qanastek/EMEA-V3 huggingface dataset:
Hold the syringe slightly tilted with the vial facing downwards.
Żomm is - siringa daqsxejn inklinata bil- kunjett iħares ’ l isfel.
G Gently swirl the vial until all the powder is dissolved.
G Dawwar il- kunjett bilmod sakemm it- trab jinħall kollu.
NovoSeven reconstituted product is a clear, colourless solution.
Is- soluzzjoni rikostitwita ta ’ NovoSeven hija ċara u bla kulur.
Keep the vial adapter or transfer needle attached to the vial.
Ħalli l- adapter għall- kunjett jew il- labra ta ’ trasferiment mwaħħlin mal- kunjett.
Although NovoSeven will be stable for 24 hours after it has been mixed, you should use it at once to avoid infection.
Għalkemm NovoSeven huwa stabbli għal 24 siegħa wara li jkun ġie mħallat, għandu jiġi użat immedjatament sabiex tevita r- riskju ta ’ xi infezzjoni.
H Ensure that the plunger is pushed all the way in before turning the syringe upside down (it may have been pushed out by the pressure in the syringe).
H Assigura ruħek li l- planġer huwa mdaħħal kollu ’ l ġewwa qabel ma ddawwar is- siringa ta ’ taħt fuq (jista ’ jkun li nħareġ ’ il barra minħabba l- pressjoni fis- siringa).
If you use a transfer needle, make sure that the transfer needle tip is in the solution.
Jekk qiegħed tuża labra ta ’ trasferiment, kun żgur li l- ponta tal- labra ta ’ trasferiment tkun fis- soluzzjoni.
Hold the syringe with the vial upside down and pull the plunger to draw all the solution into the syringe.
Żomm is- siringa bil - kunjett rasu ’ l isfel u iġbed lura l- planġer sabiex iddaħħal is- soluzzjoni kollha fis- siringa.
I If you use a vial adapter, unscrew the vial adapter with the empty vial.
I Jekk qiegħed tuża adapter għall- kunjett, ħoll l- adapter għall- kunjett bil- kunjett vojt.
If you use a transfer needle, remove the transfer needle from the vial, replace the transfer needle cap, and twist the transfer needle off the syringe.
Jekk qiegħed tuża labra ta ’ trasferiment, aqla 'l- labra ta ’ trasferiment minn mal- kunjett, għatti l- labra ta ’ trasferiment bl -
102 J Safely dispose of the syringe, vials, any unused product and other waste materials as instructed by your health care professional.
J Armi s- siringa, kunjetti, kull prodott li ma ntużax u skart ieħor f’ kontenituri adattati skond kif spjegalek il- professjonist tal- kura tas- saħħa tiegħek.
Noxafil 40 mg/ ml oral suspension
Noxafil 40 mg/ ml suspensjoni orali
Each ml of oral suspension contains 40 mg of posaconazole.
Kull ml ta ’ suspensjoni orali fih 40 mg ta ’ posaconazole.
Oral suspension White suspension
Suspensjoni orali Suspensjoni bajda
Noxafil is indicated for use in the treatment of the following fungal infections in adults (see section 5.1):
Noxafil jintuża għall- kura ta ’ infezzjonijiet tal- fungu f’ adulti (ara sezzjoni 5. 1):
- Invasive aspergillosis in patients with disease that is refractory to amphotericin B or
- Asperġillożi invażiva f’ pazjenti b’ mard li hu refrattarju għal amphotericin B jew itraconazole
itraconazole or in patients who are intolerant of these medicinal products;
jew f’ pazjenti intolleranti għal dawn il- prodotti mediċinali;
- Fusariosis in patients with disease that is refractory to amphotericin B or in patients who are
- Fusarjożi f’ pazjenti b’ mard li hu refrattarju għal amphotericin B jew f’ pazjenti intolleranti għal
intolerant of amphotericin B;
amphotericin B;
- Chromoblastomycosis and mycetoma in patients with disease that is refractory to itraconazole
- Kromoblastomikożi u miċetoma f’ pazjenti b’ mard li hu refrattarju għal itraconazole jew
or in patients who are intolerant of itraconazole;
f’ pazjenti intolleranti għal itraconazole;
- Coccidioidomycosis in patients with disease that is refractory to amphotericin B, itraconazole or
- Kokkidajojdomikożi f’ pazjenti b’ mard li hu refrattarju għal amphotericin B, itraconazole jew
fluconazole or in patients who are intolerant of these medicinal products;
fluconazole jew f’ pazjenti intolleranti għal dawn il- prodotti mediċinali;
- Oropharyngeal candidiasis: as first-line therapy in patients who have severe disease or are
- Kandidijażi orofarinġali: bħala l- kura preferita f’ pazjenti li għandhom mard sever jew li
immunocompromised, in whom response to topical therapy is expected to be poor.
għandhom is- sistema immuni kompromessa, li jkunu mistennija li jkollhom rispons fqir għal terapija topika.
Refractoriness is defined as progression of infection or failure to improve after a minimum of 7 days of prior therapeutic doses of effective antifungal therapy.
Tkun definita refrattarja meta l- infezzjoni tavvanza jew ma titjiebx wara mill- anqas 7 ijiem ta ’ dożi terapewtiċi b’ terapija effettiva kontra l- fungu li jkunu ngħataw qabel.
Noxafil is also indicated for prophylaxis of invasive fungal infections in the following patients:
Noxafil huwa indikat ukoll għal profilassi ta ’ infezzjonijiet tal- fungu invasiva fil- pazjenti li ġejjin:
- Patients receiving remission-induction chemotherapy for acute myelogenous leukemia (AML)
- Pazjenti li qed jirċievu kimoterapija ta ’ remissjoni- induzzjoni għall- lewkimja majeloġenuża
or myelodysplastic syndromes (MDS) expected to result in prolonged neutropenia and who are at high risk of developing invasive fungal infections;
(AML) jew għal sindromi majelodisplastiċi (MDS) li jkunu mistennija li jikkawżaw newtropenja u li jkollhom riskju għoli li jiżviluppaw infezzjonijiet tal- fungu invażivi;
- Hematopoietic stem cell transplant (HSCT) recipients who are undergoing high-dose
- Persuni li jkunu rċevew trapjant ta ’ ċelluli stem ħematopojetiċi (HSCT) li jkunu qed jingħataw
immunosuppressive therapy for graft versus host disease and who are at high risk of developing invasive fungal infections.
dożi għoljin ta ’ terapija immunosopprimenti għal mard tat- tilqima kontra l- host u li jkollhom riskju akbar li jiżviluppaw infezzjonijiet ta ’ mard tal- fungu invażivi.
Treatment should be initiated by a physician experienced in the management of fungal infections or in the supportive care in the high risk patients for which posaconazole is indicated as prophylaxis.
Il- kura għandha tinbeda minn tabib li jkollu esperjenza fl- immaniġġar ta ’ infezzjonijiet tal- fungu jew taħt kura ta ’ support fil- pazjenti li jkollhom riskju għoli meta posaconazole jingħata bħala profilassi.
Recommended dosage is shown in Table 1.
Id- dużaġġ rakkomandat jidher f’ Tabella 1.
Recommended dose according to indication
Doża rakkomandata skond l- indikazzjoni
Dose and duration of therapy
Doża u tul tat- terapija
Refractory Invasive Fungal 400 mg (10 ml) twice a day.
Infezzjonijiet Refrattarji tal - 400 mg (10 ml) darbtejn kuljum.
In patients who cannot tolerate a Infections (IFI)/ Intolerant meal or a nutritional supplement, Noxafil should be patients with IFI
F’ pazjenti li ma jifilħux ikla Fungu (IFI) / Pazjenti li ma jifilħux b’ IFI
administered at a dose of 200 mg (5 ml) four times a day.
jew xi suppliment nutrizzjonali, Noxafil għandu jingħata bħala doża ta ’ 200 mg (5 ml) erba ’ darbiet kuljum.
Duration of therapy should be based on the severity of the underlying disease, recovery from immunosuppression, and clinical response.
It- terapija għandha ddum skon is- severità ta ’ l- infezzjoni li jkun hemm, irkupru minn sopressjoni tas- sistema immuni u r- rispons kliniku.
Oropharyngeal Candidiasis
Kandidijażi Orofarinġali
Loading dose of 200 mg (5 ml) once a day on the first day, then 100 mg (2.5 ml) once a day for 13 days.
Doża ta ’ tagħbija ta ’ 200 mg (5 ml) darba kuljum fl- ewwel jum, imbagħad 100 mg (2. 5 ml) darba kuljum għal 13- il ġurnata.
Each dose of Noxafil should be administered with a meal, or with a nutritional supplement in patients who cannot tolerate food to enhance the oral absorption and to ensure adequate exposure.
Kull doża ta ’ Noxafil għandha tingħata ma ’ ikla, jew ma ’ suppliment nutrizzjonali f’ pazjenti li ma jistgħux iżommu ikel sabiex jgħin għall- assorbiment orali u jiżgura esponiment xieraq.
Prophylaxis of Invasive Fungal Infections
Profilassi ta ’ Infezzjonijiet Invażivi tal - Fungu
200 mg (5 ml) three times a day.
200 mg (5 ml) tliet darbiet kuljum.
Each dose of Noxafil should be administered with a meal, or with a nutritional supplement in patients who cannot tolerate food to enhance the oral absorption and to ensure adequate exposure.
Kull doża ta ’ Noxafil għandha tingħata ma ’ ikla, jew ma ’ suppliment nutrizzjonali f’ pazjenti li ma jistgħux iżommu ikel sabiex jgħin għall - assorbiment orali u jiżgura esponiment xieraq.
The duration of therapy is based on recovery from neutropenia or immunosuppression.
It- terapija għadha ddum skond l- irkupru min- newtropenja jew l - immunosoppressjoni.
For patients with acute myelogenous leukemia or myelodysplastic syndromes, prophylaxis with Noxafil should start several days before the anticipated onset of neutropenia and continue for 7 days after the neutrophil count rises above 500 cells per mm3.
Għal pazjenti b’ sindromi ta ’ lewkimja majeloġenuża jew majelodisplastika, profilassi b’ Noxafil għandha tibda ħafna ġranet qabel ma tkun mistennija li tfeġġ in- newtropenja u titkompla għal 7 ijiem wara li l- għadd tan - newtrofili jitla ’ fuq il- 500 ċellula kull mm3.
There are limited pharmacokinetic data in patients with severe gastrointestinal dysfunction (such as severe diarrhoea).
Hemm tagħrif farmakokinetiku limitat f’ pazjenti b’ funzjoni ħażina b’ mod sever gastro- intestinali (bħal dijarea severa).
Patients who have severe diarrhoea or vomiting should be monitored closely for breakthrough fungal infections.
Pazjenti li jkollhom dijarea severa jew rimettar għandhom jinżammu taħt osservazzjoni mill- qrib għal infezzjonijiet tal - fungu avvanzati.
The oral suspension must be shaken well before use.
Is- suspensjoni orali għandha titħawwad sew qabel l- użu.
An effect of renal impairment on the pharmacokinetics of posaconazole is not expected and no dose adjustment is recommended (see section 5.2).
Mhux mistenni li jkun hemm effett minn indeboliment renali fuq il - farmakokinetiċi ta ’ posaconazole u mhux rakkomandat li tinbidel id- doża (ara sezzjoni 5. 2).
There are limited pharmacokinetic data in patients with hepatic impairment; therefore, no recommendation for dose adjustment can be made.
Hemm tagħrif limitat fuq il- farmakokinetiċi f’ pazjenti b’ indeboliment epatiku; għalhekk, ma tistax issir rakkomandazzjoni għal tibdil fid- doża.
In the small number of subjects studied who had hepatic impairment, there was an increase in exposure and half-life with a decrease in hepatic function (see sections 4.4 and 5.2).
Fin- numru żgħir ta ’ pazjenti li kellhom indeboliment epatiku, kien hemm żieda fl- esponiment u l- half- life ma ’ tnaqqis fil- funzjoni epatika (ara sezzjonijiet 4. 4 u 5. 2).
Use in children:
L- użu fi tfal:
Safety and efficacy in children and adolescents below the age of 18 years have not been established.
Ma ġewx stabiliti s- sigurtà u l- effikaċja fi tfal u adolexxenti taħt it- 18- il sena.
Therefore posaconazole is not recommended for use in patients below 18 years of age (see sections 5.1 and 5.2).
Għalhekk posaconazole mhux rakkomandat għall- użu f’ pazjenti taħt it- 18- il sena (ara sezzjonijiet 5. 1 u 5. 2).
Co-administration with ergot alkaloids (see section 4.5).
L- għotja flimkien ma ’ ergot alkaloids (ara sezzjoni 4. 5).
Co-administration with the CYP3A4 substrates terfenadine, astemizole, cisapride, pimozide, halofantrine or quinidine since this may result in increased plasma concentrations of these medicinal products, leading to QTc prolongation and rare occurrences of torsades de pointes (see sections 4.4 and 4.5).
L- għotja flimkien ma ’ sustrati ta ’ CYP3A4 terfenadine, astemizole, cisapride, pimozide, halofantrine jew quinidine peress li dan jista ’ jwassal għal żieda tal- konċentrazzjonijiet fil- plażma ta ’ dawn il - prodotti mediċinali, li jwasslu sabiex il- QTc jitwal u jkun hemm każijiet rari ta ’ torsades de pointes (ara sezzjonijiet 4. 4 u 4. 5).
Co-administration with the HMG-CoA reductase inhibitors simvastatin, lovastatin and atorvastatin (see section 4.5).
L- għotja flimkien ma ’ impedituri ta ’ HMG- CoA reductase simvastatin, lovastatin u atorvastatin (ara sezzjoni 4. 5).
There is no information regarding cross-sensitivity between posaconazole and other azole antifungal agents.
M’ hemmx tagħrif dwar cross- sensitivity bejn posaconazole u sustanzi oħrajn azole kontra l- fungu.
Caution should be used when prescribing Noxafil to patients with hypersensitivity to other azoles.
Għandha ssir attenzjoni meta jiġi ordnat Noxafil għal pazjenti li jkollhom sensittività eċċessiva għal azoles oħrajn.
Hepatic toxicity:
Tossiċità epatika:
Hepatic reactions (e. g. mild to moderate elevations in ALT, AST, alkaline phosphatase, total bilirubin and/ or clinical hepatitis) have been reported during treatment with posaconazole.
Reazzjonijiet epatiċi (eż. żiediet ħfief għal moderati fl- ALT, AST, alkaline phosphatase, bilirubin totali u/ jew epatite klinika) kienu rrappurtati waqt kura b’ posaconazole.
Elevated liver function tests were generally reversible on discontinuation of therapy and in some instances these tests normalised without interruption of therapy.
Testijiet għoljin tal- funzjoni tal- fwied kienu fil- parti l- kbira riversibbli malli twaqqfet it- terapija u f’ xi każijiet it- testijiet reġgħu lura għan- normal mingħajr ma twaqqfet it- terapija.
Rarely, more severe hepatic reactions with fatal outcomes have been reported.
Rarament, reazzjonijiet epatiċi aktar severi li wasslu għall- mewt kienu rrappurtati.
Posaconazole should be used with caution in patients with severe hepatic impairment.
Posaconazole għandu jintuża b’ attenzjoni f’ pazjenti b’ indeboliment epatiku sever.
In these patients, the prolonged elimination half-life may lead to increased exposure.
F’ dawn il- pazjenti, peress li l- half- life ta ’ l- eliminazzjoni jiġi mtawwal jista ’ jkun hemm żieda fl- esponiment.
Monitoring of hepatic function:
Monitoraġġ tal- funzjoni epatika:
Patients who develop abnormal liver function tests during Noxafil therapy must be routinely monitored for the development of more severe hepatic injury.
Pazjenti li jiżviluppaw anormalitajiet fit- testijiet tal- funzjoni tal - fwied waqt terapija b’ Noxafil għandhom ikunu eżaminati regolarment għall- iżvilupp ta ’ ħsara epatika aktar serja.
Patient management should include laboratory evaluation of hepatic function (particularly liver function tests and bilirubin).
L- imaniġġar tal- pazjenti għandu jinkludi evalwazzjoni permezz ta ’ laboratorju tal- funzjoni epatika (l- aktar testijiet tal- funzjoni tal- fwied u bilirubin).
Discontinuation of Noxafil should be considered if clinical signs and symptoms are consistent with development of liver disease.
It- twaqqif ta ’ Noxafil għandu jitqies jekk is - sinjali u s- sintomi kliniċi juru żvilupp ta ’ mard epatiku.
QTc prolongation:
It- titwil ta ’ QTc:
Some azoles have been associated with prolongation of the QTc interval.
Xi azoles kienu assoċjati ma ’ titwil ta ’ l- intervall QTc.
Noxafil must not be administered with medicinal products that are substrates for CYP3A4 and are known to prolong the QTc interval (see sections 4.3 and 4.5).
Noxafil m’ għandux jingħata ma ’ prodotti mediċinali li huma sottostrati għal CYP3A4 u magħrufin li jtawlu l- intervall QTc (ara sezzjonijiet 4. 3 u 4. 5).
Noxafil should be administered with caution to patients with pro-arrhythmic conditions such as: • Congenital or acquired QTc prolongation • Cardiomyopathy, especially in the presence of cardiac failure • Sinus bradycardia • Existing symptomatic arrhythmias • Concomitant use with medicinal products known to prolong the QTc interval (other than those mentioned in section 4.3).
Noxafil għandu jingħata b’ attenzjoni lill- pazjenti b’ kundizzjonijiet pro- arritmiċi bħal: • Meta l- QTc jiġi prolongat minħabba raġunijiet konġeniti jew b’ mod akkwiżit • Kardjomajopatija, l- aktar meta jkun hemm insuffiċjenza kardijaka • Sinus bradikardja • Preżenza ta ’ arritmiji sintomatiċi • L- użu fl- istess ħin ta ’ prodotti mediċinali magħrufin li jtawwlu l- interval QTc (minbarra dawk imsemmijin f’ sezzjoni 4. 3).
Electrolyte disturbances, especially those involving potassium, magnesium or calcium levels, should be monitored and corrected as necessary before and during posaconazole therapy.
Disturbi ta ’ elettroliti, l- aktar dawk li jinvolvu potassium, magnesium jew livelli ta ’ calcium, għandhom ikunu monitorati u rranġati kif meħtieġ qabel u waqt terapija b’ posaconazole.
Posaconazole is an inhibitor of CYP3A4 and should only be used under specific circumstances during treatment with other medicinal products that are metabolised by CYP3A4 (see section 4.5).
Posaconazole huwa impeditur ta ’ CYP3A4 u għandu jintuża biss taħt ċirkustanzi speċifiċi waqt kura bi prodotti mediċinali oħrajn li jiġu metabolizzati b’ CYP3A4 (ara sezzjoni 4. 5).
Concomitant use with posaconazole should be avoided unless the benefit to the patient outweighs the risk (see section 4.5).
L- użu fl- istess ħin ma ’ posaconazole għandu jkun evitat sakemm il- benefiċċju għall- pazjent ma jegħlibx ir- riskju (ara sezzjoni 4. 5).
Rifamycin antibacterials (rifampicin, rifabutin), certain anticonvulsants (phenytoin, carbamazepine, phenobarbital, primidone), efavirenz and cimetidine:
Antibatteriċi ta ’ rifamycin (rifampicin, rifabutin), ċerti mediċini kontra l- aċċessjonijiet (phenytoin, carbamazepine, phenobarbital, primidone), efavirenz u cimetidine:
Posaconazole concentrations may be significantly lowered in combination; therefore, concomitant use with posaconazole should be avoided unless the benefit to the patient outweighs the risk (see section 4.5).
Il- konċentrazzjonijiet ta ’ posaconazole jistgħu jitbaxxew b’ mod sinifikanti; għalhekk l- użu fl- istess ħin ma ’ posaconazole għandu jkun evitat sakemm il- benefiċċju għall- pazjent ma jegħlibx ir- riskju (ara sezzjoni 4. 5).
This medicinal product contains approximately 1.75 g of glucose per 5 ml of suspension.
Dan il- prodott mediċinali fih madwar 1. 75 g ta ’ glucose għal kull 5 ml ta ’ sospensjoni.
Patients with glucose-galactose malabsorption should not take this medicine.
Pazjenti b’ malassorbiment ta ’ glucose- galactose m’ għandhomx jieħdu din il- mediċina.
Effects of other medicinal products on posaconazole:
Effetti ta ’ prodotti mediċinali oħrajn fuq posaconazole:
Posaconazole is metabolised via UDP glucuronidation (phase 2 enzymes) and is a substrate for p- glycoprotein (P-gp) efflux in vitro.
Posaconazole jiġi metabolizzat permezz ta ’ glukoronidazzjoni UDP (enzimi ta ’ fażi 2) u huwa sottostrat għall- effluss ta ’ glikoproteina- p (P- gp) in vitro.
Therefore, inhibitors (e. g. verapamil, ciclosporin, quinidine, clarithromycin, erythromycin, etc.) or inducers (e. g. rifampicin, rifabutin, certain anticonvulsants, etc.) of these clearance pathways may increase or decrease posaconazole plasma concentrations, respectively.
Għalhekk, impedituri (eż. verapamil, ciclosporin, quinidine, clarithromycin, erythromycin, eċċ.) jew indutturi (eż. rifampicin, rifabutin, xi mediċini kontra l- aċċessjonijiet, eċċ.) ta ’ dawn il- mezzi ta ’ tneħħija jistgħu jżidu jew inaqqsu il - konċentrazzjonijiet fil- plażma ta ’ posaconazole rispettivament.
4 Rifabutin (300 mg once a day) decreased the Cmax (maximum plasma concentration) and AUC (area under the plasma concentration time curve) of posaconazole to 57% and 51%, respectively.
4 Rifabutin (300 mg darbtejn kuljum) inaqqas is- Cmax (l- ogħla konċentrazzjoni fil- plażma) u l- AUC (erja taħt il- kurva tal- konċentrazzjoni fil- plażma mal- ħin) ta ’ posaconzole għal 57% u 51% rispettivament.
Concomitant use of posaconazole and rifabutin and similar inducers (e. g. rifampicin) should be avoided unless the benefit to the patient outweighs the risk.
L- użu fl- istess ħin ta ’ posaconazole u rifabutin u indutturi simili (eż. rifampicin) għandu jkun evitat sakemm il- benefiċċju għall- pazjent ma jkunx jegħleb ir- riskju.
See also below regarding the effect of posaconazole on rifabutin plasma levels.
Ara wkoll hawn taħt dwar l- effett ta ’ posaconazole fuq il- livelli fil- plażma ta ’ rifabutin.
Efavirenz (400 mg once a day) decreased the Cmax and AUC of posaconazole by 45% and 50%, respectively.
Efavirenz (400 mg darba kuljum) naqqas is- Cmax u l- AUC ta ’ posaconazole b’ 45% u 50%, rispettivament.
Concomitant use of posaconazole and efavirenz should be avoided unless the benefit to the patient outweighs the risk.
L- użu fl- istess ħin ta ’ posaconazole u efavirenz għandu jiġi evitat sakemm il - benefiċċju għall- pazjent jegħleb ir- riskju.
Phenytoin (200 mg once a day) decreased the Cmax and AUC of posaconazole by 41% and 50%, respectively.
Phenytoin (200 mg darba kuljum) jnaqqas is- Cmax u l- AUC ta ’ posaconazole b’ 41% u 50% rispettivament.
Concomitant use of posaconazole and phenytoin and similar inducers (e. g. carbamazepine, phenobarbital, primidone) should be avoided unless the benefit to the patient outweighs the risk.
L- użu fl- istess ħin ta ’ posaconazole u phenytoin u indutturi simili (eż. carbamazepine, phenobarbital, primidone) għandu jkun evitat sakemm il- benefiċċju għall- pazjent ma jkunx jegħleb ir - riskju.
H2 receptor antagonists and proton pump inhibitors:
Antagonisti tar- riċettur H2 u impedituri tal- pompa tal- protoni:
Posaconazole plasma concentrations (Cmax and AUC) were reduced by 39% when posaconazole was administered with cimetidine (400 mg twice a day) due to reduced absorption possibly secondary to a decrease in gastric acid production.
Il- konċentrazzjonijiet fil- plażma ta ’ posaconazole (Cmax u AUC) kienu mnaqqsa b’ 39% meta posaconazole ingħata ma ’ cimetidine (400 mg darbtejn kuljum) minħabba tnaqqis fl- assorbiment li jista ’ jkun effett sekondarju għal tnaqqis ta ’ l- aċidu gastriku.
Concomitant use of posaconazole and cimetidine should be avoided unless the benefit to the patient outweighs the risk.
L- użu fl- istess ħin ta ’ posaconazole u cimetidine għandu jkun evitat sakemm il- benefiċċju għall - pazjent ma jkunx jegħleb ir- riskju.
The effect of other H2 receptor antagonists (e. g. famotidine, ranitidine) and proton pump inhibitors (e. g. omeprazole) that may suppress gastric acidity for several hours on plasma levels of posaconazole has not been studied but a reduction in bioavailability may occur so that co- administration should be avoided if possible.
L- effett ta ’ antagonisti oħrajn tar- riċettur H2 (eż. famotidine, ranitidine) u impedituri tal- pompa tal- protoni (eż. omeprazole) li jistgħu jikkawżaw soppressjoni ta ’ l - aċidità gastrika għal bosta sigħat fuq il- livelli fil- plażma ta ’ posaconazole ma ġiex studjat iżda tnaqqis fil- biodisponibilità jista ’ jseħħ u għalhekk l- użu fl- istess ħin għandu jkun evitat jekk ikun possibli.
Effects of posaconazole on other medicinal products:
L- effetti ta ’ posaconazole fu prodotti mediċinali oħrajn:
Posaconazole is a potent inhibitor of CYP3A4.
Posaconzole huwa impeditur qawwi ta ’ CYP3A4.
Co-administration of posaconazole with CYP3A4 substrates may result in large increases in exposure to CYP3A4 substrates as exemplified by the effects on tacrolimus, sirolimus, atazanavir and midazolam below.
L- għotja fl- istess ħin ta ’ posaconazole ma ’ sottostrati ta ’ CYP3A4 jista’ jwassal għal żidiet kbar fl- esponiment għas- sottostrati ta ’ CYP3A4 hekk kif qed jiġi spjegat b’ eżempji għall- effetti fuq tacrolimus, sirolimus, atazanavir u midazolam hawn taħt.
Caution is advised during co- administration of posaconazole with CYP3A4 substrates administered intravenously and the dose of the CYP3A4 substrate may need to be reduced.
Hija konsiljata l- attenzjoni waqt kura fl- istess ħin b’ posaconazole ma ’ sottostrati ta ’ CYP3A4 mogħtija għal ġol- vina u d- doża tas- sottostrat ta ’ CYP3A4 jista ’ jkollha bżonn titnaqqas.
If posaconazole is used concomitantly with CYP3A4 substrates that are administered orally, and for which an increase in plasma concentrations may be associated with unacceptable adverse events, plasma concentrations of the CYP3A4 substrate and/ or adverse events should be closely monitored and the dose adjusted as needed.
Jekk posaconazole jintuża flimkien ma ’ sottostrati ta ’ CYP3A4 li jittieħdu mill- ħalq u li żieda tal - konċentrazzjonijiet fil- plażma jistgħu jkunu assoċjati ma ’ każijiet avversi inaċċettabli, il - konċentrazzjonijiet fil- plażma tas- sottostrati ta ’ CYP3A4 u/ jew każijiet avversi għandhom jiġu monitorati mill- qrib u d- doża mibdula kif meħtieġ.
Several of the interaction studies were conducted in healthy volunteers in whom a higher exposure to posaconazole occurs compared to patients administered the same dose.
Ħafna mill- istudji dwar l- interazzjoni saru f’ voluntiera b’ saħħithom li jkollhom esponimenti għal posaconazole ogħla meta mqabbla ma ’ pazjenti li jingħataw l- istess doża.
The effect of posaconazole on CYP3A4 substrates in patients might be somewhat lower than that observed in healthy volunteers, and is expected to be variable between patients due to the variable posaconazole exposure in patients.
L- effett ta ’ posaconazole fuq is- sottostrati ta ’ CYP3A4 jista ’ jkun kemmxejn aktar baxx minn dak li jidher f’ voluntiera b’ saħħithom, u huwa mistenni li jvarja bejn il- pazjenti minħabba l- esponiment varjabbli għal posaconazole fil- pazjenti.
The effect of co- administration with posaconazole on plasma levels of CYP3A4 substrates may also be variable within a patient, unless posaconazole is administered in a strictly standardised way with food, given the large food effect on posaconazole exposure (see section 5.2).
L- effett ta ’ meta jingħataw flimkien ma ’ posaconazole fuq il- livelli fil- plażma tas- sottostrati ta ’ CYP3A4 jista ’ jvarja wkoll fl- istess pazjent, sakemm posaconazole ma jingħatax strettament b’ mod standard ma ’ l- ikel, peress li l- ikel għandu effett qawwi fuq l- esponiment ta ’ posaconazole (ara sezzjoni 5. 2).
Terfenadine, astemizole, cisapride, pimozide, halofantrine and quinidine (CYP3A4 substrates):
Terfenadine, astemizole, cisapride, pimozide, halofantrine u quinidine (sottostrati ta ’ CYP3A4):
Co-administration of posaconazole and terfenadine, astemizole, cisapride, pimozide, halofantrine or quinidine is contraindicated.
L- użu fl- istess ħin ta ’ posaconazole u terfenadine, astemizole, cisapride, pimozide, halofantrine jew quinidine huwa kontra- indikat.
Co-administration may result in increased plasma concentrations of these medicinal products, leading to QTc prolongation and rare occurrences of torsades de pointes (see section 4.3).
L- użu fl- istess ħin jista ’ jikkawża żiediet tal- konċentrazzjonijiet fil - plażma ta ’ dawn il- prodotti mediċinali, li jwasslu għal titwil tal- QTc u f’ każijiet rari seħħew torsades de pointes (ara sezzjoni 4. 3).
Ergot alkaloids:
Alkalojdi ergot:
Posaconazole may increase the plasma concentration of ergot alkaloids (ergotamine and dihydroergotamine), which may lead to ergotism.
Posaconzole jista ’ jżid il- konċentrazzjoni fil- plażma ta ’ alkalojdi ergot (ergotamine u dihydroergotamine), li jista ’ jwassal għal ergotiżmu.
Co-administration of posaconazole and ergot alkaloids is contraindicated (see section 4.3).
L- użu fl- istess ħin ta ’ posaconazole u alkalojdi ergot huwa kontra- indikat (ara sezzjoni 4. 3).
HMG-CoA reductase inhibitors metabolised through CYP3A4 (e. g. simvastatin, lovastatin, and atorvastatin):
Impedituri ta ’ HMG- CoA reductase metabolizzati permezz ta ’ CYP3A4 (eż. simvastatin, lovastatin u atorvastatin):
Posaconazole may substantially increase plasma levels of HMG-CoA reductase inhibitors that are metabolised by CYP3A4.
Posaconazole jista ’ jżid b’ mod sostanzjali l- livelli fil- plażma ta ’ impedituri ta ’ HMG - CoA reductase li huma metabolizzati minn CYP3A4.
Treatment with these HMG-CoA reductase inhibitors
Kura b’ dawn l- impedituri ta ’ HMG- CoA
5 should be discontinued during treatment with posaconazole as increased levels have been associated with rhabdomyolysis (see section 4.3).
5 reductase għandha titwaqqaf waqt il- kura b’ posaconazole għax żiediet fil- livelli kienu assoċjati ma ’ rabdomajelożi (ara sezzjoni 4. 3).
Vinca alkaloids:
Alkalojdi vinka:
Posaconazole may increase the plasma concentration of vinca alkaloids (e. g. vincristine and vinblastine), which may lead to neurotoxicity.
Posaconazole jista ’ jżid il- konċentrazzjoni fil- plażma ta ’ alkalojdi vinka (eż. vincristine u vinblastine), li tista ’ twassal għal newrotossiċità.
Therefore, concomitant use of posaconazole and vinca alkaloids should be avoided unless the benefit to the patient outweighs the risk.
Għalhekk l- użu fl- istess ħin ta ’ posaconazole u alkalojdi vinka għandu jkun evitat sakemm il- benefiċċju għall- pazjent ma jkunx jegħleb ir- riskju.
If co-administered, then it is recommended that dose adjustment of vinca alkaloids be considered.
F’ każ li jintużaw fl- istess ħin, huwa rakkomandat li jkun meqjus tibdil fid- doża ta ’ l - alkalojdi vinka.
Posaconazole increased the Cmax and AUC of rifabutin by 31% and 72%, respectively.
Posaconazole żied is- Cmax u l- AUC ta ’ rifabutin b’ 31% u 72%, rispettivament.
Concomitant use of posaconazole and rifabutin should be avoided unless the benefit to the patient outweighs the risk (see also above regarding the effect of rifabutin on plasma levels of posaconazole).
L- użu fl - istess ħin ta’ posaconazole u rifabutin għandu jkun evitat sakemm il- benefiċċju għall- pazjent ma jkunx jegħleb ir- riskju (ara wkoll hawn fuq dwar l- effett ta ’ rifabutin fuq il- livelli ta ’ posaconazole fil - plażma).
If these medicinal products are co-administered, careful monitoring of full blood counts and adverse events related to increased rifabutin levels (e. g. uveitis) is recommended.
Jekk dawn il- prodotti mediċinali jingħataw fl- istess ħin, huwa rakkomandat monitoraġġ bir - reqqa ta ’ l- għadd komplet tad- demm u każijiet avversi relatati ma ’ żiediet fil- livelli ta ’ rifabutin (eż uvejite).
In heart transplant patients on stable doses of ciclosporin, posaconazole 200 mg once daily increased ciclosporin concentrations requiring dose reductions.
F’ pazjenti b’ trapjant tal- qalb li qegħdin fuq dożi fissi ta ’ ciclosporin, posaconazole 200 mg darba kuljum żied il- konċentrazzjonijiet ta ’ ciclosporin li kienu jeħtieġu tnaqqis tad- dożi.
Cases of elevated ciclosporin levels resulting in serious adverse events, including nephrotoxicity and one fatal case of leukoencephalopathy, were reported in clinical efficacy studies.
Każijiet ta ’ żiediet fil- livelli ta ’ ciclosporin li wasslu għal każijiet avversi severi, inkluża nefrotossiċità u każ fatali ta ’ lewko- enċefalopatija, kienu rrappurtati fi studji dwar l- effikaċja klinika.
When initiating treatment with posaconazole in patients already receiving ciclosporin, the dose of ciclosporin should be reduced (e. g. to about three quarters of the current dose).
Meta tkun se tinbeda l- kura b’ posaconazole f’ pazjenti li jkunu diġa qed jirċievu ciclosporin, id- doża ta ’ ciclosporin għandha titnaqqas (eż. għal tlett kwarti tad- doża kurrenti).
Thereafter blood levels of ciclosporin should be monitored carefully during co-administration, and upon discontinuation of posaconazole treatment, and the dose of ciclosporin should be adjusted as necessary.
Għalhekk il- livelli ta ’ ciclosporin fid- demm għandhom ikunu monitorati sew waqt l- użu fl- istess ħin, u meta titwaqqaf il- kura b’ posaconazole, u d - doża ta ’ ciclosporin għandha tinbidel kif ikun meħtieġ.
Posaconazole increased Cmax and AUC of tacrolimus (0.05 mg/ kg body weight single dose) by 121% and 358%, respectively.
Posaconazole żied is- Cmax u l- AUC ta ’ tacrolimus (0. 05 mg/ kg piż tal- ġisem doża waħda) b’ 121% u 358%, rispettivament.
Clinically significant interactions resulting in hospitalisation and/ or posaconazole discontinuation were reported in clinical efficacy studies.
Interazzjonijiet li kienu klinikament sinifikanti li minħabba fihom il - pazjenti kellhom jiddaħħlu l- isptar u/ jew jitwaqqaf posaconazole, kienu rappurtati fi studji dwar l - effikaċja klinika.
When initiating posaconazole treatment in patients already receiving tacrolimus, the dose of tacrolimus should be reduced (e. g. to about one third of the current dose).
Meta tinbeda l- kura b’ posaconazole f’ pazjenti li diġa qed jirċievu tacrolimus, id- doża ta ’ tacrolimus għandha titnaqqas (eż. għal madwar terz tad- doża kurrenti).
Thereafter blood levels of tacrolimus should be monitored carefully during co-administration, and upon discontinuation of posaconazole, and the dose of tacrolimus should be adjusted as necessary.
Għalhekk il- livelli ta ’ tacrolimus fid- demm għandhom ikunu monitorati sew meta jingħataw fl- istess ħin, u meta jitwaqqaf posaconazole, u d- doża ta ’ tacrolimus mibdula kif meħtieġ.
Repeat dose administration of oral posaconazole (400 mg twice daily for 16 days) increased the Cmax and AUC of sirolimus (2 mg single dose) an average of 6.7-fold and 8.9-fold (range 3.1 to 17.5-fold), respectively, in healthy subjects.
L- għotja ta ’ dożi ripetuti ta ’ posaconazole mill- ħalq (400 mg darbtejn kuljum għal 16- il jum) żiedet is- Cmax u l- AUC ta’ sirolimus (2 mg doża waħda) b’ medja ta ’ 6. 7- il darba u 8. 9- il darba (medda 3. 1 sa 17. 5- il darba), rispettivament, f’ voluntiera b’ saħħithom.
The effect of posaconazole on sirolimus in patients is unknown, but is expected to be variable due to the variable posaconazole exposure in patients.
L- effett ta ’ posaconazole fuq sirolimus fil- pazjenti mhux magħruf, iżda huwa mistenni li jvarja minħabba l - esponiment varjabbli għal posaconazole fil- pazjenti.
Co- administration of posaconazole with sirolimus is not recommended and should be avoided whenever possible.
L- għotja fl- istess ħin ta ’ posaconazole ma ’ sirolimus mhux rakkomandat u għandu jiġi evitat kull meta jkun possibli.
If it is considered that co-administration is unavoidable, then it is recommended that the dose of sirolimus should be greatly reduced at the time of initiation of posaconazole therapy and that there should be very frequent monitoring of trough concentrations of sirolimus in whole blood.
F’ każ li jkun meqjus li l - għotja fl- istess ħin ma tistax tiġi evitata, huwa rakkomandat li d- doża ta ’ sirolimus titnaqqas ħafna meta tkun ser tinbeda t- terapija b’ posaconazole u li jkun hemm monitoraġġ frekwenti ħafna tal - konċentrazzjonijiet l- aktar baxxi ta ’ sirolimus fid- demm.
Sirolimus concentrations should be measured upon initiation, during co-administration, and at discontinuation of posaconazole treatment, with sirolimus doses adjusted accordingly.
Il- konċentrazzjonijiet ta ’ sirolimus għandhom jitkejjlu fil- mument meta jibda jingħata, waqt l- għotja fl- istess ħin, u meta titwaqqaf il- kura b’ posaconazole, u d- dożi ta ’ sirolimus mibdula kif ikun xieraq.
It should be noted that the relationship between sirolimus trough concentration and AUC is changed during co-administration with posaconazole.
Ta ’ min jinnota li r- relazzjoni bejn l - aktar konċentrazzjoni baxxa ta ’ sirolimus u l- AUC tinbidel meta jingħata flimkien ma ’ posaconazole.
As a result, sirolimus trough concentrations that fall within the usual therapeutic range may result in sub-therapeutic levels.
B’ hekk, il- konċentrazzjonijiet baxxi ta ’ sirolimus li jaqgħu fil- medda terapewtika tas- soltu jistgħu jwasslu għall- livelli aktar baxxi minn dak terapewtiku.
Therefore trough concentrations that fall in the upper part of the usual therapeutic range should be targetted and careful attention should be paid to clinical signs and symptoms, laboratory parameters and tissue biopsies.
Għalhekk konċentrazzjonijiet baxxi li jaqgħu fil- parti ta ’ fuq tal- medda terapewtika tas- soltu għandhom jiġu mmirati u għandha tingħata attenzjoni bir- reqqa għal sinjali u sintomi kliniċi, parametri tal- laboratorju u bijopsiji tat- tessuti.
HIV Protease Inhibitors:
Impedituri ta ’ l- HIV protease:
As HIV protease inhibitors are CYP3A4 substrates, it is expected that posaconazole will increase plasma levels of these antiretroviral agents.
Peress li l- impedituri ta ’ HIV protease huma sottostrati ta ’ CYP3A4, huwa mistenni li posaconazole jżid il- livelli fil- plażma ta ’ dawn l- aġenti kontra r- retrovajrus.
Following co-administration of oral posaconazole (400 mg twice daily) with atazanavir (300 mg once daily) for 7 days in healthy subjects Cmax and AUC of atazanavir increased by an average of 2.6-fold and 3.7-fold (range 1.2 to 26- fold), respectively.
Wara l - għotja fl- istess ħin ta ’ posaconazole mill- ħalq (400 mg darbtejn kuljum) ma ’ atazanavir (300 mg darba kuljum) għal 7 ijiem f’ individwi b’ saħħithom is- Cmax u l- AUC ta ’ atazanavir żdied b’ medja ta ’ 2. 6- il darba u 3. 7- il darba (medda 1. 2 sa 26- il darba), rispettivament.
Following co-administration of oral posaconazole (400 mg twice daily) with atazanavir and ritonavir (300/ 100 mg once daily) for 7 days in healthy subjects Cmax and AUC of atazanavir increased by an average of 1.5-fold and 2.5-fold (range 0.9 to 4.1-fold), respectively.
Wara l- għotja fl- istess ħin ta ’ posaconazole mill- ħalq (400 mg darbtejn kuljum) ma ’ azatanavir u ritonavir (300/ 100 mg darba kuljum) għal 7 ijiem f’ individwi b’ saħħithom is- Cmax u l- AUC ta ’ atazanavir żdiedu b’ medja ta ’
Frequent monitoring for adverse events and toxicity related
Iż- żieda ta ’ posaconazole mat - terapija b’ atazanavir jew b’ atazanavir ma ’ ritonavir kienet assoċjata ma ’ żiediet fil- livelli ta ’ bilirubin fil- plażma.
6 to antiretroviral agents that are substrates of CYP3A4 is recommended during co-administration with posaconazole.
Monitoraġġ frekwenti ta ’ każijiet avversi u tossiċità relatata ma ’ aġenti kontra r- retrovajrus li huma sottostrati ta ’ CYP3A4 huwa rakkomandat meta jingħataw flimkien ma ’ posaconazole.
Midazolam and other benzodiazepines metabolised by CYP3A4:
Midazolam u benzodijażepini oħrajn metabolizzati b’ CYP3A4:
In a study in healthy volunteers posaconazole (200 mg once daily for 10 days) increased the exposure (AUC) of IV midazolam (0.05 mg/ kg) by 83%.
Fi studju b’ voluntiera b’ saħħithom posaconazole (200 mg darba kuljum għal 10 ijiem) żied l- esponiment (AUC) ta ’ midazolam mogħti minn ġol- vina (0. 05 mg/ kg) bi 83%.
In another study in healthy volunteers, repeat dose administration of oral posaconazole (200 mg twice daily for 7 days) increased the Cmax and AUC of IV midazolam (0.4 mg single dose) by an average of 1.3- and 4.6-fold (range 1.7 to 6.4-fold), respectively; Posaconazole 400 mg twice daily for 7 days increased the IV midazolam Cmax and AUC by 1.6 and 6.2-fold (range 1.6 to 7.6-fold), respectively.
Fi studju ieħor b’ voluntiera b’ saħħithom, l- għotja ta ’ dożi ripetuti ta ’ posaconazole mill- ħalq (200 mg darbtejn kuljum għal 7 ijiem) żdied is- Cmax u l- AUC ta ’ midazolam mogħti minn ġol- vina (0. 4 mg doża waħda) b’ medja ta’ 1. 3 u 4. 6- il darba (medda 1. 7 sa 6. 4- il darba), rispettivament; Posaconazole 400 mg darbtejn kuljum għal 7 ijiem żied is- Cmax u l- AUC ta ’ midazolam mogħti minn ġol- vina b’ 1. 6 u 6. 2- il darba (medda 1. 6 sa 7. 6- il darba), rispettivament.
Both doses of posaconazole increased Cmax and AUC of oral midazolam (2 mg single oral dose) by 2.2 and 4.5-fold, respectively.
Iż- żewġ dożi ta ’ pozaconazole it- tnejn li huma żiedu s- Cmax u l- AUC ta ’ midazolam mill- ħalq (2 mg doża waħda mill- ħalq) b’ 2. 2 u 4. 5- il darba, rispettivament.
In addition, oral posaconazole (200 mg or 400 mg) prolonged the mean terminal half-life of midazolam from approximately 3-4 hours to 8- 10 hours during co-administration.
Minbarra hekk, posaconazole mill- ħalq (200 mg jew 400 mg) tawwal il- medja tal- half- life terminali ta ’ midazolam minn madwar 3- 4 sigħat għal 8- 10 sigħat meta ngħataw flimkien.
Due to the risk of prolonged sedation it is recommended that dose adjustments should be considered when posaconazole is administered concomitantly with any benzodiazepine that is metabolised by CYP3A4 (e. g. midazolam, triazolam, alprazolam).
Minħabba r- riskju li l- pazjent jitraqqad għal żmien twil huwa rakkomandat li jiġi kkonsidrat li d- dożi jiġu aġġustati meta posaconazole jingħata fl- istess ħin ma ’ kwalunkwe benzodiazepin li jiġi metabolizzat minn CYP3A4 (eż midazolam, triazolam, alprazolam).
Calcium channel blockers metabolised through CYP3A4 (e. g. diltiazem, verapamil, nifedipine, nisoldipine):
Imblukkaturi tal- kanali ta ’ calcium metabolizzati permezz ta ’ CYP3A4 (eż. diltiazem, verapamil, nifedipine, nisoldipine):
Frequent monitoring for adverse events and toxicity related to calcium channel blockers is recommended during co-administration with posaconazole.
Monitoraġġ frekwenti għal każijiet avversi u tossiċi relatati ma ’ l - imblukkaturi tal- kanali ta ’ calcium huwa rakkomandat waqt l- għotja fl- istess ħin ma ’ posaconazole.
Dose adjustment of calcium channel blockers may be required.
Tibdil fid- doża ta ’ l- imblukkaturi tal- kanali ta ’ calcium jistgħu jkunu meħtieġa.
Administration of other azoles has been associated with increases in digoxin levels.
L- għotja ta ’ ażoles oħrajn kienet assoċjata ma ’ żiediet fil- livelli ta ’ digoxin.
Therefore, posaconazole may increase plasma concentration of digoxin and digoxin levels need to be monitored when initiating or discontinuing posaconazole treatment.
Għalhekk, posaconazole jista ’ jżid il- konċentrazzjoni fil- plażma ta ’ digoxin u l- livelli ta ’ digoxin għandhom ikunu monitorati meta tinbeda jew titwaqqaf il- kura b’ posaconazole.
Sulfonylureas:
Sulfonajlurejas:
Glucose concentrations decreased in some healthy volunteers when glipizide was co- administered with posaconazole.
Il- konċentrazzjonijiet ta ’ glucose naqsu f’ xi voluntiera b’ saħħithom meta glipizide ingħata flimkien ma ’ posaconazole.
Monitoring of glucose concentrations is recommended in diabetic patients.
Monitoraġġ tal- konċentrazzjonijiet ta ’ glucose huwa rakkomandat f’ pazjenti dijabetiċi.
There is insufficient information on the use of posaconazole in pregnant women.
M’ hemmx tagħrif biżżejjed dwar l- użu ta ’ posaconazole f’ nisa waqt it- tqala.
Studies in animals have shown reproductive toxicity (see section 5.3).
Studji fuq annimali urew ħsara fuq is- sistema riproduttiva (ara sezzjoni 5. 3).
Women of childbearing potential have to use effective contraception during treatment.
Nisa li jistgħu joħorġu tqal għandhom jużaw kontraċettiv effettiv waqt it- trattament.
Posaconazole must not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the foetus.
Posaconazole m’ għandux jintuża waqt it- tqala ħlief meta l- benefiċċju għall- omm ma jkunx jegħleb b’ mod ċar ir - riskju li jista ’ jkun hemm għall- fetu.
Posaconazole is excreted into the milk of lactating rats (see section 5.3).
Posaconazole joħrog mal- ħalib ta ’ firien li jkunu qed ireddgħu (ara sezzjoni 5. 3).
The excretion of posaconazole in human breast milk has not been investigated.
L- eskrezzjoni ta ’ posaconazole fil- ħalib tal- mara għadu ma ’ ġiex mistħarreġ.
Breast-feeding must be stopped on initiation of treatment with posaconazole.
It- treddigħ għandu jitwaqqaf malli tibda l - kura b’ posaconazole.
No studies on the effects of posaconazole on the ability to drive and use machines have been performed.
Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni.
The safety of posaconazole has been assessed in > 2,400 patients and healthy volunteers enrolled in clinical trials and from post-marketing experience.
Is- sigurtà ta ’ posaconazole ġiet stmata f ’ > 2, 400 pazjent u voluntiera b’ saħħithom li ddaħħlu fi provi kliniċi u minn esperjenza ta ’ wara t- tqegħid fis- suq.
The most frequently reported serious related adverse events included nausea, vomiting, diarrhoea, pyrexia, and increased bilirubin.
L- aktar każijiet avversi li kienu rrappurtati ta ’ spiss kienu jinkludu dardir, remettar, dijarea, deni u żieda fil- bilirubin.
Table 2.
7 Tabella 2.
Treatment-related adverse events (TRAE) by body system and frequency Common (≥ 1/ 100, < 1/ 10); uncommon (≥ 1/ 1,000, < 1/ 100); rare (≥ 1/ 10,000, < 1/ 1,000)
Każijiet avversi relatati mal- kura (TRAE) skond is- sistema tal- ġisem u l- frekwenza Komuni (≥1/ 100, < 1/ 10); Mhux komuni (≥1/ 1, 000, < 1/ 100); rari (≥1/ 10, 000, < 1/ 1, 000) Disturbi tad- demm u tas- sistema limfatika Komuni:
neutropenia thrombocytopenia, leukopenia, anaemia, eosinophilia, lymphadenopathy
newtropenja tromboċitopenia, lewkopenja, anemija, eżinofilja, limfadenopatija
haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura, pancytopenia, coagulopathy, haemorrhage
sindrome ħemolitika uremika, purpura trombotika tromboċitopenika, panċitopenja, koagulopatija, emorraġġija
allergic reaction hypersensitivity reaction
reazzjoni allerġika reazzjoni ta ’ sensittività eċċessiva
adrenal insufficiency, blood gonadotropin decreased
insuffiċjenza adrenali, tnaqqis tal- gonadotropin fid- demm
electrolyte imbalance, anorexia hyperglycaemia
skwilibriju fl- elettroliti, anoressija ipergliċemija
Uncommon:
Disturbi fl- għajnejn Mhux komuni:
Cardiac disorders
Disturbi fil- widnejn u fis- sistema labirintika Rari:
Uncommon:
Disturbi fil- qalb Mhux komuni:
torsade de pointes, sudden death, ventricular tachycardia, cardio-respiratory arrest, cardiac failure, myocardial infarction
disturb psikotiku, dipressjoni parasteżija, sturdament, ngħas, uġigħ ta ’ ras aċċessjonijiet, newropatija, ipoesteżija, tregħid inċident ċerebrovaskulari, enċefalopatija, newropatija periferali, sinkope vista mċajpra diplopja, skotoma tnaqqis tas- smigħ sindrome ta ’ titwil tal- QT§, elettrokardjogramma anormali§, palpitazzjonijiet torsade de pointes, mewt f’ daqqa, takikardija ventrikulari, arrest kardjo- respiratorju, insuffiċjenza kardijaka, infart majokardijaku
hypertension, hypotension pulmonary embolism, deep vein thrombosis
pressjoni għolja, pressjoni baxxa emboliżmu pulmonari, trombożi fil- vini fondi
Respiratory, thoracic and mediastinal disorders Rare: pulmonary hypertension, interstitial pneumonia, pneumonitis Gastrointestinal disorders Common:
Disturbi respiratorji, toraċiċi u medjastinali Rari: ipertensjoni pulmonari, pulmonite fl- interstizzju, infezzjoni fil- pulmun Disturbi gastro- intestinali Komuni:
vomiting, nausea, abdominal pain, diarrhoea, dyspepsia, dry mouth, flatulence
rimettar, tqallih, uġigħ addominali, dijarea, dispepsja, ħalq xott, tifwieq
pancreatitis gastrointestinal haemorrhage, ileus
pankrejatite emorraġġija gastro- intestinali, iljus
Common:
8 Disturbi fil- fwied u fil- marrara Komuni:
liver function tests raised (ALT increased, AST increased, bilirubin increased, alkaline phosphatase increased, GGT increased)
testijiet tal- funzjoni tal- fwied jiġu għoljin (ALT jiżdied, AST jiżdied, bilirubin jiżdied, alkaline phosphatase jiżdied, GGT jiżdied)
hepatocellular damage*, hepatitis, jaundice, hepatomegaly hepatic failure, hepatitis cholestatic, cholestasis,
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
8 hepatosplenomegaly, liver tenderness, asterixis
ħsara epatoċellulari *, epatite, suffejra, epatomegalija insuffiċjenza epatika, epatite kolestatika, kolestażi, epatosplenomegalija, tenerezza tal- fwied, asteriksis
Skin and subcutaneous tissue disorders Common:
Komuni:
rash mouth ulceration, alopecia Stevens Johnson syndrome, vesicular rash
raxx ulċeri fil- ħalq, alopeċja sindrome ta ’ Stevens Johnson, raxx vessikulari
back pain
uġigħ fid- dahar
acute renal failure, renal failure, blood creatinine increased renal tubular acidosis, interstitial nephritis
insuffiċjenza renali akuta, insuffiċjenza renali, krejatinina fid- demm jiżdied
General disorders and administration site conditions
Disturbi fis- sistema riproduttiva u fis- sider
menstrual disorder breast pain
aċidożi tat- tubi renali ż- żgħar, nefrite fl- interstizzju
Common:
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata Komuni:
pyrexia (fever), asthenia, fatigue oedema, pain, chills, malaise tongue oedema, face oedema
deni (ssir taħraq), astenja, għeja edima, uġigħ, degħxiet, tħossok ma tiflaħx edima ta ’ l- ilsien, edima tal- wiċċ
Uncommon: § See section 4.4.
Mhux komuni: § Ara sezzjoni 4. 4
* During post-marketing surveillance severe
tibdil fil- livelli ta ’ mediċini
hepatic injury with fatal outcome has been reported (see section 4.4).
* Waqt is- sorveljanza ta ’ wara t- tqegħid fis- suq kienet irrappurtata ħsara severa fil- fwied li wasslet għall- mewt (ara sezzjoni 4. 4).
During clinical trials, patients who received posaconazole doses up to 1,600 mg/ day experienced no different adverse reactions from those reported with patients at the lower doses.
Waqt il- provi kliniċi, pazjenti li rċevew dożi ta ’ posaconazole sa 1, 600 mg/ jum ma kellhomx reazzjonijiet avversi differenti minn dawk rappurtati f’ pazjenti b’ dożi aktar baxxi.