa tax- xellug naqas minn 53% (10/ 19) għal 17% (3/ 18), u l- medja tal- piż ventrikulari tax- xellug normalizzat għall - erja tas- superfiċje tal- ġisem naqas b’ 0. 9 Punteġġ Z (n=17).
Several patients showed an increase in height (n=7) and weight (n=3) for age Z-score.
Diversi pazjenti wrew żieda fit- tul (n=7) u fil- piż (n=3) għall- Punteġġ Z ta ’ l- età.
The younger patients with the severe phenotype (< 2.5 years) and all 4 patients with the intermediate phenotype exhibited a normal rate of mental development, whereas the older patients with a severe phenotype made limited or no gains in cognition.
Il- pazjenti aktar żgħar fl- età bil- fenotip sever (< 2. 5 snin) u l- 4 pazjenti kollha bil- fenotip intermedju, urew rata normali ta ’ żvilupp mentali, filwaqt li pazjenti akbar fl- età b’ fenotip sever kellhom titjib limitat jew l- ebda progress fil- konjizzjoni.
A phase 4 study was conducted to evaluate the pharmacodynamic effects on urinary GAGs, liver volume, and 6MWT, of different Aldurazyme dose regimens.
Studju ta ’ fażi 4 sar biex jevalwa l- effetti farmakodinamiċi fuq il- GAGs urinarji, il- volum tal- fwied, u 6MWT, ta ’ korsijiet ta ’ doża differenti ta ’ Aldurazyme.
In this 26-week open label study, 33 MPS1 patients received 1 of 4 dose regimens of Aldurazyme:
F’ dan l- istudju open label ta ’ 26 ġimgħa, 33 pazjenti MPS1 irċivew minn 1 sa 4 korsijiet ta ’ doża ta ’ Aldurazyme:
100 U/ Kg IV every week (recommended dose), 200 U/ Kg IV every week, 200 U/ Kg IV every 2 weeks; or 300 U/ KgIV every 2 weeks.
100 U/ Kg IV kull ġimgħa (doża rakkomandata), 200 U/ Kg IV kull ġimgħa, 200 U/ Kg IV kull ġimagħtejn jew 300 U/ Kg IV kull ġimagħtejn.
No definite benefit was shown with the higher doses over the recommended dose.
Ma ntwera l- ebda benefiċċju definit b’ dożi ogħla mid- doża rakkomandata.
The 200 U/ Kg IV every 2 weeks regimen may be an acceptable alternative for patients with difficulty receiving weekly infusions; however, there is no evidence that the long term clinical efficacy of these two dose regimens is equivalent.
Il- kors ta ’ 200 U/ Kg IV kull ġimagħtejn jista ’ jkun alternattiva aċċettabbli għal pazjenti li għandhom diffikultà biex jirċievu l- infużjonijiet kull ġimgħa; madankollu, m’ hemm l- ebda evidenza li l- effikaċja klinika fit- tul ta ’ dawn iż- żewġ korsijiet tad- doża hi ekwivalenti.
This medicinal product has been authorised under “ Exceptional Circumstances”.
Dan il- prodott mediċinali kien awtorizzat taħt ‘ Ċirkustanzi ta ’ Eċċezzjoni ’
This means that due to the rarity of the disease it has not been possible to obtain complete information on this medicinal product.
8 Dan ifisser li minħabba li l- marda li qed tbati minnha hija rari, kien impossibbli li tinkiseb informazzjoni kompleta dwar din il- mediċina.
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 tip ta ’ informazzjoni ġdida li toħroġ kull sena u dan il- fuljett ser jiġi aġġornat, skond il- bżonn.
After intravenous administration of laronidase with an infusion time of 240 minutes and at a dose of 100 U/ kg body weight pharmacokinetic properties were measured at Weeks 1, 12 and 26.
Wara l- għoti fil- vini ta ’ laronidase b’ ħin ta ’ l- infużjoni ta ’ 240 minuta u b’ doża ta ’ 100 U/ kg ta ’ piż tal- ġisem, il- proprjetajiet farmakokinetiċi tkejlu f’ Ġimgħat 1, 12 U 26.
Infusion 1
Infużjoni 1
Infusion 12
Infużjoni 12
Infusion 26
Infużjoni 26
Mean ± SD
Medja ± SD 0. 197 ± 0. 052
Mean ± SD
Medja ± SD 0. 210 ± 0. 079
Mean ± SD
Medja ± SD 0. 302 ± 0. 089
0.197 ± 0.052 0.930 ± 0.214 1.96 ± 0.495 0.604 ± 0.172 0.440 ± 0.125 3.61 ± 0.894
0. 440 ± 0. 125
0.210 ± 0.079 0.913 ± 0.445 2.31 ± 1.13 0.307 ± 0.143 0.252 ± 0.079 2.02 ± 1.26
0. 252 ± 0. 079
0.302 ± 0.089 1.191 ± 0.451 1.68 ± 0.763 0.239 ± 0.128 0.217 ± 0.081 1.94 ± 1.09
0. 217 ± 0. 081
Cmax showed an increase over time.
Is- Cmax wera żieda matul iż- żmien.
The volume of distribution decreased with continued treatment, possibly related to antibody formation and/ or decreased liver volume.
Il- volum tad- distribuzzjoni naqas mat- tkomplija tal- kura, u dan kien possibbilment marbut mal- formazzjoni ta ’ l- antikorpi u/ jew mat- tnaqqis fil- volum tal- fwied.
The pharmacokinetic profile in patients less than 5 years old was similar to that of older and less severely affected patients.
Il- profil farmakokinetiku f’ pazjenti li kellhom inqas minn 5 snin kien simili għal dak ta ’ pazjenti li kellhom iktar żmien u li kienu affettwati b’ mod inqas sever.
8 Laronidase is a protein and is expected to be metabolically degraded through peptide hydrolysis.
Laronidase hu proteina u hu mistenni li jiddegrada metabolikament permezz ta ’ l- idrolisi tal- peptidi.
Consequently, impaired liver function is not expected to affect the pharmacokinetics of laronidase in a clinically significant way.
Konsegwentement, l- indeboliment fil- funżjoni tal- fwied mhux mistenni li jaffettwa l- farmakokinetika ta ’ laronidase b’ mod li hu klinikament sinifikanti.
Renal elimination of laronidase is considered to be a minor pathway for clearance (see section 4.2).
It- tneħħija renali ta ’ laronidase hi kkunsidrata bħala rotta minuri għat- tneħħija (ara sezzjoni 4. 2).
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, single dose toxicity, repeated dose toxicity and toxicity to reproduction.
Informazzjoni li mhix klinika, magħmula fuq studji konvenzjonali ta ’ sigurtà farmakoloġika, effett tossiku minn dożi waħidhom, effett tossiku minn dożi ripetuti u l- effett tossiku fuq is- sistema riproduttiva, ma turi l- ebda periklu speċjali għall- bnedmin.
Genotoxic and carcinogenic potential are not expected.
Il- potenzjal ġenotossiku u karċinoġeniku mhuwiex mistenni.
Sodium chloride Sodium phosphate monobasic, monohydrate Sodium phosphate dibasic, heptahydrate Polysorbate 80 Water for injections
Sodium chloride Sodium phosphate monobasic, monohydrate Sodium phosphate dibasic, heptahydrate Polysorbate 80 Ilma għall- injezzjonijiet
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except those mentioned in 6.6.
Minħabba li ma sarux studji li juru liema huma l- prodotti li ma jablux miegħu, dan il- prodott mediċinali m’ għandux jitħallat ma ’ prodotti mediċinali oħrajn.
6.3 Shelf life
9 6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
Diluted solutions:
Soluzzjonijiet dilwiti:
From a microbiological safety point of view, the product should be used immediately.
Mill- aspett mikrobijoloġiku dwar is- sigurtà, il- prodott għandu jintuża immedjatament.
If not used immediately, in-use storage should not be longer than 24 hours at 2°C - 8°C provided that dilution has taken place under controlled and validated aseptic conditions.
Jekk ma jintużax immedjatament, il- ħażna tal- prodott waqt l- użu m’ għandhiex tkun ta ’ iktar minn 24 siegħa f’ temperatura ta ’ 2°C - 8°C, dejjem jekk id- dilwizzjoni tkun seħħet taħt kundizzjonijiet asettiċi kkontrollati u validati.
5 ml concentrate for solution in a vial (type I glass) with a stopper (siliconised chlorobutyl rubber) and a seal (aluminium) with a flip-off cap (polypropylene).
5 ml ta ’ konċentrat għal soluzzjoni f’ kunjett (ħġieġ ta ’ tip I) b’ tapp (lastku siliconised tal- chlorobutyl) u siġill (aluminju) b’ għatu flip- off (polypropylene).
Not all pack sizes may be marketed.
1, 10 u 25 kunjett Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali.
Each vial of Aldurazyme is intended for single use only.
Kull kunjett ta ’ Aldurazyme hu intenzjonat biex jintuża darba biss.
The concentrate for solution for infusion has to be diluted with sodium chloride 9 mg/ ml (0.9%) solution for infusion using aseptic technique.
Il- konċentrat għal soluzzjoni għall- infużjoni għandu jkun dilwit b’ soluzzjoni għall- infużjoni ta ’ 9 mg/ ml (0. 9%) ta ’ sodium chloride billi tuża t- teknika asettika.
It is recommended that the diluted Aldurazyme solution be administered to patients using an infusion set equipped with a 0.2 µm in-line filter.
Hu rakkomandat li s- soluzzjoni dilwita ta ’ Aldurazyme tingħata lill - pazjenti permezz ta ’ sett ta ’ l- infużjoni mgħammar b’ filtru in- line ta ’ 0. 2 µm.
9 Preparation of the Aldurazyme Infusion (Use Aseptic Technique) Determine the number of vials to be diluted based on the individual patient's weight.
Preparazzjoni ta ’ l- Infużjoni ta ’ Aldurazyme (Uża t- Teknika Asettika) Iddeċiedi n- numru ta ’ kunjetti li trid tiddilwa, skond il- piż tal- pazjent individwali.
Remove the required vials from the refrigerator approximately 20 minutes in advance in order to allow them to reach room temperature (below 30˚ C).
Oħroġ il- kunjetti li teħtieġ mill- friġg madwar 20 minuta qabel sabiex tippermettilhom jilħqu t- temperatura tal- kamra (taħt 30˚C).
Before dilution, visually inspect each vial for particulate matter and discoloration.
Qabel id- dilwizzjoni, eżamina kull kunjett għal xi frak jew xi tibdil fil- kulur.
The clear to slightly opalescent and colourless to pale yellow solution should be free of visible particles.
Is- soluzzjoni ċara sa kemm kemm opalexxenti, u bla kulur jew isfar ċar, għandha tkun ħielsa minn partikuli viżibbli.
Do not use vials exhibiting particles or discoloration.
Tużax kunjetti li jkun fihom xi partikuli jew li jkunu biddlu l- kulur.