qanastek/EMEA-V3 huggingface dataset:
No pharmacokinetic data are available for patients with severe hepatic cirrhosis (Child-Pugh C).
Mhux disponibbli tagħrif farmakokinetiku għal pazjenti b' ċirrożi epatika severa (Child- Pugh C).
Repeated-dose toxicity studies with voriconazole indicated the liver to be the target organ.
Studji ta 'doża ripetuta dwar it- tossiċità b' voriconazole indikaw il- fwied bħala l- organu fil- mira.
Hepatotoxicity occurred at plasma exposures similar to those obtained at therapeutic doses in humans, in common with other antifungal agents.
Epatotossiċità nstabet f' esponimenti tal- plasma simili għal dawk miksuba f' dożi terapewtiċi fin- nies, l - istess bħal aġenti antifungali oħra.
In rats, mice and dogs, voriconazole also induced minimal adrenal changes.
Fil- firien, ġrieden u klieb, voriconazole kkawża wkoll bidliet adrenali minimi.
Conventional studies of safety pharmacology, genotoxicity or carcinogenic potential did not reveal a special hazard for humans.
Studji konvenzjonali tal- farmakoloġija tas- sigurtà, ġenotossiċità jew potenzjal karċinoġeniku ma kixfux periklu speċjali għan- nies.
In reproduction studies, voriconazole was shown to be teratogenic in rats and embryotoxic in rabbits at systemic exposures equal to those obtained in humans with therapeutic doses.
Fi studji dwar ir- riproduzzjoni, voriconazole ntwera li huwa teratoġeniku fil- firien u embrijutossiku fil- fniek f' esponimenti sistemiċi ugwali għal dawk miksuba fin- nies b' dożi terapewtiċi.
In the pre and postnatal development study in rats at exposures lower than those obtained in humans with therapeutic doses, voriconazole prolonged the duration of gestation and labour and produced dystocia with consequent maternal mortality and reduced perinatal survival of pups.
Fl- istudju dwar l- iżvilupp ta 'qabel u wara t- twelid fil- firien f' esponimenti aktar baxxi minn dawk miksuba fin- nies b' dożi terapewtiċi, voriconazole tawwal iż- żmien tat- tqala u l- ħlas u kkawża distoċja bil- mewt konsegwenti ta' l- omm u sopravivenza mnaqqsa wara t- twelid tal- frieħ.
The effects on parturition are probably mediated by species-specific mechanisms, involving reduction of oestradiol levels, and are consistent with those observed with other azole antifungal agents.
L- effetti fuq it- twelid probabbli huma medjati minn mekkaniżmi speċifiċi għall- ispeċi, li jinkludu t- tnaqqis tal- livelli ta 'oestradiol, u huma konsistenti ma' dawk osservati b' aġenti antifungali oħra azoli.
Lactose Monohydrate Pregelatinised Starch Croscarmellose Sodium Povidone Magnesium Stearate
Lactose Monohydrate Pregelatinised Starch Croscarmellose Sodium Povidone Magnesium Stearate
Hypromellose Titanium Dioxide (E171) Lactose Monohydrate Glycerol Triacetate
Hypromellose Titanium Dioxide (E171) Lactose Monohydrate Glycerol Triacetate
20 6.3 Shelf life
6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
No special precautions for storage.
M' hemmx prekawzjonijiet speċjali għall- ħażna.
HDPE tablet containers of 2, 30 and 100.
Kontenituri tal- HDPE għall- pilloli ta '2, 30 u 100.
Not all bottle sizes may be marketed.
Jista 'jkun li mhux il- pakketti kollha tal- fliexken jiġu kummerċjalizzati.
PVC / Aluminium blister in cartons of 2, 10, 14, 20, 28, 30, 50, 56 and 100.
Blister tal- PVC / Aluminium f' pakketti ta '2, 10, 14, 20, 28, 30, 50, 56 u 100.
Pfizer Limited, Ramsgate Road, Sandwich, Kent CT13 9NJ, United Kingdom
Pfizer Limited, Ramsgate Road, Sandwich, Kent CT13 9NJ, Renju Unit
21 March 2002 Date of last renewal:
21 ta 'Marzu 2002 Data ta' l- aħħar tiġdid:
21 March 2007
21 ta 'Marzu 2007
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu
Tagħrif dettaljat dwar dan il- prodott mediċinali huwa disponibbli fuq il- website ta 'l- Aġenzija Ewropea għall- Mediċini (EMEA) http: // www. emea. europa. eu
VFEND 200 mg film-coated tablets
VFEND 200 mg pilloli miksijin b' rita
Each tablet contains 200 mg voriconazole.
Kull pillola fiha 200 mg ta 'voriconazole.
Excipient: lactose monohydrate 253.675 mg For a full list of excipients, see section 6.1.
Sustanza mhux attiva: lactose monohydrate 253. 675 mg Għal- lista kompleta ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
White, capsule-shaped tablet, debossed “ Pfizer” on one side and “ VOR200” on the reverse.
Pillola bajda, f' għamla ta 'kapsula, bi “ Pfizer ” imnaqqax fuq naħa u “ VOR200 ” fuq in- naħa l- oħra.
VFEND is also available as 50 mg film-coated tablets, 200 mg powder for solution for infusion and 40 mg/ ml powder for oral suspension.
VFEND huwa disponibbli wkoll bħala pilloli miksijin b' rita ta '50 mg, trab ta' 200 mg għal soluzzjoni għal infużjoni u trab ta '40 mg/ ml għal suspensjoni orali.
22 Detailed information on dosage recommendations is provided in the following table:
24 Tagħrif dettaljat dwar ir- rakkomandazzjonijiet tad- dożaġġ huwa pprovdut fit- tabella segwenti:
Dosage adjustment
mg darbtejn kuljum
If patient response is inadequate, the maintenance dose may be increased to 300 mg twice daily for oral administration.
Aġġustament tad- doża Jekk ir- rispons tal- pazjent ma jkunx adegwat, id- doża ta 'manteniment tista' tiżdied għal 300 mg darbtejn kuljum fil- każ ta 'amministrazzjoni orali.
A four hour haemodialysis session does not remove sufficient amount of voriconazole to warrant dose adjustement.
Sessjoni ta 'ħemodijaliżi ta' erba 'sigħat ma tneħħix ammont suffiċjenti ta' voriconazole biex teħtieġ aġġustament tad- doża.
23 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).
25 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).
Use in children VFEND is not recommended for use in children below 2 years due to insufficient data on safety and efficacy (see also sections 4.8 and 5.1).
Użu fi tfal VFEND mhux mhux irrakkomandat għall- użu fit- tfal taħt is- sentejn peress li m’ hemmx biżżejjed informazzjoni dwar is- sigurtà u l- effikaċja (ara wkoll sezzjoni 4. 8 u 5. 1).
Adolescents (12 to 16 years of age): should be dosed as adults.
John’ s Wort (fexfiex) huwa kontraindikat.
Coadministration of VFEND with rifampicin, carbamazepine and phenobarbital is contraindicated since these medicinal products are likely to decrease plasma voriconazole concentrations significantly (see section 4.5).
26 L- amministrazzjoni ta 'VFEND ma' rifampicin, carbamazepine u phenobarbital hija kontra- indikata billi dawn il- prodotti mediċinali huma probabbli li jnaqqsu l- konċentrazzjonijiet ta 'voriconazole fil - plasma b' mod sinifikanti.
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).
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).
24 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).
 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 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).
Instances of hepatic reactions were noted to occur primarily in patients with serious underlying medical conditions (predominantly haematological malignancy).
Każi ta 'reazzjonijiet epatiċi kienu nnotati li jseħħu primarjament f' pazjenti b' kondizzjonijiet mediċi serji eżistenti (l- aktar tumuri ematoloġiċi).
Transient hepatic reactions, including hepatitis and jaundice, have occurred among patients with no other identifiable risk factors.
Reazzjonijiet epatiċi għaddiena, fosthom epatite u suffejra, seħħew fost pazjenti b' ebda fatturi ta 'riskju oħra identifikabbli.
Visual adverse events:
Episodji avversi tal- vista:
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- vistamhux mixtieqa, inklużi vista mċajpra, newrite ta ’ l- għajn u papilloedema (ara sezzjoni 4. 8).
Renal adverse events:
27 Episodji avversi renali:
25 Monitoring of renal function:
Monitoraġġ tal- funzjoni renali:
Monitoring of serum amylase or lipase may be considered in this clinical situation.
Eżami ta ’ l- amylase u ta ’ lipase jista ’ jkun indikat f’ dawn iċ- ċirkustanzi.
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 relatata mal- methadone, inkluż titwil tal- QTc, meta l- methadone jingħata ma 'voriconazole billi l- livelli tal- methadone żdiedu wara li ġie amministrat ma' voriconazole.
Dose reduction of methadone may be needed (see section 4.5).
Jista 'jkun meħtieġ tnaqqis fid- doża ta' methadone (ara sezzjoni 4. 5).
Short Acting Opiates (CYP3A4 substrate):
Opiates li jaħdmu għal żmien qasir (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 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 in combination 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 (100mg 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).
Efavirenz (CYP450 inducer; CYP3A4 inhibitor and substrate):
28 Efavirenz (induttur ta 'CYP450; inibitur u sostratt ta' CYP3A4):
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 sezzjoni jiet 4. 2 u 4. 5).
26 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.
Effects of other medicinal products on voriconazole
Effetti ta 'prodotti mediċinali oħra fuq voriconazole
Voriconazole is metabolised by cytochrome P450 isoenzymes, CYP2C19, CYP2C9 and CYP3A4.
Voriconazole huwa metabolizzat mill- isoenzimi taċ- ċitokromu P450, CYP2C19, CYP2C9 u CYP3A4.
The effect of the coadministration of voriconazole (200 mg twice daily) and high dose (400 mg) and low dose (100 mg) oral ritonavir was investigated in two separate studies in healthy volunteers.
L- effett ta 'l- amministrazzjoni flimkien ta' voriconzaole (200 mg darbtejn kuljum) u doża għolja (400 mg) u doża baxxa (100 mg) ta 'ritonavir orali 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 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.
Administration of voriconazole did not have a significant effect on mean Cmax and AUCτ of ritonavir 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 ta' ritonavir fl- istudju bid- doża l- għolja, għalkemm kien osservat tnaqqis żgħir f’ Cmax u AUC stabbli ta 'ritonavir b' medja ta' 25% u 13% rispettivament fl - istudju ta 'l- interazzjoni b' doża baxxa ta' ritonavir.
Cimetidine (non-specific CYP450 inhibitor and increases gastric pH):
Cimetidine (inibitur mhux speċifiku ta 'CYP450 u jżid il- pH gastriku):
Ranitidine (increases gastric pH):
29 Ranitidine (iżid il- pH gastriku):
27 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.
When there is also a potential for voriconazole to increase the plasma levels of substances metabolised by CYP3A4 isoenzymes (certain antihistamines, quinidine, cisapride, pimozide) co-administration is contraindicated (see section 4.3).
Meta jkun hemm ukoll possibbilta 'li voriconazole jżid il- livelli fil- plasma ta' sustanzi metabolizzati minn isoenzimi CYP3A4 (ċerti anti- istamini, quinidine, cisapride, pimozide), l - amministrazzjoni konġunta hija kontra- indikata (ara sezzjoni 4. 3).
Voriconazole plasma concentrations during coadministration of methadone were comparable to voriconazole levels (historical data) in healthy subjects without any comedication.
Il- konċentrazzjonijiet ta 'voriconazole fil- plasma waqt amministrazzjoni mal- methadone kienu komparabbli mal- livelli ta' voriconazole (dejta storika) f' suġġetti b' saħħithom mingħajr medikazzjoni konġunta.
Frequent monitoring for adverse events and toxicity related to increased plasma concentrations of methadone, including QT prolongation, is recommended during coadministration.
Monitoraġġ frekwenti għal episodji avversi u tossiċità marbuta ma 'konċentrazzjonijiet akbar ta' methadone fil- plasma, fosthom titwil tal- QT, huwa rakkomandat waqt amministrazzjoni flimkien.
Short Acting Opiates (CYP3A4 substrate): steady-state administration of oral voriconazole increased the AUCτ 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.
28 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):
Digoxin (P-glycoprotein mediated transport):
Digoxin (trasport medjat bil- gyloproteina- P):
Non-Steroidal Anti-Inflammatory Drugs (CYP2C9 substrates):
31 Mediċini anti- infjammatorji non- sterojdali (sostratti ta ’ CYP2C9):
Frequent monitoring for adverse events and toxicity related to NSAIDs is recommended.
Huwa rrakkomandat monitoraġġ tal- episodji avversi u tossiċita ’ li għandha x’ taqsam ma NSAIDS.
Adjustment of dosage of NSAIDs may be needed.
Jista jkun hemm bżonn aġġustament fid- doża tal- NSAIDS.
Concomitant use of voriconazole and phenytoin should be avoided unless the benefit outweighs the risk.
L- użu f' daqqa ta 'voriconazole u phenytoin għandu jiġi evitat sakemm il- vantaġġ ma jkunx akbar mir- riskju.
Phenytoin may be coadministered with voriconazole if the maintenance dose of voriconazole is 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.
29 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.
Coadministration of voriconazole and an oral contraceptive (1 mg norethisterone and 0.035 mg ethinylestradiol; once daily) in healthy female subjects resulted in increases in the Cmax and AUC of ethinylestradiol (36% and 61% respectively) and norethisterone (15% and 53% respectively).
L- amministrazzjoni ta 'voriconazole ma' kontraċettiv orali (1 mg norethisterone u 0. 035 mg ethinylestradiol; darba kuljum) f' suġġetti nisa b' saħħithom irriżultat f' żidiet f’ Cmax u AUC ta 'ethinylestradiol (36% u 61% rispettivament) u norethisterone (15% u 53% rispettivament).
Voriconazole Cmax and AUCτ increased by 14% and 46% respectively.
Cmax u AUC ta 'voriconazole żdiedu b' 14% u 46% rispettivament.
As the ratio between norethisterone and ethinylestradiol remained similar during interaction with voriconazole, their contraceptive activity would probably not be affected.
Billi r- relazzjoni bejn norethisterone u ethinylestradiol baqgħet simili waqt l- interazzjoni ma 'voriconazole, l- attività kontraċettiva tagħhom probabbli ma tkunx affettwata.
Antiretroviral Agents:
32 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' inibituri tal- protease ta 'l- HIV (pereżempju saquinavir, amprenavir u nefinavir).
Standard doses of voriconazole and standard doses of efavirenz must not be coadministered.
Dożi standard ta ’ voriconazole u dożi standard ta ’ efavirenz ma għandhomx ikunu mogħtija flimkien.
Steady-state efavirenz (400 mg orally once daily) decreased the steady state Cmax and AUCτ of voriconazole by an average of 61% and 77%, respectively, in healthy subjects.
Efavirenz stabbli (400 mg b' mod orali darba kuljum) naqqas Cmax u AUC stabbli ta 'voriconazole b' medja ta' 61% u 77%, rispettivament, f' suġġetti b' saħħithom.
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.
When voriconazole is coadministered with efavirenz, voriconazole maintenance dose should be increased to 400 mg twice daily and the efavirenz dose should be reduced by 50%, i. e. to 300 mg once daily (see section 4.2).
Meta voriconazole jiġi amministrat flimkien ma 'efavirenz, id- doża ta' manteniment ta 'voriconazole għandha tiżdied għal 400 mg darbtejn kuljum u d- doża ta' efavirenz għandha titnaqqas b' 50%, jiġifieri għal 300 mg darba kuljum.
When treatment with voriconazole is stopped, the initial dosage of efavirenz should be restored.
(ara sezzjoni 4. 2) Meta titwaqqaf il- kura b' voriconazole, għandu jerġa 'jiddaħħal id- dożaġġ inizjali ta' efavirenz.
Pregnancy No adequate information on the use of VFEND in pregnant women is available.
Tqala M' hemmx tagħrif adegwat mill- użu ta 'VFEND f' nisa tqal.
Women of child-bearing potential Women of child-bearing potential must always use effective contraception during treatment.
33 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 and/ or photophobia.
Voriconazole jista 'jikkawża bidliet għaddiena u riversibbli fil- vista, fosthom ċpar, perċezzjoni mibdula/ imkabbra u/ jew fotofobija.
Patients must avoid potentially hazardous tasks, such as driving or operating machinery while experiencing these symptoms.
Il- pazjenti jridu jevitaw attivitajiet li jistgħu jkunu perikolużi, bħal ngħidu aħna jsuqu jew iħaddmu makkinarju waqt li jħossu dawn is- sintomi.
In the table below, since the majority of the studies were of an open nature all causality adverse events, by system organ class and frequency (very common ≥ 1/ 10, common ≥ 1/ 100 and < 1/ 10, uncommon ≥ 1/ 1000 and < 1/ 100, rare, ≥ 1/ 10 000 and < 1/ 1000 and very rare, < 1/ 10 000) if possibly causally related are listed.
Fit- tabella ta 'hawn isfel, billi l- maġġoranza ta' l- istudji kienu ta 'natura miftuħa, l- episodji avversi kollha ta' kawżalità, skond is- sistema tal- klassifika ta 'l- organi u l- frekwenza (komuni ħafna ≥1/ 10, komuni ≥1/ 100 u < 1/ 10, mhux komuni ≥1/ 1000 u < 1/ 100, rari ≥1/ 10 000 u < 1/ 1000 u rari ħafna < 1/ 10 000) huma elenkati jekk jistgħu jkunu marbuta mal- kawża.
Within each frequency grouping, undesirable effects are presented in order
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa għandhom jitniżżlu skond is- serjetà tagħhom.
31 of decreasing seriousness.
L- effetti li huma l- aktar serji għandhom jitniżżlu l- ewwel, segwiti minn dawk anqas serji.
Undesirable effects reported in subjects receiving voriconazole:
Effetti mhux mixtieqa rrapportati f' suġġetti li kienu qegħdin jirċeivu voriconazole
Blood and Lymphatic system disorders Common
34 Mard tad- demm u tas- sistema limfatika Komuni
Visual disturbances (including blurred vision (see Section 4.4), chromotopsia 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
32 Gastrointestinal disorders Very common Uncommon
Komuni ħafna Mhux komuni
Renal and urinary disorders Common Uncommon Rare
Mard tal- kliewi u tas- sistema urinarja Komuni Mhux komuni Rari
Endocrine disorders
35
Uncommon Rare
Mard fis- sistema endokrinarja Mhux komuni Rari
33 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.
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 perjodu qasir kif ukoll fuq perjodu twil, madwar 30% tas- suġġetti esperjenzaw perċezzjoni viżwali mibdula/ mkabbra, vista mċajpra, tibdil fil- vista tal- kulur jew fotofobija.
The visual disturbances were generally mild, rarely resulted in discontinuation and were not associated with long-term sequelae.
Id- disturb viżwali ġeneralment kien ħafif, rari wassal għal twaqqif tal- kura u ma kienx assoċjat ma 'sintomi morbużi għal perjodu twil.
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.
36 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.
34 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 kompassiv, 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 aktar fid- demm (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.
There is no known antidote to voriconazole.
M' hemmx antidotu magħruf għal voriconazole.
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.
Barra minn hekk
In addition voriconazole shows in vitro fungicidal activity against emerging fungal pathogens, including those such as Scedosporium or Fusarium which have limited susceptibility to existing antifungal agents.
37 voriconazole juri attività fungiċida in vitro kontra patoġeni fungali emerġenti, fosthom dawk bħal Scedosporium jew Fusarium li għandhom suxxettibilità limitata għal aġenti antifungali eżistenti.
Microbiology
Mikrobijoloġija
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.
35 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:
Clinical isolates with decreased susceptibility to voriconazole have been identified.
Kienu identifikati iżolati kliniċi b' suxxettibilità mnaqqsa għal voriconazole.
Clinical Experience
Esperjenza Klinika
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.
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
Candidaemia in non-neutropenic patients.
Candidaemia f' pazjenti mhux newtropeniċi.
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.
The Investigator’ s assessment of successful outcome at each of these time points is shown in the following table.
Il- valutazzjoni ta 'l- Investigatur ta' l - eżitu b' suċċess f' kull wieħed minn dawn il- punti taż- żmien hija murija fit- tabella li ġejja:
36 Timepoint _
Punt taż- żmien
Scedosporium and Fusarium infections Voriconazole was shown to be effective against the following rare fungal pathogens:
39 Infezzjonijiet bi Scedosporium u Fusarium Voriconazole ntwera li kien effettiv kontra l- patoġeni fungali rari li ġejjin:
37 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.
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.
No 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.
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.
40 kuljum b' konċentrazzjonijiet stabbli ta 'voriconazole fil- plasma jinkisbu sa jum 6 fil- maġġoranza tas - suġġetti.
Cerebrospinal fluid samples from eight patients in a compassionate programme showed detectable oriconazole concentrations in all patients.
Kampjuni tal- fluwidu ċerebrospinali minn tmien pazjenti fi programm ta 'kompassjoni wrew konċentrazzjonijiet rilevabbli ta' voriconazole fil- pazjenti kollha.
Subjects who are heterozygous extensive metabolisers have on average 2- fold higher voriconazole exposure than their homozygous extensive metaboliser counterparts.
Suġġetti li huma metabolizzaturi eterozigoti estensivi għandhom, bħala medja, esponiment għal voriconazole darbtejn ogħla mill- metabolizzaturi emozigoti estensivi.
38 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 is recovered in the urine after multiple intravenous dosing and 83% in the urine after multiple oral dosing.
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.
Pharmacokinetic-Pharmacodynamic analyses of clinical trial data identified positive associations between plasma voriconazole concentrations and both liver function test abnormalities and visual disturbances.
41 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
Farmakokinetika fi gruppi ta 'pazjenti speċjali
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).
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).
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.
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.
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
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).
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.
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.
42 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.
40 Film-coat:
Kisja tar- rita:
6.5 Nature and contents of container
43 6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
VFEND 200 mg powder for solution for infusion
VFEND 200 mg trab għal soluzzjoni għall- infużjoni
Each ml contains 10 mg of voriconazole after reconstitution (see section 6.6) - once reconstituted further dilution is required before administration.
Kull ml fih 10 mg ta 'voriconazole wara rikostituzzjoni (ara sezzjoni 6. 6) - ladarba jiġi rikostitwit jeħtieġ li jiġi mħallat aktar bl- ilma qabel jingħata.
Each vial contains 200 mg of voriconazole.
Kull kunjett fih 200 mg ta 'voriconazole.
Excipient: each vial contains 217.6 mg sodium For a full list of excipients, see section 6.1.
Sustanza mhux attiva: kull kunjett fih 217. 6 mg sodju Għal- lista kompleta ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
White lyophilised powder
Trab abjad ixxottat bil- friża
Treatment of candidemia in non-neutropenic patients
Kura ta 'candidemia f' pazjenti mhux newtropeniċi.
Treatment of fluconazole-resistant serious invasive Candida infections (including C. krusei)
Kura ta 'infezzjonijiet invażivi serji Candida reżistenti għal fluconazole (fosthom C. krusei).
VFEND requires reconstitution and dilution (see section 6.6) prior to administration as an intravenous infusion.
VFEND jeħtieġ rikostituzzjoni u dilwizzjoni (ara sezzjoni 6. 6) qabel jingħata bħala infużjoni fil- vini.
It is recommended that VFEND is administered at a maximum rate of 3 mg/ kg per hour over 1 to 2 hours.
Huwa rrikmandat li VFEND jingħata b' rata massima ta '3 mg/ kg fis- siegħa fuq siegħa jew sagħtejn.
VFEND must not be infused into the same line or cannula concomitantly with other intravenous products.
VFEND ma għandux jiġi infuż fl- istess linja jew kannula fl- istess ħin ma 'prodotti oħra għal ġol- vini.
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 konċentrata ta ’ elettroliti, anki jekk iż- żewġ infużjonijiet ikunu għaddejjin f' linji separati.
Total parenteral nutrition (TPN) need not be discontinued when prescribed with VFEND, but does need to be infused through a separate line (see section 6.2).
In- nutrizzjoni parenterali totali (TPN) m' hemmx għalfejn tiġi mwaqqfa meta ordnata ma 'VFEND, iżda trid tiġi infuża minn linja separata (ara sezzjoni 6. 2).
42 VFEND is also available as 50 mg and 200 mg film-coated tablets and 40 mg/ ml powder for oral suspension.
VFEND huwa disponibbli wkoll bħala pilloli miksijin b' rita ta '50 mg u 200 mg u 40 mg/ ml trab għal suspensjoni orali.
Use in adults Therapy must be initiated with the specified loading dose regimen of either intravenous or oral VFEND to achieve plasma concentrations on Day 1 that are close to steady state.
Fuq il- bażi tal -
On the basis of the high oral bioavailability (96%; see section 5.2), switching between intravenous and oral administration is appropriate when clinically indicated.
45 bijodisponibilità orali għolja (96%; ara sezzjoni 5. 2), il- qalba bejn amministrazzjoni fil- vini u orali hija f' waqtha meta klinikament indikata.
Detailed information on dosage recommendations is provided in the following table:
Tagħrif dettaljat dwar ir- rakkomandazzjonijiet tad- dożaġġ huwa pprovdut fit- tabella segwenti:
Regimen (first 24 hours)
siegħa (għall- ewwel 24
(for the first 24 hours)
siegħa (għall- ewwel 24
(for the first 24 hours)
(l- ewwel 24
(for the first 24 hours)
(għall- ewwel 24 siegħa)
Maintenance Dose (after first 24 hours)
Doża ta 'Manteniment (wara l- ewwel 24 siegħa)
Dosage adjustment If patients are unable to tolerate treatment at 4 mg/ kg twice daily, reduce the intravenous dose to 3 mg/ kg twice daily.
Aġġustament tad- doża Jekk il- pazjenti ma jkunux kapaċi jifilħu trattament ta '4 mg/ kg darbtejn kuljum, naqqas id- doża ġol - vina għal 3 mg/ kg darbtejn kuljum.
Rifabutin or phenytoin may be coadministered with voriconazole if the maintenance dose of voriconazole is increased to 5 mg/ kg intravenously twice daily, see sections 4.4 and 4.5.
Rifabutin jew phenytoin jistgħu jingħataw flimkien ma 'voriconazole jekk id- doża ta' manteniment ta 'voriconazole tiżdied għal 5 mg/ kg ġol- vini darbtejn kuljum, ara sezzjonijiet 4. 4 and 4. 5.
When treatment with voriconazole is stopped, the initial dosage of efavirenz should be restored (see sections 4.4 and 4.5).
Meta t- trattament b’ voriconazole huwa mwaqqaf, id- dużaġġ tal- bidu ta ’ efavirenz għandu jkun mibdul għal li kien (ara sezzjonijiet 4. 4 u 4. 5).
The duration of treatment with the intravenous formulation should be no longer than 6 months (see section 5.3).
It- tul tat- trattament b' formolazzjoni ġol- vini ma għandux ikunu itwal minn 6 xhur (ara sezzjoni 5. 3).
Use in patients with renal impairment In patients with moderate to severe renal dysfunction (creatinine clearance < 50 ml/ min), accumulation of the intravenous vehicle, SBECD, occurs.
Użu f' pazjenti b' indeboliment tal- kliewi F' pazjenti b' disfunzjoni renali moderata għal severa (tneħħija tal- kreatinina < 50 ml/ min), isseħħ l - akkumulazzjoni tal- prodott mogħti ġol- vini, SBECD.
Oral voriconazole should be administered to these patients, unless an assessment of the risk benefit to the patient justifies the use of intravenous voriconazole.
Voriconazole orali għandu jingħata lil dawn il - pazjenti, sakemm valutazzjoni tal- benefiċċju tar- riskju tal- pazjent ma tiġġustifikax l- użu ta 'voriconazole ġol- vini.
Serum creatinine levels should be closely monitored in these patients and, if increases occur, consideration should be given to changing to oral voriconazole therapy (see section 5.2).
Il- livelli ta 'kreatinina fis- serum għandhom jiġu mmonitorjati mill- qrib f' dawn il- pazjenti u, jekk isiru xi żjidiet, għandha tingħata kunsiderazzjoni li t- terapija b' voriconazole orali tiġi mibdula (ara sezzjoni 5. 2).
The intravenous vehicle, SBECD, is haemodialysed with a clearance of 55 ml/ min.
Il- prodott mogħti ġol- vini, SBECD, jiġi ħemodijalizzat bi tneħħija ta '55 ml/ min.
43 Use in patients with hepatic impairment No dose adjustment is necessary in patients with acute hepatic injury, manifested by elevated liver function tests (ALAT, ASAT) (but continued monitoring of liver function tests for further elevations is recommended).
Użu f' pazjenti b' indeboliment tal- fwied Mhux meħtieġ aġġustament tad- doża f' pazjenti b' ferita epatika akuta, murija b' testijiet tal- funzjoni elevata tal- fwied (ALAT, ASAT) (iżda monitoraġġ kontinwu tat- testijiet tal- funzjoni tal- fwied huwa rakkomandat).
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).
46 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).
Patients with severe hepatic impairment must be carefully monitored for drug toxicity (see also section 4.8).
Il- pazjenti b' indeboliment tal- fwied sever iridu jiġu mmonitorjati sewwa għat- tossiċità mill- mediċina (ara wkoll sezzjoni 4. 8).
Use in children VFEND is not recommended for use in children below 2 years due to insufficient data on safety and efficacy (see also sections 4.8 and 5.1).
Użu fi tfal VFEND mhux rakkomandat biex jintuża fi tfal ta 'anqas minn sentejn minħabba tagħrif insuffiċjenti dwar is- sigurtà u l- effikaċja.
Intravenous*
Fil- vini *
Oral**
Orali **
No oral or intraveneous loading dose is recommended
Mhix rakkomandata loading dose orali jew fil- vini.
Maintenance Dose
Doża ta 'Manteniment
If paediatric patients are unable to tolerate an intravenous dose of 7 mg/ kg twice daily, a dose reduction from 7 mg/ kg to 4 mg/ kg twice daily may be considered based on the population pharmacokinetic analysis and previous clinical experience.
Jekk pazjenti pedjatriċi ma jkunux jistgħu jittolleraw doża ġol- vini ta '7 mg/ kg darbtejn kuljum, tnaqqis fid- doża minn 7 mg/ kg għal 4 mg/ kg darbtejn kuljum jista' jiġi kkunsidrat fuq il- bażi ta 'l - analiżi farmakokinetika tal- popolazzjoni u esperjenza klinika preċedenti.
This provides equivalent exposure to 3 mg/ kg twice daily in adults (see section 4.2 use in adults).
4. 3 Kontra- indikazzjonijiet
Adolescents (12 to 16 years of age): should be dosed as adults.
Sensittività eċċessiva għas- sustanza( i) attiva( i) jew għal sustanzi mhux attivi.
Coadministration of VFEND with rifampicin, carbamazepine and phenobarbital is contraindicated since these medicinal products are likely to decrease plasma voriconazole concentrations significantly (see section 4.5).
L- amministrazzjoni ta 'VFEND ma' rifampicin, carbamazepine u phenobarbital hija kontra- indikata billi dawn il- prodotti mediċinali huma probabbli li jnaqqsu l- konċentrazzjonijiet ta 'voriconazole fil - plasma b' mod sinifikanti.
44 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).
47 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).
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).
The concomitant use of voriconazole with St John’ s Wort is contraindicated (see section 4.5).
John’ s Wort (fexfiex) huwa kontraindikat (ara sezzjoni 4. 5).
Some azoles, including voriconazole have been associated with QT interval prolongation.
Ċerti sustanzi antifungali, fosthom voriconazole ġew assoċjati ma 'titwil ta' l - intervall QT.
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 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).
A study has been conducted in healthy volunteers which examined the effect on QT interval of single doses of voriconazole up to four times the usual daily dose.
Sar studju fost voluntiera b' saħħithom li eżamina l- effett fuq l- intervall QT ta 'dożi waħdiena ta' voriconazole sa erba 'darbiet aktar mid- doża normali ta' kuljum.
Infusion-related reactions:
Reazzjonijiet relatati ma 'l- infużjoni: