qanastek/EMEA-V3 huggingface dataset:
Use in children (including neonates) and adolescents < 16 years of age
Użu fi tfal (li jinkludu trabi li għadhom jitwieldu) u f’ adoloxxenti ≤ 16- il sena
Treatment of invasive candidiasis Prophylaxis of Candida infection
Trattament ta ’ kandidjasi invażiva Profilassi ta ’ infezzjoni Candida
100 mg/ day* 50 mg/ day
100 mg/ kuljum * 50 mg/ kuljum
2 mg/ kg/ day* 1 mg/ kg/ day
2 mg/ kg/ kuljum * 1 mg/ kg/ kuljum
*If the patient’ s response is inadequate, e. g. persistence of cultures or if clinical condition does not improve, the dose may be increased to 200 mg/ day in patients weighing > 40 kg or 4 mg/ kg/ day in patients weighing ≤ 40 kg.
* Kemm- il darba r- rispons tal- pazjent ma jkunx adegwat, eż. persistenza tal- kulturi jew jekk il- kundizzjoni klinika ma titjiebx, id- doża tista ’ tiżdied għal 200 mg/ kuljum f’ pazjenti li jiżnu > 40 kg jew 4 mg/ kg/ kuljum f’ pazjenti li jiżnu ≤ 40 kg.
For prophylaxis of Candida infection, Mycamine should be administered for at least one week after neutrophil recovery.
Għall- profilassi ta ’ infezzjoni Candida, Mycamine għandu jingħata għal ta ’ lanqas ġimgħa wara l- irkupru tan- newtrofili.
Experience with Mycamine in patients less than 2 years of age is limited.
L- esperjenza b’ Mycamine fuq pazjenti li għandhom anqas minn sentejn hija limitata.
Gender/ Race No dose adjustment is necessary based on gender or race (see section 5.2).
Ġeneru/ Razza M’ hemmx bżonn ta ’ aġġustament fid- doża bbażat fuq is- sess jew ir- razza (ara sezzjoni 5. 2).
Use in patients with hepatic impairment No dose adjustment is necessary in patients with mild or moderate hepatic impairment (see section 5.2).
Użu f’ pazjenti b’ indeboliment epatiku M’ hemmx bżonn ta ’ aġġustament tad- doża f’ pazjenti b’ indeboliment epatiku ħafif jew moderat (ara sezzjoni 5. 2).
There are currently no data available for the use of Mycamine in patients with severe hepatic impairment and its use is not recommended in these patients (see section 4.4).
Attwalment m’ hemmx informazzjoni disponibbli dwar l- użu ta ’ Mycamine f’ pazjenti b’ indeboliment epatiku sever u l- użu tiegħu m’ huwiex rakkomandat f’ dawn il- pazjenti (ara sezzjoni 4. 4).
Use in patients with renal impairment No dose adjustment is necessary in patients with renal impairment (see section 5.2).
Użu f’ pazjenti b’ indeboliment renali M’ hemmx bżonn ta ’ aġġustament fid- doża għal pazjenti b’ indeboliment renali (ara sezzjoni 5. 2).
After reconstitution and dilution, the solution should be administered by intravenous infusion over approximately 1 hour.
3 Wara r- rikostituzzjoni u d- dilwazzjoni, is- soluzzjoni għandha tingħata permezz ta ’ infużjoni ġol- vini għal madwar siegħa.
More rapid infusions may result in more frequent histamine mediated reactions.
Infużjoniet aktar malajr jistgħu jirriżultaw f’ reazzjonijiet aktar spissi li jseħħu minħabba histamine.
For reconstitution instructions see section 6.6.
Għal struzzjonijiet dwar ir- rikostituzzjoni ara sezzjoni 6. 6
Hepatic effects:
Effetti epatiċi:
The development of foci of altered hepatocytes (FAH) and hepatocellular tumours after a treatment period of 3 months or longer were observed in rats.
L- iżvilup ta ’ foċi ta ’ epatoċiti mibdula (FAH) u tumuri epatoċellulari wara perijodu ta ’ trattament ta ’ 3 xhur jew aktar kienu osservati fil- firien.
The assumed threshold for tumour development in rats is approximately in the range of clinical exposure.
Il- linja ta ’ riferiment preżunta għall- iżvilupp ta ’ tumuri fil- firien hi madwar il- firxa ta ’ l- espożizzjoni klinika.
The relevance of this finding for the therapeutic use in patients can not be excluded.
Ir- rilevanza ta ’ dan ir- riżultat għal użu terapewtiku fuq pazjenti ma jistax jiġi eskluż.
Liver function should be carefully monitored during micafungin treatment.
Il- funzjoni tal - fwied għandha tiġi monitorata b’ attenzjoni waqt it- trattament b’ micafungin.
To minimise the risk of adaptive regeneration and potentially subsequent liver tumour formation, early discontinuation in the presence of significant and persistent elevation of ALT/ AST is recommended.
Sabiex jiġi mnaqqas ir- riskju ta ’ riġenerazzjoni adattabbli u l- formazzjoni sussegwenti ta ’ tumur tal- fwied, it- twaqqif bikri f’ każ ta ’ livelli għolja u persistenti ta ’ ALT/ AST hu rakkomandat.
Micafungin treatment should be conducted on a careful risk/ benefit basis, particularly in patients having severe liver function impairment or chronic liver diseases known to represent preneoplastic conditions, such as advanced liver fibrosis, cirrhosis, viral hepatitis, neonatal liver disease or congenital enzyme defects, or receiving a concomitant therapy including hepatotoxic and/ or genotoxic properties.
It- trattament b’ micafungin għandu jitwettaq b’ analiżi reqqa fuq bażi ta ’ riskju/ benefiċċju, b’ mod partikolari fuq pazjenti li għandhom indeboliment sever fil- funzjoni tal- fwied jew mard kroniku tal- fwied li hu magħruf li jirrapreżenta kondizzjonijiet preneoplastiċi, bħal fibrożi avvanzata fil- fwied, ċirrosi, epatite virali, mard tal- fwied ta ’ trabi li għadhom jitwieldu jew difetti konġenitali ta ’ l- enzimi, jew li qed jirċievu terapiji konkomitanti li jinkludu karatteristiċi epatotossiċi u/ jew ġenotossiċi.
Micafungin treatment was associated with significant impairment of liver function (increase of ALT, AST or total bilirubin > 3 times ULN) in both healthy volunteers and patients.
It- trattament b’ micafungin kien assoċjat b’ indeboliment sinifikanti tal- funzjoni tal- fwied (żieda fl - ALT, AST jew bilirubin totali > 3 darbiet ULN) kemm f’ voluntieri b’ saħħithom u pazjenti.
In some patients more severe hepatic dysfunction, hepatitis, or hepatic failure including fatal cases have been reported.
F’ xi pazjenti problemi aktar severi fil- funzjoni epatika, epatite, jew insuffiċjenza epatika li jinkludu każijiet fatali li ġew irrapportati.
Paediatric patients < 1 year of age might be more prone to liver injury (see section 4.8).
Pazjenti pedjatriċi < 1 sena jafu jkunu suxxettibbli għal aktar ħsara fil- fwied (ara sezzjoni 4. 8).
There are insufficient data on the pharmacokinetics of micafungin in patients with severe hepatic impairment (see section 5.2).
M’ hemmx tagħrif biżżejjed dwar il- farmakokinetika ta ’ micafungin f’ pazjenti li għandhom indeboliment epatiku sever (ara sezzjoni 5. 2).
During administration of micafungin, anaphylactoid reactions including shock may occur.
Waqt l- amministrazzjoni ta ’ micafungin, jista ’ jkun hemm reazzjonijiet anafilattojdi li jistgħu jinkludu xokk.
If these reactions occur, micafungin infusion should be discontinued and appropriate treatment administered.
Jekk iseħħu reazzjonijiet bħal dawn, l- infużjoni ta ’ micafungin għandha titwaqqaf u għandu jingħata trattament xieraq.
Rare cases of haemolysis including acute intravascular haemolysis or haemolytic anaemia have been reported in patients treated with micafungin.
Każijiet rari ta ’ emolisi li jinkludu emolisi intravaskulari jew anemija emolitika ġew rapportati f’ pazjenti ttrattati b’ micafungin.
Patients who develop clinical or laboratory evidence of haemolysis during micafungin therapy should be monitored closely for evidence of worsening of these conditions and evaluated for the risk/ benefit of continuing micafungin therapy.
Pazjenti li jiżviluppaw evidenza klinika jew tal- laboratorju ta ’ emolisi waqt it- terapija b’ micafungin għandhom jiġi sorveljati mill- qrib jekk dawn il- kundizzjonijiet imorru għall- agħar u dawn għandhom jiġu evalwati biex jiġi stabbilit ir- riskju/ siwi dwar jekk it- terapija għandhiex titkompla.
Micafungin may cause kidney problems, renal failure, and abnormal renal function test.
Micafungin jista ’ jikkaġuna problemi fil- kliewi, insuffiċjenza renali u riżultati anormali fil- funzjoni renali.
Patients should be closely monitored for worsening of renal function.
Il- pazjenti għandhom jiġu mmonitorati mill- qrib għal aggravar tal- funzjoni renali.
The incidence of some adverse reactions was higher in paediatric patients than in adult patients (see section 4.8).
L- inċidenza ta ’ xi reazzjonijiet avversi kienu ogħla f’ pazjenti pedjatriċi milli f’ pazjenti adulti (ara sezzjoni 4. 8).
This medicinal product for intravenous use contains lactose.
Dan il- prodott mediċinali li jittieħed minn ġol- vina fih lactose.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Pazjenti li għandhom problemi ereditarji rari ta ’ intolleranza għal galactose, defiċjenza ta ’ Lapp lactase jew assorbiment ħażin ta ’ glucose- galactose m’ għandhomx jieħdu din il- mediċina.
Micafungin has a low potential for interactions with medicines metabolised via CYP3A mediated pathways.
4 Micafungin għandu potenzjal baxx ta ’ interazzjoni ma ’ mediċini metabolizzati permezz ta ’ proċessi medjati minn CYP3A.
Drug interaction studies in healthy human subjects were conducted to evaluate the potential for interaction between micafungin and mycophenolate mofetil, ciclosporin, tacrolimus, prednisolone, sirolimus, nifedipine, fluconazole, ritonavir, rifampicin, itraconazole, voriconazole and amphotericin B.
Saru studji ta ’ l- interazzjoni ma ’ mediċini oħra f’ individwi b’ saħħithom biex jiġi evalwat il- potenzjal ta ’ interazzjoni bejn micafungin u mycophenolate mofetil, ciclosporin, tacrolimus, prednisolone, sirolimus, nifedipine, fluconazole, ritonavir, rifampicin, itraconazole, voriconazole u amphotericin B.
In these studies, no evidence of altered pharmacokinetics of micafungin was observed.
F’ dawn l- istudji, ma kienet osservata l- ebda evidenza ta ’ tibdil fil- farmakokinetika ta ’ micafungin.
No micafungin dose adjustments are necessary when these medicines are administered concomitantly.
M’ hemmx bżonn ta ’ aġġustamenti fid- doża ta ’ micafungin meta dawn il- mediċini jingħataw flimkien.
4 Exposure (AUC) of itraconazole, sirolimus and nifedipine was slightly increased in the presence of micafungin (22%, 21% and 18% respectively).
L- esponiment (AUC) ta ’ itraconazole, sirolimus u nifedipine żdied kemmxejn fil- preżenza ta ’ micafungin (22%, 21% u 18% rispettivament).
Patients receiving sirolimus, nifedipine or itraconazole in combination with Mycamine should be monitored for sirolimus, nifedipine or itraconazole toxicity and the sirolimus, nifedipine or itraconazole dosage should be reduced if necessary.
Pazjenti li jirċievu sirolimus, nifedipine jew itraconazole flimkien ma ’ Mycamine għandhom jiġu mmonitorjati għal tossiċità minn sirolimus, nifedipine jew itraconazole u d- doża ta ’ sirolimus, nifedipine jew itraconazole għandha titnaqqas jekk ikun meħtieġ.
There are no data from the use of micafungin in pregnant women.
M’ hemmx tagħrif biżżejjed dwar l- użu ta ’ micafungin waqt it- tqala.
In animal studies micafungin crossed the placental barrier and reproductive toxicity was seen (see section 5.3).
Fi studji fuq bhejjem micafungin qasam is- sekonda u dehret anke ħsara fis- sistema riproduttiva (ara sezzjoni 5. 3).
The potential risk for humans is unknown.
Mhux magħruf ir - riskju potenzjali fuq il- bniedem.
Mycamine should not be used during pregnancy unless clearly necessary.
Mycamine m’ għandux jintuża waqt it- tqala jekk m’ hemmx bżonn ċar.
It is not known whether micafungin is excreted in human breast milk.
Mhux magħruf jekk micafungin jiġix eliminat fil- ħalib ta ’ l- omm.
Animal studies have shown excretion of micafungin in breast milk.
Studji fuq l- annimali wrew li micanfungin jiġi eliminat fil- ħalib.
A decision on whether to continue/ discontinue breast-feeding or to continue/ discontinue therapy with Mycamine should be made taking into account the benefit of breast-feeding to the child and the benefit of Mycamine therapy to the mother.
Deċiżjoni dwar jekk wieħed għandux ikompli/ iwaqqafx it- treddigħ jew ikompli/ iwaqqafx it- terapija b’ Mycamine għandha tittieħed billi wieħed iqis is- siwi tat- treddigħ lill- wild u s- siwi ta ’ terapija ta ’ Mycamine lill- omm.
Testicular toxicity was observed in animal studies (see section 5.3).
Tossiċità testikulari kienet osservata fi studju fuq l- annimali (ara sezzjoni 5. 3).
Micafungin may have the potential to affect male fertility in humans.
Micafungin għandu mnejn li jista ’ jaffetwa l- fertilità ta ’ l- irġiel.
However, adverse reactions may occur, which may influence the ability to drive and use machines (see section 4.8).
Madankollu jistgħu jseħħu reazzjonijiet avversi, li jistgħu jinfluwenzaw il- ħila tas- sewqan jew ta ’ tħaddim ta ’ magni (ara sezzjoni 4. 8).
The safety profile of micafungin is based on 3028 patients treated with micafungin in clinical studies:
Il- profil tas- sigurtà ta ’ micafungin huwa bbażat fuq 3028 pazjent trattati b’ micafungin fi studji kliniċi:
2.002 patients with Candida infections (including candidaemia, invasive candidiasis and oesophageal candidiasis), 375 with invasive aspergillosis (primarily refractory infections) and 651 for prophylaxis of systemic fungal infections.
2002 pazjenti b’ infezzjonijiet Candida (fosthom kandidemija, kandidjasi invażiva u kandidjasi esofagali), 375 pazjent b’ asperġillosi invażiva (prinċipalment infezzjonijiet refrattorji) u 651 pazjent għal profilassi ta ’ infezzjonijiet fungali sistemiċi.
The patients treated with micafungin in clinical studies represent a critically ill patient population that requires multiple medicinal products including antineoplastic chemotherapy, potent systemic immunosuppressants and broad spectrum antibiotics.
Il- pazjenti trattati b’ micafungin fl- istudji kliniċi jirrappreżentaw popolazzjoni marida serjament ta ’ pazjenti li teħtieġ diversi prodotti mediċinali li jinkludu kimoterapija antineoplastika, immunosoppressanti sistemiċi qawwija u antibijotiċi ta ’ spettru wiesa ’.
These patients had a wide variety of complex underlying conditions such as haematological malignancies and HIV-infection or were transplant recipients and/ or treated in intensive care.
Dawn il- pazjenti kellhom varjetà wiesgħa ta ’ kundizzjonijiet bażiċi kumplessi bħal tumuri malinni ematoloġiċi u infezzjonijiet ta ’ l- HIV jew kienu reċipjenti ta ’ trapjanti u/ jew trattati fil- kura intensiva.
Patients treated prophylactically with micafungin were those undergoing haematopoetic stem cell transplantation (HSCT) who were at high risk for fungal infections.
Il- pazjenti trattati b’ mod profilattiku b’ micafungin kienu dawk sottoposti għal trapjant ta ’ ċelluli stem ematopojetiċi (HSCT) li kienu f’ riskju għoli ta ’ infezzjonijiet fungali.
Overall 32.2% of the patients experienced adverse drug reactions.
B’ mod globali, 32. 2% tal- pazjenti esperjenzaw reazzjonijiet avversi tal- mediċina.
The most frequently reported adverse reactions were nausea (2.8%), blood alkaline phosphatase increased (2.7%), phlebitis (2.5%, primarily in HIV infected patients with peripheral lines), vomiting (2.5%), and aspartate aminotransferase increased (2.3%).
L- aktar reazzjonijiet avversi rrappurtati b’ mod frekwenti kienu dardir (2. 8%), żieda fl- alkaline phosphatase fid- demm (2. 7%), flebite (2. 5%, l- aktar f’ pazjenti infettati bl- HIV b’ linji periferali), rimettar (2. 5%), u żieda fl - aspartate aminotransferase (2. 3%).
No clinically significant differences were seen when the safety data were analysed by gender or race.
Ma dehru l- ebda differenzi kliniċi sinifikanti meta d- dejta tas - sigurtà ġiet analizzata skond is- sess jew ir- razza.
In the following table adverse reactions are listed by system organ class and MedDRA preferred term.
5 Fit- tabella li ġejja, ir- reazzjonijiet avversi huma elenkati skond is- sistema tal- klassifika ta ’ l- organi u t - terminu preferut MedDRA.
Not known
Mhux
Class
tal- Klassifika ta ’ l -
≥ 1/ 100 to < 1/ 10
≥ 1/ 100 sa < 1/ 10
≥ 1/ 1,000 to < 1/ 100
≥ 1/ 1, 000 sa < 1/ 100
≥
magħruf
1/10,000 to < 1/1,000
Organi
(frequency cannot be
< 1/ 1, 000
estimated from available data)
(frekwenza ma tistax tiġi stmata mit - tagħrif disponibbli)
5 System Organ
Disturbi tad -
Common
lewkopenja,
Uncommon
panċitopenija,
Not known
demm u tas -
≥ 1/100 to < 1/10
newtropenja, anemija
≥ 1/1,000 to < 1/100
tromboċitopenija,
≥
emolitika,
1/10,000 to < 1/1,000
sistema limfatika
(frequency cannot be
esinofilja,
leukopenia, neutropenia, anaemia
emolisi (ara
pancytopenia, thrombocytopenia, eosinophilia, hypoalbuminaemia
Disturbi fis- sistema immuni Disturbi fis- sistema endokrinarja
haemolytic anaemia, haemolysis (see section 4.4)
ipoalbuminemija reazzjoni anafilattika / anafilattojdi (ara sezzjoni 4. 4), sensittività eċċessiva iperidrosi
anaphylactic / anaphylactoid reaction (see section 4.4), hypersensitivity
sezzjoni 4. 4)
Endocrine disorders
Disturbi fil -
hyperhidrosis
ipokalemija,
Metabolism and nutritional disorders
iponatremija,
hypokalaemia, hypomagnesaemia, hypocalcaemia
metaboliżmu u n -
Psychiatric disorders
ipomagnesimja,
insomnia, anxiety, confusion
iperkalemija,
Nervous system disorders Cardiac disorders
nutrizzjoni Disturbi psikjatriċi
headache
ipokalċimja
somnolence, tremor, dizziness, dysgeusia tachycardia, palpitations, bradycardia
ipofosfatemija, anoreksja nuqqas ta ’ irqad, ansjetà, konfużjoni
Vascular disorders
Disturbi fis- sistema nervuża Disturbi fil- qalb
phlebitis
uġigħ ta ’ ras
hypotension, hypertension, flushing
ngħas, rogħda, sturdament, disgewżja takikardja, palpitazzjonijiet, bradikardja
Respiratory, thoracic and mediastinal disorders
Disturbi vaskulari Disturbi respiratorji, toraċiċi u medjastinali
dyspnoea
flebite
nausea, vomiting, diarrhoea, abdominal pain
pressjoni baxxa, pressjoni għolja, fwawar dispnea
dyspepsia, constipation
xokk
Hepatobiliary disorders
Disturbi gastro - intestinali
Skin and subcutaneous tissue disorders
dardir, rimettar, dijarea, uġigħ addominali
urticaria, pruritus, erythema
dispepsja, stitikezza
6 System Organ
6 Sistema
≥ 1/100 to < 1/10
≥ 1/ 100 sa < 1/ 10
≥ 1/1,000 to < 1/100
≥ 1/ 1, 000 sa < 1/ 100
≥
Organi
1/10,000 to < 1/1,000
< 1/ 1, 000
(frequency cannot be
li tinkludi każijiet fatali (ara sezzjoni 4. 4)
estimated from available data) Renal and urinary disorders
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
blood creatinine increased, blood urea increased, renal failure aggravated
urea tad- demm,
renal impairment (see section 4.4), acute renal failure
sezzjoni 4. 4).
General disorders and administration site conditions
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata Investigazzjonijiet
pyrexia, rigors
deni, tertir
injection site thrombosis, infusion site inflammation, injection site pain, peripheral oedema
insuffiċjenza renali aggravata trombożi fil- post ta ’ l- injezzjoni, infjammazzjoni fil - post ta ’ l- infużjoni, uġigħ fil- post ta ’ l - injezzjoni, edema periferali żieda ta ’ lactate dehydrogenase fid - demm
Investigations
falliment renali akut
blood lactate dehydrogenase increased
Sintomi possibbli jixbћu
Possible allergic-like symptoms Symptoms such as rash and rigors have been reported in clinical studies.
Sintomi bħal raxx u tertir ġew irrappurtati fi studji kliniċi.
The majority were of mild to moderate intensity and not treatment limiting.
Il- maġġoranza kienu ta ’ intensità ħafifa għal moderata u ma llimitawx it- trattament.
Serious reactions (e.g. anaphylactoid reaction 0.2%, 6/3028) were uncommonly reported during therapy with micafungin and only in patients with serious underlying conditions (e.g. advanced AIDS, malignancies) requiring multiple co-medications.
AIDS avvanzata, tumuri malinni) li kienu jeħtieġu diversi medikazzjonijiet f’ daqqa.
Hepatic adverse reactions The overall incidence of hepatic adverse reactions in the patients treated with micafungin in clinical studies was 8.6% (260/3028).
Reazzjonijiet epatiċi avversi L- inċidenza globali tar- reazzjonijiet epatiċi avversi fl- istudji kliniċi b’ micafungin kienet ta ’ 8. 6% (260/ 3028) tal- pazjenti ttrattati b’ micafungin.
The majority of hepatic adverse reactions were mild and moderate.
Il- maġġoranza tar- reazzjonijiet epatiċi avversi kienu ħfief u moderati.
Most frequent reactions were increase in AP (2.7%), AST (2.3%), ALT (2.0%), blood bilirubin (1.6%) and liver function test abnormal (1.5%).
L- aktar reazzjonijiet frekwenti kienu żieda fl- AP (2. 7%), AST (2. 3%), ALT (2. 0%), bilirubina fid- demm (1. 6%) u riżultat tat- test tal- funzjoni tal- fwied anormali (1. 5%).
Few patients (1.1%; 0.4% serious) discontinued treatment due to a hepatic event.
Għadd żgħir ta ’ pazjenti (1. 1%; 0. 4% serji) waqqfu t- trattament minħabba każ epatiku.
Cases of serious hepatic dysfunction occurred uncommonly (see section 4.4).
Każijiet ta ’ disfunzjoni epatika serja seħħew b’ mod mhux komuni (ara sezzjoni 4. 4).
Injection-site reactions None of the injection-site adverse reactions were treatment limiting.
Reazzjonijiet fil- post ta ’ l- injezzjoni L- ebda waħda mir- reazzjonijiet avversi fil- post ta ’ l- injezzjoni ma llimitat it- trattament.
Paediatric patients The incidence of some adverse reactions (listed in the table below) was higher in paediatric patients than in adult patients.
7 Pazjenti pedjatriċi L- inċidenza ta ’ xi reazzjonijiet avversi (elenkati fit- tabella hawn isfel) kienu ogħla f’ pazjenti tfal milli f’ pazjenti adulti.
Additionally, paediatric patients < 1 year of age experienced about two times more often an increase in ALT, AST and AP than older paediatric patients (see section 4.4).
Barraminhekk, pazjenti pedjatriċi < 1 sena esperjenzaw bi frekwenza ta ’ darbtejn aktar ta ’ spiss żieda fl- ALT, AST u AP minn pazjenti pedjatriċi akbar (ara sezzjoni 4. 4).
The most likely reason for these differences were different underlying conditions compared with adults or older paediatric patients observed in clinical studies.
Ir- raġuni l - aktar plawsibbli għal din id- differenza kienet id- differenza fil- kundizzjonijiet fl- isfond meta mqabbla ma ’ adulti jew pazjenti pedjatriċi akbar osservati fi studji kliniċi.
At the time of entering the study, the proportion of paediatric patients with neutropenia was several-fold higher than in adult patients (40.2% and 7.3% of children and adults, respectively), as well as allogeneic HSCT (29.4% and 13.4%, respectively) and haematological malignancy (29.1% and 8.7%, respectively).
Fiż- żmien li daħlu fl- istudju, il- proporzjon ta ’ pazjenti pedjatriċi b’ newtropenja kien diversi drabi ogħla minn ta ’ pazjenti adulti (40. 2% u 7. 3% ta ’ tfal u adulti, rispettivament), kif ukoll HSCT alloġenika (29. 4% u 13. 4%, rispettivament) u mallinità ematoloġika (29. 1% u 8. 7% rispettivament).
Blood and lymphatic system disorders common
Disturbi tad- demm u tas- sistema limfatika komuni
thrombocytopenia
tromboċitopenija
tachycardia
takikardja
Vascular disorders common
Disturbi vaskulari komuni
hypertension, hypotension
pressjoni għolja, pressjoni baxxa
hyperbilirubinaemia, hepatomegaly
iperbilirubinemija, epatomegali
7 Renal and urinary disorders common
Disturbi fil- kliewi u fis- sistema urinarja komuni
acute renal failure, blood urea increased
insuffiċjenza renali akuta, żieda fl- urea fid- demm
Repeated daily doses up to 8 mg/kg (maximum total dose 896 mg) in adult patients have been administered in clinical trials with no reported dose-limiting toxicity.
Dożi ta ’ kuljum ripetuti sa 8 mg/ kg (doża totali massima 896 mg) f’ pazjenti adulti ġew mogħtija fi provi kliniċi mingħajr ebda tossiċità rrappurtata li tillimita d- doża.
One case of mis-dosage of 7.8 mg/kg/day for 7 days was reported in a newborn patient.
Kien irrappurtat każ wieħed ta ’ dożaġġ ħażin ta ’ 7. 8 mg/ kg/ kuljum għal 7 ijiem f’ pazjent li kien għadu kif jitwieled.
No adverse reactions associated with this high dose were noted.
Ma kienu nnotati l- ebda reazzjonijiet avversi assoċjati ma ’ din id- doża għolja.
There is no experience with overdoses of micafungin.
M’ hemm ebda esperjenza dwar doża eċċessiva b’ micafungin.
In case of overdose, general supportive measures and symptomatic treatment should be administered.
F’ każ ta ’ doża eċċessiva, għandhom jiġu pprovduti miżuri t’ appoġġ ġenerali.
Micafungin is highly protein-bound and not dialysable.
Micafungin jeħel ħafna mal- proteini tad- demm u ma jitneħħiex b’ dijalisi.
Other antimycotics for systemic use, ATC code:
Antimikotiċi oħra għal użu sistemiku, Kodiċi ATC:
Mode of action Micafungin non-competitively inhibits the synthesis of 1,3-β-D-glucan, an essential component of the fungal cell wall.
Kif jaħdem Micafungin jinibixxi b’ mod mhux kompetittiv is- sintesi ta ’ 1, 3- β- D- glucan, komponent essenzjali tar - riti ċellulari fungali.
1,3-β-D-glucan is not present in mammalian cells.
1, 3- β- D- glucan m’ huwiex preżenti fiċ- ċelloli mammiferi.
Micafungin exhibits fungicidal activity against most Candida species and prominently inhibits actively growing hyphae of Aspergillus species.
Micafungin juri attività fungiċida kontra l- maġġoranza ta ’ l- ispeċi Candida u jimpedixxi b’ mod prominenti t- tkabbir attiv ta ’ hyphae ta ’ l- ispeċi Aspergillus.
PK/PD relationship An additive or synergistic pharmacodynamic interaction of micafungin and amphotericin B was found in a mouse model of pulmonary aspergillosis (immunosuppression with hydrocortisone, intranasal infection with Aspergillus fumigatus).
Relazzjoni PK/ PD Instabet interazzjoni farmakodinamika addittiva jew sinerġistika ta ’ micafungin u amphotericin B f’ mudell tal- ġurdien ta ’ asperġillosi pulmonari (immunosoppressjoni b’ hydrocortisone, infezzjoni ġo l- imnieħer bl- Aspergillus fumigatus).
Mechanism(s) of resistance As for all antimicrobial agents, cases of reduced susceptibility and resistance have been reported and cross-resistance with other echinocandins cannot be excluded.
8 Għall- aġenti kollha ta ’ kontra l- mikrobi, ġew irrapportati każijiet ta ’ suxxetibilità mnaqqsa u każijiet ta ’ reżistenza inkroċjata ma ’ echinocandins oħrajn ma jistgħux jiġu esklużi.
Reduced susceptibility to echinocandins has been associated with mutations in the Fks1 gene coding for a major subunit of glucan synthase.
Suxxetibilità mnaqqsa għal echinocandins ġiet assoċjata ma ’ mutazzjonijiet fil- kodiċi tal- ġene FKs1 għal sottounità maġġuri ta ’ glucan synthase.
Breakpoints Susceptibility testing was performed with modifications according to the Clinical and Laboratory Standards Institute (CLSI) methods M27-A2 (Candida species) and M38-A (Aspergillus species), respectively.
Punti ta ’ riferiment L- ittestjar tas- suxxettibilità sar b’ modifikazzjonijiet skond il- metodi M27- A2 (speċi Candida) u M38 - A (speċi Aspergillus), rispettivament, ta ’ l- Istitut għall- Istandards Kliniċi u tal- Laboratorju (CLSI).
To date, standardised techniques for susceptibility testing for 1,3-β-D-glucan synthesis inhibitors have not been established and results of susceptibility testing do not necessarily correlate with clinical outcome.
Sal- lum, ma ġewx stabbiliti tekniki standardizzati għall- ittestjar tas- suxxettibilità għall- inibituri tas - sintesi ta ’ 1, 3- β- D- glucan u r- riżultati ta ’ l- ittestjar tas- suxxettibilità mhux neċessarjament jikkorrelataw ma ’ l- eżitu kliniku.
Although no MIC breakpoints for echinocandins have been established, a MIC of < 2 mg/l encompasses > 99% of all clinical isolates of Candida spp. without bisecting any species group and represents a concentration that is easily maintained throughout the dosing interval.
Għalkemm ma ġie stabbilit l- ebda punt ta ’ riferiment għal echinocandins, MIC ta ’ < 2 mg/ l ikopri > 99% tar- razez kliniċi kollha ta ’ Candida spp. mingħajr tifriq ta ’ speċijiet oħrajn u jirrappreżenta konċentrazzjoni li hija faċilment mantnuta matul l- intervall kollu tad- dożaġġ.
Infections due to Candida spp. in this MIC range are likely to respond to therapy.
Infezzjonijiet dovuti għal Candida spp. f’ din il- firxa x’ aktarx jirrispondu għat- terapija.
The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections.
Il- prevalenza ta ’ reżistenza għandha mnejn tvarja ġeografikament u biż- żmien għal speċijiet selettivi u tagħrif lokali dwar ir- reżistenza huwa mixtieq, b’ mod partikolari meta jiġu trattati infezzjonijiet severi.
This information is only a guide to the probabilities of whether micro-organisms will be susceptible to micafungin or not.
Dan it- tagħrif huwa biss gwida għall- probabiltajiet ta ’ jekk mikro- organiżmi ikunux suxxetibbli għal micafungin jew le.
Where applicable the information on the European range of acquired resistance for the individual micro-organisms is indicated in brackets.
Meta applikabbli, it- tagħrif dwar il- firxa Ewropeja ta ’ reżistenza miksuba għal mikro- organiżmi individwali hija indikata fil- parentesi.
8 Candida albicans [0.007 - 0.25] Candida glabrata [0.007 - 0.12] Candida tropicalis [0.007 - 0.12] Candida krusei [0.015 - 0.12] Candida kefyr [0.03 - 0.06] Candida parapsilosis [0.12 - 2] Candida guilliermondii [0.5] Candida lusitaniae [0.12 - 0.25] Candida spp.
Speċijiet komunement suxxettibbli [Firxiet MIC fl- Ewropa, mcg/ ml] Candida albicans [0. 007- 0. 25] Candida glabrata [0. 007- 0. 12] Candida tropicalis [0. 007- 0. 12] Candida krusei [0. 015- 0. 12] Candida kefyr [0. 03- 0. 06] Candida parapsilosis [0. 12- 2] Candida guilliermondii [0. 5] Candida lusitaniae [0. 12- 0. 25] Candida spp.
C. famata, C. dubliniensis, C. lipolytica, C. pelliculosa, C. rugosa, C. stellatoidea and C. zeylanoides)
[0. 015- 0. 5] (li jinkludu C. famata, C. dubliniensis, C. lipolytica, C. pelliculosa, C. rugosa, C. stellatoidea u C. zeylanoides)
The mycelial form of dimorphic fungi (e.g.
L- għamla miċelja ta ’ fungi dimorfiku (e. g.
Species for which acquired resistance may be a problem None
Speċijiet li għalihom ir- reżistenza miksuba taf tkun problema Xejn
Inherently resistant organisms Cryptococcus spp.
Organiżmi reżistenti b’ mod inerenti Cryptococcus spp.
Information from clinical studies Candidaemia and Invasive Candidiasis:
9 Tagħrif minn studji kliniċi Kandidemija u Kandidjasi invażiva:
Micafungin (100 mg/day or 2 mg/kg/day) was as effective as and better tolerated than liposomal amphotericin B (3 mg/kg) as first-line treatment of candidaemia and invasive candidiasis in a randomised, double-blind, multinational non-inferiority study.
Micafungin (100 mg/ kuljum jew 2 mg/ kg/ kuljum) kien effettiv daqs u tollerat aħjar minn amphotericin B liposomali (3 mg/ kg) bħala l- ewwel trattament ta ’ preferenza ta ’ kandidemija u kandidjasi invażiva fi studju ta ’ nuqqas ta ’ inferjorità multinazzjonali, double- blind u randomised.
Micafungin and liposomal amphotericin B were received for a median duration of 15 days (range, 4 to 42 days in adults; 12 to 42 days in children).
4 sa 42 jum f’ adulti; 12 sa 42 jum fi tfal).
Non-inferiority was proven for adult patients, and similar findings were demonstrated for the paediatric subpopulations (including neonates and premature infants).
In- nuqqas ta ’ inferjorità ġiet ipprovata għal pazjenti adulti, u ntwerew riżultati simili għas- sotto- popolazzjonijiet pedjatriċi (li jinkludu trabi li għadhom jitwieldu u trabi li twieldu qabel iż - żmien).
Efficacy findings were consistent, independent of the infective Candida species, primary site of infection and neutropenic status (see Table).
Ir- riżultati dwar l- effikaċja kienu konsistenti, indipendentement mill- ispeċijiet ta ’ Candida infettiva, is- sit prinċipali ta ’ infezzjoni u stat newtropeniku (ara Tabella).
Micafungin demonstrated a smaller mean peak decrease in estimated glomerular filtration rate during treatment (p < 0.001) and a lower incidence of infusion-related reactions (p=0.001) than liposomal amphotericin B.
Micafungin wera tnaqqis massimu medju iżgħar fir- rata stmata ta ’ filtrazzjoni glomerulari waqt it- trattament (p < 0. 001) u inċidenza aktar baxxa ta ’ reazzjonijiet relatati ma ’ l- infużjoni (p=0. 001) mill- amphotericin B liposomali.
Overall Treatment Success in the Per Protocol Set, Invasive Candidiasis Study
Suċċess Globali tat- Trattament fis- Sett Skond il- Protokoll, Studju dwar il- Kandidjasi Invażiva
Micafungin
Pazjenti Adulti
Amphotericin B
Amphotericin B Liposomali N n (%)
Adult Patie nts
% Differenza [95% CI]
Overall Treatment Success
Suċċess Globali tat- Trattament
202
202 181 (89. 6)
181 (89.6) 190
190 170 (89. 5)
170 (89.5) 0.1 [-5.9, 6.1] †
0. 1 [- 5. 9, 6. 1] †
Overall Treatment Success by Neutropenic Status
Suċċess Globali tat- Trattament skond l- Istat Newtropeniku
Neutropenia at baseline
Newtropenja fil- linja bażi
18 (75.0)
18 (75. 0)
12 (80.0)
12 (80. 0)
0.7 [-5.3, 6.7] ‡
0. 7 [- 5. 3, 6. 7] ‡
No neutropenia at baseline
Ebda newtropenja fil- linja bażi
178
178 163 (91. 6)
158 (90.3)
158 (90. 3)
Paediatric Patients
Pazjenti Pedjatriċi
Overall Treatment Success < 2 years old Premature Infants Neonates (0 days to < 4 weeks)
< 2 sentejn
35 (72.9) 21 (80.8) 7 (70.0) 7 (100)
21 (80. 8)
38 (76.0) 24 (77.4) 6 (66.7) 4 (80)
24 (77. 4) 6 (66. 7)
-2.7 [-17.3, 11.9] §
Trabi prematuri
2 to 15 years old
2 sa 15- il sena
14 (63.6)
14 (63. 6)
14 (73.7)
14 (73. 7)
Adults and Children Combined, Overall Treatment Success by Candida Species
Adulti u Tfal Ikkombinati, Suċċess Globali tat- Trattament bl- Ispeċi ta ’ Candida
102 151 59 48 23 9
151 133 (88. 1) 140
91 (89.2) 133 (88.1) 54 (91.5) 41 (85.4) 19 (82.6) 8 (88.9)
48 41 (85. 4) 23 19 (82. 6) 9 8 (88. 9)
89 (90.8) 123 (87.9) 49 (96.1) 35 (79.5) 14 (82.4) 6 (85.7)
35 (79. 5) 14 (82. 4) 6 (85. 7)
† Micafungin rate minus the liposomal amphotericin B rate, and 2-sided 95% confidence interval for the difference in overall success rate based on large sample normal approximation. ‡ Adjusted for neutropenic status; primary endpoint. § The paediatric population was not sized to test for non-inferiority. ¶ Clinical efficacy was also observed (< 5 patients) in the following Candida species:
† Ir- rata ta ’ micafungin tnaqqas minnha r- rata ta ’ amphotericin B liposomali, u intervall ta ’ kunfidenza ta ’ 95% b’ żewġ naħat għad- differenza fir- rata globali ta ’ suċċess ibbażata fuq approssimazzjoni normali ta ’ kampjun kbir. ‡ Aġġustata għall- istat newtropeniku; punt finali primarju. § Il- popolazzjoni pedjatrika ma tkejlitx biex tkun ittestjata n- non- inferjorità. ¶ L- effikaċja klinika ġiet osservata wkoll (< 5 pazjenti) fl- ispeċijiet ta ’ Candida li ġejjin:
C. guilliermondii, C. famata, C. lusitaniae, C. utilis, C. inconspicua and C. dubliniensis.
C. guilliermondii, C. famata, C. lusitaniae, C. utilis, C. inconspicua u C. dubliniensis.
Oesophageal Candidiasis:
Kandidjasi esofagali:
In a randomised, double-blind study of micafungin versus fluconazole in the first-line treatment of oesophageal candidiasis, 518 patients received at least a single dose of study drug.
Fi studju randomised u double- blind ta ’ micafungin kontra fluconazole bħala l - ewwel trattament preferenzjali ta ’ kandidjasi esofagali, 518- il pazjent irċevew mill- anqas doża waħda tal- mediċina studjata.
The median treatment duration was 14 days and the median average daily dose was 150 mg for micafungin (N=260) and 200 mg for fluconazole (N=258).
It- tul medjan tat- trattament kien ta ’ 14- il jum u d- doża medja medjana ta ’ kuljum kienet ta ’ 150 mg għal micafungin (N=260) u 200 mg għal fluconazole (N=258).
An endoscopic grade of 0 (endoscopic cure) at the end of treatment was observed for 87.7% (228/260) and 88.0% (227/258) of patients in the micafungin and fluconazole groups, respectively (95% CI for difference:
Grad endoskopu ta ’ 0 (kura endoskopika) fi tmiem it- trattament ġie osservat għal 87. 7% (228/ 260) u 88. 0% (227/ 258) ta ’ pazjenti fil- gruppi ta ’ micafungin u fluconazole, rispettivament (95% CI għal differenza:
The lower limit of the 95% CI was above the predefined non-inferiority margin of -10%, proving non-inferiority.
[- 5. 9%, 5. 3%]) Il- limitu ta ’ isfel ta ’ 95% CI kien ogħla mill- marġni ta ’ nuqqas ta ’ inferjorità mfissra qabel ta ’ - 10% u gћalhekk ġie approvat nuqqas ta ’ inferjorità.
The nature and incidence of adverse events were similar between treatment groups.
In- natura u l- inċidenza ta ’ reazzjonijiet avversi kienu simili bejn il- gruppi ta ’ trattament.
Prophylaxis:
10 Profilassi:
Micafungin was more effective than fluconazole in preventing invasive fungal infections in a population of patients at high risk of developing a systemic fungal infection (patients undergoing haematopoietic stem cell transplantation [HSCT] in a randomised, double-blind, multicentre study).
Micafungin kien aktar effettiv minn fluconazole sabiex jipprevjeni infezzjonijiet fungali invażivi f’ popolazzjoni ta ’ pazjenti li jinsabu f’ riskju għoli li jiżviluppaw infezzjoni fungali sistemiċi (pazjenti li jkunu ser jagħmlu trapjant ta ’ celluli stem ematopojetiċi (HSCT) fi studju randomised multi- ċentrali u double- blind).
Treatment success was defined as the absence of a proven, probable, or suspected systemic fungal infection through the end of therapy and absence of a proven or probable systemic fungal infection through the end of study.
Is- suċċess tat- trattament kien definit bħala n- nuqqas ta ’ infezzjoni fungali sistemika ppruvata, probabbli, jew suspettata fit- tmiem tat- terapija u n- nuqqas ta ’ infezzjoni fungali sistemika ppruvata jew probabbli fit- tmiem ta ’ l- istudju.
Most patients (97%, N=882) had neutropenia at baseline (< 200 neutrophils/µL).
Il- maġġoranza tal- pazjenti (97%, N=882) kellhom newtropenja fil- linja bażi (< 200 newtrofili/ µL).
Neutropenia persisted for a median of 13 days.
In- newtropenja ippersistiet għal medja ta ’ 13- il jum.
There was a fixed daily dose of 50 mg (1.0 mg/kg) for micafungin and 400 mg (8 mg/kg) for fluconazole.
Kien hemm doża fissa kuljum ta ’ 50 mg( 1. 0 mg/ kg) għal micafungin u 400 mg (8 mg/ kg) għal fluconazole.
The mean period of treatment was 19 days for micafungin and 18 days for fluconazole in the adult population (N=798) and 23 days for both treatment arms in the paediatric population (N=84).
Il- perijodu medju ta ’ trattament kien ta ’ 19- il jum għal micafungin u 18- il jum għal fluconazole fil- popolazzjoni adulta (N=798) u 23 jum għaż- żewġ fergħat tat- trattament fil- popolazzjoni pedjatrika (N=84).
The rate of treatment success was statistically significantly higher for micafungin than fluconazole (1.6% versus 2.4% breakthrough infections).
Ir- rata ta ’ suċċess ta ’ trattament kienet statistikament ferm ogħla għal micafungin milli għal fluconazole (1. 6% kontra 2. 4% għal infezzjonijiet fil- punt ta ’ riferiment finali).
Breakthrough Aspergillus infections were observed in 1 versus 7 patients, and proven or probable breakthrough Candida infections were observed in 4 versus 2 patients in the micafungin and fluconazole groups, respectively.
Il- punt ta ’ riferiment finali għal infezzjonijiet ta ’ Aspergillus kienu osservati f’ pazjent 1 kontra 7 u l- prova jew probabilità tal- punt ta ’ riferiment finali ta ’ infezzjonijiet ta ’ Candida kienu osservati f’ 4 kontra 2 pazjenti fil - gruppi ta ’ micafungin u fluconazole rispettivament.
Other breakthrough infections were caused by Fusarium (1 and 2 patients, respectively) and Zygomycetes (1 and 0 patients, respectively).
Infezzjonijiet oħra li żviluppaw kienu kkawżati minn Fusarium (pazjent 1 jew 2 rispettivament) u Zygomycetes (pazjent 1 u 0, rispettivament).
The nature and incidence of adverse reactions were similar between treatment groups.
In - natura u l- inċidenza ta ’ reazzjonijiet avversi kienu l- istess bejn iż- żewġ gruppi.
Absorption Micafungin is an intravenously administered medication.
Assorbiment Micafungin huwa medikazzjoni li tingħata fil- vini.
Pharmacokinetics are linear over the daily dose range of 12.5 mg to 200 mg and 3 mg/kg to 8 mg/kg.
Il- farmakokinetika hija linejari fuq il- medda tad- doża ta ’ kuljum ta ’ 12. 5 mg sa 200 mg u 3 mg/ kg sa 8 mg/ kg.
There is no evidence of systemic accumulation with repeated administration and steady-state is generally reached within 4 to 5 days.
M’ hemmx evidenza ta ’ akkumulazzjoni sistemika u stat fiss ġeneralment jintlaħaq fi żmien 4 sa 5 ijiem.
Distribution Following intravenous administration concentrations of micafungin show a biexponential decline.
Distribuzzjoni Wara għoti fil- vini, il- konċentrazzjonijiet ta ’ micafungin juru tnaqqis biesponenzjali.
The drug is rapidly distributed into tissues.
Il- mediċina hija distribwita malajr fit- tessuti.
10 In systemic circulation, micafungin is highly bound to plasma protein (> 99%), primarily to albumin.
F’ ċirkulazzjoni sistemika, micafungin jeħel ħafna mal- proteini tal- plażma (> 99%), l- aktar ma ’ l - albumina.
Binding to albumin is independent of micafungin concentration (10-100 µg/ml).
Ir- rabta ma ’ l- albumina huwa indipendenti mill- konċentrazzjoni ta ’ micafungin (10 – 100 µg/ ml).
The volume of distribution at steady state (Vss) was approximately 18-19 litres.
Il- volum tad- distribuzzjoni fiss (Vss) kien madwar 18- 19- il litru.
Metabolism Unchanged micafungin is the principal circulating compound in systemic circulation.
Metaboliżmu Micafungin mhux mibdul huwa l- kompost prinċipali li jiċċirkola f’ ċirkulazzjoni sistemika.
Micafungin has been shown to be metabolised to several compounds; of these M-1 (catechol form), M-2 (methoxy form of M-1) and M-5 (hydroxylation at the side chain) of micafungin have been detected in systemic circulation.
Micafungin intwera li jiġi metabolizzat għal diversi komposti; minn dawn M- 1 (forma catechol), M- 2 (forma methoxy ta ’ M1) u M- 5 (idroksilazzjoni fil- katina tal- ġenb) ta ’ micafungin ġew rilevati f’ ċirkulazzjoni sistemika.
Exposure to these metabolites is low and metabolites do not contribute to the overall efficacy of micafungin.
L- esponiment għal dawn il- metaboliti huwa baxx u l- metaboliti ma jikkontribwixxux għall- effikaċja globali ta ’ micafungin.
Even though micafungin is a substrate for CYP3A in vitro, hydroxylation by CYP3A is not a major pathway for micafungin metabolism in vivo.
Anki jekk micafungin huwa substrat għal CYP3A in vitro, l- idroksilazzjoni b’ CYP3A m’ hix triq prinċipali għall- metaboliżmu ta ’ micafungin in vivo.
Elimination and excretion The mean terminal half-life is approximately 10-17 hours and stays consistent across doses up to 8 mg/kg and after single and repeated administration.
Eliminazzjoni u eskrezzjoni Il- medja tal- half- life terminali hija madwar 10- 17- il siegħa u tibqa ’ konsistenti tul dożi sa 8 mg/ kg u wara għoti wieħed u ripetut.
Total clearance was 0.15-0.3 ml/min/kg in healthy subjects and adult patients and is independent of dose after single and repeated administration.
It- tneħħija totali kienet ta ’ 0. 15- 0. 3 ml/ min/ kg f’ suġġetti b’ saħħithom u pazjenti adulti u hija indipendenti mid- doża wara għoti wieħed u ripetut.
Following a single intravenous dose of 14C-micafungin (25 mg) to healthy volunteers, 11.6% of the radioactivity was recovered in the urine and 71.0% in the faeces over 28 days.
Wara doża waħda fil- vini ta ’ 14C- micafungin (25 mg) lil voluntiera b’ saħħithom, 11. 6% tar - radjuattività kienet irkuprata fl- awrina u 71. 0% fl- ippurgar fuq 28 jum.
These data indicate that elimination of micafungin is primarily non-renal.
Din id- dejta tindika li t - tneħħija ta ’ micafungin hija primarjament mhux renali.
In plasma, metabolites M-1 and M-2 were detected only at trace concentrations and metabolite M-5, the more abundant metabolite, accounted for a total of 6.5% relative to parent compound.
Fil- plażma, il- metaboliti M- 1 u M- 2 instabu biss f’ konċentrazzjonijiet ta ’ traċċa u l- metabolit M- 5, l- aktar metabolit abbundanti, ammonta għal 6. 5% meta mqabbel mal- kompost prinċipali.
Special populations Paediatric patients:
Popolazzjonijiet speċjali Pazjenti pedjatriċi:
In paediatric patients AUC values were dose proportional over the dose range of 0.5-4 mg/kg.
F’ pazjenti pedjatriċi, il- valuri AUC kienu proporzjonali mad- doża fuq il- medda tad- doża ta ’ 0. 5- 4 mg/ kg.
Clearance was influenced by age, with mean values of clearance in younger children (2-11 years) being approximately 1.3 -fold greater than those in older children (12-17 years).
11 iżgħar (2- 11- il sena) ikunu madwar 1. 3 darbiet aktar minn dawk fi tfal akbar (12- 17 - il sena).
Older children had mean clearance values similar to those determined in adult patients.
Tfal akbar kellhom valuri medji ta ’ tneħħija simili għal dawk stabbiliti f’ pazjenti adulti.
Mean clearance in premature infants (gestational age approximately 26 weeks) is approximately 5-fold greater than in adults.
Il- medja tat - tneħħija fi trabi prematuri (età tal- ġestazzjoni ta ’ madwar 26 ġimgħa) hija madwar 5 darbiet aktar milli fl- adulti.
When administered as a single 1-hour infusion of 50 mg the pharmacokinetics of micafungin in the elderly (aged 66-78 years) were similar to those in young (20-24 years) subjects.
Meta ngħata bħala infużjoni waħda ta ’ 50 mg fuq siegħa, il- farmakokinetiċi ta ’ micafungin fl- anzjani (età ta ’ bejn 66- 78 sena) kienu simili għal dawk f’ individwi żgħażagħ (20- 24 sena).
No dose adjustment is necessary for the elderly.
M’ hemmx bżonn ta ’ aġġustament fid- doża għall- anzjani.
In a study performed in patients with moderate hepatic impairment (Child-Pugh score 7-9), (n=8), the pharmacokinetics of micafungin did not significantly differ from those in healthy subjects (n=8).
Fi studju mwettaq fuq pazjenti b’ indeboliment epatiku moderat (punteġġ Child- Pugh 7- 9), (n=8), il- farmakokinetiċi ta ’ micafungin b’ mod sinifikanti ma kinux wisq differenti minn dawk ta ’ suġġetti b’ saħħithom (n=8).
Therefore, no dose adjustment is necessary for patients with mild to moderate hepatic impairment.
Għalhekk, m’ hemmx bżonn ta ’ aġġustament fid - doża għal pazjenti b’ indeboliment epatiku ħafif għal moderat.
The pharmacokinetics of micafungin has not been studied in patients with severe hepatic insufficiency.
Il- farmakokinetiċi ta ’ micafungin ma ġewx studjati f’ pazjenti b’ insuffiċjenza epatika severa.
Severe renal impairment (Glomerular Filtration Rate [GFR] < 30 ml/min) did not significantly affect the pharmacokinetics of micafungin.
Indeboliment renali sever (Rata ta ’ Filtrazzjoni Glomerulari [GFR] < 30 ml/ min) ma affettwax il- farmakokinetiċi ta ’ micafungin b’ mod sinifikanti.
No dose adjustment is necessary for patients with renal impairment.
M’ hemmx bżonn ta ’ aġġustament fid- doża għal pazjenti b’ indeboliment renali.
Gender/Race:
Ġeneru/ Razza:
Gender and race (Caucasian, Black and Oriental) did not significantly influence the pharmacokinetic parameters of micafungin.
Il- ġeneru u r- razza (Kawkasi, Suwed u Orjentali) ma influwenzawx b’ mod sinifikanti l- parametri farmakokinetiċi ta ’ micafungin.
No dose adjustment of micafungin is required based on gender or race.
M’ hemmx bżonn ta ’ aġġustament fid- doża ta ’ micafungin ibbażat fuq is- sess jew ir- razza.
The development of foci of altered hepatocytes (FAH) and hepatocellular tumours in rats was dependent on both dose and duration of micafungin treatment.
L- iżvilupp ta ’ foċi epatoċiti mibdula (FAH) u ta ’ tumuri epatoċellulari fil- firien kien dipendenti kemm fuq id- doża u ż- żmien li dam jingħata micafungin.
FAH recorded after treatment for 13 weeks or longer persisted after a 13-week withdrawal period and developed into hepatocellular tumours following a treatment free period which covered the life span of rats.
L- FAH reġistrati wara t- trattament għal 13- il ġimgħa jew aktar ippersistew għal perijodu ta ’ 13- il ġimgħa wara l- waqfien u żviluppaw f’ tumuri epatoċellulari wara perijodu li fih ma sar l- ebda trattament li kopriet ħajjet il- firien.
In both studies
Ma saru ebda studji karċinoġeniċi standard iżda l- iżvilupp ta ’ FAH kien analizzat fil- firien nisa sa perijodu ta ’ 20 xahar u 18- il xahar wara il- waqfien ta ’ trattament li dam sejjer għal 3 u 6 xhur rispettivament.
11 increased incidences/numbers of hepatocellular tumours were observed after the 18 and 20 month treatment free period in the high dose group of 32 mg/kg/day as well as in a lower dose group (although not statistically significant).
Fiż - żewġ studji l- inċidenza/ l- għadd ogħla ta ’ tumuri epatoċellulari kienu osservati 18- il xahar u 20 xahar wara l- perijodu li fih ma sar l- ebda trattament fil- grupp li ngħata doża għolja ta ’ 32 mg/ kg/ kuljum kif ukoll fi grupp li ngħata doża iżgħar (għalkemm mhux statistikament sinifikanti).
The plasma exposure at the assumed threshold for tumour development in rats (i.e. the dose where no FAH and liver tumours were detected) was in the same range as the clinical exposure.
L- espożizzjoni fil - plażma tal- livell ta ’ riferiment preżunt għall- iżvilupp ta ’ tumuri fil- firien (i. e. id- doża li fiha l- ebda FAH u tumuri tal- fwied ma ġew intraċċati) kienet fl- istess firxa bħal fl- espożizzjoni klinika.