qanastek/EMEA-V3 huggingface dataset:
Infusion-related reactions, predominantly flushing and nausea, have been observed during administration of the intravenous formulation of voriconazole.
Reazzjonijiet relatati ma 'l- infużjoni, predominantament fwawar u dardir, ġew osservati matul amministrazzjoni tal- formolazzjoni ġol- vini ta' voriconazole.
Depending on the severity of symptoms, consideration should be given to stopping treatment (see section 4.8).
Jiddependi fuq is- severità tas- sintomi, għandha tingħata kunsiderazzjoni għat- twaqqif tat- trattament (ara sezzjoni 4. 8).
There have been reports of prolonged visual adverse events, including blurred vision, optic neuritis and papilloedema (see Section 4.8).
Kien hemm rapporti ta ’ episodji twal ta ’ effetti tal- vista mhux mixtieqa, inklużi vista mċajpra, newrite ta ’ l- għajn u papilloedema (ara sezzjoni 4. 8).
45 Renal adverse events:
48 Episodji avversi renali:
Patient being treated with voriconazole are likely to be treated concomitantly with nephrotoxic medications and have concurrent conditions that may result in decreased renal function (see section 4.8).
Il- pazjenti li jkunu qed jiġu kkurati b' voriconazole huma probabbli li jiġu kkurati fl- istess waqt b' medikazzjonijiet nefrotossiċi u jkollhom kondizzjonijiet konkorrenti li jistgħu jwasslu għal funzjoni mnaqqsa tal- kliewi (ara sezzjoni 4. 8).
Monitoring of renal function:
Monitoraġġ tal- funzjoni renali:
Methadone (CYP3A4 substrate):
Methadone (sostratt CYP3A4).
Frequent monitoring for adverse events and toxicity related to methadone, including QTc prolongation, is recommended when coadministered with voriconazole since methadone levels increased following co-administration of voriconazole.
Huwa rakkomandat monitoraġġ frekwenti għal episodji avversi u tossiċità marbuta mal- methadone, inkluż titwil tal- QTc, meta l- methadone jiġi amministrat flimkien ma 'voriconazole billi l- livelli tal- methadone żdiedu wara li ġie amministrat flimkien ma' voriconazole.
As the half-life of alfentanil is prolonged in a four-fold manner when alfentanyl is coadministered with voriconazole, a longer respiratory monitoring period may be necessary.
Peress li il- half- life ta ’ alfentanil hija mtawwla b’ erba darbiet iktar meta alfentanil huwa amministrat flimkien ma voriconazole, hemm mnejn ikun hemm bżonn ta ’ perijodu itwal ta ’ monitoraġġ respiratorju.
Coadministration of voriconazole and low dose ritonavir (100 mg twice daily) should be avoided unless an assessment of the benefit/ risk justifies the use of voriconazole (see section 4.5, for higher doses see section 4.3).
L- amministrazzjoni ta 'voriconazole ma' doża baxxa ta 'ritonavir (100 mg darbtejn kuljum) għandha tiġi evitata sakemm valutazzjoni tal- vantaġġ/ riskju ma tiġġustifikax l- użu ta' voriconazole (ara sezzjoni jiet 4. 2 u 4. 5).
When voriconazole is coadministered with efavirenz the dose of voriconazole should be increased to 400 mg every 12 hours and that of efavirenz should be decreased to 300 mg every 24 hours (see sections 4.2 and 4.5).
49 efavirenz għandha tiġi mnaqqsa għal 300 mg kull 24 siegħa (ara sezzjoni 4. 5; għal kontra- indikazzjoni b' dożi standard ta 'voriconazole u efavirenz ara sezzjoni 4. 3).
Sodium content:
Kontenut ta 'sodju:
Each vial of VFEND contains 217.6 mg of sodium.
Kull kunjett ta 'VFEND fih 217. 6 mg ta' sodju.
This should be taken into consideration for patients on a controlled sodium diet.
Dawk il- pazjenti li qegħdin fuq dieta ta 'sodju kkontrollat għandhom jikkunsidraw dan.
46 4.5 Interaction with other medicinal products and other forms of interaction
4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
This section addresses the effects of other medicinal products on voriconazole, the effects of voriconazole on other medicinal products and two-way interactions.
Din is- sezzjoni tindirizza l- effetti ta 'prodotti mediċinali oħra fuq voriconazole, l- effetti ta' voriconazole fuq prodotti mediċinali oħra u l- interazzjonijiet miż- żewġ naħat.
The effect of the coadministration of oral voriconazole (200 mg twice daily) and high dose (400 mg) and low dose (100 mg) oral ritonavir (400 mg and 100 mg) was investigated in two separate studies in healthy volunteers.
L- effett ta 'l- amministrazzjoni flimkien ta' voriconzaole orali (200 mg darbtejn kuljum) u doża għolja (400 mg) u doża baxxa (100 mg) ta 'ritonavir orali (400 mg u 100 mg) kien eżaminat f' żewġ studji separati fuq voluntiera b' saħħithom.
High doses of ritonavir (400 mg twice daily) decreased the steady state Cmax and AUCτ of oral voriconazole by an average of 66% and 82%, whereas low doses of ritonavir (100 mg twice daily) decreased the Cmax and AUCτ of oral voriconazole by an average of 24% and 39% respectively.
Dożi għoljin ta 'ritonavir (400 mg darbtejn kuljum) naqqsu Cmax u AUC stabbli ta' voriconazole orali b' medja ta '66% u 82%, filwaqt li dożi baxxi ta' ritonavir (100 mg darbtejn kuljum) naqqsu l- Cmax u AUC ta 'voriconazole orali b' medja ta' 24% u 39% rispettivament.
Administration of voriconazole did not have a significant effect on mean Cmax and AUCτ in the high dose study although a minor decrease in steady state Cmax and AUCτ of ritonavir with an average of 25% and 13% respectively was observed in the low dose ritonavir interaction study.
L - amministrazzjoni ta 'voriconazole ma kellhiex effett sinifikanti fuq Cmax u AUC medji fl- istudju bid - doża l- għolja, għalkemm tnaqqis żgħir f’ Cmax u AUC stabbli ta' ritonavir b' medja ta '25% u 13% rispettivament kien osservat fl- istudju ta' l- interazzjoni b' doża baxxa ta 'ritonavir.
Coadministration of voriconazole and high doses of ritonavir (400 mg and above twice daily) is contraindicated).
L - amministrazzjoni ta 'voriconazole ma' dożi għoljin ta 'ritonavir (400 mg u aktar darbtejn kuljum) hija kontra- indikata.
Coadministration of voriconazole and low dose ritonavir (100 mg twice daily) should be avoided unless an assessment of the benefit/ risk justifies the use of voriconazole (see section 4.3 and 4.4).
L- amministrazzjoni ta 'voriconazole ma' doża baxxa ta 'ritonavir (100 mg darbtejn kuljum) għandha tiġi evitata sakemm valutazzjoni tal- vantaġġ/ riskju ma tiġġustifikax l- użu ta' voriconazole (ara sezzjoni 4. 3 u 4. 4).
Although not studied, carbamazepine or phenobarbital is likely to significantly decrease plasma voriconazole concentrations.
Għalkemm mhux studjat, carbamazepine jew phenobarbital huma probabbli li jnaqqsu b' mod sinifikanti l- konċentrazzjonijiet ta 'voriconazole fil- plasma.
Ranitidine (increases gastric pH):
50 Ranitidine (iżid il- pH gastriku):
47 St John’ s Wort (CYP450 inducer; P-gp inducer):
John’ s Wort (fexfiex) (inibitur CYP450, u induttur P- gp):
Effects of voriconazole on other medicinal products
Effetti ta 'voriconazole fuq prodotti mediċinali oħra
Voriconazole inhibits the activity of cytochrome P450 isoenzymes, CYP2C19, CYP2C9 and CYP3A4.
Voriconazole jimpedixxi l- attività ta 'l- isoenzimi taċ- ċitokromu P450, CYP2C19, CYP2C9 u CYP3A4.
Voriconazole should be administered with caution in patients with concomitant medication that is known to prolong QT interval.
Voriconazole għandu jingħata b' kawtela f' pazjenti b' medikazzjoni konkomitanti li tkun magħrufa li ttawwal l- intervall QT.
In stable, renal transplant recipients, voriconazole increased ciclosporin Cmax and AUCτ by at least 13% and 70%, respectively.
F' riċevituri stabbli ta 'trapjant tal- kliewi, voriconazole żied Cmax u AUC ta' ciclosporin b' mill- anqas 13% u 70%, rispettivament.
Short Acting Opiates (CYP3A4 substrate):
51 Opiates li jaħdmu fuq qasir żmien (sustratt CYP3A4):
Steady-state administration of oral voriconazole increased the AUC∞ of a single dose of alfentanil by 6-fold.
Amministrazzjoni Steady- state ta ’ voriconazole b’ mod orali żiedet l- AUC∞ ta ’ doża waħdanija ta ’ alfentanil b’ 6 darbiet.
Reduction in the dose of alfentanil and other short acting opiates similar in structure to alfentanil and metabolised by CYP3A4 (e. g fentanyl and sufentanil), should be considered when coadministered with voriconazole (see section 4.4).
Tnaqqis fid- doża ta ’ alfentanil u opiates oħra li jaħdmu fuq qasir żmien bi struttura simili għal alfentanil u metabolizzati minn CYP3A4 (eż. fentanyl u sufentanil), għandhom ikunu kkunsidrati meta mogħtija flimkien ma voriconazole.
48 Tacrolimus (CYP3A4 substrate):
Tacrolimus (sostratt ta 'CYP3A4):
Other oral anticoagulants e. g. phenprocoumon, acenocoumarol (CYP2C9, CYP3A4 substrates):
Sustanzi oħra orali kontra l- koagulazzjoni tad- demm eż. phenprocoumon, acenocoumarol (sostratti ta 'CYP2C9, CYP3A4):
Therefore, voriconazole is likely to increase the plasma levels of benzodiazepines that are metabolised by CYP3A4 (e. g. midazolam and triazolam) and lead to a prolonged sedative effect.
Għalhekk, voriconazole huwa probabbli li jżid il- livelli fil- plasma ta 'benzodiazepines li huma metabolizzati minn CYP3A4 (eż. midazolam u triazolam) u jwassal għal effett sedattiv fit- tul.
Non-Steroidal Anti-Inflammatory Drugs (CYP2C9 substrates):
52 Mediċini anti- infjammatorji non- sterojdali (sostratti ta ’ CYP2C9):
Phenytoin (300 mg once daily)
Phenytoin (300 mg darba kuljum) naqqas Cmax u AUC ta 'voriconazole b' 49% u 69%, rispettivament.
Concomitant use of voriconazole and rifabutin should be avoided unless the benefit outweighs the risk. Rifabutin (300 mg once daily) decreased the Cmax and AUCτ of voriconazole at 200 mg twice daily by 69% and 78%, respectively.
Rifabutin (300 mg darba kuljum) naqqas Cmax u AUC ta 'voriconazole f' doża ta' 200 mg darbtejn kuljum b' 69% u 78%, rispettivament.
During coadministration with rifabutin, the Cmax and AUCτ of voriconazole at 350 mg twice daily were 96% and 68% of the levels when administered alone at 200 mg twice daily.
Meta ngħata ma 'rifabutin, Cmax u AUC ta' voriconazole f' doża ta '350 mg darbtejn kuljum kienu 96% u 68% tal- livelli ta' meta ngħata waħdu fid- doża ta '200 mg darbtejn kuljum.
At a voriconazole dose of 400 mg twice daily C max and AUCτ were 104% and 87% higher, respectively, compared with voriconazole alone at 200 mg twice daily.
F' doża ta 'voriconazole ta' 400 mg darbtejn kuljum Cmax u AUC kienu 104% u 87% ogħla, rispettivament, meta mqabbel ma 'voriconazole waħdu f' doża ta' 200 mg darbtejn kuljum.
If rifabutin coadministration with voriconazole is justified then the maintenance dose of voriconazole may be increased to 5 mg/ kg intravenously twice daily or from 200 mg to 350 mg orally, twice daily (100 mg to 200 mg orally, twice daily in patients less than 40kg) (see section 4.2).
(100 mg għal 200 mg b' mod orali, darbtejn kuljum fil- każ ta 'pazjenti li jiżnu anqas minn 40kg) (ara sezzjoni 4. 2).
Antiretroviral Agents:
53 Aġenti antiretrovirali:
In vitro studies suggest that voriconazole may inhibit the metabolism of HIV protease inhibitors (e. g. saquinavir, amprenavir and nelfinavir).
Studji in vitro jissuġġerixxu li voriconazole jista 'jwaqqaf il- metaboliżmu ta' l- inibituri tal- protease ta 'l- HIV (pereżempju saquinavir, amprenavir u nelfinavir).
However results of the combination of voriconazole with other HIV protease inhibitors cannot be
Madankollu r- riżultati tat- taħlit ta 'voriconazole ma' inibituri oħra tal- protease ta 'l- HIV ma jistgħux jiġu previsti fin- nies minn studji in vitro waħedhom.
In a separate study in healthy subjects voriconazole dose of 300 mg BID in combination with low dose efavirenz (300 mg once daily) did not lead to sufficient voriconazole exposure.
Fi studju separat f’ suġġetti f’ saħħithom, doża ta ’ 300 mg ta ’ voriconazole BID ma doża baxxa ta ’ efavirenz (300 mg darba kuljum) ma wasslitx għal esposizzjoni suffiċjenti ta ’ voriconazole.
Following coadministration of voriconazole 400 mg twice daily with efavirenz 300 mg orally once daily, in healthy subjects, the AUCτ of voriconazole was decreased by 7% and Cmax was increased by 23%, compared to voriconazole 200 mg twice daily alone.
Wara l- amministrazzjoni ta 'voriconazole 400 mg darbtejn kuljum ma' efavirenz 300 mg b' mod orali darba kuljum, f' suġġetti b' saħħithom, AUC ta 'voriconazole naqas 7% u l- Cmax żdied bi 23%, meta mqabbel ma' voriconazole 200 mg darbtejn kuljum waħdu.
When treatment with voriconazole is stopped, the initial dosage of efavirenz should be restored.
Meta titwaqqaf il- kura b' voriconazole, għandu jerġa 'jiddaħħal id- dożaġġ inizjali ta' efavirenz.
The potential risk for humans is unknown.
Ir- riskju potenzjali għan- nies mhux magħruf.
Women of child-bearing potential Women of child-bearing potential must always use effective contraception during treatment.
54 Nisa li jistgħu jinqabdu tqal In- nisa li jistgħu jinqabdu tqal iridu dejjem jużaw kontraċezzjoni effettiva waqt il- kura.
It may cause transient and reversible changes to vision, including blurring, altered/ enhanced visual perception
Voriconazole jista 'jikkawża bidliet għaddiena u riversibbli fil- vista, fosthom ċpar, perċezzjoni mibdula/ imkabbra u/ jew fotofobija.
Undesirable effects reported in subjects receiving voriconazole:
55 Effetti mhux mixtieqa rrapportati f' suġġetti li kienu qegħdin jirċeivu voriconazole
Headache Dizziness, confusional state, tremor, agitation, paraesthesia Brain oedema, ataxia, diplopia, vertigo, hypoaesthesia Convulsion, encephalopathy, Guillain-Barre syndrome, extrapyramidal symptoms, somnolence during infusion
Uġigħ ta 'ras Sturdament, stat konfużjonali, tregħid, aġitazzjoni, parasteżija Edima fil- moħħ, atassja, diplopia, vertiġini, ipoestesija Konvulżjoni, enċefalopatija, sindrome ta' Guillain- Barre, sintomi ekstrapiramidali, ngħas waqt l- infużjoni
52 Eye disorders Visual disturbances (including blurred vision (see Section Very common 4.4), chromotopsia and photophobia) Uncommon
Disturbi viżwali (inklużi vista mċajpra (ara Sezzjoni 4. 4), kromatopsija u fotofobja)
Papilloedema (se 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
Gastrointestinal disorders Very common Uncommon
Komuni ħafna Mhux komuni
Renal and urinary disorders Common Uncommon Rare
56 Mard tal- kliewi u tas- sistema urinarja Komuni Mhux komuni Rari
53 Vascular disorders Common Rare
Mard vaskulari
Hepato-biliary disorders Common Uncommon
Mard tal- fwied u tal- marrara Komuni Mhux komuni
Visual disturbances In clinical trials, voriconazole treatment-related visual disturbances were very common.
57 Disturbi viżwali Fi studji kliniċi, disturbi viżwali marbuta mal- kura b' voriconazole kienu komuni ħafna.
The majority of abnormal liver function tests either resolved during treatment without dose adjustment or following
L- anormalitajiet fit - testijiet tal- funzjoni tal- fwied jistgħu jkunu assoċjati ma 'konċentrazzjonijiet akbar fil- plasma u/ jew dożi ogħla.
54 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.
Infusion-Related Reactions During infusion of the intravenous formulation of voriconazole in healthy subjects, anaphylactoid-type reactions, including flushing, fever, sweating, tachycardia, chest tightness, dyspnoea, faintness, nausea, pruritus and rash have occurred.
Reazzjonijiet Relatati ma 'l- Infużjoni Matul infużjoni tal- formolazzjoni ta' voriconazole f' suġġetti b' saħħithom, seħħew reazzjonijiet tat- tip anafilattiċi, inkluż fwawar, ħruġ ta 'għaraq, takikardja, għafis fuq is- sider, dispneja, sturdamenti, dardir, prurite u raxx.
Symptoms appeared immediately upon initiating the infusion (see also section 4.4).
Sintomi dehru minnufih wara li bdiet l- infużjoni (ara wkoll sezzjoni 4. 4).
In the 22 patients less than 2 years old who received voriconazole in a compassionate use programme, the following adverse events (for which a relationship to voriconazole could not be excluded) were reported: photosensitivity reaction (1), arrhythmia (1), pancreatitis (1), 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).
4.9 Overdose
58 4. 9 Doża eċċessiva
In an overdose, haemodialysis may assist in the removal of voriconazole and SBECD from the body.
F' doża eċċessiva, ħemodijaliżi tista 'tgħin fit- tneħħija ta' voriconazole u SBECD mill- ġisem.
55 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, see below under Clinical Experience) 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, ara taħt Esperjenza Klinika) 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 the following pathogens has been shown, but the clinical significance is unknown:
59 Kienet murija attività in vitro kontra l- patoġeni li ġejjin, iżda l- importanza klinika mhix magħrufa:
Clinical Experience Succesful 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.
56 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.
Timepoint
Punt taż- żmien
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 response) 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.
57 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.
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.
61 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.
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 fiss għal voriconazole huwa stmat għal 4. 6 l/ kg, li jissuġġerixxi distribuzzjoni estensiva fit- tessuti.
58 The inter-individual variability of voriconazole pharmacokinetics is high.
Il- varjabilità tal- farmakokinetika ta 'voriconazole bejn individwi differenti hija għolja.
The major metabolite of voriconazole is the N-oxide, which accounts for 72% of the circulating radiolabelled metabolites in plasma.
62 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.
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).
59 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.
Paediatrics The recommended intravenous dose in paediatric patients is based on a population pharmacokinetic analysis of data pooled from 82 immunocompromised paediatric patients aged 2 to < 12 years old who were evaluated in three pharmacokinetic studies (examining single intravenous doses of 3 and 4 mg/ kg twice daily, multiple intravenous doses of 3, 4, 6 and 8 mg/ kg twice daily and multiple oral suspension doses of 4 and 6 mg/ kg twice daily).
63 Pedjatriċi Id- doża ġol- vina rakkomandata fit- tfal hija bbażata fuq analiżi farmakokinetika tal- popolazzjoni ta 'dejta miksuba minn 82 pazjent pedjatriku immunokompromess fl- etajiet ta' 2 sa < 12- il sena li ġew evalwati fi tliet studji farmakokinetiċi (li eżaminaw dożi ġol- vini singoli ta '3 u 4 mg/ kg darbtejn kuljum, dożi ġol- vini multipli ta' 3, 4, 6 u 8 mg/ kg darbtejn kuljum u dożi multipli ta 'suspensjoni orali ta' 4 u 6 mg/ kg darbtejn kuljum).
The majority of patients received more than one dose level with a maximum duration of dosing of 30 days.
Il- maġġoranza tal- pazjenti rċevew akatr minn livell ta 'doża waħda b' tul massimu tad- doża ta' 30 jum.
A comparison of the paediatric and adult population pharmacokinetic data indicated that in order to obtain comparable exposures to those obtained in adults following intravenous maintenance doses of 4 mg/ kg twice daily, intravenous maintenance doses of 7 mg/ kg twice daily are required in paediatric patients.
Paragun tad- dejta farmakokinetika tal- popolazzjoni pedjatrika u adulta indika li biex jinkisbu esponimenti komparabbli għal dawk miksuba fl- adulti wara dożi ta 'manteniment ta' 4 mg/ kg darbtejn kuljum, dożi ta 'manteniment ġol- vini ta' 7 mg/ kg darbtejn kuljum huma meħtieġa fil- pazjenti pedjatriċi.
The higher intravenous maintenance dose in paediatric patients relative to adults reflects the higher elimination capacity in paediatric patients due to a greater liver mass to body mass ratio.
Aktar ma tkun kbira d- doża ta 'manteniment f' pazjenti pedjatriċi fir- rigward ta' l- adulti jirrifletti l- kapaċità ta 'eliminazzjoni ogħla f' pazjenti pedjatriċi dovuta għal proporzjoni bejn il- massa tal- fwied ul- piż tal- ġisem ikbar.
In order to obtain comparable exposures to those obtained in adults following intravenous maintenance doses of 3 mg/ kg twice daily, intravenous maintenance doses of 4 mg/ kg twice daily are required in paediatric patients.
Sabiex jinkisbu espożizzjonijiet komparabbli għal dawk miksubin fl - adulti wara dożi ta 'manteniment ta' 3 mg/ kg darbtejn kuljum, dożi ta 'manteniment ġol- vini ta' 4 mg/ kg darbtejn kuljum huma meħtieġa fil- pazjenti pedjatriċi.
Based on the population pharmacokinetic analysis, no loading dose or dosage adjustment according to age is warranted in patients aged 2 to < 12 years old.
Fuq il- bażi ta 'l- analiżi farmakokinetika tal- popolazzjoni, mhux garantit loading tad- dożaġġ jew aġġustament tad- dożaġġ skond l- età f' pazjenti fl- etajiet ta' 2 sa < 12- il sena.
Renal impairment In patients with moderate to severe renal dysfunction (serum creatinine levels > 2.5 mg / dl), accumulation of the intravenous vehicle, SBECD, occurs.
Indeboliment tal- kliewi F' pazjenti b' disfunzjoni renali moderata għal severa (livelli tal- kreatinina fis- serum > 2. 5 mg / dl), isseħħ l- akkumulazzjoni tal- prodott mogħti ġol- vini, SBECD.
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.
60 Preclinical data on the intravenous vehicle, SBECD indicated that the main effects were vacuolation of urinary tract epithelium and activation of macrophages in the liver and lungs in the repeated-dose toxicity studies.
Tagħrif prekliniku fuq il- prodott li jiddaħħal ġol- vini, SBECD indika li l- effetti prinċipali keinu vakulazzjoni fl- epitelju tal- passaġġ ta 'l- awrina u attivazzjoni ta' makrofagi fil- fwied u pulmuni fl - istudji tat- tossiċità ta 'doża ripetuta.
As GPMT (guinea pig maximisation test) result was positive, prescribers should be aware of the hypersensitivity potential of the intravenous formulation.
Minħabba li r- riżultat GPMT (prova ta 'massimizzazzjoni tal - fenek ta' l- Indi) kien pożittiv, dawk lijiktbu r- riċetta għandhom ikunu konxji tal- potenzjal għal sensittività eċċessiva tal- formulazzjoni ġol- vini.
Standard genotoxicity and reproduction studies with the excipient SBECD reveal no special hazard for humans.
64 bis- sustanza mhux attiva SBECD ma juru ebda periklu speċjali għall- umani.
Carcinogenicity studies were not performed with SBECD.
Ma sarux studji tal - karċinoġeniċità b' SBECD.
An impurity, present in SBECD, has been shown to be an alkylating mutagenic agent with evidence for carcinogenicity in rodents.
Impurità, preżenti f' SBECD, intweriet li kienet aġent mutaġeniku alkalitiku b' evidenza għal karċinoġeniċità f' annimali gerriema.
This impurity should be considered a substance with carcinogenic potential in humans.
Din l- impurità għandha titqies sustanza b' potenzjal karċinoġeniku fl- umani.
In the light of these data the duration of treatment of the intravenous formulation should be no longer than 6 months.
Fid- dawl ta 'dan it- tagħrif, it- tul tat- trattament tal- formulazzjoni ġol- vini ma għandux ikun itwali minn 6 xhur.
Sulphobutylether beta cyclodextrin sodium (SBECD)
Sulphobutylether beta cyclodextrin sodium (SBECD).
When the VFEND infusion is complete, the line may be used for administration of other intravenous products.
Meta l- infużjoni ta 'VFEND tkun lesta, il- linja tista' tintuża biex jingħataw prodotti prodotti għal ġol - vina.
Blood products and short-term infusion of concentrated solutions of electrolytes:
Prodotti tad- demm u infużjoni ta ’ ftit żmien ta ’ soluzzjoni kkonċentrata ta ’ elettroliti:
Electrolyte disturbances such as hypokalemia, hypomagnesemia and hypocalcemia should be corrected prior to initiation of voriconazole therapy (see section 4.2 and section 4.4).
Disturbi ta 'l- elettroliti bħal ipokalimja, hypomagnesemia u ipokalċimja għandhom jiġu korretti qabel ma tinbeda l- kura b' voriconazole (ara sezzjoni 4. 2 u sezzjoni 4. 4).
VFEND must not be administered simultaneously with any blood product or any short-term infusion of concentrated solutions of electrolytes, even if the two infusions are running in separate lines.
VFEND m' għandux jingħata fl - istess ħin ma 'xi prodott tad- demm jew xi infużjoni għal ftit żmien ta ’ soluzzjoni kkonċentrata ta ’ elettroliti, anki jekk iż- żewġ infużjonijiet ikunu għaddejjin f' linji separati.
Total parenteral nutrition:
Nutrizzjoni parenterali totali:
Total parenteral nutrition (TPN) need not be discontinued when prescribed with VFEND, but does need to be infused through a separate line.
In- nutrizzjoni parenterali totali (TPN) m' hemmx għalfejn tiġi mwaqqfa meta ordnata ma 'VFEND, iżda trid tiġi infuża minn linja separata.
If infused through a multiple-lumen catheter, TPN needs to be administered using a different port from the one used for VFEND.
Jekk tiġi infuża permezz ta 'kateter multiple lumen, it- TPN trid tiġi infuża billi tintuża toqba differenti minn dik użata għal VFEND.
VFEND must not be diluted with 4.2% Sodium Bicarbonate Infusion.
VFEND m' għandux jiġi dilwit b' 4. 2% Infużjoni ta 'Bikarbonat tas- Sodju.
Compatibility with other concentrations is unknown.
Il- kompatibilità ma 'konċentrazzjonijiet oħra m' hiex magħrufa.
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
Dan il- prodott mediċinali ma għandux jitħallat ma 'prodotti mediċinali oħra għajr dawk imsemmija f' sezzjoni 6. 6.
VFEND powder for solution for infusion:
VFEND trab għal soluzzjoni għall- infużjoni:
VFEND is a single dose unpreserved sterile lyophile.
VFEND huwa lijofil sterili mhux priservat.
Therefore, from a microbiological point of view, once reconstituted, the product must be used immediately.
Għalhekk, minn lat mikrobijoloġiku, ladarba rikostitwit, il- prodott għandu jintuża minnufih.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.
Jekk ma jintużax minnufih, il- ħinijiet u l- kundizzjonijiet ta 'ħżin waqt l- użu huma r- responsabbiltà ta' l- utent u normalment ma għandhomx ikunu iktar minn 24 siegħa f' 2C sa 8C, sakemm ir- rikostituzzjoni ma tkunx seħħet f' kundizzjonijiet ikkontrollati u asettiċi.
Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 8°C.
L- istabbiltà kimika u fiżika waqt l- użu ntweriet għal 24 siegħa f' 2C sa 8C.
Reconstituted concentrate:
Il- konċentrat rikostitwit:
Store at 2°C-8°C for up to 24 hours (in a refrigerator).
Aħżen fi 2C- 8C għal 24 siegħa (fi friġġ).
61 6.5 Nature and contents of container
65 6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
Packs of 1 single use 30 ml clear Type I glass vials with rubber stoppers and aluminium caps with plastic seals.
Pakketti ta 'kunjett wieħed ta' 30 ml li jintuża darba biss magħmul minn ħġieġ ċar tat- Tip I bi stoppers tal- lastku u tappijiet ta 'l- aluminju b' siġilli tal- plastik.
6.6 Special precautions for disposal and other handling
6. 6 Prekawzjonijiet speċjali għar- rimi ta 'prodotti mediċinali u maniġġar ieħor
Any unused product or waste material should be disposed of in accordance with local requirements.
Kwalunkwe prodott mhux użat jew skart minn dawn il- prodott għandu jintrema skond il- liġijiet lokali.
The powder is reconstituted with 19 ml of Water for Injections to obtain an extractable volume of 20 ml of clear concentrate containing 10 mg/ ml of voriconazole.
It- trab huwa rikostitwit bi 19- il ml ta 'Ilma għall- Injezzjonijiet sabiex jinkiseb volum li jista' jinġibed ta '20 ml ta' konċentrat ċar li fih 10 mg/ ml ta 'voriconazole.
Discard the VFEND vial if vacuum does not pull the diluent into the vial.
Armi l- kunjett ta 'VFEND jekk il- vakum ma jiġbidx id- dilwent għal ġol- kunjett.
It is recommended that a standard 20 ml (non-automated) syringe be used to ensure that the exact amount (19.0 ml) of Water for Injections is dispensed.
Huwa rakkomandat li tintuża siringa standard ta '20 ml (mhux awtomatika) sabiex jiġi żgurat li jingħata l- ammont eżatt (19. 0 ml) ta' Ilma għall- Injezzjonijiet.
This medicinal product is for single use only and any unused solution should be discarded and only clear solutions without particles should be used.
Dan il - prodott mediċinali għandu jintuża darba biss u kwalunkwe soluzzjoni mhux użata trid tintrema u għandhom jintużaw biss soluzzjonijiet ċari mingħajr partikoli.
For administration, the required volume of the reconstituted concentrate is added to a recommended compatible infusion solution (detailed below) to obtain a final voriconazole solution containing 0.5-5 mg/ ml.
Biex jingħata, il- volum meħtieġ tal- konċentrat rikostitwit jiġi miżjud ma 'soluzzjoni kompatibbli rakkomandata għal infużjoni (dettaljata isfel) biex tinkiseb soluzzjoni finali ta' voriconazole li fiha 0. 5- 5 mg/ ml.
Required Volumes of 10 mg/ ml VFEND Concentrate
Volumi Meħtieġa ta '10 mg/ ml ta' Konċentrat VFEND
Volume of VFEND Concentrate (10 mg/ ml) required for:
Volum ta 'Konċentrat VFEND (10 mg/ ml) meħtieġ għal:
3 mg/ kg dose (number of vials) - - - - 9.0 ml (1) 10.5 ml (1) 12.0 ml (1) 13.5 ml (1) 15.0 ml (1) 16.5 ml (1) 18.0 ml (1) 19.5 ml (1) 21.0 ml (2) 22.5 ml (2) 24.0 ml (2) 25.5 ml (2) 27.0 ml (2) 28.5 ml (2) 30.0 ml (2)
10. 5 ml (1) 12. 0 ml (1) 13. 5 ml (1) 15. 0 ml (1) 16. 5 ml (1) 18. 0 ml (1) 19. 5 ml (1) 21. 0 ml (2) 22. 5 ml (2) 24. 0 ml (2) 25. 5 ml (2) 27. 0 ml (2) 28. 5 ml (2) 30. 0 ml (2)
4 mg/ kg dose (number of vials) 4.0 ml (1) 6.0 ml (1) 8.0 ml (1) 10.0 ml (1) 12.0 ml (1) 14.0 ml (1) 16.0 ml (1) 18.0 ml (1) 20.0 ml (1) 22.0 ml (2) 24.0 ml (2) 26.0 ml (2) 28.0 ml (2) 30.0 ml (2) 32.0 ml (2) 34.0 ml (2) 36.0 ml (2) 38.0 ml (2) 40.0 ml (2)
14. 0 ml (1) 16. 0 ml (1) 18. 0 ml (1) 20. 0 ml (1) 22. 0 ml (2) 24. 0 ml (2) 26. 0 ml (2) 28. 0 ml (2) 30. 0 ml (2) 32. 0 ml (2) 34. 0 ml (2) 36. 0 ml (2) 38. 0 ml (2) 40. 0 ml (2)
6 mg/ kg dose (number of vials) - - - - 18.0 ml (1) 21.0 ml (2) 24.0 ml (2) 27.0 ml (2) 30.0 ml (2) 33.0 ml (2) 36.0 ml (2) 39.0 ml (2) 42.0 ml (3) 45.0 ml (3) 48.0 ml (3) 51.0 ml (3) 54.0 ml (3) 57.0 ml (3) 60.0 ml (3)
21. 0 ml (2) 24. 0 ml (2) 27. 0 ml (2) 30. 0 ml (2) 33. 0 ml (2) 36. 0 ml (2) 39. 0 ml (2) 42. 0 ml (3) 45. 0 ml (3) 48. 0 ml (3) 51. 0 ml (3) 54. 0 ml (3) 57. 0 ml (3) 60. 0 ml (3)
7 mg/ kg dose (number of vials) 7.0 ml (1) 10.5 ml (1) 14.0 ml (1) 17.5 ml (1) 21.0 ml (2) 24.5 ml (2) 28.0 ml (2) 31.5 ml (2) 35.0 ml (2) - - - - - - - - - -
ml (2) ml (2) ml (2) ml (2) - - - - - - - - - -
Voriconazole is a single dose unpreserved sterile lyophile.
Voriconazole huwa lijofil sterili mhux priservat ta 'doża waħda.
Therefore, from a microbiological point of view, the reconstituted solution must be used immediately.
Għalhekk, minn lat mikrobijoloġiku, is- soluzzjoni rikostitwita għandha tintuża minnufih.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.
Jekk ma tintużax minnufih, il- ħinijiet u l - kundizzjonijiet ta 'ħżin waqt l- użu huma r- responsabbiltà ta' l- utent u normalment ma għandhomx ikunu iktar minn 24 siegħa f' 2 sa 8C, sakemm ir- rikostituzzjoni ma tkunx seħħet f' kundizzjonijiet ikkontrollati u asettiċi.
62 The reconstituted solution can be diluted with:
66 Is- soluzzjoni rikostitwita tista 'tiġi dilwita ma':
9 mg/ ml (0.9%) Sodium Chloride for Infusion Lactated Ringer’ s Intravenous Infusion 5% Glucose and Lactated Ringer’ s Intravenous Infusion 5% Glucose and 0.45% Sodium Chloride Intravenous Infusion 5% Glucose Intravenous Infusion 5% Glucose in 20 mEq Potassium Chloride Intravenous Infusion 0.45% Sodium Chloride Intravenous Infusion 5% Glucose and 0.9% Sodium Chloride Intravenous Infusion
9 mg/ ml (0. 9%) Sodium Chloride għal Infużjoni Lactated Ringer’ s Intravenous Infusion 5% Glucose u Lactated Ringer’ s Intravenous Infusion 5% Glucose u 0. 45% Infużjoni Ġol- Vini ta 'Sodium Chloride 5% Infużjoni Ġol- Vini ta' Glucose 5% Glucose fi 20 mEq ta 'Infużjoni Ġol- Vini ta' Potassium Chloride 0. 45% Infużjoni Ġol- Vini ta 'Sodium Chloride 5% Glucose u 0. 9% Infużjoni Ġol- Vini ta' Sodium Chloride
The compatibility of voriconazole with diluents other than described above or in section 6.2 is unknown.
Il- kompatibilità ta 'voriconazole ma' dilwenti mhux dawk deskritti fuq jew fis- sezzjoni 6. 2. m' hiex magħrufa.
63 1.
67 1.
VFEND 40 mg/ ml powder for oral suspension
VFEND 40 mg/ ml trab għal suspensjoni orali
Each ml of oral suspension contains 40 mg of voriconazole when reconstituted with water (see section 6.6).
Kull ml ta 'suspensjoni orali fih 40 mg ta' voriconazole meta rikostitwit bl- ilma (ara sezzjoni 6. 6).
For a full list of excipients, see section 6.1.
Kull ml ta 'suspensjoni fih 0. 54 g ta' sucrose Għal- lista kompleta ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
White to off-white powder
Trab abjad għal offwajt
Voriconazole, is a broad spectrum, triazole antifungal agent and is indicated as follows:
4. 1 Indikazzjonijiet terapewtiċi Voriconazole huwa aġent antifungali triazole bi spettru wiesa 'li huwa indikat kif ġej:
Treatment of invasive aspergillosis
Kura ta 'asperġillosi invażiva.
VFEND oral suspension is to be taken at least one hour before, or two hours following, a meal.
VFEND suspensjoni orali għandhom jittieħdu mill- inqas siegħa qabel, jew sagħtejn wara, ikla.
VFEND is also available as 50 mg and 200 mg film-coated tablets and 200 mg powder for solution for injection.
VFEND huwa disponibbli wkoll bħala pilloli miksijin b' rita ta '50 mg u 200 mg u 200 mg trab għal suspensjoni orali.
64 Detailed information on dosage recommendations is provided in the following table:
68 Tagħrif dettaljat dwar ir- rakkomandazzjonijiet tad- dożaġġ huwa pprovdut fit- tabella segwenti:
Oral Suspension
Suspensjoni Orali
Patients less than 40 kg
minn 40 kg
400 mg (10 ml) every
400 mg (10 ml) kull 12 - 200 mg (5 ml) kull 12 -
200 mg (5 ml) every 12
il siegħa għall- ewwel
Regimen
(l- ewwel
(for the first 24 hours)
24
12 hours (for the first
siegħa)
hours (for the first 24
siegħa) 24 siegħa
(first 24 hours)
24 siegħa
24 hours)
Doża ta 'Manteniment (wara l- ewwel 24 siegħa)
200 mg (5 ml) twice
200 mg (5 ml) darbtejn kuljum
100 mg (2.5 ml) twice
100 mg (2. 5 ml) darbtejn kuljum
65 It is recommended that the standard loading dose regimens be used but that the maintenance dose be halved in patients with mild to moderate hepatic cirrhosis (Child-Pugh A and B) receiving VFEND (see section 5.2).
69 Huwa rakkomandat li jintużaw ir- reġimi standard tal- loading dose iżda li d- doża ta 'manteniment titnaqqas bin- nofs f' pazjenti b' cirrożi epatika ħafifa għal moderata (Child- Pugh A u B) li jkunu qegħdin jirċievu VFEND (ara sezzjoni 5. 2).
Loading Dose Regimen
Reġim tal- Loading Dose
Oral Suspension**
Suspensjoni Orali **
No oral or intravenous loading dose is recommended
Mhix rakkomandata loading dose orali jew fil- vini.
It is therefore recommended to use the oral suspension formulation in children 2- < 12.
Għalhekk huwa rakkomandat li tintuża l- formulazzjoni tas- suspensjoni orali fi tfal ta '2 sa < 12- il sena.
Coadministration of VFEND with high dose ritonavir (400 mg and above twice daily) is contraindicated because ritonavir significantly decreases plasma voriconazole concentrations in healthy subjects at this dose (see section 4.5, for lower doses see section 4.4).
70 L- amministrazzjoni ta 'VFEND ma' doża għolja ta 'ritonavir (400 mg u aktar darbtejn kuljum) hija kontra- indikata billi ritonavir inaqqas b' mod sinifikanti l- konċentrazzjonijiet ta' voriconazole fil - plasma f' suġġetti b' saħħithom f' din id- doża (ara sezzjoni 4. 5, għal dożi aktar baxxi ara sezzjoni 4. 4).
66 Coadministration of ergot alkaloids (ergotamine, dihydroergotamine), which are CYP3A4 substrates, is contraindicated since increased plasma concentrations of these medicinal products can lead to ergotism (see section 4.5).
L- amministrazzjoni f' daqqa ta 'alkalojdi ta' l- ergotina (ergotamine, dihydroergotamine), li huma sostratti ta 'CYP3A4, hija kontra- indikata billi konċentrazzjonijiet akbar ta' dawn il- prodotti mediċinali fil- plasma jistgħu jwasslu għal ergotiżmu (ara sezzjoni 4. 5).
Voriconazole should be administered with caution to patients with potentially proarrhythmic conditions, such as  Congenital or acquired QT-prolongation  Cardiomyopathy, in particular when heart failure is present  Sinus bradycardia  Existing symptomatic arrhythmias  Concomitant medication that is known to prolong QT interval Electrolyte disturbances such as hypokalaemia, hypomagnesaemia and hypocalcaemia should be monitored and corrected, if necessary, prior to initiation and during voriconazole therapy (see section 4.2).
Voriconazole għandu jingħata b' kawtela lil pazjenti li għandhom kondizzjonijiet potenzjalment proarritmiċi, bħal  Titwil konġenitu jew akkwiżit tal- QT  Kardjomijopatija, b' mod partikolari meta jkun hemm insuffiċjenza tal- qalb  Taħbit tal- qalb bil- mod ħafna  Arritmiji sintomatiċi eżistenti  Medikazzjoni konkomitanti li hija magħrufa li ttawwal l- intervall QT Disturbi ta 'l- elettroliti bħal ipokalimja, hypomagnesaemia u ipokalċimja għandhom jiġu mmonitorjati u korretti, jekk ikun meħtieġ, qabel ma tinbeda u waqt terapija b' voriconazole (ara sezzjoni 4. 2).
Patients being treated with voriconazole are likely to be treated concomitantly with nephrotoxic medications and have concurrent conditions that may result in decreased renal function (see section 4.8).
71 probabbli li jiġu kkurati fl- istess waqt b' medikazzjonijiet nefrotossiċi u jkollhom kondizzjonijiet konkorrenti li jistgħu jwasslu għal funzjoni mnaqqsa tal- kliewi (ara sezzjoni 4. 8).
67 Monitoring of pancreatic function:
Monitoraġġ ta ’ funzjoni pankreatika:
In addition VFEND has been associated with photosensitivity skin reaction especially during long-term therapy.
Barra minn hekk VFEND kien assoċjat ma 'reazzjoni ta' fotosensittività tal- ġilda speċjalment waqt terapija fuq perjodu fit- tul.
Careful monitoring of full blood counts and adverse reactions to rifabutin (e. g. uveitis) is recommended when rifabutin is coadministered with voriconazole.
Huwa rakkomandat monitoraġġ attent ta 'l- għadd sħiħ ta' ċelloli bojod u ħomor fid- demm u ta 'reazzjonijiet avversi għal rifabutin (ngħidu aħna uveite) meta rifabutin jiġi amministrat flimkien ma' voriconazole.
Reduction in the dose of alfentanil and other short acting opiates similar in structure to alfentanil and metabolised by CYP3A4 (e. g. alfentanyl and sufentanil) should be considered when co-administered with voriconazole (see section 4.5).
Tnaqqis fid- doża ta ’ alfentanil u opiates oħra li jaħdmu għal żmien qasir, bi struttura simili għal alfentanil u metabolizzati minn CYP3A4 (eż. fentanyl u sufentanil) għandhom ikunu kkunsidrati meta hemm amministrazzjoni flimkien ma voriconazole (ara sezzjoni 4. 5).
As the half-life of alfentanil is prolonged in a four-fold manner when alfentanil is coadministered with voriconazole, a longer respiratory monitoring period may be necessary.
Peress li il- half- life ta ’ alfentanil hija mtawwla b’ erba darbiet iktar meta alfentanil huwa amministrat flimkien ma voriconazole, hemm mnejn ikun hemm bżonn ta ’ perijodu itwal ta ’ monitoraġġ respiratorju.
Ritonavir (Potent CYP450 inducer; CYP3A4 inhibitor and substrate):
Ritonavir (induttur qawwi ta 'CYP450; inibitur u sostratt ta' CYP3A4):
Coadministration of voriconazole and low dose ritonavir (100 mg twice daily) should be avoided unless an assessment of the benefit/ risk justifies the use of voriconazole (see section 4.5, for higher doses see section 4.3).
L- amministrazzjoni ta 'voriconazole ma' doża baxxa ta 'ritonavir (100 mg darbtejn kuljum) għandha tiġi evitata sakemm valutazzjoni tal- vantaġġ/ riskju ma tiġġustifikax l- użu ta' voriconazole (ara sezzjoni 4. 5, għal dożi ogħla ara sezzjoni 4. 3).
When voriconazole is coadministered with efavirenz the dose of voriconazole should be increased to 400 mg every 12 hours and that of efavirenz should be decreased to 300 mg every 24 hours (see sections 4.2 and 4.5).
Meta voriconazole jiġi amministrat ma 'efavirenz, id- doża ta' voriconazole għandha tiżdied għal 400 mg kull 12- il siegħa u dik ta 'efavirenz għandha tiġi mnaqqsa għal 300 mg kull 24 siegħa (ara sezzjonijiet 4. 2 u 4. 5).
VFEND oral suspension contains sucrose and should not be given to patients with rare hereditary problems of fructose intolerance, sucrase-isomaltase deficiency or glucose-galactose malabsorption.
72 Is- suspensjoni orali VFEND fiha sucrose u m' għandhiex tingħata lil pazjenti bi problemi ereditarji rari ta 'intolleranza għall- fructose, sucrase- isomaltase deficiency jew assorbiment ħażin tal- glucose - galactose.
68 This section addresses the effects of other medicinal products on voriconazole, the effects of voriconazole on other medicinal products and two-way interactions.
Din is- sezzjoni tindirizza l- effetti ta 'prodotti mediċinali oħra fuq voriconazole, l- effetti ta' voriconazole fuq prodotti mediċinali oħra u l- interazzjonijiet miż- żewġ naħat.
Rifampicin (600 mg once daily) decreased the Cmax (maximum plasma concentration) and AUCτ (area under the plasma concentration time curve within a dose interval) of voriconazole by 9 3% and 96%, respectively.
Rifampicin (600 mg darba kuljum) naqqas Cmax (konċentrazzjoni massima fil- plasma) u AUC (l- arja taħt il- kurva tal- konċentrazzjoni fil- plasma mal- ħin) ta 'voriconazole bi 93% u 96%, rispettivament.
High doses of ritonavir (400 mg twice daily) decreased the steady state Cmax and AUCτ of oral voriconazole by an average of 66% and 82%, whereas low doses of ritonavir (100 mg twice daily) decreased the Cmax and AUCτ of voriconazole by an average of 24% and 39% respectively.
Dożi għoljin ta 'ritonavir (400 mg darbtejn kuljum) naqqsu Cmax u AUC stabbli ta' voriconazole orali b' medja ta '66% u 82%, filwaqt li dożi baxxi ta' ritonavir (100 mg darbtejn kuljum) naqqsu l- Cmax u AUC ta 'voriconazole b' medja ta' 24% u 39% rispettivament.
One outlier subject with raised voriconazole levels was identified in each of the ritonavir interaction studies. Coadministration of voriconazole and ritonavir (400 mg and above twice daily) is contraindicated.
L- amministrazzjoni ta 'voriconazole ma' ritonavir (400 mg u aktar darbtejn kuljum) hija kontra- indikata.
Ranitidine (increases gastric pH):
73 Ranitidine (iżid il- pH gastriku):
69 Effects of voriconazole on other medicinal products
Effetti ta 'voriconazole fuq prodotti mediċinali oħra
Short Acting Opiates (CYP3A4 substrate):
74 Opiates li jaħdmu fuq qasir żmien (sustratt CYP3A4):
Reduction in the dose of alfentanil and other short acting opiates similar in structure to alfentanil and metabolised by CYP3A4 (e. g. fentanyl and sufentanil) should be considered when coadministered with voriconazole (see section 4.4).
Tnaqqis fid- doża ta ’ alfentanil u opiates oħra li jaħdmu fuq qasir żmien bi struttura simili għal alfentanil u metabolizzati minn CYP3A4 (eż. fentanyl u sufentanil), għandhom ikunu kkunsidrati meta mogħtija flimkien ma voriconazole.
70 Oral anticoagulants:
Sustanzi orali kontra l- koagulazzjoni tad- demm:
Non-Steroidal Anti-Inflammatory Drugs (CYP2C9 substrates):
75 Mediċini anti- infjammatorji non- sterojdali (sostratti ta ’ CYP2C9):
Concomitant use of voricoazole and phenytoin should be avoided unless the benefit outweighs the risk.
L- użu f' daqqa ta 'voriconazole u phenytoin għandu jiġi evitat jekk il- vantaġġ ma jkunx akbar mir- riskju.
71 increased to 5 mg / kg intravenously twice daily or from 200 mg to 400 mg orally, twice daily (100 mg to 200 mg orally, twice daily in patients less than 40 kg), see section 4.2.
Phenytoin jista 'jingħata ma' voriconazole jekk id- doża ta 'manteniment ta' voriconazole tiżdied għal 5 mg / kg fil- vina darbtejn kuljum jew minn 200 mg għal 400 mg b' mod orali, darbtejn kuljum (100 mg għal 200 mg b' mod orali, darbtejn kuljum f' pazjenti li jiżnu anqas minn 40 kg), ara sezzjoni 4. 2.