natgillin/translations-raw huggingface dataset:
What you need to know before you take Posaconazole Accord
Što morate znati prije nego počnete uzimati Posakonazol Accord
menstrual disorder
poremećaj menstrualnog ciklusa
If you take more Posaconazole Accord than you should If you think that you may have taken too much Posaconazole Accord, talk to a doctor or go to the hospital straight away.
Ako uzmete više lijeka Posakonazol Accord nego što ste trebali Ako mislite da ste uzeli previše lijeka Posakonazol Accord, odmah se obratite liječniku ili otiđite u bolnicu.
Posaconazole is a potent inhibitor of CYP3A4.
Posakonazol je snažan inhibitor CYP3A4.
Similar recommendations apply to posaconazole tablets; however, a specific study has not been conducted with the posaconazole tablets.
Slične preporuke vrijede i za tablete posakonazola; međutim, nije provedeno posebno ispitivanje s tabletama posakonazola.
Study 5615 was conducted in a similar patient population to that previously studied in the pivotal posaconazole oral suspension clinical program.
Ispitivanje 5615 provedeno je u populaciji bolesnika koja je bila slična onoj prethodno ispitanoj u glavnom kliničkom programu ispitivanja oralne suspenzije posakonazola.
Quartile pCav Range (ng/mL)
Kvartil pCav raspon (ng/ml)
As HIV protease inhibitors are CYP3A4 substrates, it is expected that posaconazole will increase plasma levels of these antiretroviral agents.
Budući da su inhibitori HIV proteaze supstrati CYP3A4, očekuje se da će posakonazol povisiti koncentraciju ovih antiretrovirusnih lijekova u plazmi.
Most of the vinca alkaloids (e.g., vincristine and vinblastine) are substrates of CYP3A4.
Većina vinka alkaloida (npr. vinkristin i vinblastin) supstrati su CYP3A4.
Posaconazole, after administration of the tablet, has a mean apparent volume of distribution of 394 L (42%), ranging between 294-583 L among the studies in healthy volunteers.
Nakon primjene tablete, posakonazol ima srednju vrijednost prividnog volumena distribucije od 394 l (42 %), koji se kreće u rasponu od 294-583 l u ispitivanjima u zdravih dobrovoljaca.
Posaconazole tablets are absorbed with a median Tmax of 4 to 5 hours and exhibits dose proportional pharmacokinetics after single and multiple dosing up to 300 mg.
Tablete posakonazola apsorbiraju se uz medijan tmax od 4 do 5 sati i pokazuju farmakokinetiku proporcionalnu dozi nakon jednokratnog i višekratnog doziranja do 300 mg.
In twelve-month neurotoxicity studies in dogs and monkeys, no functional effects were observed on the central or peripheral nervous systems at systemic exposures greater than those achieved therapeutically.
U dvanaestomjesečnim ispitivanjima neurotoksičnosti na psima i majmunima nisu opaženi funkcionalni učinci na središnji ili periferni živčani sustav pri sistemskoj izloženosti većoj od one koja se postiže tijekom liječenja.
The addition of posaconazole to therapy with atazanavir or with atazanavir plus ritonavir was associated with increases in plasma bilirubin levels.
Dodavanje posakonazola terapiji s atazanavirom ili atazanavirom i ritonavirom bilo je povezano s povišenim razinama bilirubina u plazmi.
blurred vision, photophobia, visual acuity reduced
zamagljen vid, fotofobija, smanjena oštrina vida
Posaconazole has been shown in vitro to be active against the following microorganisms: Aspergillus species (Aspergillus fumigatus, A. flavus, A. terreus, A. nidulans, A. niger, A. ustus), Candida species (Candida albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis, C. dubliniensis, C. famata, C. inconspicua, C. lipolytica, C. norvegensis, C. pseudotropicalis), Coccidioides immitis, Fonsecaea pedrosoi, and species of Fusarium, Rhizomucor, Mucor, and Rhizopus.
Pokazalo se da posakonazol in vitro djeluje na sljedeće mikroorganizme: vrste roda Aspergillus (Aspergillus fumigatus, A. flavus, A. terreus, A. nidulans, A. niger, A. ustus), vrste roda Candida (Candida albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis, C. dubliniensis, C. famata, C. inconspicua, C. lipolytica, C. norvegensis, C. pseudotropicalis), Coccidioides immitis, Fonsecaea pedrosoi te vrste rodova Fusarium, Rhizomucor, Mucor i Rhizopus.
Overall efficacy of posaconazole oral suspension at the end of treatment for invasive aspergillosis in comparison to an external control group
Tablica 4. Ukupna djelotvornost oralne suspenzije posakonazola na završetku liječenja invazivne aspergiloze u usporedbi s vanjskom kontrolnom skupinom Oralna suspenzija posakonazola
Do not switch between taking Posaconazole Accord tablets and posaconazole oral suspension without talking to your doctor or pharmacist because it may result in a lack of efficacy or an increased risk of adverse reactions.
Nemojte prijeći s Posakonazol Accord tableta na oralnu suspenziju posakonazola ili obrnuto bez razgovora s liječnikom ili ljekarnikom jer to može dovesti do smanjenja djelotvornosti lijeka i povećanog rizika za pojavu nuspojava.
Calcium channel blockers metabolised through CYP3A4 (e.g. diltiazem, verapamil, nifedipine, nisoldipine)
Blokatori kalcijevih kanala koji se metaboliziraju putem CYP3A4 (npr. diltiazem, verapamil, nifedipin, nizoldipin)
Therefore, trough concentrations that fall in the upper part of the usual therapeutic range should be targeted and careful attention should be paid to clinical signs and symptoms, laboratory parameters and tissue biopsies.
Stoga treba ciljati da najniža koncentracija sirolimusa bude u gornjem dijelu uobičajenog raspona terapijskih vrijednosti, te u tom smislu treba pozorno pratiti kliničke znakove i simptome, laboratorijske nalaze i nalaze biopsije tkiva.
However, the safety profile of posaconazole between the Black and Caucasian subjects was similar.
Ipak, sigurnosni profil posakonazola bio je sličan u ispitanika crne i bijele rase.
Limited data on the effect of hepatic impairment (including Child-Pugh C classification of chronic liver disease) on the pharmacokinetics of posaconazole demonstrate an increase in plasma exposure compared to subjects with normal hepatic function, but do not suggest that dose adjustment is necessary (see sections 4.4 and 5.2).
Ograničeni podaci o učinku oštećenja funkcije jetre (uključujući kroničnu bolest jetre stadija C prema Child-Pugh klasifikaciji) na farmakokinetiku posakonazola pokazuju povećanu izloženost u plazmi u usporedbi s ispitanicima s normalnom funkcijom jetre, ali ne ukazuju na potrebu prilagodbe doze (vidjeti dijelove 4.4 i 5.2).
Monitoring of glucose concentrations is recommended in diabetic patients.
Preporučuje se kontrolirati koncentraciju glukoze u bolesnika sa šećernom bolešću.
The safety of posaconazole oral suspension has been assessed in > 2,400 patients and healthy volunteers enrolled in clinical trials and from post-marketing experience.
Sigurnost primjene oralne suspenzije posakonazola ocijenjena je u >2400 bolesnika i zdravih dobrovoljaca uključenih u klinička ispitivanja i na temelju podataka prikupljenih nakon stavljanja lijeka u promet.
Chromoblastomycosis/Mycetoma
Kromoblastomikoza/micetom
Concomitant administration of azole antifungals, including posaconazole, with vincristine has been associated with neurotoxicity and other serious adverse reactions, including seizures, peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion, and paralytic ileus.
Istodobna primjena azolnih antimikotika, uključujući posakonazol, s vinkristinom povezana je s neurotoksičnošću i drugim ozbiljnim nuspojavama, uključujući napadaje, perifernu neuropatiju, sindrom neodgovarajućeg lučenja antidiuretskog hormona i paralitički ileus.
Effects of other medicinal products on posaconazole
Učinci drugih lijekova na posakonazol
- Candida albicans: S ≤0.06 mg/L, R >0.06 mg/L - Candida tropicalis: S ≤0.06 mg/L, R >0.06 mg/L - Candida parapsilosis: S ≤0.06 mg/L, R >0.06 mg/L
(R)] su: - Candida albicans: S ≤ 0,06 mg/l, R > 0,06 mg/l - Candida tropicalis: S ≤ 0,06 mg/l, R > 0,06 mg/l - Candida parapsilosis: S ≤ 0,06 mg/l, R > 0,06 mg/l
Liver function tests should be evaluated at the start of and during the course of posaconazole therapy.
Pretrage funkcije jetre treba procijeniti na početku i tijekom liječenja posakonazolom.
Renal clearance is a minor elimination pathway, with 14% of the radiolabelled dose excreted in urine (< 0.2% of the radiolabelled dose is parent compound).
Posakonazol se manjim dijelom eliminira putem bubrega, uz 14% radioaktivno označene doze izlučene mokraćom (<0,2% radioaktivno označene doze je izvorni spoj).
Safety and efficacy in paediatric patients below the age of 18 years have not been established.
Sigurnost i djelotvornost posakonazola u bolesnika mlađih od 18 godina nisu ustanovljene.
Posaconazole is excreted into the milk of lactating rats (see section 5.3).
Posakonazol se izlučuje u mlijeko ženki štakora tijekom laktacije (vidjeti dio 5.3).
At exposures lower than those obtained at therapeutic doses in humans, posaconazole caused skeletal variations and malformations, dystocia, increased length of gestation, reduced mean litter size and postnatal viability.
Pri izloženosti manjoj od one koja se postiže terapijskim dozama u ljudi posakonazol je prouzročio koštane varijacije i malformacije, distociju, produljeno trajanje gestacije, smanjenu prosječnu veličina okota i smanjenu sposobnost postnatalnog preživljavanja.
INFORMATION IN BRAILLE Posaconazole Accord 100 mg
16. PODACI NA BRAILLEOVOM PISMU Posakonazol Accord 100 mg
After administration of 14C-posaconazole, radioactivity was predominantly recovered in the faeces (77% of the radiolabelled dose) with the major component being parent compound (66% of the radiolabelled dose).
Nakon primjene 14C-posakonazola, radioaktivnost se uglavnom otkrila u stolici (77% radioaktivno označene doze), a glavnu je komponentu činio izvorni spoj (66% radioaktivno označene doze).
cerebrovascular accident, encephalopathy, peripheral neuropathy, syncope
cerebrovaskularni događaj, encefalopatija, periferna neuropatija, sinkopa
However, as posaconazole is not significantly renally eliminated, an effect of severe renal impairment on the pharmacokinetics of posaconazole is not expected and no dose adjustment is recommended.
Međutim, kako se posakonazol ne eliminira putem bubrega u značajnoj mjeri, ne očekuje se da će teško oštećenje funkcije bubrega utjecati na farmakokinetiku posakonazola te se prilagođavanje doze ne preporučuje.
If you are already taking rifabutin, you will need a blood test and you will need to look out for some possible side effects of rifabutin.
trebat ćete napraviti krvnu pretragu i paziti na neke moguće nuspojave rifabutina.
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.
Liječenje mora započeti liječnik s iskustvom u liječenju gljivičnih infekcija ili pružanju suportivne skrbi visokorizičnim bolesnicima u kojih je indicirana profilaksa posakonazolom.
No clinically relevant changes in the mean QTc (Fridericia) interval from baseline were observed.
Nisu opažene klinički značajne promjene prosječnog QTc-intervala (Fridericia) u odnosu na početne vrijednosti.
The mean duration of therapy was 29 days for posaconazole and 25 days for fluconazole/itraconazole.
Prosječno trajanje liječenja posakonazolom iznosilo je 29 dana, a flukonazolom/itrakonazolom 25 dana.
If these medicinal products are co-administered, careful monitoring of full blood counts and adverse reactions related to increased rifabutin levels (e.g. uveitis) is recommended.
Ako se ovi lijekovi primjenjuju istodobno, preporučuje se pozorno nadzirati kompletnu krvnu sliku kao i nuspojave povezane s povećanom koncentracijom rifabutina (npr. uveitis).
Midazolam and other benzodiazepines metabolised by CYP3A4
Midazolam i drugi benzodiazepini koji se metaboliziraju putem CYP3A4
Increased systolic and arterial blood pressures (up to 29 mm-Hg) were seen in rats and monkeys at systemic exposures 2.1-fold and 8.5-fold greater, respectively, than those achieved with the human therapeutic doses.
Zabilježeno je povišenje sistoličkog i arterijskog krvnog tlaka (do 29 mmHg) u štakora i majmuna pri sistemskoj izloženosti 2,1 puta odnosno 8,5 puta većoj od one koja se postiže terapijskim dozama u ljudi.
The safety of posaconazole tablets has been assessed in 230 patients enrolled in the pivotal clinical study.
Sigurnost tableta posakonazola procijenjena je u 230 bolesnika uključenih u glavno kliničko ispitivanje.
A key secondary endpoint was the incidence of proven/probable IFIs during the on-treatment period (first dose to last dose of study medicinal product + 7 days).
Ključna sekundarna mjera ishoda bila je incidencija dokazane/vjerojatne IGI tijekom perioda liječenja (od prve do zadnje doze ispitivanog lijeka + 7 dana).
Posaconazole oral suspension
Oralna suspenzija posakonazola
Among eighteen patients who were intolerant or had infections refractory to amphotericin B or itraconazole, seven patients were classed as responders.
Od 18 bolesnika koji nisu podnosili amfotericin B ili itrakonazol ili su imali infekcije otporne na te lijekove, sedam ih je odgovorilo na liječenje.
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.
Moguće je da je učinak posakonazola na supstrate CYP3A4 u bolesnika nešto manji od učinka opaženog u zdravih dobrovoljaca, a očekuju se i razlike između pojedinih bolesnika zbog različitog stupnja izloženosti posakonazolu.
However, this was not a prospective, randomised controlled study and so all comparisons with the external control group should be viewed with caution.
kontrolirano ispitivanje, svaku se usporedbu s vanjskom kontrolnom skupinom mora razmotriti uz oprez.
In both prophylaxis studies, aspergillosis was the most common breakthrough infection.
U oba ispitivanja profilaktičke primjene, najčešća probojna infekcija koja se pojavila bila je aspergiloza.
There is insufficient information on the use of posaconazole in pregnant women.
Nema dovoljno podataka o primjeni posakonazola u trudnica.
Patients who have severe diarrhoea or vomiting should be monitored closely for breakthrough fungal infections.
Bolesnike koji imaju jaki proljev ili povraćaju treba pomno nadzirati zbog mogućih probojnih gljivičnih infekcija.
Do not take Posaconazole Accord - if you are allergic to posaconazole or any of the other ingredients of this medicine (listed in section 6).
- ako ste alergični na posakonazol ili neki drugi sastojak ovog lijeka (naveden u dijelu 6.);
You may need to have blood tests while you are taking this medicine.
Dok uzimate ovaj lijek, možda ćete morati raditi pretrage krvi;
Caution should be used when prescribing Posaconazole Accord to patients with hypersensitivity to other azoles.
Potreban je oprez kad se Posakonazol Accord propisuje bolesnicima preosjetljivima na druge azole.
The safety of posaconazole tablet has been assessed in 336 patients and healthy volunteers enrolled in clinical trials.
Sigurnost primjene tableta posakonazola ocijenjena je u 336 bolesnika i zdravih dobrovoljaca uključenih u klinička ispitivanja.
200 mg four times daily (hospitalized) then 400 mg twice daily
200 mg četiri puta na dan (hospitalizirani) a zatim 400 mg dvaput na dan
Posaconazole does not have any major circulating metabolites and its concentrations are unlikely to be altered by inhibitors of CYP450 enzymes.
Posakonazol nema značajnijih cirkulirajućih metabolita i nije vjerojatno da bi inhibitori enzima CYP450 promijenili njegovu koncentraciju.
Posaconazole tablets are the preferred formulation to optimize plasma concentrations and generally provide higher plasma drug exposures than posaconazole oral suspension.
Tablete posakonazola formulacija su kojoj se daje prednost za optimiziranje koncentracija u plazmi i općenito osiguravaju veću izloženost lijeku u plazmi od oralne suspenzije posakonazola.
Fixed-time periodc
U definiranom vremenskom razdobljuc
Maximum duration of exposure to the tablet formulation was shorter than with the oral suspension.
Maksimalno trajanje izloženosti formulacije u obliku tablete bilo je kraće nego formulacije u obliku oralne suspenzije.
As observed with other azole antifungal agents, these effects on reproduction were considered to be due to a treatment-related effect on steroidogenesis.
Smatra se da su, kao i kod drugih azolskih antimikotika, navedeni učinci na reprodukciju posljedica utjecaja terapije na steroidogenezu.
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).
Kada se započinje liječenje posakonazolom u bolesnika koji već primaju ciklosporin, treba smanjiti dozu ciklosporina (npr. na otprilike tri četvrtine dotadašnje doze).
In rabbits, posaconazole was embryotoxic at exposures greater than those obtained at therapeutic doses.
U kunića je posakonazol pokazao embriotoksične učinke pri izloženosti većoj od one koja se postiže terapijskim dozama.
It is recommended to exercise caution due to the potential for higher plasma exposure.
ali se savjetuje oprez zbog moguće veće izloženosti u plazmi.
Patients were immunocompromised with underlying conditions including haematological malignancy, neutropenia post-chemotherapy, GVHD, and post HSCT.
Bolesnici su bili imunokompromitirani, s osnovnim stanjima kao što su hematološka zloćudna bolest, neutropenija nakon kemoterapije, GVHD i stanje nakon HSCT.
Pharmacokinetic modeling with an oral tablet formulation suggests that patients weighing greater than 120 kg may have lower posaconazole exposure.
Prema farmakokinetičkom modeliranju s lijekom u obliku tableta za peroralnu primjenu, bolesnici s tjelesnom težinom većom od 120 kg mogu biti manje izloženi posakonazolu.
Controla Proportion (%) of patients with proven/probable Aspergillosis On-treatment period b
Kontrolna skupinaa Udio (%) bolesnika s dokazanom/vjerojatnom aspergilozom
Prophylaxis of invasive fungal infections
Profilaksa invazivnih gljivičnih infekcija
Posaconazole may increase the plasma concentration of ergot alkaloids (ergotamine and dihydroergotamine), which may lead to ergotism.
Posakonazol može povećati koncentraciju ergot alkaloida (ergotamina i dihidroergotamina) u plazmi, što može dovesti do ergotizma.
Posaconazole is highly protein bound (> 98%), predominantly to serum albumin.
Posakonazol se u visokom postotku veže za proteine (>98 %), uglavnom za serumski albumin.
Posaconazole Accord may possibly increase the risk of side effects of some other medicines by increasing the amount of these medicines in the blood.
Posakonazol Accord može povećati rizik od nuspojava nekih drugih lijekova jer može povećati količinu tih lijekova u krvi.
Results from clinical studies in prophylaxis of Invasive Fungal Infections Study
Rezultati kliničkih ispitivanja profilakse invazivnih gljivičnih infekcija
Safety data at higher exposure levels achieved with posaconazole tablets are at present limited.
Trenutno dostupni podaci o sigurnosti pri izlaganju višim koncentracijama kod primjene tableta posakonazola su ograničeni.
Supportive care may be considered.
Može se razmotriti pružanje potpornih mjera.
Unbound concentrations were not determined and it cannot be excluded that there is a larger increase in unbound posaconazole exposure than the observed 60% increase in total AUC.
Nisu određene koncentracije nevezanog lijeka te se ne može isključiti da je porast izloženosti nevezanom posakonazolu veći od opaženog porasta ukupnog AUC-a od
A key secondary endpoint was the incidence of proven/probable IFIs at 100 days post-randomization.
Ključna sekundarna mjera ishoda bila je incidencija dokazane/vjerojatne IGI 100 dana nakon randomizacije.
H2 receptor antagonists and proton pump inhibitors No clinically relevant effects were observed when posaconazole tablets are concomitantly used with antacids, H2-receptor antagonists and proton pump inhibitors.
Antagonisti H2-receptora i inhibitori protonske pumpe Nisu opaženi klinički važni učinci kad su se tablete posakonazola istodobno primjenjivale s antacidima, antagonistima H2-receptora i inhibitorima protonske pumpe.
There are limited pharmacokinetic data in patients with severe gastrointestinal dysfunction (such as severe diarrhoea).
Gastrointestinalna disfunkcija Farmakokinetički podaci u bolesnika s teškom gastrointestinalnom disfunkcijom (npr. jakim proljevom)
Posaconazole is not removed by haemodialysis.
Posakonazol se ne može ukloniti hemodijalizom.
During post-marketing surveillance of posaconazole oral suspension, severe hepatic injury with fatal outcome has been reported (see section 4.4).
Tijekom praćenja nakon stavljanja u promet oralne suspenzije posakonazola prijavljena su teška oštećenja jetre sa smrtnim ishodom (vidjeti dio 4.4).
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 reactions, plasma concentrations of the CYP3A4 substrate and/or adverse reactions should be closely monitored and the dose adjusted as needed.
Ako se posakonazol primjenjuje istodobno sa supstratima CYP3A4 koji se primjenjuju peroralno, a kod kojih porast koncentracije u plazmi može biti povezan s razvojem neprihvatljivih nuspojava, preporučuje se pomno nadzirati koncentracije supstrata CYP3A4 u plazmi i/ili nuspojave te po potrebi prilagoditi njihovu dozu.
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.
Ako se smatra da je istodobna primjena neizbježna, preporučuje se jako sniziti dozu sirolimusa tijekom započinjanja liječenja posakonazolom te vrlo često kontrolirati koncentracije sirolimusa u punoj krvi na kraju intervala doziranja.
Of the circulating metabolites, the majority are glucuronide conjugates of posaconazole with only minor amounts of oxidative (CYP450 mediated) metabolites observed.
Većina metabolita u cirkulaciji su glukuronidni konjugati posakonazola, a opažene su samo manje količine oksidativnih metabolita (posredstvom enzima CYP450).
Posaconazole should be used with caution in patients with hepatic impairment due to limited clinical experience and the possibility that posaconazole plasma levels may be higher in these patients (see sections 4.2 and 5.2).
Posakonazol se mora primjenjivati uz oprez u bolesnika s oštećenjem funkcije jetre zbog ograničenog kliničkog iskustva i mogućnosti većih koncentracija posakonazola u plazmi u tih bolesnika (vidjeti dijelove 4.2 i 5.2).
Patients were enrolled in a non-comparative pharmacokinetic and safety trial of posaconazole tablets when given as antifungal prophylaxis.
Bolesnici su bili uključeni u nekomparativno ispitivanje farmakokinetike i sigurnosti tableta posakonazola kad se posakonazol davao kao antimikotička profilaksa.
The excretion of posaconazole in human breast milk has not been investigated.
Izlučivanje posakonazola u majčino mlijeko u ljudi nije se ispitivalo.
Administration of other azoles has been associated with increases in digoxin levels.
Primjena drugih azola povezuje se s povećanjem koncentracije digoksina.
If concomitant administration is required, close monitoring for breakthrough fungal infections is recommended.
Ako je istodobna primjena neophodna, preporučuje se pomno nadziranje zbog mogućih probojnih gljivičnih infekcija.
Treatment with these HMG-CoA reductase inhibitors should be discontinued during treatment with posaconazole as increased levels have been associated with rhabdomyolysis (see section 4.3).
Liječenje inhibitorima HMG-CoA reduktaze mora se prekinuti tijekom liječenja posakonazolom jer se povećane koncentracije povezuju s rabdomiolizom (vidjeti dio 4.3).
If you are not sure, talk to your doctor or pharmacist before taking this medicine.
obratite se svom liječniku ili ljekarniku prije uzimanja ovog lijeka.
Posaconazole increased the Cmax and AUC of rifabutin by 31% and 72%, respectively.
Rifabutin Posakonazol je povećao Cmax rifabutina za 31%, a AUC za 72%.