qanastek/EMEA-V3 huggingface dataset:
Electrocardiogram QT corrected interval prolonged, blood urea increased, blood cholesterol increased
Intervall QT korrett itwal fuq l- elettrokardjograma, żieda fl- urea fid- demm, żieda fil- kolesterol fid- demm
Very common Uncommon
Komuni ħafna Mhux komuni
Oedema peripheral Ventricular fibrillation, ventricular arrhythmia, syncope, supraventricular arrhythmia, supraventricular tachycardia, tachycardia, bradycardia
Edima periferika Fibrillazzjoni ventrikolari, arritmija ventrikolari, sinkope, arritmija supraventrikolari, takikardija supraventrikolari, takikardija, brakikardija
Torsades de pointes, ventricular tachycardia, atrioventricular complete block, bundle branch block, nodal rhythm
Torsades de pointes, takikardija ventrikolari, atrioventricular complete block, bundle branch block, nodal rhythm
Blood and Lymphatic system disorders Common
Mard tad- demm u tas- sistema limfatika Komuni
Pancytopenia, bone marrow depression, leukopenia, thrombocytopenia, purpura, anaemia
Pancytopenia, depressjoni tal- mudullun ta 'l- għadam, leukopenia, thrombocytopenia, purpura, anemija
Disseminated intravascular coagulation, agranulocytosis, lymphadenopathy, eosinophilia
Koagulazzjoni intravaskulari mifruxa, agranulocytosis, lymphadenopathy, eosinophilia
Nervous system disorders Very common Common Uncommon Rare
Mard tas- sistema nervuża Komuni ħafna Komuni Mhux komuni Rari
Headache Dizziness, confusional state, tremor, agitation, paraesthesia Brain oedema, ataxia, diplopia, vertigo, hypoaesthesia Convulsion, encephalopathy, Guillain-Barre syndrome, extrapyramidal symptoms
Uġigħ ta 'ras Sturdament, stat konfużjonali, tregħid, aġitazzjoni, parasteżija Edima fil- moħħ, atassja, diplopia, vertiġini, ipoestesija Konvulżjoni, enċefalopatija, sindrome ta' Guillain- Barre, sintomi ekstrapiramidali
Eye disorders Very common
Mard ta 'l- għajnejn
Visual disturbances (including blurred vision (see Section 4.4), chromatopsia and photophobia)
Disturbi viżwali (inklużi vista mċajpra (ara Sezzjoni 4. 4), kromatopsija u fotofobja)
Papilloedema (see Section 4.4), optic nerve disorder (including optic neuritis, see Section 4.4), nystagmus, scleritis, blepharitis
Papilloedima (ara Sezzjoni 4. 4), mard tan- nerv ottiku (inkluża newrite ta ’ l- għajn, ara Sezzjoni 4. 4), nystagmus, sklerite, blefarite
Retinal haemorrhage, optic atrophy, oculogyration, corneal opacity
Emorraġija tar- retina, atrofija ottika, oculogyration, opaċità tal - kornea
Ear and labyrinth disorders Rare Hypoacusis, tinnitus
Mard tal- widnejn u tas- sistema labirintika Rari Hypoacusis, żanżin fil- widnejn
Respiratory, thoracic and mediastinal disorders Common
Mard respiratorju, toraċiku u medjastinali Komuni
Acute respiratory distress syndrome, pulmonary oedema, respiratory distress, chest pain
Sindrome ta 'dwejjaq respiratorji akuti, edima pulmonari, dwejjaq respiratorji, uġigħ tas- sider
12 Gastrointestinal disorders Very common Uncommon
Komuni ħafna Mhux komuni
Abdominal pain, nausea, vomiting, diarrhoea Pancreatitis, peritonitis, duodenitis, gingivitis, glossitis, swollen tongue, dyspepsia, constipation
Uġigħ addominali, dardir, rimettar, dijarea Pankreatite, peritonite, duwodenite, ġenġivite, glossite, ilsien minfuħ, dispepsja, kostipazzjoni
Renal and urinary disorders Common Uncommon Rare
13 Mard tal- kliewi u tas- sistema urinarja Komuni Mhux komuni Rari
Renal failure acute, haematuria Nephritis, proteinuria Renal tubular necrosis
Insuffiċjenza renali akuta, ematurja Nefrite, proteinurja Nekrosi tubulari tal- kliewi
Skin and subcutaneous tissue disorders Very common Common
Mard tal- ġilda u tat- tessuti ta 'taħt il- ġilda Komuni ħafna Komuni
Rash Exfoliative dermatitis, face oedema, photosensitivity reaction, maculo-papular rash, macular rash, papular rash, cheilitis, pruritus, alopecia, erythema
Raxx Dermatite sfoljattiva, edima fil- wiċċ, reazzjoni ta 'fotosensittività, raxx makulari bl- infafet, raxx makulari, raxx bl- infafet, cheilitis, ħakk, alopeċja, eritema
Stevens-Johnson syndrome, angioneurotic oedema, allergic dermatitis, urticaria, drug hypersensitivity, psoriasis
Sindrome ta 'Stevens- Johnson, edima anġjonewrotika, dermatite allerġika, urtikarja, sensittività eċċessiva għall- mediċina, psorajiżi
Toxic epidermal necrolysis, erythema multiforme, discoid lupus erythematosis
Nekroliżi epidermika tossika, eritema multiformi, discoid lupus erythematosis
Musculoskeletal and connective tissue disorders Common Uncommon Rare
Mard muskolo- skeletali u tat- tessut konnettiv Komuni Mhux komuni Rari
Back pain Arthritis Hypertonia
Uġigħ tad- dahar Artrite Ipertonija
Endocrine disorders
Mard fis- sistema endokrinarja Mhux komuni Rari
Adrenal insufficiency Hyperthyroidism, hypothyroidism
Insuffiċjenza adrenali Ipertirojdiżmu, ipotirojdiżmu
Metabolism and nutrition system disorders Common
Mard marbut mal- metaboliżmu u n- nutrizzjoni Komuni
Hypoglycaemia, hypokalaemia
Ipogliċemija, ipokalimja
Infections and infestation Common Rare
Infezzjonijiet u infestazzjoni Komuni Rari
Gastroenteritis, influenza-like illness Pseudomembranous colitis
Gastroenterite, mard jixbah lill- influwenza Kolite psewdomembranika
Vascular disorders
Mard vaskulari
Common Rare
Komuni Rari
Hypotension, thrombophlebitis, phlebitis Lymphangitis
Pressjoni baxxa, tromboflebite, flebite Limfanġite
General disorders and administrative site conditions Very common Common
Mard ġenerali u kondizzjonijiet ta 'mnejn jingħata Komuni ħafna Komuni
Pyrexia Injection site reaction / inflammation, chills, asthenia,
Deni Reazzjoni fil- post ta 'l- injezzjoni, kesħa, astenja
Immune system disorders Common Uncommon
Mard tas- sistema immuni
Sinusitis Anaphylactoid reaction, hypersensitivity
Sinożite Reazzjoni anaphylactoid, sensittività eċċessiva
13 Hepato-biliary disorders Common Uncommon
Mard tal- fwied u tal- marrara Komuni Mhux komuni
Jaundice, cholestatic jaundice Hepatic failure, hepatitis, hepatomegaly, cholecystitis, cholelithiasis
Suffejra, suffejra kolestatika Insuffiċjenza epatika, epatite, epatomegalija, koleċistite, cholelithiasis
Hepatic coma
Koma epatika
Psychiatric disorders
Mard psikjatriku
Depression, anxiety, hallucination Insomnia
Depressjoni, ansjetà, alluċinazzjoni Nuqqas ta 'rqad
Visual disturbances In clinical trials, voriconazole treatment-related visual disturbances were very common.
14 Disturbi viżwali Fi studji kliniċi, disturbi viżwali marbuta mal- kura b' voriconazole kienu komuni ħafna.
In these studies, short-term as well as long-term treatment, approximately 30% of subjects experienced altered/ enhanced visual perception, blurred vision, colour vision change or photophobia.
F' dawn it - testijiet kliniċi, b' kura kemm fuq perijodu qasir kif ukoll fuq perijodu twil, madwar 30% tas- suġġetti esperjenzaw perċezzjoni viżwali mibdula/ mkabbra, vista mċajpra, tibdil fil- vista tal- kulur jew fotofobija.
These visual disturbances were transient and fully reversible, with the majority spontaneously resolving within 60 minutes and no clinically significant long-term visual effects were observed.
Dawn id- disturbi viżwali ma damux u kompletament riversibbli, bil- maġġoranza jmorru b' mod spontanju fi żmien 60 minuta u ma kienu osservati ebda effetti viżwali klinikament sinifikanti fuq perjodu fit- tul.
There was evidence of attenuation with repeated doses of voriconazole.
Kien hemm evidenza ta 'attenwazzjoni b' dożi ripetuti ta' voriconazole.
The visual disturbances were generally mild, rarely resulted in discontinuation and were not associated with long-term sequelae.
Id- disturb viżwali kien ġeneralment ħafif, rari wassal għal twaqqif tal- kura u ma kienx assoċjat ma 'sintomi morbużi għal perjodu twil.
Visual disturbances may be associated with higher plasma concentrations and/ or doses.
Id- disturbi viżwali jistgħu jkunu assoċjati ma 'konċentrazzjonijiet akbar fil - plasma u/ jew dożi ogħla.
The mechanism of action is unknown, although the site of action is most likely to be within the retina.
Il- mekkaniżmu ta 'azzjoni mhux magħruf, għalkemm il- post ta' l- azzjoni wisq probabbli li jkun fir - retina.
In a study in healthy volunteers investigating the impact of voriconazole on retinal function, voriconazole caused a decrease in the electroretinogram (ERG) waveform amplitude.
Fi studju fost voluntiera b' saħħithom li eżamina l- impatt ta 'voriconazole fuq il- funzjoni tar- retina, voriconazole kkawża tnaqqis fl- electroretinogram (ERG) waveform amplitude.
The ERG measures electrical currents in the retina.
L- ERG ikejjel il - kurrenti elettriċi fir- retina.
The ERG changes did not progress over 29 days of treatment and were fully reversible on withdrawal of voriconazole.
Il- bidliet ta 'l- ERG ma avanzawx f' 29 jum ta' kura u kienu kompletament riversibbli mat- twaqqif ta 'voriconazole.
Dermatological reactions Dermatological reactions were common in patients treated with voriconazole in clinical trials, but these patients had serious underlying diseases and were receiving multiple concomitant medications.
Reazzjonijiet dermatoloġiċi Ir- reazzjonijiet dermatoloġiċi kienu komuni f' pazjenti kkurati b' voriconazole f' testijiet kliniċi, iżda dawn il- pazjenti kellhom mard serju preżenti u kienu qegħdin jirċievu diversi medikazzjonijiet konkomitanti.
The majority of rashes were of mild to moderate severity.
Il- maġġoranza tar- raxxijiet kienu ta 'severità ħafifa għal moderata.
Patients have rarely developed serious cutaneous reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme during treatment with VFEND.
Il- pazjenti rari żviluppaw reazzjonijiet kutanji serji, inkluż is- sindrome ta 'Stevens- Johnson, nekroliżi epidermika tossika u eritema multiformi waqt kura b' VFEND.
Photosensitivity reactions have been reported, especially during long-term therapy (see also section 4.4).
Kienu rrapportati reazzjonijiet ta 'fotosensittività, speċjalment waqt terapija fuq perjodu fit- tul (ara wkoll sezzjoni 4. 4).
Liver Function Tests The overall incidence of clinically significant transaminase abnormalities in the voriconazole clinical programme was 13.4% (200/ 1493) of subjects treated with voriconazole.
Testijiet tal- Funzjoni tal- Fwied L- inċidenza globali ta 'anormalitajiet transaminase klinikament sinifikanti fil- programm kliniku b' voriconazole kienet 13. 4% (200/ 1493) tas- suġġetti kkurati b' voriconazole.
Liver function test abnormalities may be associated with higher plasma concentrations and/ or doses.
L- anormalitajiet fit - testijiet tal- funzjoni tal- fwied jistgħu jkunu assoċjati ma 'konċentrazzjonijiet akbar fil- plasma u/ jew dożi ogħla.
The majority of abnormal liver function tests either resolved during treatment without dose adjustment or following dose adjustment, including discontinuation of therapy.
Il- maġġoranza tat- testijiet abnormali tal- funzjoni tal- fwied kienu riżolti waqt kura mingħajr aġġustament fid- doża jew wara aġġustament fid- doża, inkluż it- twaqqif tat- terapija.
Voriconazole has been infrequently associated with cases of serious hepatic toxicity in patients with other serious underlying conditions.
Voriconazole ġie assoċjat mhux ta 'spiss ma' każijiet ta 'tossiċità epatika serja f' pazjenti b' kondizzjonijiet serji oħra eżistenti.
This includes cases of jaundice, and rare cases of hepatitis and hepatic failure leading to death (see section 4.4).
Dan jinkludi każijiet ta 'suffejra, u każi ta' epatite u insuffiċjenza epatika li twassal għall- mewt (ara sezzjoni 4. 4).
Paediatric Use The safety of voriconazole was investigated in 245 paediatric patients aged 2 to < 12 years who were treated with voriconazole in pharmacokinetic studies (87 paediatric patients) and in compassionate use programs (158 paediatric patients).
Użu pedjatriku Is- sigurtà ta 'voricoanzole ġiet studjata f' 245 pazjent pedjatriku fl- etajiet ta' 2 sa < 12- il sena li kienu kkurati b' voriconazole fi studji farmakokinetiċi (87 pazjent pedjatriku) u fi programmi ta 'użu ħanin (158 pazjent pedjatriku).
The adverse event profile of these 245 paediatric patients was similar to that in adults.
Il- profil ta 'l- episodji avversi ta' dawn il- 245 pazjent pedjatriku kien simili għal dak ta 'l- adulti.
14 blood bilirubin increased (1), hepatic enzymes increased (1), rash (1) and papilloedema (1).
Fit- 22 pazjent ta 'anqas minn sentejn li rċevew voriconazole fi programm ta' użu ħanin, kienu rrapportati l- episodji avversi li ġejjin (li għalihom ma setgħetx tiġi eskluża relazzjoni ma 'voriconazole): reazzjoni ta' fotosensittività (1), arritmija (1), pankreatite (1), bilirubin fid- demm aktar (1), enzimi epatiċi aktar (1), raxx (1) u papilloedima (1).
There have been post-marketing reports of pancreatitis in paediatric patients.
Kien hemm rapporti ta ’ pankreatite fit- tfal wara t- tqegħid tal- prodott fis- suq..
In clinical trials there were 3 cases of accidental overdose.
F' testijiet kliniċi kien hemm 3 każijiet ta 'doża eċċessiva aċċidentali.
All occurred in paediatric patients, who received up to five times the recommended intravenous dose of voriconazole.
Kollha seħħew f' pazjenti pedjatriċi, li rċevew sa ħames darbiet aktar id- doża rakkomandata fil- vina ta 'voriconazole.
A single adverse event of photophobia of 10 minutes duration was reported.
Kien irrapportat episodju avvers wieħed ta 'fotofobija li dam 10 minuti.
There is no known antidote to voriconazole.
15 M' hemmx antidotu magħruf għal voriconazole.
In an overdose, haemodialysis may assist in the removal of voriconazole from the body.
F' doża eċċessiva, ħemodijaliżi tista 'tgħin fit- tneħħija ta' voriconazole mill- ġisem.
J02A C03 Antimycotics for Systemic Use – Triazole derivatives
J02A C03 Antimikosiċi għal Użu Sistemiku - Derivattivi tat- Triazole
Mechanism of action In vitro, voriconazole displays broad-spectrum antifungal activity with antifungal potency against Candida species (including fluconazole resistant C. krusei and resistant strains of C. glabrata and C. albicans) and fungicidal activity against all Aspergillus species tested.
In vitro, voriconazole juri attività antifungali ta 'spettru wiesgħa b' qawwa antifungali kontra speċi Candida (fosthom C. krusei reżistenti għal fluconazole u forom reżistenti ta' C. glabrata u C. albicans) u attività fungiċida kontra l- ispeċi Aspergillus kollha ttestjati.
Its mode of action is inhibition of fungal cytochrome P450-mediated 14α -sterol demethylation, an essential step in ergosterol biosynthesis.
Il - mod ta 'azzjoni tiegħu huwa t- twaqqif ta' 14- sterol demethylation medjata miċ- ċitokromu fungali P450, pass importanti fil- bijosintesi ta 'l- ergosterol.
In animal studies there is a correlation between minimum inhibitory concentration values and efficacy against experimental mycoses.
Fl- istudji fuq l- annimali hemm korrelazzjoni bejn il- valuri minimi ta 'konċentrazzjoni inibitorja u l - effikaċja kontra mikosijiet sperimentali.
By contrast, in clinical studies, there appears to be no correlation between minimum inhibitory concentration values and clinical outcome.
B' kuntrast, fl- istudji kliniċi, ma jidhirx li hemm korrelazzjoni bejn il- valuri minimi ta 'konċentrazzjoni inibitorja u l- eżitu kliniku.
Furthermore, there does not appear to be a correlation between plasma levels and clinical outcome.
Barra dan, ma jidhirx li hemm korrelazzjoni bejn il- livelli fil- plasma u l- eżitu kliniku.
This is typical of azole antimycotics.
Dan huwa tipiku ta 'l- antimikosiċi azole.
Microbiology Clinical efficacy (with partial or complete response, see below under Clinical Experience) has been demonstrated for Aspergillus spp. including A. flavus, A. fumigatus, A. terreus, A. niger, A. nidulans, Candida spp., including C. albicans, C. glabrata, C. krusei, C. parapsilosis and C. tropicalis and limited numbers of C. dubliniensis, C. inconspicua, and C. guilliermondii, Scedosporium spp., including S. apiospermum, S. prolificans and Fusarium spp.
Kienet murija effikaċja klinika (b' rispons parzjali jew sħiħ, ara isfel taħt Esperjenza Klinika) għal Aspergillus spp. fosthom A. flavus, A. fumigatus, A. terreus, A. niger, A. nidulans, Candida spp., fosthom C. albicans, C. glabrata, C. krusei, C. parapsilosis u C. tropicalis u ammonti limitati ta 'C. dubliniensis, C. inconspicua, u C. guilliermondii, Scedosporium spp., fosthom S. apiospermum, S. prolificans u Fusarium spp.
Other treated fungal infections (with often partial or complete response) included isolated cases of Alternaria spp., Blastomyces dermatitidis, Blastoschizomyces capitatus, Cladosporium spp., Coccidioides immitis, Conidiobolus coronatus, Cryptococcus neoformans, Exserohilum rostratum, Exophiala spinifera, Fonsecaea pedrosoi, Madurella mycetomatis, Paecilomyces lilacinus, Penicillium spp. including P. marneffei, Phialophora richardsiae, Scopulariopsis brevicaulis and Trichosporon spp. including T. beigelii infections.
Infezzjonijiet fungali oħra kkurati (b' rispons sikwit parzjali jew sħiħ) kienu jinkludu każi iżolati ta 'Alternaria spp., Blastomyces dermatitidis, Blastoschizomyces capitatus, Cladosporium spp., Coccidioides immitis, Conidiobolus coronatus, Cryptococcus neoformans, Exserohilum rostratum, Exophiala spinifera, Fonsecaea pedrosoi, Madurella mycetomatis, Paecilomyces lilacinus, Penicillium spp. fosthom P. marneffei, Phialophora richardsiae, Scopulariopsis brevicaulis u Trichosporon spp. fosthom T. infezzjonijiet beigelii.
In vitro activity against clinical isolates has been observed for Acremonium spp., Alternaria spp., Bipolaris spp., Cladophialophora spp., Histoplasma capsulatum, with most strains being inhibited by concentrations of voriconazole in the range 0.05 to 2µg/ ml.
Attività in vitro kontra iżolati kliniċi kienet osservata għal Acremonium spp., Alternaria spp., Bipolaris spp., Cladophialophora spp., Histoplasma capsulatum, bil- maġġoranza tal- forom jiġu mwaqqfa b' konċentrazzjonijiet ta 'voriconazole fil- medda ta' 0. 05 sa 2 g/ ml.
15 In vitro activity against the following pathogens has been shown, but the clinical significance is unknown:
Kienet murija attività in vitro kontra l- patoġeni li ġejjin, iżda l- importanza klinika mhix magħrufa:
Curvularia spp. and Sporothrix spp.
Curvularia spp. u Sporothrix spp.
Specimens for fungal culture and other relevant laboratory studies (serology, histopathology) should be obtained prior to therapy to isolate and identify causative organisms.
Kampjuni għal koltura fungali u studji oħra rilevanti fil- laboratorju (seroloġija, istopatoloġija) għandhom jiġu miksuba qabel it- terapija sabiex jiġu iżolati u identifikati organiżmi kawżattivi.
Therapy may be instituted before the results of the cultures and other laboratory studies are known; however, once these results become available, anti-infective therapy should be adjusted accordingly.
It - terapija tista 'tinbeda qabel ma r- riżultati tal- kolturi u ta' studji oħra fil- laboratorju jkunu magħrufa; madankollu, meta dawn ir- riżultati jkunu disponibbli, it- terapija kontra l- infezzjonijiet għandha tiġi aġġustata kif dovut.
Clinical isolates with decreased susceptibility to voriconazole have been identified.
16 Kienu identifikati iżolati kliniċi b' suxxettibilità mnaqqsa għal voriconazole.
However, elevated minimum inhibitory concentrations did not always correlate with clinical failure and clinical success has been observed in patients infected with organisms resistant to other azoles.
Madankollu, konċentrazzjonijiet inibitorji minimi elevati mhux dejjem ikkorrelataw ma 'falliment kliniku u kien osservat suċċess kliniku f' pazjenti infettati b' organiżmi reżistenti għal azoles oħrajn.
Correlation of in vitro activity with clinical outcome is difficult owing to the complexity of the patients studied in clinical trials; breakpoints for voriconazole remain to be established.
Korrelazzjoni ta 'l- attività in vitro ma' l- eżitu kliniku hija diffiċli minħabba l- kumplessità tal- pazjenti studjati fit- testijiet kliniċi; il- breakpoints għal voriconazole għad iridu jiġu stabbiliti.
Clinical Experience Successful outcome in this section is defined as complete or partial response.
Eżitu ta 'suċċess f' din is- sezzjoni huwa definit bħala rispons sħiħ jew parzjali.
Aspergillus infections – efficacy in aspergillosis patients with poor prognosis Voriconazole has in vitro fungicidal activity against Aspergillus spp.
Infezzjonijiet bl- aspergillus - effikaċja f' pazjenti b' aspergillosi bi pronjosi fqira Voriconazole għandu attività fungiċida in vitro kontra l- Aspergillus spp.
The efficacy and survival benefit of voriconazole versus conventional amphotericin B in the primary treatment of acute invasive aspergillosis was demonstrated in an open, randomised, multicentre study in 277 immunocompromised patients treated for 12 weeks.
L- effikaċja u l- vantaġġ għas - sopravivenza ta 'voriconazole kontra amphotericin B konvenzjonali fil- kura primarja ta' asperġillosi invażiva akuta kienu murija fi studju miftuħ tat- tip multicentre magħmul b' mod każwali f' 277 pazjent immunokompromessi kkurati għal 12- il ġimgħa.
A satisfactory global response (complete or partial resolution of all attributable symptoms signs, radiographic/ bronchoscopic abnormalities present at baseline) was seen in 53% of voriconazole-treated patients compared to 31% of patients treated with comparator.
Intwera rispons globali sodisfaċenti (għajbien sħiħ jew parzjali tas- sinjali kollha tas- sintomi attribwibbli, anormalitajiet radjugrafiċi/ bronkoskopiċi preżenti fil- linja bażi) fi 53% tal- pazjenti kkurati b' voriconazole meta mqabbel mal- 31% tal- pazjenti kkurati bil- komparatur.
The 84-day survival rate for voriconazole was statistically significantly higher than that for the comparator and a clinically and statistically significant benefit was shown in favour of voriconazole for both time to death and time to discontinuation due to toxicity.
Ir- rata ta 'sopravivenza ta' 84 jum għal voriconazole kienet statistikament notevolment ogħla minn dik tal- komparatur u ntwera vantaġġ klinikament u statistikament sinifikanti favur voriconazole kemm għaż- żmien sal- mewt kif ukoll għaż- żmien sat- twaqqif tal- kura minħabba tossiċità.
This study confirmed findings from an earlier, prospectively designed study where there was a positive outcome in subjects with risk factors for a poor prognosis, including graft versus host disease, and, in particular, cerebral infections (normally associated with almost 100% mortality).
Dan l- istudju kkonferma sejbiet minn studju preċedenti, mfassal b' mod prospettiv fejn kien hemm eżitu pożittiv f' suġġetti b' fatturi ta 'riskju għal pronjosi fqira, fosthom graft versus host disease, u b' mod partikolari, infezzjonijiet ċerebrali (normalment assoċjati ma' kważi 100% mortalità).
The studies included cerebral, sinus, pulmonary and disseminated aspergillosis in patients with bone marrow and solid organ transplants, haematological malignancies, cancer and AIDS.
L- istudji kienu jinkludu asperġillosi ċerebrali, tas- sinus, pulmonari u mifruxa f' pazjenti bi trapjanti tal- mudullun u ta 'organi solidi, tumuri ematoloġiċi, kanċer u AIDS.
Candidaemia in non-neutropenic patients The efficacy of voriconazole compared to the regimen of amphotericin B followed by fluconazole in the primary treatment of candidaemia was demonstrated in an open, comparative study.
L- effikaċja ta 'voriconazole f' konfront mar- reġim ta' amphotericin B segwit bi fluconazole fil- kura primarja ta 'candidaemia kienet murija fi studju komparattiv miftuħ.
Three hundred and seventy non-neutropenic patients (above 12 years of age) with documented candidaemia were included in the study, of whom 248 were treated with voriconazole.
Tliet mija u sebgħin pazjent mhux newtropeniku (ta '' l fuq minn 12- il sena) b' candidaemia dokumentata kienu inklużi fl- istudju, li minnhom 248 ġew ikkurati b' voriconazole.
Nine subjects in the voriconazole group and five in the amphotericin B followed by fluconazole group also had mycologically proven infection in deep tissue.
Disa 'suġġetti fil- grupp ta' voriconazole u ħamsa fil- grupp ta 'amphotericin B segwit bi fluconazole wkoll kellhom infezzjoni ppruvata b' mod mikoloġiku fit - tessut fond.
Patients with renal failure were excluded from this study.
Pazjenti b' insuffiċjenza renali kienu esklużi minn dan l- istudju.
The median treatment duration was 15 days in both treatment arms.
It- tul medjan tal- kura kien 15- il ġurnata fiż- żewġ gruppi ta 'kura.
In the primary analysis, successful response as assessed by a Data Review Committee (DRC) blinded to study medication was defined as resolution/ improvement in all clinical signs and symptoms of infection with eradication of Candida from blood and infected deep tissue sites at 12 weeks after the end of therapy (EOT).
Fl- analiżi primarja, rispons ta 'suċċess kif stmat minn Kumitat ta' Valutazzjoni tad- Dejta (DRC - Data Review Committee) li ma kienx jaf x' medikazzjoni ntużat fl - istudju ġie mfisser bħala għajbien/ titjib fis- sinjali u s- sintomi kliniċi kollha ta 'l- infezzjoni bil- qerda ta' Candida mid- demm u t- tessut fond infettat 12- il ġimgħa wara t- tmiem tat- terapija (EOT).
Patients who did not have an assessment 12 weeks after EOT were counted as failures.
Il- pazjenti li ma kellhomx valutazzjoni 12- il ġimgħa wara l- EOT kienu magħduda li ma rnexxewx.
In this analysis a successful response was seen in 41% of patients in both treatment arms.
F' din l- analiżi deher rispons ta 'suċċess f' 41% tal- pazjenti fiż- żewġ gruppi ta' kura.
In a secondary analysis, which utilised DRC assessments at the latest evaluable time point (EOT, or 2, 6, or 12 weeks after EOT) voriconazole and the regimen of amphotericin B followed by fluconazole had successful response rates of 65% and 71%, respectively.
F' analiżi sekondarja, li użat valutazzjonijiet tad- DRC fl- aħħar punt taż- żmien valutabbli (EOT, 2, 6, jew 12- il ġimgħa wara l- EOT) voriconazole u r- reġim ta 'amphotericin B segwit bi fluconazole kellhom rata ta' rispons ta 'suċċess ta' 65% u 71%, rispettivament.
The Investigator’ s assessment of successful outcome at each of these time points is shown in the following table.
17
16 Timepoint _
Punt taż- żmien
Voriconazole (N=248)
Voriconazole (N=248)
Amphotericin B → fluconazole (N=122)
Amphotericin B → fluconazole (N=122)
EOT 2 weeks after EOT
EOT ġimagħtejn wara EOT
12 weeks after EOT
12- il ġimgħa wara EOT
Serious refractory Candida infections The study comprised 55 patients with serious refractory systemic Candida infections (including candidaemia, disseminated and other invasive candidiasis) where prior antifungal treatment, particularly with fluconazole, had been ineffective.
Infezzjonijiet refrattorji serji b' Candida L- istudju kien jinkludi 55 pazjent b' infezzjonijiet refrattorji sistemiċi serji b' Candida (fosthom candidaemia, candidiasis imxerrda u invażiva oħra) fejn kura antifungali preċedenti, b' mod partikolari bi fluconazole, ma kinetx effettiva.
Successful response was seen in 24 patients (15 complete, 9 partial responses).
Rispons ta 'suċċess kien muri f' 24 pazjent (15- il rispons sħiħ, 9 risponsi parzjali).
In fluconazole-resistant non albicans species, a successful outcome was seen in 3/ 3 C. krusei (complete responses) and 6/ 8 C. glabrata (5 complete, 1 partial response) infections.
Fi speċi mhux albicans reżistenti għal fluconazole, eżitu ta 'suċċess kien muri fi 3/ 3 infezzjonijiet bil - C. krusei (risponsi sħaħ) u 6/ 8 infezzjonijiet bil - C. glabrata (5 risponsi sħaħ, rispons 1 parzjali).
The clinical efficacy data were supported by limited susceptibility data.
Id- dejta dwar l- effikaċja klinika kienet sostnuta b' dejta limitata dwar is - suxxettibilità.
Scedosporium and Fusarium infections Voriconazole was shown to be effective against the following rare fungal pathogens:
Infezzjonijiet bi Scedosporium u Fusarium Voriconazole ntwera li kien effettiv kontra l- patoġeni fungali rari li ġejjin:
Successful response to voriconazole therapy was seen in 16 (6 complete, 10 partial responses) of 28 patients with S. apiospermum and in 2 (both partial responses) of 7 patients with S. prolificans infection.
Rispons ta 'suċċess għal terapija b' voriconazole kien muri f' 16 (6 risponsi sħaħ, 10 parzjali) minn 28 pazjent b' infezzjoni ta' S. apiospermum u fi 2 (it- tnejn risponsi parzjali) minn 7 pazjenti b' infezzjoni ta 'S. prolificans.
In addition, a successful response was seen in 1 of 3 patients with infections caused by more than one organism including Scedosporium spp.
Barra minn hekk, rispons ta 'suċċess kien muri f' 1 minn 3 pazjenti b' infezzjonijiet ikkawżati minn aktar minn organiżmu wieħed fosthom Scedosporium spp.
Seven (3 complete, 4 partial responses) of 17 patients were successfully treated with voriconazole.
Sebgħa (3 risponsi sħaħ, 3 parzjali) minn 17- il pazjent kienu kkurati b' suċċess b' voriconazole.
Of these 7 patients, 3 had eye, 1 had sinus, and 3 had disseminated infection.
Minn dawn is- 7 pazjenti, 3 kellhom infezzjoni f' għajnejhom, 1 kellu infezzjoni tas - sinus, u 3 kellhom infezzjoni mifruxa.
Four additional patients with fusariosis had an infection caused by several organisms; two of them had a successful outcome.
Erba 'pazjenti oħra b' fusariosis kellhom infezzjoni kkawżata minn diversi organiżmi; tnejn minnhom kellhom eżitu ta' suċċess.
The majority of patients receiving voriconazole treatment of the above mentioned rare infections were intolerant of, or refractory to, prior antifungal therapy.
Il- maġġoranza tal- pazjenti li rċevew kura b' voriconazole għall- infezzjonijiet rari msemmija fuq kienu intolleranti għal, jew refrattorji għal, terapija antifungali preċedenti.
Duration of treatment In clinical trials, 561 patients received voriconazole therapy for greater than 12 weeks, with 136 patients receiving voriconazole for over 6 months.
Tul tal- kura F' testijiet kliniċi, 561 pazjent irċevew terapija b' voriconazole għal aktar minn 12- il ġimgħa, b' 136 pazjent jingħataw voriconazole għal aktar minn 6 xhur.
Experience in paediatric patients Sixty one paediatric patients aged 9 months up to 15 years who had definite or probable invasive fungal infections, were treated with voriconazole.
Esperjenza f' pazjenti pedjatriċi Wieħed u sittin pazjenti pedjatriku ta 'bejn 9 xhur u 15- il sena li kellhom infezzjonijiet fungali invażivi ċerti jew probabbli, ingħataw kura b' voriconazole.
This population included 34 patients 2 to < 12 years old and 20 patients 12-15 years of age.
Din il- popolazzjoni kienet tinkludi 34 pazjent bejn 2 u < 12- il sena u 20 pazjent bejn 12 u 15- il sena.
The majority (57/ 61) had failed previous antifungal therapies.
Il- maġġoranza tagħhom (57/ 61) kienu fallew terapiji antifungali preċedenti.
Therapeutic studies included 5 patients aged 12-15 years, the remaining patients received voriconazole in the compassionate use programmes.
L- istudji terapewtiċi kienu jinkludu 5 pazjenti bejn 12 u 15- il sena, il- bqija tal- pazjenti rċevew voriconazole fil- programmi ta 'użu ħanin.
Underlying diseases in these patients included haematological malignancies and aplastic anaemia (27 patients) and chronic granulomatous disease (14 patients).
Il- mard primarju f' dawn il- pazjenti kien jinkludi tumuri ematoloġiċi u anemija aplastika (27 pazjent) u chronic granulomatous disease (14- il pazjent).
The most commonly treated fungal infection was aspergillosis (43/ 61; 70%).
L- aktar infezzjoni fungali kkurata b' mod komuni kienet l- asperġillosi (43/ 61; 70%).
Clinical Studies Examining QT Interval A placebo-controlled, randomized, single-dose, crossover study to evaluate the effect on the QT interval of healthy volunteers was conducted with three oral doses of voriconazole and ketoconazole.
18 Studji Kliniċi li Eżaminaw l- Intervall QT Studju tat- tip crossover ta 'doża waħda kkontrollat bil- plaċebo, magħmul b' mod każwali biex jiġi valutat l- effett fuq l- intervall QT ta' voluntiera b' saħħithom ġie mwettaq bi tliet dożi orali ta 'voriconazole u ketoconazole.
The placebo-adjusted mean maximum increases in QTc from baseline after 800, 1200 and 1600 mg of voriconazole were 5.1, 4.8, and 8.2 msec, respectively and 7.0 msec for ketoconazole 800 mg.
Iż- żidiet massimi medji aġġustati bil- plaċebo fil- QTc mil- linja bażika wara 800, 1200 u 1600 mg ta 'voriconazole kienu 5. 1, 4. 8, u 8. 2 msec, rispettivament u 7. 0 msec għal ketoconazole 800 mg.
No 17 subject in any group had an increase in QTc of ≥ 60 msec from baseline.
L- ebda suġġett f' xi grupp ma kellu żieda fil- QTc ta '≥60 msec mil- linja bażika.
No subject experienced an interval exceeding the potentially clinically relevant threshold of 500 msec.
L- ebda suġġett ma esperjenza intervall li qabeż il- limitu potenzjalment klinikament rilevanti ta '500 msec.
General pharmacokinetic characteristics The pharmacokinetics of voriconazole have been characterised in healthy subjects, special populations and patients.
Karatteristiċi farmakokinetiċi ġenerali Il- farmakokinetika ta 'voriconazole ġiet deskritta f' suġġetti b' saħħithom, popolazzjonijiet speċjali u pazjenti.
During oral administration of 200 mg or 300 mg twice daily for 14 days in patients at risk of aspergillosis (mainly patients with malignant neoplasms of lymphatic or haematopoietic tissue), the observed pharmacokinetic characteristics of rapid and consistent absorption, accumulation and non- linear pharmacokinetics were in agreement with those observed in healthy subjects.
Waqt amministrazzjoni orali ta '200 mg jew 300 mg darbtejn kuljum għal 14- il jum f' pazjenti fil- periklu ta' asperġillosi (l- aktar pazjenti b' neoplażmi malinnji ta 'tessut limfatiku jew haematopoietic), il- karatteristiċi farmakokinetiċi osservati ta' assorbiment rapidu u konsistenti, akkumulazzjoni u farmakokinetika mhux lineari kienu jaqblu ma 'dawk osservati f' suġġetti b' saħħithom.
The pharmacokinetics of voriconazole are non-linear due to saturation of its metabolism.
Il- farmakokinetika ta 'voriconazole mhix lineari minħabba s- saturazzjoni tal- metaboliżmu tiegħu.
Greater than proportional increase in exposure is observed with increasing dose.
Kienet osservata żieda akbar minn proporzjonali fl- esponiment ma 'dożi akbar.
It is estimated that, on average, increasing the oral dose from 200 mg twice daily to 300 mg twice daily leads to a 2.5-fold increase in exposure (AUCτ).
Huwa stmat li, bħala medja, iż- żieda tad- doża orali minn 200 mg darbtejn kuljum għal 300 mg darbtejn kuljum twassal għal żieda ta '2. 5 drabi aktar fl- esponiment (AUC).
When the recommended intravenous or oral loading dose regimens are administered, plasma concentrations close to steady state are achieved within the first 24 hours of dosing.
Meta jiġu amministrati r- reġimi rakkomandati tal - loading dose fil- vina jew orali, konċentrazzjonijiet fil- plasma qrib l- istat stabbli jinkisbu fl- ewwel 24 siegħa tad- dożaġġ.
Without the loading dose, accumulation occurs during twice daily multiple dosing with steady- state plasma voriconazole concentrations being achieved by day 6 in the majority of subjects.
Mingħajr il- loading dose, isseħħ akkumulazzjoni waqt dożaġġ multiplu darbtejn kuljum b' konċentrazzjonijiet stabbli ta 'voriconazole fil- plasma jinkisbu sa jum 6 fil- maġġoranza tas - suġġetti.
Absorption Voriconazole is rapidly and almost completely absorbed following oral administration, with maximum plasma concentrations (Cmax) achieved 1-2 hours after dosing.
Assorbiment Voriconazole huwa assorbit malajr u kważi kompletament wara amministrazzjoni orali, b' konċentrazzjonijiet massimi fil- plasma (Cmax) jinkisbu siegħa sa sagħtejn wara d- doża.
The absolute bioavailability of voriconazole after oral administration is estimated to be 96%.
Il - bijodisponibilità assoluta ta 'voriconazole wara amministrazzjoni orali hija stmata għal 96%.
When multiple doses of voriconazole are administered with high fat meals, Cmax and AUCτ are reduced by 34% and 24%, respectively.
Meta dożi multipli ta 'voriconazole jiġu mogħtija ma' ikliet b' kontenut għoli ta 'xaħam, Cmax u AUC jitnaqqsu b' 34% u 24%, rispettivament.
The absorption of voriconazole is not affected by changes in gastric pH.
L- assorbiment ta 'voriconazole mhux affettwat minn bidliet fil- pH gastriku.
Distribution The volume of distribution at steady state for voriconazole is estimated to be 4.6 l/ kg, suggesting extensive distribution into tissues.
Distribuzzjoni Il- volum tad- distribuzzjoni f' qagħda stabbli għal voriconazole huwa stmat għal 4. 6 l/ kg, li jissuġġerixxi distribuzzjoni estensiva fit- tessuti.
Plasma protein binding is estimated to be 58%.
It- twaħħil mal- proteini tal- plasma huwa stmat għal 58%.
Cerebrospinal fluid samples from eight patients in a compassionate programme showed detectable voriconazole concentrations in all patients.
Kampjuni tal- fluwidu ċerebrospinali minn tmien pazjenti fi programm ta 'kompassjoni wrew konċentrazzjonijiet rilevabbli ta' voriconazole fil- pazjenti kollha.
Metabolism In vitro studies showed that voriconazole is metabolised by the hepatic cytochrome P450 isoenzymes, CYP2C19, CYP2C9 and CYP3A4.
Metaboliżmu Studji in vitro wrew li voriconazole huwa metabolizzat mill- isoenzimi taċ- ċitokromu epatiku P450, CYP2C19, CYP2C9 U CYP3A4.
The inter-individual variability of voriconazole pharmacokinetics is high.
Il- varjabilità tal- farmakokinetika ta 'voriconazole bejn individwi differenti hija għolja.
In vivo studies indicated that CYP2C19 is significantly involved in the metabolism of voriconazole.
Studji in vivo indikaw li CYP2C19 huwa involut b' mod sinifikanti fil- metaboliżmu ta 'voriconazole.
This enzyme exhibits genetic polymorphism.
Dan l- enzim jippreżenta polimorfiżmu ġenetiku.
For example, 15-20% of Asian populations may be expected to be poor metabolisers.
Ngħidu aħna, 15- 20% tal- popolazzjonijiet Asjatiċi aktarx li jkunu metabolizzaturi ħżiena.
For Caucasians and Blacks the prevalence of poor metabolisers is 35%.
Fil- każ tal- Kawkasi u s- Suwed il- prevalenza ta 'metabolizzaturi ħżiena hija 3- 5%.
Studies conducted in Caucasian and Japanese healthy subjects have shown that poor metabolisers have, on average, 4-fold higher voriconazole exposure (AUCτ) than their homozygous extensive metaboliser counterparts.
Studji mwettqa fost suġġetti Kawkasi u Ġappuniżi b' saħħithom urew li l - metabolizzaturi ħżiena għandhom, bħala medja, esponiment għal voriconazole (AUC) erba 'darbiet ogħla mill- metabolizzaturi omozigoti estensivi.
Subjects who are heterozygous extensive metabolisers have on average 2- fold higher voriconazole exposure than their homozygous extensive metaboliser counterparts.
19 għandhom, bħala medja, esponiment għal voriconazole darbtejn ogħla mill- metabolizzaturi emozigoti estensivi.
The major metabolite of voriconazole is the N-oxide, which accounts for 72% of the circulating radiolabelled metabolites in plasma.
Il- metabolit prinċipali ta 'voriconazole huwa l- ossidu N, li jammonta għal 72% tal- metaboliti radjutikkettati li jiċċirkolaw fil- plasma.
This metabolite has minimal antifungal activity and does not contribute to the overall efficacy of voriconazole.
Dan il- metabolit għandu attività antifungali limitata u ma jikkontribwixxix għall- effikaċja globali ta 'voriconazole.
Excretion Voriconazole is eliminated via hepatic metabolism with less than 2% of the dose excreted unchanged in the urine.
Tneħħija Voriconazole jitneħħa permezz tal- metaboliżmu epatiku b' anqas minn 2% tad- doża mneħħija ma tkunx modifikata fl- awrina.
After administration of a radiolabelled dose of voriconazole, approximately 80% of the radioactivity
Wara l- amministrazzjoni ta 'doża radjutikkettata ta' voriconazole, madwar 80% tar- radjuattività tiġi rkuprata fl- awrina wara dożar multiplu fil- vini u 83% fl- awrina wara dożar multiplu orali.
The majority (> 94%) of the total radioactivity is excreted in the first 96 hours after both oral and intravenous dosing.
Il- biċċa l - kbira (> 94%) tar- radjuattività totali titneħħa fl- ewwel 96 siegħa kemm wara dożar orali kif ukoll wara doża fil- vini.
The terminal half-life of voriconazole depends on dose and is approximately 6 hours at 200 mg (orally).
Il- half life terminali ta 'voriconazole tiddependi fuq id- doża u hija madwar 6 sigħat b' doża ta' 200 mg (orali).
Because of non-linear pharmacokinetics, the terminal half-life is not useful in the prediction of the accumulation or elimination of voriconazole.
Minħabba farmakokinetika mhux lineari, il- half life terminali mhix ta 'siwi fit- tbassir ta' l - akkumulazzjoni jew tneħħija ta 'voriconazole.
Pharmacokinetic-Pharmacodynamic relationships In 10 therapeutic studies, the median for the average and maximum plasma concentrations in individual subjects across the studies was 2425 ng/ ml (inter-quartile range 1193 to 4380 ng/ ml) and 3742 ng/ ml (inter-quartile range 2027 to 6302 ng/ ml), respectively.
Relazzjonijiet Farmakokinetiċi- Farmakodinamiċi F' 10 studji terapewtiċi, il- punt medjan għall- konċentrazzjonijiet medji u massimi fil- plasma f' suġġetti individwali madwar l- istudji kien 2425 ng/ ml (medda inter- quartile 1193 sa 4380 ng/ ml) u 3742 ng/ ml (medda inter- quartile 2027 sa 6302 ng/ ml), rispettivament.
A positive association between mean, maximum or minimum plasma voriconazole concentration and efficacy in therapeutic studies was not found.
Ma nstabitx relazzjoni pożittiva bejn konċentrazzjoni medja, massima jew minima ta 'voriconazole fil- plasma u l- effikaċja fl- istudji terapewtiċi.
Pharmacokinetic-Pharmacodynamic analyses of clinical trial data identified positive associations between plasma voriconazole concentrations and both liver function test abnormalities and visual disturbances.
Analiżi farmakokinetiċi- farmakodinamiċi ta 'dejta minn testijiet kliniċi identifikaw relazzjonijiet pożittivi bejn il- konċentrazzjonijiet ta' voriconazole fil- plasma u l- anormalitajiet fit- testijiet tal - funzjoni tal- fwied u d- disturbi viżwali.
Pharmacokinetics in special patient groups Gender In an oral multiple dose study, Cmax and AUCτ for healthy young females were 83% and 113% higher, respectively, than in healthy young males (18-45 years).
Sess Fi studju ta 'doża multipla orali, Cmax u AUC għal nisa żgħażagħ b' saħħithom kienu 83% u 113% ogħla, rispettivament, milli f' irġiel żgħażagħ b' saħħithom (18- 45 sena).
In the same study, no significant differences in Cmax and AUCτ were observed between healthy elderly males and healthy elderly females (≥ 65 years).
Fl- istess studju, ma kinux osservati differenzi sinifikanti f’ Cmax u AUC bejn irġiel anzjani b' saħħithom u nisa anzjani b' saħħithom ( 65 sena).
In the clinical programme, no dosage adjustment was made on the basis of gender.
Fil- programm kliniku, ma sar ebda aġġustament tad- doża fuq il- bażi tas- sess.
The safety profile and plasma concentrations observed in male and female patients were similar.
Il- profil tas- sigurtà u l - konċentrazzjonijiet fil- plasma osservati f' pazjenti rġiel u nisa kienu simili.
Therefore, no dosage adjustment based on gender is necessary.
Għalhekk, mhux meħtieġ aġġustament tad- doża fuq il- bażi tas- sess.
Elderly In an oral multiple dose study Cmax and AUCτ in healthy elderly males (≥ 65 years) were 61% and 86% higher, respectively, than in healthy young males (18-45 years).
Anzjani Fi studju ta 'doża multipla orali l- Cmax u AUC f' irġiel anzjani b' saħħithom ( 65 sena) kienu 61% u 86% ogħla, rispettivament, milli f' irġiel żgħażagħ b' saħħithom (18- 45 sena).
No significant differences in Cmax and AUCτ were observed between healthy elderly females (≥ 65 years) and healthy young females (18- 45 years).
Ma kinux osservati differenzi sinifikanti f’ Cmax u AUC bejn nisa anzjani b' saħħithom ( 65 sena) u nisa żgħażagħ b' saħħithom (18- 45 sena).
In the therapeutic studies no dosage adjustment was made on the basis of age.
Fl- istudji terapewtiċi ma sar ebda aġġustament tad- doża fuq il- bażi ta 'l- età.
A relationship between plasma concentrations and age was observed.
Kienet osservata relazzjoni bejn il- konċentrazzjonijiet fil- plasma u l- età.
The safety profile of voriconazole in young and elderly patients was similar and, therefore, no dosage adjustment is necessary for the elderly (see section 4.2).
Il- profil tas- sigurtà ta 'voriconazole f' pazjenti żgħażagħ u anzjani kien simili u, għalhekk, mhux meħtieġ aġġustament tad- doża għall- anzjani.
Paediatric The recommended oral dose in paediatrics is based on a population pharmacokinetic analysis of data obtained from 47 immunocompromised paediatric patients aged 2 to < 12 years old who were evaluated in a pharmacokinetic study examining multiple oral suspension doses of 4 and 6 mg/ kg twice daily.
20 Tfal Id- doża orali rakkomandata fit- tfal hija bbażata fuq analiżi farmakokinetika tal- popolazzjoni ta 'dejta miksuba minn 47 pazjent pedjatriku immunokompromess fl- etajiet ta' 2 sa < 12- il sena li ġew evalwati fi studju farmakokinetiku li eżamina dożi multipli ta 'suspensjoni orali ta' 4 u 6 mg/ kg darbtejn kuljum.
A comparison of the paediatric and adult population pharmacokinetic data indicated that in order to obtain comparable exposures to those obtained in adults following a maintenance dose of 200 mg twice daily, 200 mg of oral suspension twice daily is required in paediatric patients, independent of body weight.
Paragun tad- dejta farmakokinetika tal- popolazzjoni pedjatrika u adulta indika li biex jinkisbu esponimenti komparabbli għal dawk miksuba fl- adulti wara doża ta 'manteniment ta' 200 mg darbtejn kuljum, huma meħtieġa 200 mg ta 'suspensjoni orali darbtejn kuljum fil- pazjenti pedjatriċi, indipendentement mill- piż tal- ġisem.
In paediatric patients there is a general trend towards low bioavailability at lower body weights and high bioavailability at higher body weights (approaching the extent demonstrated in adults).
Fil- pazjenti pedjatriċi hemm tendenza ġenerali lejn bijodisponibilità baxxa f' piżijiet tal- ġisem aktar baxxi u bijodisponibilità għolja f' piżijiet tal- ġisem ogħla (li tavviċina l- miżura murija fl- adulti).
Based on the population pharmacokinetic analysis, no dosage adjustment according to age or weight is warranted in patients aged 2 to < 12 years old at the 200 mg b. i. d. oral suspension dosing regimen.
Fuq il- bażi ta 'l- analiżi farmakokinetika tal- popolazzjoni, mhux meħtieġ aġġustament tad- dożaġġ skond l- età jew il- piż f' pazjenti fl- etajiet ta' 2 sa < 12- il sena bir- reġim ta 'dożaġġ ta' 200 mg ta 'suspensjoni orali darbtejn kuljum.
A loading dose is not indicated in paediatric patients.
Mhix indikata loading dose f' pazjenti pedjatriċi.
Oral bioavailability may, however, be limited in paediatric patients with malabsorption and very low body weight for their age.
Il- bijodisponibilità orali tista ', madankollu, tkun limitata f' pazjenti pedjatriċi b' assorbiment ħażin u piż baxx ħafna tal- ġisem għall- età tagħhom.
19 Renal impairment In an oral single dose (200 mg) study in subjects with normal renal function and mild (creatinine clearance 41-60 ml/ min) to severe (creatinine clearance < 20 ml/ min) renal impairment, the pharmacokinetics of voriconazole were not significantly affected by renal impairment.
Indeboliment tal- kliewi Fi studju ta 'doża waħda orali (200 mg) f' suġġetti b' funzjoni normali tal- kliewi u indeboliment ħafif (tneħħija ta' krejatinina 41- 60 ml/ min) għal sever (tneħħija ta 'krejatinina < 20 ml/ min) tal- kliewi, il - farmakokinetika ta' voriconazole ma kinetx affettwata b' mod sinifikanti mill- indeboliment tal- kliewi.
The plasma protein binding of voriconazole was similar in subjects with different degrees of renal impairment.
It- tqabbid ta 'voriconazole mal- proteini tal- plasma kien simili f' suġġetti bi gradi differenti ta' indeboliment tal- kliewi.
See dosing and monitoring recommendations under sections 4.2 and 4.4.
Ara r- rakkomandazzjonijiet dwar id- dożaġġ u l- monitoraġġ taħt sezzjonijiet 4. 2 u 4. 4.
Hepatic impairment After an oral single dose (200 mg), AUC was 233% higher in subjects with mild to moderate hepatic cirrhosis (Child-Pugh A and B) compared with subjects with normal hepatic function.
Indeboliment tal- fwied Wara doża waħda orali (200 mg), AUC kien 233% ogħla f' suġġetti b' ċirrożi epatika ħafifa għal moderata (Child- Pugh A u B) meta mqabbel ma 'pazjenti b' funzjoni normali tal- fwied.
Protein binding of voriconazole was not affected by impaired hepatic function.
It- tqabbid ta 'voriconazole mal- proteini tad- demm ma kienx affettwat minn funzjoni indebolita tal- fwied.
In an oral multiple dose study, AUCτ was similar in subjects with moderate hepatic cirrhosis (Child- Pugh B) given a maintenance dose of 100 mg twice daily and subjects with normal hepatic function given 200 mg twice daily.
Fi studju ta 'doża multipla orali, AUC kien simili f' suġġetti b' ċirrożi epatika moderata (Child- Pugh B) mogħtija doża ta' manteniment ta '100 mg darbtejn kuljum u suġġetti b' funzjoni normali tal- fwied mogħtija 200 mg darbtejn kuljum.