qanastek/EMEA-V3 huggingface dataset:
ECALTA should be reconstituted with the solvent to a concentration of 3.33 mg/ ml and subsequently diluted to a concentration of 0.36 mg/ ml before use according to the instructions given in section 6.6.
ECALTA għandu jiġi rikostitwit bis- solvent għal konċentrazzjoni ta ’ 3. 33 mg/ ml u suċċessivament dilwit għal konċentrazzjoni ta ’ 0. 36 mg/ ml qabel l- użu skond l- istruzzjonijiet mogħtija f’ sezzjoni 6. 6.
It is recommended that ECALTA be administered at a rate of infusion that does not exceed 1.1 mg/ minute (equivalent to 3.0 ml/ minute).
Huwa rrakkomandat li ECALTA jingħata b’ rata ta ’ infużjoni li ma taqbiżx 1. 1 mg/ ml (ekwivalenti għal 3. 0 ml/ minuta).
Infusion associated reactions are infrequent when the rate of anidulafungin infusion does not exceed 1.1 mg/ minute.
Reazzjonijiet assoċjati ma ’ l- infużjonijiet huma rari meta r- rata ta ’ l- infużjoni ta ’ anidulafungin ma taqbiżx 1. 1 mg/ minuta.
ECALTA should not be administered as a bolus injection.
ECALTA m’ għandux jingħata bħala injezzjoni bolus.
2 No dosing adjustments are required for patients with mild, moderate, or severe hepatic impairment.
2 Indeboliment tal- kliewi u tal- fwied M’ hemmx bżonn ta ’ aġġustament fid- doża għal pazjenti b’ indeboliment ħafif, moderat jew sever tal - fwied.
No dosing adjustments are required for patients with any degree of renal insufficiency, including those on dialysis.
M’ hemmx bżonn ta ’ aġġustament fid- doża għal pazjenti bi kwalunkwe livell ta ’ insuffiċjenza tal- kliewi, inkluż dawk fuq dijalisi.
ECALTA can be given without regard to the timing of haemodialysis (see section 5.2).
ECALTA jista ’ jingħata mingħajr rigward għall- ħin tal - ħemodijalisi (ara sezzjoni 5. 2).
Duration of treatment There are insufficient data to support the 100 mg dose for longer than 35 days of treatment.
Tul tal- kura M’ hemmx informazzjoni biżżejjed li jsostni kura ta ’ 100mg għal iktar minn 35 ġurnata.
Other special populations No dosing adjustments are required for adult patients based on gender, weight, ethnicity, HIV positivity, or geriatric status (see section 5.2).
Popolazzjonijiet speċjali oħrajn M’ hemmx bżonn ta ’ aġġustament fid- doża għal pazjenti adulti fuq il- bażi tas- sess tal- persuna, il- piż, l - etniċità, il- pożittività għall- HIV, jew l- istatus ġerjatriku (ara sezzjoni 5. 2).
Children and adolescents ECALTA is not recommended for use in children below 18 due to insufficient data on safety and efficacy (see section 5.2).
Tfal u adoloxxenti ECALTA mhux irrakkomandat għal użu fi tfal ta ’ taħt it- 18- il sena minħabba nuqqas ta ’ informazzjoni dwar sigurta ’ u effikaċja (ara sezzjoni 5. 2).
Hypersensitivity to the active substance, or to any of the excipients.
Sensittività eċċessiva għas- sustanza attiva, jew għal xi sustanzi mhux attivi.
Hypersensitivity to other medicinal products of the echinocandin class.
Sensittività eċċessiva għal prodotti mediċinali oħra tal- klassi echinocandin.
The efficacy of ECALTA in neutropenic patients with candidaemia and in patients with deep tissue Candida infections or intra-abdominal abscess and peritonitis has not been established.
L- effikaċja ta ’ ECALTA f’ pazjenti newtropeniċi b’ candidemia u f’ pazjenti b’ infezzjoni Candida fit - tessut fond jew b’ axxess intra- addominali u peritonite ma ġietx stabbilita.
Clinical efficacy has been evaluated primarily in non-neutropenic patients with C. albicans infections and in a smaller number of patients infected with non-albicans, mainly C. glabrata, C. parapsilosis and C. tropicalis.
L- effikaċja klinika ġiet evalwata primarjament f’ pazjenti mhux newtropeniċi, b’ infezzjoni ta ’ C. albicans u f’ numru iżgħar ta ’ pazjenti b’ infezzjoni Candida mhux albicans, l- aktar C. glabrata, C. parapsilosis u C. tropicalis.
Patients with candida endocarditis, osteomyelitis or meningitis and known C. krusei infection have not been studied.
Pazjenti b’ endokardite b’ candida, ostjomajelite jew meninġite u dawk li huma magħrufa li għandhom infezzjoni b’ C. krusei ma kienux studjati.
Hepatic effects Increased levels of hepatic enzymes have been seen in healthy subjects and patients treated with anidulafungin.
Effetti fuq il- fwied Żieda fil- livelli tal- enzimi epatiċi dehret f’ suġġetti b’ saħħithom u pazjenti kkurati b’ anidulafungin.
In some patients with serious underlying medical conditions who were receiving multiple concomitant medicines along with anidulafungin, clinically significant hepatic abnormalities have occurred.
F’ ċerti pazjenti b’ kondizzjonijiet mediċi serji preżenti li kienu qegħdin jirċievu diversi mediċini konkomitanti flimkien ma ’ anidulafungin, seħħew anormalitajiet epatiċi klinikament sinifikanti.
Isolated cases of significant hepatic dysfunction, hepatitis, or worsening hepatic failure have been reported.
Kienu rrapportati każijiet iżolati ta ’ disfunzjoni epatika sinifikanti, epatite, jew insuffiċjenza tal- fwied li ggravat.
Patients with increased hepatic enzymes during anidulafungin therapy should be monitored for evidence of worsening hepatic function and evaluated for risk/ benefit of continuing anidulafungin therapy.
Pazjenti li jiżviluppaw żieda fl- enzimi epatiċi, waqt terapija b’ anidulafungin għandhom jiġu mmonitorjati għal evidenza ta ’ tħassir tal- funzjoni tal- fwied u evalwati għar- riskju/ benefiċċju tat - tkomplija tat- terapija b’ anidulafungin.
Infusion-related reactions Exacerbation of infusion-related reactions by coadministration of anaesthetics has been seen in a non- clinical (rat) study (see section 5.3).
Reazzjonijiet relatati ma ’ l- infużjoni Aggravament ta ’ reazzjonijiet relatati ma ’ l- infużjoni bl- għoti ta ’ anestetiċi ma ’ anidulafungin intwera fi studju mhux kliniku (fuq il- firien) (ara sezzjoni 5. 3).
The clinical relevance of this is unknown.
Ir- rilevanza klinika ta ’ dan mhux magħrufa.
Nevertheless, care should be taken when co-administering anidulafungin and anaesthetic agents.
Madankollu, wieħed irid joqgħod attent meta jagħti anidulafungin ma ’ aġenti anestetiċi.
Alcohol content This medicinal product contains 24 vol% ethanol (alcohol); this is equivalent to 6 g ethanol in the 100 mg maintenance dose (administered over a 1.5-hour period), and 12 g ethanol in the 200 mg loading dose (administered over a 3-hour period).
Kontenut ta ’ alkoħol Dan il- prodott mediċinali fih 24% bil- volum ta ’ ethanol (alkoħol); dan huwa ekwivalenti għal 6 g ethanol fid- doża ta ’ manutenzjoni ta ’ 100 mg (mogħtija fuq perjodu ta ’ 1. 5 sigħat), u 12 g ethanol fil - loading dose ta ’ 200 mg (mogħtija fuq perjodu ta ’ 3 sigħat).
Ethanol could be harmful for those suffering from alcoholism.
L- ethanol jista ’ jagħmel ħsara lil dawk li jbatu mill- alkoħoliżmu.
This should be taken into account in pregnant or breast-feeding women, children, and in high-risk groups such as those with liver disease or epilepsy.
Dan għandu jiġi kkunsidrat fil- każ ta ’ nisa tqal jew ireddgħu, tfal, u fi gruppi b’ riskju għoli bħal persuni li jbatu minn mard tal- fwied jew epilessija.
The amount of alcohol in this medicinal product may alter the effects of other medicines.
L- ammont ta ’ alkoħol f’ dan il- prodott mediċinali jista jaffettwa l- effetti ta ’ mediċini oħra.
The amount of alcohol in this medicinal product may impair the ability to drive or use machines.
3 L- ammont ta ’ alkoħol f’ dan il- prodott mediċinali jista jkollu effetti fuq il- ħila tas- sewqan jew tħaddim ta ’ makkinarji.
3 Fructose content Patients with rare hereditary problems of fructose intolerance should not take this medicine.
Kontenut ta ’ fructose Pazjenti bi problemi ereditarji rari ta ’ intolleranza għall- fructose m’ għandhomx jieħdu din il- mediċina.
Anidulafungin is not a clinically relevant substrate, inducer, or inhibitor of cytochrome P450 isoenzymes (1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A).
Anidulafungin mhux sottostrat, induttur, jew inibitur klinikament rilevanti ta ’ l- isoenzimi taċ - ċitokromu P450 (1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A).
Of note, in vitro studies do not fully exclude possible in vivo interactions.
Importanti, l- istudji in vitro ma jeskludux għal kollox interazzjonijiet in vivo li jista ’ jkun hemm.
Drug interaction studies were performed with anidulafungin and other medicinal products likely to be co-administered.
L- istudji dwar l- interazzjoni tal- mediċina saru b’ anidulafungin u prodotti mediċinali oħra li jistgħu jingħataw miegħu.
No dosage adjustment of either medicinal product is recommended when anidulafungin is co-administered with ciclosporin, voriconazole or tacrolimus, and no dosage adjustment for anidulafungin is recommended when co-administered with amphotericin B or rifampicin.
Mhux rakkomandat aġġustament fid- doża ta ’ xi mediċina meta anidulafungin jingħata ma ’ ciclosporin, voriconazole jew tacrolimus, u mhux rakkomandat aġġustament fid- doża ta ’ anidulafungin meta jingħata ma ’ amphotericin B jew ma ’ rifampicin.
There are no data regarding the use of anidulafungin in pregnant women.
M’ hemm l’ ebda informazzjoni dwar l- użu ta ’ anidulafungin f’ nisa tqal.
Slight developmental effects have been observed in rabbits administered anidulafungin during pregnancy, in the presence of maternal toxicity (see section 5.3).
Kienu osservati effetti ħfief fuq l- iżvilupp fi fniek li ngħataw anidulafugin waqt it- tqala, fil- preżenza ta ’ tossiċità fl- omm (ara sezzjoni 5. 3).
The potential risk for humans is unknown.
Mhux magħruf ir- riskju potenzjali għall- bniedem.
Therefore anidulafungin is not recommended in pregnancy.
Għalhekk anidulafungin mhux rakkomandat fit- tqala.
Animal studies have shown excretion of anidulafungin in breast milk.
Studji fuq l- annimali wrew tneħħija ta ’ anidulafungin fil- ħalib tas- sider.
It is not known whether anidulafungin is excreted in human breast milk.
Mhux magħruf jekk anidulafungin jitneħħiex fil- ħalib tas- sider fil- bniedem.
A decision on whether to continue/ discontinue breast- feeding or therapy with anidulafungin should be made taking into account the benefit of breast-feeding to the child and the benefit of anidulafungin to the mother.
Deċiżjoni dwar jekk jissoktax/ jitwaqqafx it - treddigħ jew it- terapija b’ anidulafungin għandha tittieħed wara li jitqies il- benefiċċju tat- treddigħ għat - tarbija u l- benefiċċju ta ’ anidulafungin għall- omm.
The amount of alcohol in this medicinal product may impair the ability to drive or use machines.
L- ammont ta ’ alkoħol f’ din il- mediċina jista jkollu effett fuq il- ħila biex issuq jew tħaddem magni.
Nine hundred and twenty-nine (929) subjects received single or multiple doses of intravenous anidulafungin in clinical trials:
Disa ’ mija u disgħa u għoxrin (929) suġġetti rċevew doża waħda jew diversi ta ’ anidulafungin ġol - vina fi provi kliniċi:
672 in Phase 2/ 3 trials (287 patients with candidaemia/ invasive candidiasis, 355 patients with oral/ oesophageal candidiasis, 30 patients with invasive aspergillosis), and 257 in Phase I studies.
672 fi studji ta ’ Fażi 2/ 3 (287 pazjent b’ candidemia/ candidiasis invażiva, 355 pazjent b’ candidiasis orali/ ta ’ l- esofagu, 30 pazjent b’ asperġillosi invażiva), u 257 fi studji ta ’ Fażi I.
Three studies (one comparative vs fluconazole, two non-comparative) assessed the efficacy of anidulafungin in patients with candidaemia and a limited number of patients with deep tissue Candida infections.
Tliet studji (wieħed komparattiv vs fluconazole, tnejn mhux komparattivi) evalwaw l- effikaċja ta ’ anidulafungin f’ pazjenti b’ candidemia u numru limitat ta ’ pazjenti oħra b’ infezzjonijiet b’ Candida fit - tessut fond.
A total of 204 patients received the recommended daily dose of 100 mg; the mean duration of intravenous treatment in these patients was 13.5 days (range, 1 to 38 days).
Total ta ’ 204 pazjenti rċevew id- doża rrakkomandata ta ’ kuljum ta ’ 100 mg, it- tul medju tal- kura għal ġol- vini f’ dawn il- pazjenti kien 13. 5- il ġurnata (medda, 1 sa 38 ġurnata).
One hundred and nineteen patients received ≥ 14 days of anidulafungin.
Mija u dsatax- il pazjent irċevew ≥ 14- il ġurnata ta ’ anidulafungin.
Adverse reactions were typically mild to moderate and seldom led to discontinuation.
Ir- reazzjonijiet avversi ġeneralment kienu ħfief għal moderati u rari wasslu għal twaqqif tal- kura.
Infusion-related adverse reactions have been reported with anidulafungin; in the pivotal ICC study, these included flushing/ hot flush (2.3%), pruritus (2.3%), rash (1.5%), and urticaria (0.8%).
Kienu rrapportati reazzjonijiet avversi relatati ma ’ l- infużjoni bl- użu ta ’ anidulafungin; fl- istudju pivitali dwar l- ICC, dawn kienu jinkludu ħmura tal- wiċċ / ħmura tal- wiċċ bil- fwawar (2. 3%), ħakk (2. 3%), raxx (1. 5%) u urtikarja (0. 8%).
Other treatment-related adverse reactions that occurred in ≥ 1% of patients in the pivotal study included hypokalemia (3.1%), diarrhoea (3.1%), ALT increased (2.3%), hepatic enzyme increased (1.5%), blood alkaline phosphatase increased (1.5%), and blood bilirubin increased (1.5%).
Reazzjonijiet avversi oħra relatati mal- kura li seħħew f’ ≥ 1% tal- pazjenti fl- istudju pivitali kienu jinkludu ipokalimja (3. 1%), dijarea (3. 1%), żieda fl- ALT (2. 3%), żieda fl- enzimi tal- fwied (1. 5%), żieda ta ’ alkaline phosphatase fid- demm (1. 5%), żieda ta ’ bilirubin fid- demm (1. 5%).
In the 100 mg ICC database (N = 204), the drug-related adverse reactions (MedDRA) listed below were reported with frequencies corresponding to Common (≥ 1/ 100 to < 1/ 10) or Uncommon (≥ 1/ 1,000
4 Fid- database ta ’ l- ICC b’ 100 mg (N = 204), ir- reazzjonijiet avversi relatati mal- mediċina (MedDRA) elenkati hawn isfel ġew irrapportati bi frekwenzi li jikkorrispondu għal Komuni (≥1/ 100 to < 1/ 10) jew Mhux Komuni (≥1/ 1, 000 to < 1/ 100).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa huma mniżżlin skond is- serjetà tagħhom.
Nervous system Common:
Disturbi fis- sistema nervuża Komuni:
disorders Convulsion, headache
Konvulżjoni, uġigħ ta ’ ras
Uncommon:
Mhux Komuni:
Diarrhoea, vomiting, nausea Abdominal pain upper
Diareja,, rimettar, dardir Uġigħ fin- naħa ta ’ fuq taż- żaqq
Renal and urinary disorders Common:
Disturbi fil- kliewi u fis- sistema urinarja Komuni:
Blood creatinine increased
Żieda fil- kreatinina tad- demm
Rash, pruritus Urticaria
Raxx, ħakk Urtikaria
Metabolism and Common:
Disturbi fil- metaboliżmu u n- nutrizzjoni Komuni:
nutrition disorders Hypokalaemia Hyperglycaemia
Ipokalimja Ipergliċemija
Vascular disorders Common:
Disturbi vaskulari Komuni:
Flushing Hypertension, hot flush
Fwawar Pressjoni għolja, ħmura tal- wiċċ bil- fwawar
General disorders and administration site conditions Uncommon:
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata Mhux Uġigħ fil- post ta ’ l- infużjoni Komuni:
Hepatobiliary disorders Common:
Disturbi tal- fwied u tal- marrara Komuni:
Alanine aminotransferase increased, blood alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, gamma-glutamyltransferase increased
Żieda fl- alanine aminotransferase, żieda fl- alkaline phosphatase fid- demm, żieda fl - aspartate aminotransferase, żieda ta ’ bilirubin fid- demm, żieda fil- gamma - glutamyltransferase
Cholestasis
Kolestasi
As with any overdose, general supportive measures should be utilised as necessary.
Bħal f’ kull każ ta ’ doża eċċessiva oħra, għandhom jintużaw miżuri ġenerali ta ’ sostenn kif ikun meħtieġ.
In case of overdose, adverse reactions may occur as mentioned in section 4.8.
F’ każ ta ’ doża eċċessiva, jista ’ jkun hemm reazzjonijiet avversi kif imsemmi f’ sezzjoni 4. 8.
During clinical trials, a single 400 mg dose of anidulafungin was inadvertently administered as a loading dose.
Waqt provi kliniċi, doża waħda ta ’ 400 mg anidulafungin ġiet mogħtija bi żball bħala loading dose.
No clinical adverse reactions were reported.
Ma ġew irrapportati l- ebda reazzjonijiet kliniċi avversi.
No dose limiting toxicity was observed in a study of 10 healthy subjects administered a loading dose of 260 mg followed by 130 mg daily; 3 of the 10 subjects experienced transient, asymptomatic transaminase elevations (≤ 3 x Upper Limit of Normal (ULN)).
L- ebda tossiċità li tillimita d- doża ma kienet 5 osservata fi studju ta ’ għaxar suġġetti b’ saħħithom li ngħataw loading dose ta ’ 260 mg segwita b’ 130 mg kuljum; 3 mill- 10 suġġetti esperjenzaw żidiet momentanji bla sintomi fit- transaminases (≤3 x Limitu ta ’ Fuq tan- Normal (ULN – Upper Limit of Normal)).
ECALTA is not dialysable.
ECALTA ma jitneħħiex b’ dijalisi.
General properties Pharmacotherapeutic group:
Tagħrif ġenerali Kategorija farmakoterapewtika:
Other antimycotics for systemic use, ATC code:
Antimikotiċi oħra għal użu sistemiku Kodiċi ATC:
JO2AX06
JO2 AX 06
Anidulafungin is a semi-synthetic echinocandin, a lipopeptide synthesised from a fermentation product of Aspergillus nidulans.
Anidulafungin huwa echinocandin semi- sintetiku, lipopeptide sintetizzat minn prodott ta ’ fermentazzjoni ta ’ l- Aspergillus nidulans.
Anidulafungin selectively inhibits 1,3-β -D glucan synthase, an enzyme present in fungal, but not mammalian cells.
Anidulafungin jinibixxi b’ mod selettiv il- glucan synthase 1, 3- β- D, enzima preżenti fiċ- ċelloli fungali, iżda mhux mammiferi.
This results in inhibition of the formation of 1,3-β -D-glucan, an essential component of the fungal cell wall.
Dan jirriżulta f’ inibizzjoni tal- ħolqien ta ’ 1, 3- β- D- glucan, komponent essenzjali tal- ħajt taċ- ċelloli fungali.
Anidulafungin has shown fungicidal activity against Candida species and activity against regions of active cell growth of the hyphae of Aspergillus fumigatus.
Anidulafungin wera attività fungiċida kontra speċi ta ’ Candida u attività kontra reġjuni ta ’ tkabbir attiv taċ- ċelloli tal- filament fil- miċelju ta ’ l- Aspergillus fumigatus.
Activity in vitro Anidulafungin exhibited in-vitro activity against C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis.
Tropicalis.
Susceptibility breakpoints for 1,3- β -D-glucan synthesis inhibitors have not been established.
L- endpoints tas- suxxettibilita ’ għal inibituri tas- sinteżi ta ’ 1, 3- β- D glucan ma ġewx stabbiliti.
For the clinical relevance of these findings see below under clinical studies.
Għar- rilevanza klinika ta ’ dawn il- valuri ara hawn taħt Studji kliniċi.
Minimum inhibitory concentration (MIC) determinations were performed according to the Clinical and Laboratory Standards Institute methods M27 and M38.
Il- kalkoli tal- konċentrazzjoni inibitorja minima (MIC – minimum inhibitory concentration) saru skond il- metodi M27 u M38 ta ’ l- Istitut dwar l- Istandards Kliniċi u tal- Laboratorju.
Candida isolates with reduced susceptibility to anidulafungin have not been isolated from treated patients.
Iżolati Candida b’ suxxettibilità mnaqqsa għal anidulafungin ma ġewx iżolati mill- pazjenti kkurati.
Among a number of isolates with elevated echinocandin MICs isolated from patients treated with other echinocandins, only two Candida isolates were reported to also have elevated anidulafungin MICs, suggesting the lack of complete cross resistance among echinocandins.
Fost numru ta ’ iżolati b’ MICs għoljin ta ’ echinocandin iżolati minn pazjenti kkurati b’ echinocandins oħra, żewġ iżolati Candida biss kienu rrapportati li kellhom ukoll MICs għoljin ta ’ anidulafungin, li jissuġġerixxi n- nuqqas ta ’ cross resistance kompleta bejn l- echinocandins.
Activity in vivo Parenterally administered anidulafungin was effective against Candida spp. in immunocompetent and immunocompromised mouse and rabbit models.
Attivita in vivo Anidalfungin mogħti b. mod parenterali, kien effettiv kontra Candida spp. f’ mudelli ta ’ ġrieden u fniek immunokompetenti u immunokompromessi.
Anidulafungin treatment prolonged survival and also reduced the organ burden of Candida spp., when determined at intervals from 24 to 96 hours after the last treatment.
Trattament b’ anidulafungin tawwal is- sopravvivenza u naqqas it- tgħabija ta ’ Candida spp fuq l- organi., meta dan ġie ddeterminat f’ intervalli bejn 24 u 96 siegħa wara l- aħħar trattament.
Experimental infections included disseminated C. albicans infection in neutropenic rabbits, oesophageal/ oropharyngeal infection of neutropenic rabbits with fluconazole-resistant C. albicans and disseminated infection of neutropenic mice with fluconazole-resistant C. glabrata.
Infezzjonijiet ta ’ prova kienu jinkludu tixrid ta ’ infezzjoni C. albicans fi fniek newtropeniċi, infezzjonijiet fl- esofagu jew fil- ħalq u l- farinġi ta ’ fniek newtropeniċi b’ C. albicans reżistenti għal fluconazole, u infezzjoni imxerrrda fi ġrieden newtropeniċi bi C. glabrata reżistenti għal fluconazole.
Information from clinical studies
Informazzjoni mill- istudji kliniċi
Candidaemia and other forms of Invasive Candidiasis
Candidemia u forom oħra ta ’ Candidiasis Invażiva
The safety and efficacy of anidulafungin were evaluated in a pivotal Phase 3, randomised, double- blind, multicentre, multinational study of primarily non-neutropenic patients with candidaemia and a limited number of patients with deep tissue Candida infections or with abscess-forming disease.
Is- sigurtà u l- effikaċja ta ’ anidulafungin ġew evalwati fi studju pivitali multiċentri, multinazzjonali, magħmul b’ għażla każwali, double- blind, ta ’ Fażi 3 fuq pazjenti primarjament mhux newtropeniċi, b’ candidemia u numru limitat ta ’ pazjenti b’ infezzjoni ta ’ Candida f’ tessuti ta ’ taħt il - ġilda, jew b’ mard li jikkawża axxessi.
[Patients with Candida endocarditis, osteomyelitis or meningitis, or those with infection due to C. krusei, were specifically excluded from the study].
[Pazjenti b’ endokardite, ostjomajelite jew meninġite b’ Candida, jew dawk b’ infezzjoni minħabba C. krusei, kienu speċifikament esklużi mill- istudju].
Patients were randomised to receive either anidulafungin (200 mg intravenous loading dose followed by 100 mg intravenous daily) or fluconazole (800 mg intravenous loading dose followed by 400 mg intravenous daily), and were stratified by APACHE II score (≤ 20 and > 20) and the presence or absence of neutropenia.
Il- pazjenti kienu magħżula b’ mod każwali biex jirċievu jew anidulafungin (loading dose ta ’ 200 mg ġol- vina segwita minn 100 mg ġol- vina kuljum) jew fluconazole (loading dose ta ’ 800 mg ġol- vina segwita minn 400 mg ġol- vina kuljum), u ġew stratifikati skond l- iskor APACHE II (≤20 and > 20) u l- preżenza jew nuqqas ta ’ neutropenia.
Treatment was administered for at least 14 and not more than 42 days.
Il -
Patients in both study arms were permitted to switch to oral fluconazole after at least 10 days of intravenous therapy, provided that they were able to tolerate oral medication and were afebrile for at least 24 hours, and that the most recent blood cultures were negative for Candida species.
6 pazjenti fiż- żewġ gruppi ta ’ studju kienu permessi li jaqilbu għal fluconazole orali wara talanqas 10 ijiem ta ’ terapija ġol- vina, bil- kondizzjoni li kienu kapaċi jittolleraw medikazzjoni orali u ma kellhomx deni għal mill- anqas 24 siegħa, u li l- aktar kolturi riċenti tad- demm kienu negattivi għal speċi Candida.
Patients who received at least one dose of study medication and who had a positive culture for Candida species from a normally sterile site before study entry were included in the modified intent-
Pazjenti li rċevew mill- anqas doża waħda tal- medikazzjoni ta ’ studju u li kellhom koltura pożittiva għal speċi Candida minn sit normalment sterili qabel l- istudju kienu inklużi fil- popolazzjoni intiża għall- kura (MITT) modifikata.
In the primary efficacy analysis, global response in the MITT populations at the end of intravenous therapy, anidulafungin was compared to fluconazole in a pre-specified two- step statistical comparison (non-inferiority followed by superiority).
Fl- analiżi primarja ta ’ l- effikaċja, ir- rispons globali fil- popolazzjonijiet MITT fit- tmiem tat- terapija ġol- vina, anidulafungin ġie mqabbel ma ’ fluconazole f’ paragun statistiku ta ’ żewġ stadji speċifikat minn qabel (mhux inferjorità segwita minn superjorità).
A successful global response required clinical improvement and microbiological eradication.
Rispons globali ta ’ suċċess kien jeħtieġ titjib kliniku u qerda totali mikrobijoloġika.
Patients were followed for six weeks beyond the end of all therapy.
Il- pazjenti kienu segwiti għal sitt ġimgħat wara t- tmiem tat- terapija kollha.
Two hundred and fifty-six patients, ranging from 16 to 91 years in age, were randomised to treatment and received at least one dose of study medication.
Mitejn u sitta u ħamsin pazjent, li varjaw minn 16 sa 91 sena, ġew magħżula b’ mod każwali għall- kura u rċevew mill- anqas doża waħda tal- medikazzjoni ta ’ studju.
The most frequent species isolated at baseline were C. albicans (63.8% anidulafungin, 59.3% fluconazole), followed by C. glabrata (15.7%, 25.4%), C. parapsilosis (10.2%, 13.6%) and C. tropicalis (11.8%, 9.3%) - with 20, 13 and 15 isolates of the last 3 species, respectively, in the anidulafungin group.
L- aktar speċi frekwenti iżolati fil- linja bażi kienu C. albicans (63. 8% anidulafungin, 59. 3% fluconazole), segwiti minn C. glabrata (15. 7%, 25. 4%), C. parapsilosis (10. 2%, 13. 6%) u C. tropicalis (11. 8%, 9. 3%) – b’ 20, 13 u 50 isolati ta ’ l - aħħar 3 speċi rispettivament, fil- grupp ta ’ anidulafungin.
The majority of patients had Apache II scores ≤ 20 and very few were neutropenic.
Il- maġġoranza tal- pazjenti kellhom punteġġi Apache II ta ’ ≤ 20 u ftit biss kienu newtropeniċi.
Efficacy data, both overall and by various subgroups, are presented below in Table 1.
It- tagħrif dwar l- effikaċja, kemm globali kif ukoll skond id- diversi sottogruppi, huwa ppreżentat hawn taħt f’ Tabella 1.
Global success in the MITT population: primary and secondary endpoints
Suċċess globali fil- popolazzjoni MITT: endpoints primarji u sekondarji
Between group difference a (95% CI)
Differenza bejn il- gruppi a (95% CI)
End of IV Therapy (1º endpoint) Candidaemia only Other sterile sitesb c
Tmiem tar- IV Terapija (l- Ewwel endpoint)
96/ 127 (75.6%) 88/ 116 (75.9%) 8/ 11 (72.7%)
96/ 127 (75. 6%)
15.42 (3.9, 27.0) 14.7 (2.5, 26.9) -
15. 42 (3. 9, 27. 0) 14. 7 (2. 5, 26. 9)
Peritoneal fluid/ IA abscess Other
Fluwidu peritonali/ Axxess IA Oħrajn
C. albicansd Non-albicans speciesd
C. albicansd Speċi mhux albicansd
60/ 74 (81.1%) 32/ 45 (71.1%)
60/ 74 (81. 1%) 32/ 45 (71. 1%)
38/ 61 (62.3%) 27/ 45 (60.0%)
38/ 61 (62. 3%) 27/ 45 (60. 0%)
Apache II score ≤ 20 Apache II score > 20
Skor Apache II ≤ 20 Skor Apache II > 20
82/ 101 (81.2%) 14/ 26 (53.8%)
82/ 101 (81. 2%) 14/ 26 (53. 8%)
60/ 98 (61.2%) 11/ 20 (55.0%)
60/ 98 (61. 2%) 11/ 20 (55. 0%)
Non-neutropenic (ANC, cells/ mm3 > 500) Neutropenic (ANC, cells/ mm3 ≤ 500) At Other Endpoints
Newtropeniċi( ANC, ċelluli/ mm3 > 500) L- Endpoints l- Oħra Kollha
End of All Therapy 2 Week Follow-up 6 Week Follow-up a
Ġimagħtejn ta ’ Kontinwazzjoni
94/ 127 (74.0%) 82/ 127 (64.6%) 71/ 127 (55.9%)
82/ 127 (64. 6%)
67/ 118 (56.8%) 58/ 118 (49.2%) 52/ 118 (44.1%)
58/ 118 (49. 2%)
17.24 (2.9, 31.6)e 15.41 (0.4, 30.4)e 11.84 (-3.4, 27.0)e
11. 84 (- 3. 4, 27. 0) e 6 Ġimgħat ta ’ Kontinwazzjoni a
Calculated as anidulafungin minus fluconazole b With or without concurrent candidaemia c Intra-abdominal d Data presented for patients with a single baseline pathogen. e 98.3% confidence intervals, adjusted post hoc for multiple comparisons of secondary time points.
Ikkalkulata bħala anidulafungin tnaqqas fluconazole b Bi jew mingħajr candidemia konkorrenti c Fiż- żaqq d Informazzjoni ppreżentata għal pazjenti b’ patoġenu wieħed fil- linja bażi. e 98. 3% intervalli ta ’ kunfidenza, aġġustati post hoc għal paraguni multipli ta ’ time points sekondarji.
Mortality rates in both the anidulafungin and fluconazole arms are presented below in Table 2:
7 Ir- rata ta ’ mwiet kemm fil- grupp ta ’ anidulafungin u f’ dak ta ’ fluconazole huwa ppreżentat hawn taħt f’ Tabella 2.
Overall study mortality Mortality during study therapy Mortality attributed to Candida infection
Mortalità globali fl- istudju Mortalità matul it- terapija ta ’ studju Mortalità attribwita għal infezzjoni b’ Candida
29/ 127 (22.8%) 10/ 127 (7.9%) 2/ 127 (1.6%)
29/ 127 (22. 8%) 10/ 127 (7. 9%) 2/ 127 (1. 6%)
37/ 118 (31.4%) 17/ 118 (14.4%) 5/ 118 (4.2%)
37/ 118 (31. 4%) 17/ 118 (14. 4%) 5/ 118 (4. 2%)
General pharmacokinetic characteristics The pharmacokinetics of anidulafungin have been characterised in healthy subjects, special populations and patients.
Karatteristiċi farmakokinetiċi ġenerali Il- farmakokinetiċi ta ’ anidulafungin ġew ikkaratterizzati f’ suġġetti b’ saħħithom, popolazzjonijiet speċjali u pazjenti.
A low intersubject variability in systemic exposure (coefficient of variation ~25%) was observed.
Kienet osservata varjabilità baxxa bejn is- suġġetti f’ espożizzjoni sistemika (ko - effiċjent ta ’ varjazzjoni~25%).
The steady state was achieved on the first day after a loading dose (twice the daily maintenance dose).
L- istat fiss inkiseb fl- ewwel ġurnata wara loading dose (id- doppju tad - doża ta ’ manutenzjoni ta ’ kuljum).
Distribution The pharmacokinetics of anidulafungin are characterised by a rapid distribution half-life (0.5-1 hour) and a volume of distribution, 30-50 l, which is similar to total body fluid volume.
Distribuzzjoni Il- farmakokinetiċi ta ’ anidulafungin huma kkaratterizzati minn half- life rapida tad- distribuzzjoni (0. 5 - 1 siegħa) u volum ta ’ distribuzzjoni, 30- 50 l, li huwa simili għall- volum ta ’ fluwidu totali fil- ġisem.
Anidulafungin is extensively bound (> 99%) to human plasma proteins.
Anidulafungin jeħel b’ mod estensiv (> 99%) mal- proteini tal- plasma umana.
No specific tissue distribution studies of anidulafungin have been done in humans.
Ma sarux studji speċifiċi dwar id- distribuzzjoni ta ’ anidulafungin fit- tessuti tal- bniedem.
Therefore, no information is available about the penetration of anidulafungin into the cerebrospinal fluid (CSF) and/ or across the blood-brain barrier.
Għalhekk, mhix disponibbli informazzjoni dwar il- penetrazzjoni ta ’ anidulafungin fil- fluwidu ċerebrospinali (CSF) u/ jew minn ġol- barrier ta ’ bejn il- moħħ u d- demm.
Biotransformation Hepatic metabolism of anidulafungin has not been observed.
Bijotrasformazzjoni Ma ġiex osservat metaboliżmu epatiku ta ’ anidulafungin.
Anidulafungin is not a clinically relevant substrate, inducer, or inhibitor of cytochrome P450 isoenzymes.
Anidulafungin mhux sottostrat, induttur, jew inibitur klinikament rilevanti ta ’ isoenzimi taċ- ċitokromu P450.
It is unlikely that anidulafungin will have clinically relevant effects on the metabolism of drugs metabolised by cytochrome P450 isoenzymes.
Mhux probabbli li anidulafungin ikollu effetti klinikament rilevanti fuq il- metaboliżmu ta ’ mediċini metabolizzati b’ isoenzimi taċ - ċitokromu P450.
Anidulafungin undergoes slow chemical degradation at physiologic temperature and pH to a ring- opened peptide that lacks antifungal activity.
Anidulafungin jiġi sottopost għal degradazzjoni kimika bil- mod f’ temperatura fiżjoloġika u pH għal ring- opened peptide nieqsa minn attività antifungali.
The in vitro degradation half-life of anidulafungin under physiologic conditions is approximately 24 hours.
Il- half life tad- degradazzjoni in vitro ta ’ anidulafungin taħt kondizzjonijiet fiżjoloġiċi hija madwar 24 siegħa.
In vivo, the ring-opened product is subsequently converted to peptidic degradants and eliminated mainly through biliary excretion.
In vivo, il- prodott ring- opened jiġi suċċessivament konvertit f’ degradanti peptidiċi u mneħħi prinċipalment permezz ta ’ eskrezzjoni biljari.
Elimination The clearance of anidulafungin is about 1 l/ h.
Eliminazzjoni It- tneħħija ta ’ anidulafungin hija madwar litru fis- siegħa.
Anidulafungin has a predominant elimination half-life of approximately 24 hours that characterizes the majority of the plasma concentration-time profile, and a terminal half-life of 40-50 hours that characterises the terminal elimination phase of the profile.
Anidulafungin għandu half- life predominanti ta ’ l- eliminazzjoni ta ’ madwar 24 siegħa li tikkaratterizza l- biċċa l- kbira tal- profil tal - konċentrazzjoni fil- plasma mal- ħin, u half- life terminali ta ’ 40- 50 siegħa li tikkaratterizza l- fażi finali ta ’ l- eliminazzjoni tal- profil.
In a single-dose clinical study, radiolabeled (14C) anidulafungin (~88 mg) was administered to healthy subjects.
Fi studju kliniku b’ doża waħda, anidulafungin (~88 mg) radjutikkettat (14C) ġie mogħti lil suġġetti b’ saħħithom.
Approximately 30% of the administered radioactive dose was eliminated in the faeces over 9 days, of which less than 10% was intact drug.
Madwar 30% tad- doża radjuattiva amministrata ġiet eliminata fl- ippurgar fuq 9 ijiem, li minnhom anqas minn 10% kienet mediċina intatta.
Less than 1% of the administered radioactive dose was excreted in the urine, indicating negligible renal clearance.
Anqas minn 1% tad- doża radjuattiva amministrata kienet imneħħija fl- awrina, li jindika tneħħija mill- kliewi negliġibbli.
Anidulafungin concentrations fell below the lower limits of quantitation 6 days post-dose.
Il- konċentrazzjonijiet ta ’ anidulafungin waqgħu taħt il- limiti l’ aktar baxxi ta ’ kwantifikazzjoni 6 ijiem wara d- doża.
Negligible amounts of drug-derived radioactivity were recovered in blood, urine, and faeces 8 weeks post-dose.
Ammonti negliġibbli ta ’ radjuattività derivata mill- mediċina kienu rkuprata fid- demm, fl- awrina, u fl- ippurgar 8 ijiem wara d- doża.
Linearity Anidulafungin displays linear pharmacokinetics across a wide range of once daily doses (15-130 mg).
8 Linearità Anidulafungin juri farmakokinetiċi lineari matul firxa wiesgħa ta ’ dożi mogħtija darba kuljum (15- 130 mg).
Special populations Patients with fungal infections The pharmacokinetics of anidulafungin in patients with fungal infections are similar to those observed in healthy subjects based on population pharmacokinetic analyses.
Popolazzjonijiet speċjali Pazjenti b’ infezzjonijiet fungali Il- farmakokinetiċi ta ’ anidulafungin f’ pazjenti b’ infezzjonijiet fungali huma simili għal dawk osservati f’ suġġetti b’ saħħithom ibbażati fuq analiżi farmakokinetiċi tal- popolazzjoni.
With the 200/ 100 mg daily dose regimen at an infusion rate of 1.1 mg/ min, the steady state Cmax and trough concentrations (Cmin) could reach approximately 7 and 3 mg/ l, respectively, with an average steady state AUC of approximately 110 mg⋅ h/ l.
Bir- reġim ta ’ dożaġġ ta ’ 200/ 100 mg kuljum b’ rata ta ’ infużjoni ta ’ 1. 1 mg/ min, il- Cmax stabbli u l - konċentrazzjonijiet minimi (Cmin) jistgħu jilħqu madwar 7 u 3 mg/ l, rispettivament, b’ medja ta ’ AUC stabbli ta ’ madwar 110 mg⋅h/ l.
Weight Although weight was identified as a source of variability in clearance in the population pharmacokinetic analysis, weight has little clinical relevance on the pharmacokinetics of anidulafungin.
Piż tal- persuna Għalkemm il- piż tal- persuna ġie identifikat bħala sors ta ’ varjabilità fit- tneħħija - fl- analiżi farmakokinetika tal- popolazzjoni, il- piż tal- persuna ftit għandu rilevanza klinika fuq il - farmakokinetiċi ta ’ anidulafungin.
8 Gender Plasma concentrations of anidulafungin in healthy men and women were similar.
Sess tal- persuna Il- konċentrazzjonijiet fil- plasma ta ’ anidulafungin f’ irġiel u nisa b’ saħħithom kienu simili.
In multiple-dose patient studies, drug clearance was slightly faster (approximately 22%) in men.
Fi studji fuq il- pazjenti b’ dożi multipli, it- tneħħija tal- mediċina kienet daqsxejn aktar mgħaġġla (madwar 22%) fl- irġiel.
Elderly The population pharmacokinetic analysis showed that median clearance differed slightly between the elderly group (patients ≥ 65, median CL = 1.07 l/ h) and the non-elderly group (patients < 65, median CL = 1.22 l/ h), however the range of clearance was similar.
Anzjani L- analiżi farmakokinetika tal- popolazzjoni wriet li t- tneħħija medjana varjat daqsxejn bejn il- grupp anzjan (pazjenti ≥ 65, CL medjana = 1. 07 l/ siegħa) u l- grupp mhux anzjan (pazjenti < 65, CL medjana = 1. 22 l/ siegħa), madankollu l- medda tat- tneħħija kienet simili.
Ethnicity Anidulafungin pharmacokinetics were similar among Caucasians, Blacks, Asians, and Hispanics.
Etniċità Il- farmakokinetiċi ta ’ anidulafungin kienu simili f’ persuni Kawkasi, Suwed, Asjatiċi, u Ispaniċi.
HIV positivity Dosage adjustments are not required based on HIV positivity, irrespective of concomitant anti- retroviral therapy.
Pożittività għall- HIV M’ hemmx bżonn ta ’ aġġustament fid- doża bbażat fuq pożittività għall- HIV, irrispettivament mit - terapija antiretrovirali konkomitanti.
Hepatic insufficiency Anidulafungin is not hepatically metabolised.
Insuffiċjenza tal- fwied Anidulafungin ma jiġix metabolizzat mill- fwied.
Anidulafungin pharmacokinetics were examined in subjects with Child-Pugh class A, B or C hepatic insufficiency.
Il- farmakokinetiċi ta ’ anidulafungin kienu studjati f’ suġġetti li kellhom insuffiċjenza tal- fwied tal- klassi Child- Pugh A, B jew C.
Anidulafungin concentrations were not increased in subjects with any degree of hepatic insufficiency.
Il- konċentrazzjonijiet ta ’ anidulafungin ma żdidux f’ pazjenti li kellhom xi livelli ta ’ insuffiċjenza tal- fwied.
Although a slight decrease in AUC was observed in patients with Child-Pugh C hepatic insufficiency, the decrease was within the range of population estimates noted for healthy subjects.
Għalkemm kien osservat tnaqqis żgħir fl- AUC f’ pazjenti li kellhom insuffiċjenza tal- fwied ta ’ Child- Pugh C, dan it - tnaqqis kien fil- medda ta ’ l- istimi għall- popolazzjoni nnotati għal suġġetti b’ saħħithom.
Renal insufficiency Anidulafungin has negligible renal clearance (< 1%).
Insuffiċjenza tal- kliewi Anidulafungin għandu tneħħija renali negliġibbli (< 1%).
In a clinical study of subjects with mild, moderate, severe or end stage (dialysis-dependent) renal insufficiency, anidulafungin pharmacokinetics were similar to those observed in subjects with normal renal function.
Fi studju kliniku ta ’ suġġetti b’ insuffiċjenza renali ħafifa, moderata, severa jew ta ’ l- aħħar stadju (dipendenti fuq id- dijalisi), il - farmakokinetiċi ta ’ anidulafungin kienu simili għal dawk osservati f’ suġġetti b’ funzjoni tal- kliewi normali.
Anidulafungin is not dialysable and may be administered without regard to the timing of hemodialysis.
Anidulafungin mhux dijalizzabbli u jista ’ jingħata mingħajr ma jitqies il- ħin tal - ħemodijalisi.
Paediatric The pharmacokinetics of anidulafungin after at least 5 daily doses were investigated in 24 immunocompromised paediatric (2 to 11 years old) and adolescent (12 to 17 years old) patients with neutropenia.
Pedjatriċi Il- farmakokinetiċi ta ’ anidulafungin wara mill- anqas 5 dożi li ngħataw darba kuljum ġew studjati f’ 24 pazjent pedjatriku (2 sa 11- il sena) u adoloxxenti (12 sa 17- il sena) immunokompromessi b’ newtropenja.
Steady state was achieved on the first day after a loading dose (twice the maintenance dose), and steady state Cmax and AUCss increase in a dose-proportional manner.
Stat fiss inkiseb fl- ewwel jum wara loading dose (doża ta ’ manutenzjoni doppja), u l - Cmax u l- AUCss fissi jiżdiedu b’ mod proporzjonali mad- doża.
Systemic exposure following daily maintenance dose of 0.75 and 1.5 mg/ kg/ day in this population were comparable to those observed in adults following 50 and 100 mg/ day, respectively.
L- espożizzjoni sistemiku wara doża ta ’ manutenzjoni kuljum ta ’ 0. 75 u 1. 5 mg/ kg/ ġurnata f’ din il- popolazzjoni kien paragunabbli ma ’ dak
5.3 Preclinical safety data
9 osservat f’ persuni adulti wara 50 u 100 mg/ ġurnata, rispettivament.
In 3 month studies, evidence of liver toxicity, including elevated enzymes and morphologic alterations, was observed in both rats and monkeys at doses 4- to 6-fold higher than the anticipated clinical therapeutic exposure.
5. 3 Tagħrif ta ’ qabel l- użu kliniku dwar is- sigurtà tal- mediċina
In vitro and in vivo genotoxicity studies with anidulafungin provided no evidence of genotoxic potential.
L- istudji in vitro u in vivo tal- ġenotossiċità b’ anidulafungin ma pprovdew ebda evidenza ta ’ potenzjal ġenotossiku.
Long-term studies in animals have not been conducted to evaluate the carcinogenic potential of anidulafungin.
Ma sarux studji fuq perjodu fit- tul fuq l- annimali biex jiġi evalwat il- potenzjal karċinoġeniku ta ’ anidulafungin.
Administration of anidulafungin to rats did not indicate any effects on reproduction, including male and female fertility.
L- amministrazzjoni ta ’ anidulafungin lill- firien ma indikat l- ebda effett fuq ir- riproduzzjoni, inkluża l - fertilità tar- raġel u tal- mara.
Anidulafungin crossed the placental barrier in rats and was detected in foetal plasma.
Anidulafungin għadda minn ġol- barrier plaċentali u kien rilevat fil- plasma tal- fetu.
Embryo-foetal development studies were conducted with doses between 0.2- and 2-fold (rats) and between 1- and 4-fold (rabbits) the proposed therapeutic maintenance dose of 100 mg/ day.
Studji fl- iżvilupp ta ’ l- embriju u tal- fetu saru minn dożi bejn 0. 2 - u 2 - il darba (fil- firien) jew bejn 1 - u 4- il darba (fil- fniek), id- doża terapewtika proposta ta ’ manutenzjoni ta ’ 100 mg.
9 Anidulafungin did not produce any drug-related developmental toxicity in rats at the highest dose tested.
Anidulafungin ma pproduċa l- ebda tossiċità ta ’ l- iżvilupp relatata mal- mediċina fil- firien bl- ogħla doża.
Developmental effects observed in rabbits (slightly reduced foetal weights) occurred only at the highest dose tested, a dose that also produced maternal toxicity.
L- effetti fuq l - iżvilupp osservati fil- fniek (tnaqqis żgħir fil- piż tal- fetu) seħħew biss fl- ogħla doża studjata, doża li pproduċiet ukoll tossiċità fl- omm.
Crossing of the blood-brain barrier by anidulafungin was limited in healthy rats; however, in rabbits with disseminated candidiasis, anidulafungin has been shown to cross the blood-brain barrier and reduce fungal burden in the brain.
Il- qsim tal- barrier ta ’ bejn id- demm u l- moħħ minn anidulafungin kien limitat ġo firien b’ saħħithom; madankollu, fi fniek li kellhom candidiasis mifruxa, intwera li anidulafungin jaqsam il- barrier ta ’ bejn il- moħħ u d- demm u jnaqqas it- tagħbija fungali fil- moħħ.
Rats were dosed with anidulafungin at three dose levels and anesthetised within one hour using a combination of ketamine and xylazine.
Il- firien ingħataw anidulafungin fi tliet livelli ta ’ dożaġġ u ġew anestetizzati fi żmien siegħa bl- użu ta ’ taħlita ta ’ ketamine u xylazine.
Rats in the high dose group experienced infusion-related reactions that were exacerbated by anaesthesia.
Il- firien fil- grupp tad- doża l- għolja esperjenzaw reazzjonijiet relatati ma ’ l- infużjoni li kienu aggravati bl- anestesija.
Some rats in the mid dose group experienced similar reactions but only after administration of anaesthesia.
Xi firien fil- grupp tad- doża tan- nofs esperjenzaw reazzjonijiet simili iżda biss wara li ngħataw l- anestesija.
There were no adverse reactions in the low- dose animals in the presence or absence of anaesthesia, and no infusion-related reactions in the mid- dose group in the absence of anaesthesia.
Ma kienx hemm reazzjonijiet avversi fl - annimali li ngħataw doża baxxa fil- preżenza jew fin- nuqqas ta ’ anestesija, u l- ebda reazzjonijiet relatati ma ’ l- infużjoni fil- grupp tad- doża tan- nofs fin- nuqqas ta ’ anestesija.
Fructose Mannitol Polysorbate 80 Tartaric acid Sodium hydroxide (for pH-adjustment) Hydrochloric acid (for pH-adjustment)
Fructose Mannitol Polysorbate 80 Tartaric acid Sodium hydroxide (għal aġġustament tal- pH) Hydrochloric acid (għal aġġustament tal- pH)
Ethanol anhydrous Water for injections
Ethanol anhydrous Ilma għall- injezzjonijiet
This medicinal product must not be mixed with other medicinal products or electrolytes except those mentioned in section 6.6.
Dan il- prodott mediċinali m’ għandux jiġi mħallat ma ’ prodotti mediċinali oħra jew elettroliti ħlief dawk imsemmija f’ sezzjoni 6. 6.
6.3 Shelf life
10 6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
Powder and solvent:
Trab u solvent:
Reconstituted solution:
Soluzzjoni rikostitwita:
The reconstituted solution should be further diluted within an hour.
Is- soluzzjoni rikostitwita għanda tkun dilwita aktar fi żmien siegħa.
Chemical and physical in-use stability of the reconstituted solution has been demonstrated for 3 hours at 25ºC and for 2 hours at 5°C.
L- istabbilità kimika u fiżika effettiva tas- soluzzjoni rikostitwita ġiet murija għal 3 siegħat f’ temperatura ta ’ 25ºC, u għal sagħtejn f’ temperatura ta ’ 5ºC Soluzzjoni għal infużjoni:
Chemical and physical in-use stability of the infusion solution has been demonstrated for 24 hours at 25ºC.
L- istabbilità kimika u fiżika effettiva tas- soluzzjoni għal infużjoni ġiet murija għal 24 siegħa f’ temperatura ta ’ 25ºC
If not used immediately, in-use storage times and conditions are the responsibility of the user.
Jekk ma jintużax immedjatament, iż- żminijiet u l- kondizzjonijiet effettivi ta ’ ħażna jkunu fir- responsabbiltà ta ’ l- utent.
10 6.4 Special precautions for storage
6. 4 Tagħrif speċjali dwar għall- ħażna
Do not store above 25ºC.
Trab u solvent Taħżinx f’ temperatura ’ l fuq minn 25ºC.
For storage conditions of the reconstituted medicinal product, see section 6.3.
Għal tagħrif dwar il- ħażna tal- prodott rikostitwit, ara sezzjoni 6. 3.
30 ml Type 1 glass vial with an elastomeric stopper and aluminium seal with flip-off cap.
Kunjett ta ’ 30 ml magħmul minn ħġieġ tat- Tip 1 bi stopper tal- lastku u siġill ta ’ l- aluminju b’ għatu flip- off.
30 ml of 20% (w/ w) ethanol anhydrous in water for injections in a Type 1 glass vial with an elastomeric stopper and aluminium seal with flip-off cap.
30 ml ta ’ 20% (w/ w) ethanol anhydrous f’ ilma għall- injezzjonijiet f’ kunjett tal- ħġieġ tat- Tip 1 b’ tapp tal- lastku u siġill ta ’ l- aluminju b’ għatu flip- off.
ECALTA will be available as a box containing 1 vial of 100 mg powder and 1 vial of 30 ml solvent.
ECALTA se jkun disponibbli bħala kaxxa li fiha kunjett ta ’ 100 mg trab u kunjett ta ’ 30 ml solvent.
ECALTA must be reconstituted with the solvent (20% (w/ w) ethanol anhydrous in water for injections) and subsequently diluted with ONLY 9 mg/ ml (0.9%) sodium chloride for infusion or 50 mg/ ml (5%) glucose for infusion.
ECALTA jrid jiġi rikostitwit bis- solvent (20% (w/ w) ethanol anhydrous f’ ilma għall- injezzjonijiet) u wara jiġi dilwit BISS b’ 9 mg/ ml (0. 9%) sodium chloride għal infużjoni jew 50 mg/ ml (5%) glukożju għal infużjoni.
The compatibility of reconstituted ECALTA with intravenous substances, additives, or medicines other than 9 mg/ ml (0.9%) sodium chloride for infusion or 50 mg/ ml (5%) glucose for infusion has not been established.
Il- kompatibilità ta ’ ECALTA rikostitwit ma ’ sustanzi, addittivi, jew mediċini għal ġol - vina għajr 9 mg/ ml (0. 9%) sodium chloride għal infużjoni jew 50 mg/ ml (5%) glukożju għal infużjoni ma ġietx stabbilita.
Reconstitution Aseptically reconstitute each vial with the solvent (20% (w/ w) ethanol anhydrous in water for injections) to provide a concentration of 3.33 mg/ ml.
Rikostituzzjoni Irrikostitwixxi b’ mod asettiku kull kunjett bis- solvent (20% (w/ w) ethanol anhydrous f’ ilma għall - injezzjonijiet) biex jipprovdi konċentrazzjoni ta ’ 3. 33 mg/ ml.
The reconstitution time can be up to 5 minutes.
Il- ħin tar- rikostituzzjoni jista ’ jieħu sa 5 minuti.
The reconstituted solution should be clear and free from visible particulates.
Is- soluzzjoni rikostitwita għandha tkun ċara u ħielsa minn frak viżibbli.
After subsequent dilution, the solution is to be discarded if particulate matter or discoloration is identified.
Wara dilwizzjoni suċċessiva, is- soluzzjoni għandha tintrema jekk jinstab frak jew tidnis tal- kulur.
The reconstituted solution must be further diluted within an hour and administered within 24 hours.
Is- soluzzjoni rikostitwita trid tiġi dilwita aktar fi żmien siegħa u mogħtija fi żmien 24 siegħa.
Dilution and infusion Aseptically transfer the contents of the reconstituted vial(s) into an intravenous bag (or bottle) containing either 9 mg/ ml (0.9%) sodium chloride for infusion or 50 mg/ ml (5%) glucose for infusion obtaining an anidulafungin concentration of 0.36 mg/ ml.
Dilwizzjoni u infużjoni Ittrasferixxi b’ mod asettiku l- kontenut tal- kunjett( i) rikostitwit( i) ġo borża (jew flixkun) għal ġol- vini li jkun fiha 9 mg/ ml (0. 9%) sodium chloride għal infużjoni jew 50 mg/ ml (5%) glukożju għal infużjoni biex tinkiseb konċentrazzjoni ta ’ anidulafungin ta ’ 0. 36 mg/ ml.
The table below provides the volumes required for each dose.
It- tabella ta ’ hawn isfel tipprovdi l - volumi meħtieġa għal kull doża.