qanastek/EMEA-V3 huggingface dataset:
The first study, which enrolled 82 patients between 2 to 17 years of age, was a randomized, double- blind study comparing CANCIDAS (50 mg/ m2 IV once daily following a 70-mg/ m2 loading dose on Day 1 [not to exceed 70 mg daily]) to liposomal amphotericin B (3 mg/ kg IV daily) in a 2:1 treatment fashion (56 on caspofungin, 26 on liposomal amphotericin B) as empirical therapy in paediatric patients with persistent fever and neutropenia.
9 L- ewwel studju, li rreġistra 82 pazjent ta ’ bejn 2 u 17- il sena, kien studju double- blind, randomizzat li qabbel CANCIDAS (50 mg/ m2 IV darba kuljum wara loading dose ta ’ 70- mg/ m2 f’ Jum 1 [li m’ għandux jaqbeż 70 mg kuljum]) ma ’ amphotericin B liposomali (3 mg/ kg IV kuljum) b’ mod ta ’ trattament ta ’ 2: 1 (56 fuq caspofungin, 26 fuq amphotericin B liposomali) bħala terapija empirika f’ pazjenti pedjatriċi b’ deni persistenti u newtropenija.
The overall success rates in the MITT analysis results, adjusted by risk strata, were as follows:
Ir- rati globali ta ’ suċċess fir- riżultati tal- analiżi MITT, aġġustati skont il- faxxa tar- riskju, kienu kif ġej:
46.6% (26/ 56) for CANCIDAS and 32.2% (8/ 25) for liposomal amphotericin B.
46. 6% (26/ 56) għal CANCIDAS u 32. 2% (8/ 25) għal amphotericin B liposomali.
The second study was a prospective, open-label, non-comparative study estimating the safety and efficacy of caspofungin in paediatric patients (ages 6 months to 17 years) with invasive candidiasis, esophageal candidiasis, and invasive aspergillosis (as salvage therapy).
It- tieni studju kien studju prospettiv, open- label, mhux komparattiv li kkalkula s- sigurtà u l- effikaċja ta ’ caspofungin f’ pazjenti pedjatriċi (6 xhur sa 17- il sena) b’ kandidjasi invażiva, kandidjasi esofagali, u asperġillożi invażiva (bħala terapija ta ’ salvataġġ).
Forty-nine patients were enrolled and received CANCIDAS at 50 mg/ m2 IV once daily following a 70-mg/ m2 loading dose on Day 1 (not to exceed 70 mg daily), of whom 48 were included in the MITT analysis.
Kienu rreġistrati disgħa u erbgħin pazjent li rċevew CANCIDAS f’ doża ta ’ 50 mg/ m2 IV darba kuljum wara loading dose ta ’ 70 mg/ m2 f’ Jum 1 (li m’ għandhiex taqbeż 70 mg kuljum), li 48 minnhom ġew inklużi fl- analiżi MITT.
Of these, 37 had invasive candidiasis, 10 had invasive aspergillosis, and 1 patient had esophageal candidiasis.
Minn dawn, 37 kellhom kandidjasi invażiva, 10 kellhom asperġillożi invażiva, u pazjent wieħed kellu kandidjasi esofagali.
The favorable response rate, by indication, at the end of caspofungin therapy was as follows in the MITT
Ir- rata ta ’ rispons favorevoli, skont l- indikazzjoni, fit- tmiem tat- terapija b’ caspofungin kienet segwenti fl- analiżi MITT:
81% (30/ 37) in invasive candidiasis, 50% (5/ 10) in invasive aspergillosis, and 100% (1/ 1) in esophageal candidiasis.
81% (30/ 37) fil- kandidjasi invażiva, 50% (5/ 10) fl- asperġillożi invażiva, u 100% (1/ 1) fil- kandidjasi esofagali.
Distribution Caspofungin is extensively bound to albumin.
Distribuzzjoni Caspofungin jeħel b’ mod estensiv mal- albumina.
The unbound fraction of caspofungin in plasma varies from 3.5% in healthy volunteers to 7.6% in patients with invasive candidiasis.
Il- frazzjoni mhux imwaħħla ta ’ caspofungin fil - plażma tvarja minn 3. 5% f’ voluntiera b’ saħħithom għal 7. 6% f’ pazjenti b’ kandidjasi invażiva.
Distribution plays the prominent role in caspofungin plasma pharmacokinetics and is the rate-controlling step in both the alpha- and beta-disposition phases.
Id - distribuzzjoni tilgħab rwol prominenti fil- farmakokinetiċi ta ’ caspofungin fil- plażma u hija l- pass li jikkontrolla r- rata fil- fażijiet ta ’ dispożizzjoni kemm alpha kif ukoll beta.
The distribution into tissues peaked at 1.5 to 2 days after dosing when 92% of the dose was distributed into tissues.
Id- distribuzzjoni fit- tessuti laħqet l- ogħla livell ma ’ 1. 5 sa 2 ġranet wara l- għoti tad- doża meta 92% tad- doża kien distribwit fit - tessuti.
It is likely that only a small fraction of the caspofungin taken up into tissues later returns to plasma as parent compound.
Huwa probabbli li frazzjoni żgħira biss tal- caspofungin li jidħol fit- tessuti jerġa ’ lura fil - plażma bħala kompost ewlieni.
Therefore, elimination occurs in the absence of a distribution equilibrium, and a true estimate of the volume of distribution of caspofungin is currently impossible to obtain.
Għaldaqstant, isseħħ eliminazzjoni fin- nuqqas ta ’ ekwilibriju ta ’ distribuzzjoni, u stima reali tal- volum ta ’ distribuzzjoni ta ’ caspofungin hija attwalment impossibbli li tinkiseb.
Metabolism Caspofungin undergoes spontaneous degradation to an open ring compound.
Metaboliżmu Caspofungin jgħaddi minn degradazzjoni spontanja għal kompost open ring.
Further metabolism involves peptide hydrolysis and N-acetylation.
Metaboliżmu ulterjuri jinvolvi idrolisi tal- peptide u N- acetylation.
Two intermediate products, formed during the degradation of caspofungin to this open ring compound, form covalent adducts to plasma proteins resulting in a low-level, irreversible binding to plasma proteins.
Żewġ prodotti intermedji, iffurmati waqt id- degradazzjoni ta ’ caspofungin għal dan il- kompost open ring, jiffurmaw adducts kovalenti għall- proteini tal- plażma li jirriżultaw f’ livell baxx irriversibbli ta ’ twaħħil mal- proteini tal- plażma.
In vitro studies show that caspofungin is not an inhibitor of cytochrome P450 enzymes 1A2, 2A6, 2C9, 2C19, 2D6 or 3A4.
Studji in vitro juru li caspofungin mhuwiex inibitur tal- enzimi taċ- ċitokromu P450 1A2, 2A6, 2C9, 2C19, 2D6 jew 3A4.
In clinical studies, caspofungin did not induce or inhibit the CYP3A4 metabolism of other medicinal products.
Fi studji kliniċi, caspofungin ma kkawżax jew impedixxa l- metaboliżmu CYP3A4 ta ’ prodotti mediċinali oħra.
Caspofungin is not a substrate for P-glycoprotein and is a poor substrate for cytochrome P450 enzymes.
Caspofungin mhuwiex substrat għall- glikoproteina P u huwa substrat fqir għall- enzimi taċ- ċitokromu P450.
Elimination and excretion The elimination of caspofungin from plasma is slow with a clearance of 10-12 ml/ min.
Eliminazzjoni u eskrezzjoni L- eliminazzjoni ta ’ caspofungin mill- plażma sseħħ bil- mod bi tneħħija ta ’ 10- 12 ml/ min.
Plasma concentrations of caspofungin decline in a polyphasic manner following single 1-hour intravenous infusions.
Il - konċentrazzjoni ta ’ caspofungin fil- plażma tonqos b’ mod polifażiku wara infużjonijiet waħdiena ta ’ siegħa ġol- vini.
A short alpha-phase occurs immediately post-infusion, followed by a beta-phase with a half- life of 9 to 11 hours.
Fażi alpha qasira sseħħ immedjatament wara l- infużjoni, segwita minn fażi beta b’ half- life ta ’ 9 sa 11- il siegħa.
An additional gamma-phase also occurs with a half-life of 45 hours.
Isseħħ ukoll fażi gamma addizzjonali b’ half- life ta ’ 45 siegħa.
Distribution, rather than excretion or biotransformation, is the dominant mechanism influencing plasma clearance.
Id - distribuzzjoni, pjuttost milli l- eskrezzjoni jew il- bijotrasformazzjoni, hija l- mekkaniżmu dominanti li jinfluwenza t- tneħħija mill- plażma.
Approximately 75% of a radioactive dose was recovered during 27 days:
Madwar 75% ta ’ doża radjuattiva ġiet irkuprata tul 27 ġurnata:
41% in urine and 34% in faeces.
41% fl- awrina u 34% fl- ippurgar.
There is little excretion or biotransformation of caspofungin during the first 30 hours after administration.
Ftit isseħħ eskrezzjoni jew bijotrasformazzjoni ta ’ caspofungin matul l- ewwel 30 siegħa wara l- għoti.
Excretion is slow and the terminal half-life of radioactivity was 12 to 15 days.
L - eskrezzjoni hija bil- mod u l- half- life terminali tar- radjuattività kienet ta ’ 12 sa 15- il ġurnata.
A small amount of caspofungin is excreted unchanged in urine (approximately 1.4% of dose).
Ammont żgħir ta ’ caspofungin jitneħħa mhux mibdul fl- awrina (madwar 1. 4% tad- doża).
Caspofungin displays moderate non-linear pharmacokinetics with increased accumulation as the dose is increased, and a dose dependency in the time to reach steady state upon multiple-dose administration.
10 Caspofungin juri farmakokinetiċi moderati mhux lineari b’ akkumulazzjoni miżjuda hekk kif tiżdied id- doża, u dipendenza fuq id- doża fil- ħin sakemm jintlaħaq stat stabbli wara l- għoti ta ’ ħafna dożi.
Special populations Increased caspofungin exposure was seen in adult patients with renal impairment and mild liver impairment, in female subjects, and in the elderly.
Popolazzjonijiet speċjali Deher esponiment akbar għal caspofungin f’ pazjenti adulti b’ indeboliment fil- kliewi u indeboliment ħafif tal- fwied, fin- nisa, u fl- anzjani.
Generally the increase was modest and not large enough to warrant dosage adjustment.
Ġeneralment iż- żieda kienet modesta u mhix kbira biżżejjed biex titlob aġġustament fid- doża.
In adult patients with moderate liver impairment or in higher weight patients, a dosage adjustment may be necessary (see below).
F’ pazjenti adulti b’ indeboliment moderat fil- fwied u f’ pazjenti itqal fil - piż, jista ’ jkun meħtieġ aġġustament fid- doża (ara taħt).
Weight:
Piż:
Weight was found to influence caspofungin pharmacokinetics in the population pharmacokinetic analysis in adult candidiasis patients.
Il- piż instab li jaffettwa l- farmakokinetiċi ta ’ caspofungin fl- analiżi farmakokinetika tal - popolazzjoni f’ pazjenti adulti f’ kandidjasi.
The plasma concentrations decrease with increasing weight.
Il- konċentrazzjonijiet fil- plażma jonqsu maż- żieda fil- piż.
The average exposure in an adult patient weighing 80 kg was predicted to be about 23% lower than in an adult patient weighing 60 kg (see section 4.2).
L- esponiment medju f’ pazjent adult li jiżen 80 kg kien imbassar li huwa madwar 23% inqas milli f’ pazjent adult li jiżen 60 kg (ara sezzjoni 4. 2).
Hepatic impairment:
Indeboliment tal- fwied:
There is no clinical experience in adult patients with severe hepatic insufficiency and in paediatric patients with any degree of hepatic insufficiency.
M’ hemmx esperjenza klinika f’ pazjenti adulti b’ insuffiċjenza epatika severa u f’ pazjenti pedjatriċi bi kwalunkwe livell ta ’ insuffiċjenza tal- fwied.
10 hepatic impairment has been shown to provide an AUC similar to that obtained in adult subjects with normal hepatic function receiving the standard regimen (see section 4.2).
Fi studju ta ’ dożi multipli, tnaqqis fid- doża għal 35 mg kuljum f’ pazjenti adulti b’ indeboliment moderat tal- fwied intwera li jipprovdi AUC simili għal dik miksuba f’ suġġetti adulti b’ funzjoni tal- fwied normali li kienu qegħdin jirċievu t- terapija standard (ara sezzjoni 4. 2).
Renal impairment:
Indeboliment tal- kliewi:
In a clinical study of single 70 mg doses, caspofungin pharmacokinetics were similar in adult volunteers with mild renal insufficiency (creatinine clearance 50 to 80 ml/ min) and control subjects.
Fi studju kliniku ta ’ dożi waħdiena ta ’ 70 mg, il- farmakokinetiċi ta ’ caspofungin kienu simili fil- voluntiera adulti b’ insuffiċjenza renali ħafifa (tneħħija tal- kreatinina ta ’ 50 sa 80 ml/ min) u s- suġġetti ta ’ kontroll.
Moderate (creatinine clearance 31 to 49 ml/ min), advanced (creatinine clearance 5 to 30 ml/ min), and end-stage (creatinine clearance < 10 ml/ min and dialysis dependent) renal insufficiency moderately increased caspofungin plasma concentrations after single-dose administration (range:
Insuffiċjenza renali moderata (tneħħija tal- kreatinina ta ’ 31 sa 49 ml/ min), avanzata (tneħħija tal- kreatinina ta ’ 5 sa 30 ml/ min), u tal- aħħar stadju (tneħħija tal - kreatinina ta ’ < 10 ml/ min u dipendenti fuq id- dijalisi) żiedet moderatament il- konċentrazzjonijiet ta ’ caspofungin fil- plażma wara l- għoti ta ’ doża waħda (medda:
30 to 49% for AUC).
30 sa 49% għall- AUC).
However, in adult patients with invasive candidiasis, oesophageal candidiasis, or invasive aspergillosis who received multiple daily doses of CANCIDAS 50 mg, there was no significant effect of mild to advanced renal impairment on caspofungin concentrations.
Madankollu, f’ pazjenti adulti b’ kandidjasi invażiva, kandidjasi esofagali, jew asperġillożi invażiva li rċevew dożi multipli kuljum ta ’ CANCIDAS 50 mg, ma kienx hemm effett sinifikanti ta ’ indeboliment renali ħafif sa avanzat fuq il- konċentrazzjonijiet ta ’ caspofungin.
No dosage adjustment is necessary for patients with renal insufficiency.
M’ hemmx bżonn ta ’ aġġustament fid- doża għal pazjenti b’ insuffiċjenza tal- kliewi.
Caspofungin is not dialysable, thus supplementary dosing is not required following haemodialysis.
Caspofungin mhuwiex dijalizzabbli, u għalhekk m’ hemmx bżonn ta ’ dożi supplimentari wara emodijalisi.
Gender:
Sess tal- persuna:
Caspofungin plasma concentrations were on average 17-38% higher in women than in men.
Bħala medja, il- konċentrazzjonijiet ta ’ caspofungin fin- nisa kienu 17- 38% ogħla milli fl- irġiel.
Elderly:
Anzjani:
A modest increase in AUC (28%) and C24h (32%) was observed in elderly male subjects compared with young male subjects.
Kienet osservata żieda modesta fl- AUC (28%) u l- C24h (32%) f’ individwi rġiel anzjani meta mqabbel ma ’ rġiel żgħażagħ.
In patients who were treated empirically or who had invasive candidiasis, a similar modest effect of age was seen in older patients relative to younger patients.
Fil- pazjenti li ġew ittrattati b’ mod empiriku jew li kellhom kandidjasi invażiva, deher effett modest simili f’ pazjenti akbar fl- età meta mqabbel ma ’ pazjenti iżgħar.
Patient pharmacokinetic data indicated that no clinically significant differences in the pharmacokinetics of caspofungin were seen among Caucasians, Blacks, Hispanics, and Mestizos.
Tagħrif farmakokinetiku mill- pazjenti indika li ma dehrux differenzi kliniċi sinifikanti fil - farmakokinetiċi ta ’ caspofungin fost il- Kawkasi, is- Suwed, l- Ispaniċi, u l- Mestizos.
Paediatric Patients:
Pazjenti pedjatriċi:
In adolescents (ages 12 to 17 years) receiving caspofungin at 50 mg/ m2 daily (maximum 70 mg daily), the caspofungin plasma AUC0-24hr was generally comparable to that seen in adults receiving caspofungin at 50 mg daily.
Fl- adoloxxenti (etajiet minn 12 sa 17- il sena) li rċevew caspofungin f’ doża ta ’ 50 mg/ m2 kuljum (massimu 70 mg kuljum), l- AUC0- 24hr ta ’ caspofungin fil- plażma kienet ġeneralment komparabbli ma ’ dik li dehret f’ persuni adulti li rċevew caspofungin f’ doża ta ’ 50 mg kuljum.
All adolescents received doses > 50 mg daily, and, in fact, 6 of 8 received the maximum dose of 70 mg/ day.
L- adoloxxenti kollha li rċevew dożi ta ’ > 50 mg kuljum, u, fil- fatt, 6 minn 8 irċevew id- doża massima ta ’ 70 mg/ kuljum.
The caspofungin plasma concentrations in these adolescents were reduced relative to adults receiving 70 mg daily, the dose most often administered to adolescents.
Il - konċentrazzjonijiet fil- plażma ta ’ caspofungin f’ dawn l- adoloxxenti kienu mnaqqsa meta mqabbla ma ’ persuni adulti li rċevew 70 mg kuljum, id- doża li ngħatat l- aktar ta ’ spiss lill- adoloxxenti.
In children (ages 2 to 11 years) receiving caspofungin at 50 mg/ m2 daily (maximum 70 mg daily), the caspofungin plasma AUC0-24hr after multiple doses was comparable to that seen in adults receiving caspofungin at 50 mg/ day.
Fit- tfal (etajiet minn 2 sa 11- il sena) li rċevew caspofungin f’ doża ta ’ 50 mg/ m2 kuljum (massimu 70 mg kuljum), l- AUC0- 24hr ta ’ caspofungin fil- plażma wara dożi multipli kienet komparabbli ma ’ dik li dehret f’ persuni adulti li rċevew caspofungin f’ doża ta ’ 50 mg/ kuljum.
In young children and toddlers (ages 12 to 23 months) receiving caspofungin at 50 mg/ m2 daily (maximum 70 mg daily), the caspofungin plasma AUC0-24hr after multiple doses was comparable to that seen in adults receiving caspofungin at 50 mg daily and to that in older children (2 to 11 years of age) receiving the 50 mg/ m2 daily dose.
11 plażma wara dożi multipli kienet komparabbli ma ’ dik li dehret f’ persuni adulti li rċevew caspofungin f’ doża ta ’ 50 mg kuljum u ma ’ dik fi tfal akbar (etajiet minn 2 sa 11- il sena) li rċevew id- doża ta ’ 50 mg/ m2 kuljum.
Overall, the available pharmacokinetic, efficacy, and safety data are limited in patients 3 to 10 months of age.
B’ mod ġenerali, l- informazzjoni disponibbli dwar il- farmakokinetika, l- effikaċja u s- sigurtà hija limitata f’ pazjenti ta ’ bejn 3 u 10 xhur.
Pharmacokinetic data from one 10-month old child receiving the 50 mg/ m2 daily dose indicated an AUC0-24hr within the same range as that observed in older children and adults at the 50 mg/ m2 and the 50 mg dose, respectively, while in one 6-month old child receiving the 50 mg/ m2 dose, the AUC0-24hr was somewhat higher.
Tagħrif farmakokinetiku minn tarbija waħda ta ’ 10 xhur li rċeviet id- doża ta ’ 50 mg/ m2 kuljum indika AUC0- 24hr fl- istess medda bħal dik osservata fi tfal akbar u l- adulti bid- doża ta ’ 50 mg/ m2 u d- doża ta ’ 50 mg, rispettivament, filwaqt li f’ tarbija waħda ta ’ 6 xhur li rċeviet id- doża ta ’ 50 mg/ m2, l- AUC0- 24hr kienet kemxejn ogħla.
In neonates and infants (< 3 months) receiving caspofungin at 25 mg/ m2 daily (corresponding mean daily dose of 2.1 mg/ kg), caspofungin peak concentration (C1 hr) and caspofungin trough concentration (C24 hr) after multiple doses were comparable to that seen in adults receiving caspofungin at 50 mg daily.
Fi trabi għadhom jitwieldu u trabi żgħar (< 3 xhur) li rċevew caspofungin f’ doża ta ’ 25 mg/ m2 kuljum (doża medja korrispondenti ta ’ 2. 1 mg/ kg kuljum), l- akbar konċentrazzjoni ta ’ caspofungin fil- plażma (C1 hr) u l- inqas konċentrazzjoni ta ’ caspofungin fil- plażma (C24 hr) wara dożi multipli kienu komparabbli ma ’ dawk li dehru f’ persuni adulti li rċevew caspofungin f’ doża ta ’ 50 mg kuljum.
On Day 1, C1 hr was comparable and C24 hr modestly elevated (36%) in these neonates and infants relative to adults.
F’ Jum 1, il- C1 hr kienet komparabbli u l- C24 hr daqsxejn għolja (36%) f’ dawn it- trabi għadhom jitwieldu u t - trabi żgħar meta mqabbel mal- adulti.
However, variability was seen in both C1 hr (Day 4 geometric mean 11.73 µg/ ml, range 2.63 to 22.05 µg/ ml) and C24 hr (Day 4 geometric mean 3.55 µg/ ml, range 0.13 to 7.17 µg/ ml).
Madankollu, dehret varjabilità kemm fil- C1 hr (Jum 4 medja ġeometrika 11. 73 µg/ ml, medda 2. 63 sa 22. 05 µg/ ml) kif ukoll fil- C24 hr (Jum 4 medja ġeometrika 3. 55 µg/ ml, medda 0. 13 sa 7. 17 µg/ ml).
AUC0-24hr measurements were not performed in this study due to the sparse plasma sampling.
Ma sarx kejl tal- AUC0- 24hr f’ dan l- istudju minħabba li ma tantx ittieħdu kampjuni ta ’ plażma.
Of note, the efficacy and safety of CANCIDAS have not been adequately studied in prospective clinical trials involving neonates and infants under 3 months of age.
Fatt importanti, l- effikaċja u s- sigurtà ta ’ CANCIDAS ma ġewx studjati adegwatament fi provi kliniċi prospettivi li kienu jinkludu trabi għadhom jitwieldu u trabi ta ’ inqas minn 3 xhur.
11 5.3 Preclinical safety data
5. 3 Tagħrif ta ’ qabel l- użu kliniku dwar is- sigurtà tal- mediċina
Repeated dose toxicity studies in rats and monkeys using doses up to 7-8 mg/ kg given intravenously showed injection site reactions in rats and monkeys, signs of histamine release in rats, and evidence of adverse effects directed at the liver in monkeys.
Studji tal- effett tossiku minn dożi ripetuti fil- firien u x- xadini bl- użu ta ’ dożi sa 7- 8 mg/ kg mogħtija ġol- vini wrew reazzjonijiet fis- sit tal- injezzjoni fil- firien u x- xadini, sinjali ta ’ rilaxx tal- istamina fil - firien, u evidenza ta ’ effetti avversi diretti fil- fwied tax- xadini.
Developmental toxicity studies in rats showed that caspofungin caused decreases in foetal body weights and an increase in the incidence of incomplete ossification of vertebra, sternebra, and skull bone at doses of 5 mg/ kg that were coupled to adverse maternal effects such as signs of histamine release in pregnant rats.
Studji tal- effett tossiku fuq l- iżvilupp fil- firien urew li caspofungin ikkaġuna tnaqqis fil- piż tal- ġisem tal- fetu u żieda fl- inċidenza ta ’ ossifikazzjoni inkompleta tal- vertebra, tal- isternebra, u tal- għadma tal- kranju b’ dożi ta ’ 5 mg/ kg li kienu msieħba ma ’ effetti ħżiena fl- omm bħal sinjali ta ’ rilaxx tal- istamina f’ firien tqal.
An increase in the incidence of cervical ribs was also noted.
Ġiet innotata wkoll żieda fl- inċidenza tal- kustilji ċervikali.
Caspofungin was negative in in vitro assays for potential genotoxicity as well as in the in vivo mouse bone marrow chromosomal test.
Caspofungin kien negattiv f’ assaġġi in vitro għall - ġenotossiċità potenzjali kif ukoll fit- test kromosomali in vivo fuq il- mudullun tal- ġurdien.
No long-term studies in animals have been performed to evaluate the carcinogenic potential.
Ma sarux studji fit- tul fuq l- annimali biex jiġi evalwat il- potenzjal karċinoġeniku.
Sucrose Mannitol Glacial acetic acid Sodium hydroxide (to adjust the pH)
Sucrose Mannitol Glacial acetic acid Sodium hydroxide (biex jaġġusta l- pH)
2 years
6. 2 Inkompatibilitajiet
Reconstituted concentrate: should be used immediately.
Il- konċentrat rikostitwit: għandu jintuża mill- ewwel.
Stability data have shown that the concentrate for solution for infusion can be stored for up to 24 hours when the vial is stored at 25°C or less and reconstituted with water for injections.
Informazzjoni dwar l- istabilità wriet li l - konċentrat għal soluzzjoni għal infużjoni jista ’ jinħażen 24 siegħa meta l- kunjett jinħażen f’ temperatura ta ’ 25°C jew inqas u jkun rikostitwit b’ ilma għall- injezzjonijiet.
Dilute patient infusion solution: should be used immediately.
Is- soluzzjoni dilwita għal infużjoni tal- pazjent: għandha tintuża mill- ewwel.
Stability data have shown that the product can be used within 24 hours when stored at 25°C or less, or within 48 hours when the intravenous infusion bag (bottle) is stored refrigerated (2 to 8°C) and diluted with sodium chloride solution 9 mg/ ml (0.9%), 4.5 mg/ ml (0.45%), or 2.25 mg/ ml (0.225%) for infusion, or lactated Ringer’ s solution.
Informazzjoni dwar l - istabilità wriet li l- prodott jista ’ jintuża fi żmien 24 siegħa meta jinħażen f’ temperatura ta ’ 25°C jew inqas, jew fi żmien 48 siegħa meta l- borża (flixkun) tal- infużjoni fil- vini tinħażen fi friġġ (2 sa 8°C) u tkun dilwita b’ soluzzjoni ta ’ klorur tas- sodju 9 mg/ ml (0. 9%), 4. 5 mg/ ml (0. 45%), jew 2. 25 mg/ ml (0. 225%) għal infużjoni, jew soluzzjoni lactated ta ’ Ringer.
CANCIDAS contains no preservatives.
CANCIDAS ma fihx preservattivi.
From a microbiological point of view, the product should be used immediately.
Minn perspettiva mikrobijoloġika, il- prodott għandu jintuża immedjatament.
If not used immediately, in use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution and dilution have taken place in controlled validated aseptic conditions.
Jekk ma jintużax mill- ewwel, iż- żminijiet u l- kundizzjonijiet effettivi ta ’ ħażna qabel l- użu huma r- responsabbiltà tal- utent u normalment ma jkunux atar minn 24 siegħa f’ temperatura ta ’ 2 sa 8°C, sakemm ir- rikostituzzjoni u d- dilwizzjoni ma jkunux saru f’ kundizzjonijiet asettiċi kkontrollati u validati.
Unopened vials: store in a refrigerator (2°C - 8°C).
Kunjetti mhux miftuħin: aħżen fi friġġ (2°C - 8°C).
For storage conditions of the reconstituted and diluted medicinal product, see section 6.3.
Għall- kundizzjonijiet ta ’ ħażna tal- prodott mediċinali rikostitwit u dilwit, ara sezzjoni 6. 3.
12 6.5 Nature and contents of container
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
10 ml Type I glass vials with a grey butyl stopper and a plastic cap with a red aluminium band for single use only.
Kunjetti tal- ħġieġ tat- Tip I ta ’ 10 ml b’ tapp griż tal- butyl u għatu tal- plastik b’ faxxa ħamra tal - aluminju għal użu ta ’ darba biss.
Supplied in packs of 1 vial.
Jiġi f’ pakketti ta ’ kunjett wieħed.
Reconstitution of CANCIDAS DO NOT USE ANY DILUENTS CONTAINING GLUCOSE, as CANCIDAS is not stable in diluents containing glucose.
Ir- rikostituzzjoni ta ’ CANCIDAS TUŻAX DILWENTI LI FIHOM IL- GLUCOSE għax CANCIDAS mhuwiex stabbli f’ dilwenti li fihom il- glucose.
DO NOT MIX OR CO-INFUSE CANCIDAS WITH ANY OTHER MEDICINES, as there are no data available on the compatibility of CANCIDAS with other intravenous substances, additives, or medicinal products.
CANCIDAS M’ GĦANDUX JIĠI MĦALLAT JEW INFUŻ MA ’ MEDIĊINI OĦRA, billi ma hemmx informazzjoni disponibbli dwar il- kompatibilità ta ’ CANCIDAS ma ’ sustanzi, addittivi, jew prodotti mediċinali oħra għal ġol- vini.
Visually inspect the infusion solution for particulate matter or discolouration.
Eżamina viżwalment is- soluzzjoni għal infużjoni għal xi frak jew tidnis.
INSTRUCTIONS FOR USE IN ADULT PATIENTS
STRUZZJONIJIET GĦALL- UŻU F’ PAZJENTI ADULTI
Step 1 Reconstitution of conventional vials To reconstitute the powder, bring the vial to room temperature and aseptically add 10.5 ml of water for injections.
Pass 1 Rikostituzzjoni ta ’ kunjetti konvenzjonali Biex tirrikostitwixxi t- trab, ġib il- kunjett għat- temperatura tal- kamra u b’ mod asettiku żid 10. 5 ml ta ’ ilma għall- injezzjonijiet.
The concentrations of the reconstituted vials will be 5.2 mg/ ml.
Il- konċentrazzjoni tal- kunjetti rikostitwiti se jkun 5. 2 mg/ ml.
The white to off-white compact lyophilised powder will dissolve completely.
It- trab kompatt abjad għal offwajt lajofiliżżat għandu jinħall kompletament.
Mix gently until a clear solution is obtained.
Ħawwad bil- mod sakemm tinkiseb soluzzjoni ċar.
Reconstituted solutions should be visually inspected for particulate matter or discolouration.
Is- soluzzjonijiet rikostitwiti għandhom jiġu eżaminati viżwalment għal xi frak jew tidnis.
This reconstituted solution may be stored for up to 24 hours at or below 25°C.
Din is- soluzzjoni rikostitwita tista ’ tinħażen sa 24 siegħa f’ temperatura ta ’ 25°C jew inqas.
Step 2 Addition of Reconstituted CANCIDAS to patient infusion solution Diluents for the final solution for infusion are: sodium chloride solution for injection, or lactated Ringer’ s solution.
Pass 2 Iż- żieda ta ’ CANCIDAS rikostitwit mas- soluzzjoni għal infużjoni tal- pazjent Id- dilwenti għas- soluzzjoni finali għal infużjoni huma: soluzzjoni ta ’ klorur tas- sodju għal injezzjoni, jew soluzzjoni lactated ta ’ Ringer.
The solution for infusion is prepared by aseptically adding the appropriate amount of reconstituted concentrate (as shown in the table below) to a 250 ml infusion bag or bottle.
Is- soluzzjoni għal infużjoni tiġi ppreparata billi b’ mod asettiku jiżdied l- ammont xieraq ta ’ konċentrat rikostitwit (kif muri fit- tabella ta ’ hawn isfel) ma ’ borża jew
Reduced volume infusions in 100 ml may be used, when medically necessary, for 50 mg or 35 mg daily doses.
Meta jkun medikament meħtieġ, jistgħu jintużaw infużjonijiet ta ’ volum imnaqqas f’ 100 ml, għad- dożi ta ’ 50 mg jew 35 mg kuljum.
Do not use if the solution is cloudy or has precipitated.
Is- soluzzjoni m’ għandhiex tintuża jekk tkun imdennsa jew preċipitat.
This infusion solution must be used within 24 hours if stored at or below 25°C, or within 48 hours if stored refrigerated at 2 to 8°C.
Din is- soluzzjoni għal infużjoni trid tintuża fi żmien 24 siegħa jekk tinħażen f’ temperatura ta ’ 25°C jew inqas, jew fi żmien 48 siegħa jekk tinħażen fi friġġ f’ temperatura ta ’ 2 sa 8°C.
Chemical and physical in-use stability of the diluted solution in sterile lactated Ringer’ s solution and sodium chloride solution 9 mg/ ml (0.9%), 4.5 mg/ ml (0.45%), and 2.25 mg/ ml (0.225%) for infusion has been demonstrated for 24 hours at 25°C and for 48 hours at 2 to 8°C.
L- istabilità kimika u fiżika waqt l- użu tas- soluzzjoni dilwita f’ soluzzjoni lactated ta ’ Ringer u f’ soluzzjoni ta ’ klorur tas- sodju 9 mg/ ml (0. 9%), 4. 5 mg/ ml (0. 45%), u 2. 25 mg/ ml (0. 225%) għal infużjoni ġiet murija għal 24 siegħa f’ temperatura ta ’ 25°C jew għal 48 siegħa f’ temperatura ta ’ 2 sa 8°C.
From a microbiological point of view, the solution must be used immediately.
Minn perspettiva mikrobijoloġika, is- soluzzjoni trid tintuża immedjatament.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution and dilution has taken place in controlled and validated aseptic conditions.
Jekk ma tintużax mill- ewwel, iż- żminijiet u l- kundizzjonijiet effettivi ta ’ ħażna qabel l- użu huma r- responsabbiltà tal- utent u normalment ma jkunux aktar minn 24 siegħa f’ temperatura ta ’ 2 sa 8°C, sakemm ir- rikostituzzjoni u d- dilwizzjoni ma jkunux saru f’ kundizzjonijiet asettiċi kkontrollati u validati.
13 PREPARATION OF THE SOLUTION FOR INFUSION IN ADULTS
PREPARAZZJONI TAS- SOLUZZJONI GĦAL INFUŻJONI FL- ADULTI
DOSE*
DOŻA *
Volume of recon- stituted CANCIDAS for transfer to intravenous bag or bottle
Volum ta ’ CANCIDAS rikostitwit għal
Standard preparation (reconstituted CANCIDAS added to 250 ml) final concentration
Infużjoni ta ’ volum imnaqqas (CANCIDAS rikostitwit
Reduced volume infusion (reconstituted CANCIDAS added to 100 ml) final concentration
100 ml)
50 mg 50 mg at reduced
50 mg 50 mg f’ volum
0.19 mg/ ml
0. 19 mg/ ml
volume 35 mg for moderate
imnaqqas 35 mg għal insuffiċjenza moderata tal- fwied
0.45 mg/ ml
0. 45 mg/ ml
hepatic insufficiency (from one 50 mg vial) 35 mg for moderate hepatic insufficiency
(minn kunjett wieħed ta ’ 50 mg) 35 mg għal insuffiċjenza moderata tal- fwied
(from one 50 mg vial) at reduced volume
(minn kunjett wieħed ta ’ 50 mg) f’ volum imnaqqas
* 10.5 ml should be used for reconstitution of all vials.
* 10. 5 ml għandhom jintużaw għar- rikostituzzjoni tal- kunjetti kollha
INSTRUCTIONS FOR USE IN PAEDIATRIC PATIENTS
STRUZZJONIJIET GĦALL- UŻU F’ PAZJENTI PEDJATRIĊI
Calculation of Body Surface Area (BSA) for paediatric dosing Before preparation of infusion, calculate the body surface area (BSA) of the patient using the following formula:
Kalkulazzjoni tal- Arja tas- Superfiċje tal- Ġisem (BSA) għal dożaġġ pedjatriku Qabel ma tipprepara l- infużjoni, ikkalkula l- arja tas- superfiċje tal- ġisem (BSA) tal- pazjent billi tuża din il- formula:
(Mosteller Formula)
(Formula Mosteller)
Preparation of the 70 mg/ m2 infusion for paediatric patients > 3 months of age (using a 50-mg vial) 1.
Preparazzjoni tal- infużjoni ta ’ 70 mg/ m2 għal pazjenti pedjatriċi minn 3 xhur ’ il fuq (billi jintuża kunjett ta ’ 50 mg) 1.
Determine the actual loading dose to be used in the paediatric patient by using the patient's BSA (as calculated above) and the following equation:
Stabbilixxi l- loading dose attwali li għandha tintuża fil- pazjent pedjatriku billi tuża l- BSA tal - pazjent (kif ikkalkulata hawn fuq) u l- ekwazzjoni segwenti:
BSA (m2) X 70 mg/ m2 = Loading Dose The maximum loading dose on Day 1 should not exceed 70 mg regardless of the patient's calculated dose.
BSA (m2) X 70 mg/ m2 = Loading Dose Il- loading dose massima f’ Jum 1 m’ għandhiex taqbeż 70 mg, irrispettivament mid- doża kkalkulata tal- pazjent.
Equilibrate the refrigerated vial of CANCIDAS to room temperature.
Ġib il- kunjett imkessaħ ta ’ CANCIDAS għat- temperatura tal- kamra.
Aseptically add 10.5 ml of 0.9% Sodium Chloride Injection, Sterile Water for Injection or Bacteriostatic Water for Injection with methylparaben and propylparaben. a This reconstituted solution may be stored for up to one hour at ≤ 25°C (≤ 77°F). b This will give a final caspofungin concentration in the vial of 5.2 mg/ ml.
B’ mod asettiku żid 10. 5 ml ta ’ 0. 9% Injezzjoni ta ’ Klorur tas- Sodju, Ilma Sterili għal Injezzjoni jew Ilma Batterjostatiku għal Injezzjoni b’ methylparaben u propylparaben. a Din is- soluzzjoni rikostitwita tista ’ tinħażen sa siegħa f’ temperatura ta ’ ≤25°C (≤77°F). b Din tagħti konċentrazzjoni finali ta ’ caspofungin fil- kunjett ta ’ 5. 2 mg/ ml.
Aseptically transfer this volume (ml)c of reconstituted CANCIDAS to an IV bag (or bottle) containing 250 ml of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection, or Lactated Ringers Injection.
Neħħi mill- kunjett il- volum ta ’ mediċina ugwali għal- loading dose kkalkulata (Pass 1) Ittrasferixxi b’ mod asettiku dan il- volum (ml) c ta ’ CANCIDAS rikostitwit għal borża (jew flixkun) IV li fiha 250 ml ta ’ 0. 9%, 0. 45%, jew 0. 225% Injezzjoni ta ’ Klorur tas- Sodju, jew Injezzjoni Lactated ta ’ Ringers.
Alternatively, the volume (ml)c of reconstituted CANCIDAS can be added to a reduced volume of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection or Lactated Ringers Injection, not to exceed a final concentration of 0.5 mg/ ml.
B’ mod alternattiv, il- volum (ml) c ta ’ CANCIDAS rikostitwit jista ’ jiġi miżjud ma ’ volum imnaqqas ta ’ 0. 9%, 0. 45%, jew 0. 225% Injezzjoni ta ’ Klorur tas - Sodju jew Injezzjoni Lactated ta ’ Ringers, li m’ għandhiex taqbeż konċentrazzjoni finali ta ’ 0. 5 mg/ ml.
This infusion solution must be used within 24 hours if stored at ≤ 25°C (≤ 77°F) or within 48 hours if stored refrigerated at 2 to 8°C (36 to 46°F).
Din is- soluzzjoni għal infużjoni trid tintuża fi żmien 24 siegħa jekk tinħażen f’ temperatura ta ’ ≤25°C (≤77°F) jew fi żmien 48 siegħa jekk tinħażen fi friġġ f’ temperatura ta ’ 2 sa 8°C (36 sa 46°F).
Preparation of the 50 mg/ m2 infusion for paediatric patients > 3 months of age (using a 50-mg vial) 1.
Preparazzjoni tal- infużjoni ta ’ 50 mg/ m2 għal pazjenti pedjatriċi minn 3 xhur ’ il fuq (billi jintuża kunjett ta ’ 50 mg) 1.
Determine the actual daily maintenance dose to be used in the paediatric patient by using the patient's BSA (as calculated above) and the following equation:
Stabbilixxi d- doża ta ’ manteniment attwali ta ’ kuljum li għandha tintuża fil- pazjent pedjatriku billi tuża l- BSA tal- pazjent (kif ikkalkulata hawn fuq) u l- ekwazzjoni segwenti:
BSA (m2) X 50 mg/ m2 = Daily Maintenance Dose The daily maintenance dose should not exceed 70 mg regardless of the patient's calculated dose.
BSA (m2) X 50 mg/ m2 = Doża ta ’ Manteniment ta ’ Kuljum Id- doża ta ’ manteniment ta ’ kuljum m’ għandhiex taqbeż 70 mg, irrispettivament mid- doża kkalkulata tal- pazjent.
3.
Ġib il- kunjett imkessaħ ta ’ CANCIDAS għat- temperatura tal- kamra 3.
14 solution may be stored for up to one hour at ≤ 25°C (≤ 77°F). b This will give a final caspofungin concentration in the vial of 5.2 mg/ ml.
B’ mod asettiku żid 10. 5 ml ta ’ 0. 9% Injezzjoni ta ’ Klorur tas- Sodju, Ilma Sterili għal Injezzjoni jew Ilma Batterjostatiku għal Injezzjoni b’ methylparaben u propylparaben. a Din is- soluzzjoni rikostitwita tista ’ tinħażen sa siegħa f’ temperatura ta ’ ≤25°C (≤77°F). b Din tagħti konċentrazzjoni finali ta ’ caspofungin fil- kunjett ta ’ 5. 2 mg/ ml.
Remove the volume of drug equal to the calculated daily maintenance dose (Step 1) from the vial.
Neħħi mill- kunjett il- volum ta ’ mediċina ugwali għad- doża ta ’ manteniment ta ’ kuljum kkalkulata (Pass 1).
Aseptically transfer this volume (ml)c of reconstituted CANCIDAS to an IV bag (or bottle) containing 250 ml of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection, or Lactated Ringers Injection.
Ittrasferixxi b’ mod asettiku dan il- volum (ml) c ta ’ CANCIDAS rikostitwit għal borża (jew flixkun) IV li fiha 250 ml ta ’ 0. 9%, 0. 45%, jew 0. 225% Injezzjoni ta ’ Klorur tas- Sodju, jew Injezzjoni Lactated ta ’ Ringers.
Alternatively, the volume (ml)c of reconstituted CANCIDAS can be added to a reduced volume of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection or Lactated Ringers Injection, not to exceed a final concentration of 0.5 mg/ ml.
B’ mod alternattiv, il- volum (ml) c ta ’ CANCIDAS rikostitwit jista ’ jiġi miżjud ma ’ volum imnaqqas ta ’ 0. 9%, 0. 45%, jew 0. 225% Injezzjoni ta ’ Klorur tas- Sodju jew Injezzjoni Lactated ta ’ Ringers, li m’ għandhiex taqbeż konċentrazzjoni finali ta ’ 0. 5 mg/ ml.
Preparation notes:
Noti dwar il- preparazzjoni:
The white to off-white cake will dissolve completely.
a Il - “ cake ” abjad għal offwajt għandu jinħall kompletament.
Mix gently until a clear solution is obtained.
Ħawwad bil- mod sakemm tinkiseb soluzzjoni ċara.
Visually inspect the reconstituted solution for particulate matter or discolouration during reconstitution and prior to infusion.
b Eżamina viżwalment is- soluzzjoni rikostitwita għal frak jew tidnis waqt ir- rikostituzzjoni u qabel l - infużjoni.
CANCIDAS is formulated to provide the full labeled vial dose (50 mg) when 10 ml is withdrawn from the vial.
ċ CANCIDAS huwa fformulat sabiex jipprovdi d- doża ttikkettjata kollha tal- kunjett (50 mg) meta jinġibdu 10 ml mill- kunjett.
MARKETING AUTHORISATION HOLDER
ID- DETENTUR TAL- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
Merck Sharp & Dohme Ltd Hertford Road, Hoddesdon Hertfordshire EN11 9BU United Kingdom
Merck Sharp & Dohme Ltd Hertford Road, Hoddesdon Hertfordshire EN11 9BU Ir- Renju Unit
MARKETING AUTHORISATION NUMBER(S)
NUMRU( I) TAL- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION
DATA TAL- EWWEL AWTORIZZAZZJONI/ TIĠDID TAL- AWTORIZZAZZJONI
Date of last renewal:
Data tal- aħħar tiġdid
CANCIDAS 70 mg powder for concentrate for solution for infusion
CANCIDAS 70 mg trab għal konċentrat għal soluzzjoni għal infużjoni
Each vial contains 70 mg caspofungin (as acetate).
Kull kunjett fih 70 mg caspofungin (bħala aċetat).
Each 70 mg vial contains 50.0 mg of sucrose.
Kull kunjett ta ’ 70mg fih 50. 0 mg ta ’ sucrose.
16 Dosage in paediatric patients (12 months to 17 years) In paediatric patients (12 months to 17 years of age), dosing should be based on the patient’ s body surface area (see Instructions for Use in Paediatric Patients, Mosteller 2 Formula).
17 Dożaġġ f’ pazjenti pedjatriċi (12- il xahar sa 17- il sena) F’ pazjenti pedjatriċi (12- il xahar sa 17- il sena), id- doża għandha tkun ibbażata fuq l- arja tas- superfiċje tal- ġisem tal- pazjent (ara l- Istruzzjonijiet għall- Użu f’ Pazjenti Pedjatriċi, Formula Mosteller 2).
An initial 70 mg loading dose should be administered on Day 1.
Fl- ewwel jum għandha tingħata doża inizjali ta ’ 70 mg.
There is no clinical experience in adult patients with severe hepatic insufficiency (Child-Pugh score greater than 9) and in paediatric patients with any degree of hepatic insufficiency (see section 4.4).
M’ hemmx esperjenza klinika f’ pazjenti adulti b’ insuffiċjenza epatika severa (punteġġ Child- Pugh akbar minn 9) u f’ pazjenti pedjatriċi bi kwalunkwe livell ta ’ insuffiċjenza tal- fwied (ara sezzjoni 4. 4).
17 4.3 Contraindications
18 4. 3 Kontra- indikazzjonijiet
Caspofungin did not influence the pharmacokinetics of amphotericin B, itraconazole,
19 Studji kliniċi fuq voluntiera adulti b’ saħħithom juru li l- farmakokinetiċi ta ’ CANCIDAS ma jinbidlux b’ mod klinikament sinifikanti b’ itraconazole, amphotericin B, mycophenolate, nelfinavir, jew tacrolimus.
18 rifampicin or mycophenolate mofetil.
Caspofungin ma influwenzax il- farmakokinetiċi ta ’ amphotericin B, itraconazole, rifampicin jew mycophenolate mofetil.
Phlebitis was a commonly reported local injection-site adverse reaction in all patient populations.
20 periferali, tumuri ematoloġiċi, tumuri solidi jew trapjanti tal- organi) li kienu jeħtieġu diversi medikazzjonijiet konkomitanti.
19 Reported clinical and laboratory abnormalities among all adult patients treated with CANCIDAS (total 989) were typically mild and rarely led to discontinuation.
L- anormalitajiet kliniċi u tal- laboratorju li ġew irrappurtati fost il- pazjenti adulti ttrattati b’ CANCIDAS (total 989) kienu ġeneralment ħfief u rari wasslu għal twaqqif tal- kura.
Paediatric Patients In clinical studies, 171 paediatric patients received single or multiple doses of CANCIDAS:
21 Pazjenti pedjatriċi Fi studji kliniċi, 171 pazjent pedjatriku rċevew dożi waħdiena jew multipli ta ’ CANCIDAS:
104 febrile, neutropenic patients; 56 patients with invasive candidiasis; 1 patient with esophageal candidiasis; and 10 patients with invasive aspergillosis.
104 pazjenti b’ newtropenija febbrili; 56 pazjent b’ kandidjasi invażiva; pazjent wieħed b’ kandidjasi esofagali; u 10 pazjenti b’ asperġillożi invażiva.
20 [Very common (≥ 1/ 10), Common (≥ 1/ 100, < 1/ 10)]
[Komuni ħafna (≥1/ 10), Komuni (≥1/ 100, < 1/ 10)]
21 Fungicidal activity with caspofungin has been demonstrated against Candida yeasts.
L- attività fungiċida b’ caspofungin ġiet murija kontra ħmejjer Candida.
Caspofungin 50 mg once daily was administered following a 70-mg loading dose, while amphotericin B was administered at 0.6 to 0.7 mg/ kg/ day to non-neutropaenic patients or 0.7 to 1.0 mg/ kg/ day to neutropaenic patients.
Caspofungin 50 mg darba kuljum ingħata wara loading dose ta ’ 70 mg, filwaqt li amphotericin B ingħata f’ doża ta ’ 0. 6 sa 0. 7 mg/ kg/ kuljum lil pazjenti mhux newtropeniċi jew 0. 7 sa 1. 0 mg/ kg/ kuljum lil pazjenti newtropeniċi.
Invasive Aspergillosis in Adult Patients:
23 Asperġillożi Invażiva f’ Pazjenti Adulti:
22 were 36% (19/ 53) and 70% (7/ 10), respectively.
Ir- rati ta ’ rispons favorevoli għall- pazjenti li kienu jew refrattorji jew intolleranti għal terapiji preċedenti kienu 36% (19/ 53) u 70% (7/ 10), rispettivament.
The first study, which enrolled 82 patients between 2 to 17 years of age, was a randomized, double- blind study comparing CANCIDAS (50 mg/ m2 IV once daily following a 70-mg/ m2 loading dose on Day 1 [not to exceed 70 mg daily]) to liposomal amphotericin B (3 mg/ kg IV daily) in a 2:1 treatment fashion (56 on caspofungin, 26 on liposomal amphotericin B) as empirical therapy in paediatric patients with persistent fever and neutropenia.
24 L- ewwel studju, li rreġistra 82 pazjent ta ’ bejn 2 u 17- il sena, kien studju double- blind, randomizzat li qabbel CANCIDAS (50 mg/ m2 IV darba kuljum wara loading dose ta ’ 70- mg/ m2 f’ Jum 1 [li m’ għandux jaqbeż 70 mg kuljum]) ma ’ amphotericin B liposomali (3 mg/ kg IV kuljum) b’ mod ta ’ trattament ta ’ 2: 1 (56 fuq caspofungin, 26 fuq amphotericin B liposomali) bħala terapija empirika f’ pazjenti pedjatriċi b’ deni persistenti u newtropenija.
In vitro studies show that caspofungin is not an inhibitor of cytochrome P450 enzymes 1A2, 2A6, 2C9, 2C19, 2D6, or 3A4.
Studji in vitro juru li caspofungin mhuwiex inibitur tal- enzimi taċ- ċitokromu P450 1A2, 2A6, 2C9, 2C19, 2D6 jew 3A4.
Caspofungin displays moderate non-linear pharmacokinetics with increased accumulation as the dose is increased, and a dose dependency in the time to reach steady state upon multiple-dose administration.
25 Caspofungin juri farmakokinetiċi moderati mhux lineari b’ akkumulazzjoni miżjuda hekk kif tiżdied id- doża, u dipendenza fuq id- doża fil- ħin sakemm jintlaħaq stat stabbli wara l- għoti ta ’ ħafna dożi.
In adult patients with moderate liver impairment or in higher weight patients, a dosage adjustment may be necessary (see below).
F’ pazjenti adulti b’ indeboliment moderat fil- fwied u f’ pazjenti itqal fil - piż, jista ’ jkun meħtieġ aġġustament fid- doża (ara taħt)..
24 hepatic impairment has been shown to provide an AUC similar to that obtained in adult subjects with normal hepatic function receiving the standard regimen (see section 4.2).
Fi studju ta ’ dożi multipli, tnaqqis fid- doża għal 35 mg kuljum f’ pazjenti adulti b’ indeboliment moderat tal- fwied intwera li jipprovdi AUC simili għal dik miksuba f’ suġġetti adulti b’ funzjoni tal- fwied normali li kienu qegħdin jirċievu t- terapija standard (ara sezzjoni 4. 2).
In young children and toddlers (ages 12 to 23 months) receiving caspofungin at 50 mg/ m2 daily (maximum 70 mg daily), the caspofungin plasma AUC0-24hr after multiple doses was comparable to that seen in adults receiving caspofungin at 50 mg daily and to that in older children (2 to 11 years of age) receiving the 50 mg/ m2 daily dose.
26 plażma wara dożi multipli kienet komparabbli ma ’ dik li dehret f’ persuni adulti li rċevew caspofungin f’ doża ta ’ 50 mg kuljum u ma ’ dik fi tfal akbar (etajiet minn 2 sa 11- il sena) li rċevew id- doża ta ’ 50 mg/ m2 kuljum.
25 5.3 Preclinical safety data
5. 3 Tagħrif ta ’ qabel l- użu kliniku dwar is- sigurtà tal- mediċina
26 6.5 Nature and contents of container
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
10 ml Type I glass vials with a grey butyl stopper and a plastic cap with a yellow/ orange aluminium band for single use only.
Kunjetti tal- ħġieġ tat- Tip I ta ’ 10 ml b’ tapp griż tal- butyl u għatu tal- plastik b’ faxxa ħamra tal - aluminju għal użu ta ’ darba biss.
Step 1 Reconstitution of conventional vials To reconstitute the powder bring the vial to room temperature and aseptically add 10.5 ml of water for injections.
Pass 1 Rikostituzzjoni ta ’ kunjetti konvenzjonali Biex tirrikostitwixxi t- trab, ġib il- kunjett għat- temperatura tal- kamra u b’ mod asettiku żid 10. 5 ml ta ’ ilma għall- injezzjonijiet.
The concentrations of the reconstituted vials will be:
Il- konċentrazzjoni tal- kunjetti rikostitwiti se jkun:
7.2 mg/ ml.
7. 2 mg/ ml.
27 PREPARATION OF THE SOLUTION FOR INFUSION IN ADULTS
PREPARAZZJONI TAS- SOLUZZJONI GĦAL INFUŻJONI FL- ADULTI
Standard preparation (reconstituted CANCIDAS added to 250 ml) final concentration
ta ’ 250 ml)
0.27 mg/ ml
0. 27 mg/ ml
Not Recommended
Mhux rakkomandat
(from two 50 mg vials)** 35 mg for moderate
(minn żewġ kunjetti ta ’ 50 mg) ** 35 mg għal insuffiċjenza moderata tal- fwied
hepatic insufficiency (from one 70 mg vial)
(minn kunjett wieħed ta ’ 70 mg)
* 10.5 ml should be used for reconstitution of all vials **If 70 mg vial is not available, the 70 mg dose can be prepared from two 50 mg vials
* 10. 5 ml għandhom jintużaw għar- rikostituzzjoni tal- kunjetti kollha ** Jekk ikun hemm kunjett ta ’ 70 mg disponibbli, id- doża ta ’ 70 mg tista ’ titħejja minn żewġ kunjetti ta ’ 50 mg.
Preparation of the 70 mg/ m2 infusion for paediatric patients > 3 months of age (using a 70-mg vial) 1.
Preparazzjoni tal- infużjoni ta ’ 70 mg/ m2 għal pazjenti pedjatriċi minn 3 xhur ’ il fuq (billi jintuża kunjett ta ’ 70 mg) 1.
Aseptically add 10.5 ml of 0.9% Sodium Chloride Injection, Sterile Water for Injection or Bacteriostatic Water for Injection with methylparaben and propylparaben. a This reconstituted solution may be stored for up to one hour at ≤ 25°C (≤ 77°F). b This will give a final caspofungin concentration in the vial of 7.2 mg/ ml.
B’ mod asettiku żid 10. 5 ml ta ’ 0. 9% Injezzjoni ta ’ Klorur tas- Sodju, Ilma Sterili għal Injezzjoni jew Ilma Batterjostatiku għal Injezzjoni b’ methylparaben u propylparaben. a Din is- soluzzjoni rikostitwita tista ’ tinħażen sa siegħa f’ temperatura ta ’ ≤25°C (≤77°F). b Din tagħti konċentrazzjoni finali ta ’ caspofungin fil- kunjett ta ’ 7. 2 mg/ ml.
Remove the volume of drug equal to the calculated loading dose (Step 1) from the vial.
Neħħi mill- kunjett il- volum ta ’ mediċina ugwali għal- loading dose kkalkulata (Pass 1).
Preparation of the 50 mg/ m2 infusion for paediatric patients > 3 months of age (using a 70-mg vial) 1.
Preparazzjoni tal- infużjoni ta ’ 50 mg/ m2 għal pazjenti pedjatriċi minn 3 xhur ’ il fuq (billi jintuża kunjett ta ’ 70 mg) 1.
28 solution may be stored for up to one hour at ≤ 25°C (≤ 77°F). b This will give a final caspofungin concentration in the vial of 7.2 mg/ ml.
B’ mod asettiku żid 10. 5 ml ta ’ 0. 9% Injezzjoni ta ’ Klorur tas- Sodju, Ilma Sterili għal Injezzjoni jew Ilma Batterjostatiku għal Injezzjoni b’ methylparaben u propylparaben. a Din is- soluzzjoni rikostitwita tista ’ tinħażen sa siegħa f’ temperatura ta ’ ≤25°C (≤77°F). b Din tagħti konċentrazzjoni finali ta ’ caspofungin fil- kunjett ta ’ 7. 2 mg/ ml.
CANCIDAS is formulated to provide the full labeled vial dose (70 mg) when 10 ml is withdrawn from the vial.
ċ CANCIDAS huwa fformulat sabiex jipprovdi d- doża ttikkettjata kollha tal- kunjett (70 mg) meta jinġibdu 10 ml mill- kunjett.
29 ANNEX II
31 ANNESS II
MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
DETENTUR( I) TAL- AWTORIZZAZZJONI TAL - MANIFATTURA RESPONSABBLI GĦALL- ĦRUĠ TAL - LOTT
CONDITIONS OF THE MARKETING AUTHORISATION
KUNDIZZJONIJIET TAL- AWTORIZZAZZJONI GĦAT - TQEGĦID FIS- SUQ
MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
DETENTUR( I) TAL- AWTORIZZAZZJONI TAL- MANIFATTURA RESPONSABBLI GĦALL- ĦRUĠ TAL- LOTT
Name and address of the manufacturer(s) responsible for batch release
Isem u indirizz tal- manifattur( i) responsabbli għall- ħruġ tal- lott
Box 581, 2003 PC Haarlem, The Netherlands
Box 581, 2003 PC Haarlem, L- Olanda
Manufacturing Authorisation issued on 21 March 2001 by the Ministry of Health, Welfare and Sport, the Public Health Supervisory Service, Inspectorate of Health Care, P. O.
L- Awtorizzazzjoni tal- Manifattura maħruġa fil- 21 ta ’ Marzu 2001 mill- Ministeru tas- Saħħa, Benesseri u Sport, is- Servizz Superviżorju dwar is- Saħħa Pubblika, Spettorat tal- Kura tas- Saħħa, P. O.
The Hague, The Netherlands.
The Hague, L- Olanda.