qanastek/EMEA-V3 huggingface dataset:
Liver dysfunction has usually been reversible on discontinuation of therapy (see section 4.8).
Id- disturb tal- funzjoni tal- fwied ġeneralment kien riversibbli bit- twaqqif tal- kura (ara sezzjoni 4. 8).
Patients at the beginning of therapy with voriconazole and patients who develop abnormal liver function tests during VFEND therapy must be routinely monitored for the development of more severe hepatic injury.
Pazjenti fil- bidu ta 'terapija b' voriconazole u pazjenti li jiżviluppaw testijiet anormali tal- funzjoni tal- fwied waqt terapija b' VFEND iridu jiġu mmonitorjati skond rutina għall- iżvilupp ta' leżjoni epatika aktar severa.
Patient management should include laboratory evaluation of hepatic function (particularly liver function tests and bilirubin).
Il- ġestjoni tal- pazjent għandha tinkludi valutazzjoni fil - laboratorju tal- funzjoni epatika (b' mod partikolari testijiet tal- funzjoni tal- fwied u bilirubin).
Discontinuation of VFEND should be considered if clinical signs and symptoms are consistent with liver disease development.
Għandu jiġi kkunsidrat it- twaqqif ta 'VFEND jekk is- sinjali u sintomi kliniċi jkunu konsistenti ma' żvilupp ta 'mard tal- fwied.
Monitoring of hepatic function should be carried out in both children and adults.
Għandu jitwettaq monitoraġġ tal- funzjoni epatika kemm fit- tfal kif ukoll fl- adulti.
Visual adverse events:
5 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 mhux mixtieqa tal- vista, inklużi vista imċajpra, newrite ta ’ l- għajn u papilloedema (ara sezzjoni 4. 8).
Renal adverse events:
Episodji avversi renali:
Acute renal failure has been observed in severely ill patients undergoing treatment with VFEND.
Insuffiċjenza akuta tal- kliewi kienet osservat f' pazjenti morda severament li kienu qegħdin jieħdu kura b' VFEND.
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).
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).
5 Monitoring of renal function:
Monitoraġġ tal- funzjoni renali:
Patients should be monitored for the development of abnormal renal function.
Il- pazjenti għandhom jiġu mmonitorjati għall- iżvilupp ta 'funzjoni renali mhux normali.
This should include laboratory evaluation, particularly serum creatinine.
Dan għandu jinkludi evalwazzjoni fil- laboratorju, b' mod partikolari l- krejatinina fis- serum.
Monitoring of pancreatic function:
Monitoraġġ ta ’ funzjoni pankreatika:
Patients, especially children, with risk factors for acute pancreatitis (e. g. recent chemotherapy, hematopoietic stem cell translplantation (HSCT)), should be monitored closely during Vfend treatment.
Pazjenti, speċjalment tfal, b’ fatturi ta ’ riskju għal pankreatite akuta (eż. kemoterapija riċenti, trapjant ta ’ ċelluli imsejħa stem fid- demm (HSCT)), għandhom ikunu mmonitorati b’ attenzjoni matul kura bil- VFEND.
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..
Dermatological reactions:
Reazzjonijiet dermatoloġiċi:
Patients have rarely developed exfoliative cutaneous reactions, such as Stevens-Johnson syndrome, during treatment with VFEND.
Il- pazjenti rari żviluppaw reazzjonijiet kutanji ta 'twaqqigħ qxur qxur, bħas- sindrome ta' Stevens- Johnson, waqt kura b' VFEND.
If patients develop a rash they should be monitored closely and VFEND discontinued if lesions progress.
Jekk il- pazjenti jiżviluppaw raxx huma għandhom jiġu mmonitorjati mill- qrib u VFEND jiġi mwaqqaf jekk il- leżjonijiet jissoktaw.
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.
It is recommended that patients should be informed to avoid sunlight during the treatment.
Huwa rakkomandat li l- pazjenti jiġu infurmati biex jevitaw id- dawl tax- xemx waqt il- kura.
Safety and effectiveness in paediatric subjects below the age of two years has not been established (see also sections 4.8 and 5.1).
Is- sigurtà u l- effikaċja f' suġġetti pedjatriċi li għandhom anqas minn sentejn ma ġietx stabbilita (ara wkoll sezzjonijiet 4. 8 u 5. 1).
Voriconazole is indicated for paediatric patients aged two years or older.
Voriconazole huwa indikat għal pazjenti pedjatriċi ta 'sentejn jew akbar.
Hepatic function should be monitored in both children and adults.
Il- funzjoni epatika għandha tiġi mmonitorjata kemm fit- tfal kif ukoll fil- kbar.
Oral bioavailability may be limited in paediatric patients aged 2- < 12 years with malabsorption and very low body weight for age.
Il - bijodisponibilità orali tista 'tkun limitata f' pazjenti pedjatriċi ta' bejn 2 u < 12- il sena b' assorbiment ħażin u piż baxx ħafna tal- ġisem għall- età tagħhom.
In that case, intravenous voriconazole administration is recommended.
F' dak il- każ, huwa rakkomandat li voriconazole jingħata fil- vina.
Phenytoin (CYP2C9 substrate and potent CYP450 inducer):
Phenytoin (sostratt ta 'CYP2C9 u induttur qawwi ta' CYP450):
Careful monitoring of phenytoin levels is recommended when phenytoin is coadministered with voriconazole.
Huwa rakkomandat monitoraġġ attent tal- livelli ta 'phenytoin meta phenytoin jiġi amministrat flimkien ma' voriconazole.
Concomitant use of voriconazole and phenytoin should be avoided unless the benefit outweighs the risk (see section 4.5).
L- użu f' daqqa ta 'voriconazole u phenytoin għandu jiġi evitat jekk il- benefiċċju ma jkunx akbar mir- riskju (ara sezzjoni 4. 5).
Rifabutin (CYP450 inducer):
Rifabutin (induttur ta 'CYP450):
Careful monitoring of full blood counts and adverse events 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 'l- episodji avversi għal rifabutin (ngħidu aħna uveite) meta rifabutin jiġi amministrat flimkien ma' voriconazole.
Concomitant use of voriconazole and rifabutin should be avoided unless the benefit outweighs the risk (see section 4.5).
L- użu f' daqqa ta 'voriconazole u rifabutin għandu jiġi evitat jekk il- benefiċċju ma jkunx akbar mir- riskju (ara sezzjoni 4. 5).
Methadone (CYP3A4 substrate):
Opiates li jaħdmu fuq qasir żmien (sustratt 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.
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 hemm amministrazzjoni flimkien ma voriconazole (ara sezzjoni 4. 5).
Dose reduction of methadone may be needed (see section 4.5).
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.
Short Acting Opiates (CYP3A4 substrate):
Methadone (sostratt ta '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).
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.
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.
Jista 'jkun meħtieġ tnaqqis fid- doża ta' methadone (ara sezzjoni 4. 5).
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
Efavirenz (CYP450 inducer; CYP3A4 inhibitor and substrate):
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 sezzjonijiet 4. 2 u 4. 5)
VFEND tablets contain lactose and should not be given to patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
Il- pilloli VFEND fihom il- lattosju u m' għandhom jingħataw lil pazjenti bi problemi ereditarji rari ta 'intolleranza għall- galactose, Lapp lactase deficiency jew assorbiment ħażin tal- glukosju- galactose.
Unless otherwise specified, drug interaction studies have been performed in healthy adult male subjects using multiple dosing to steady state with oral voriconazole at 200 mg twice daily.
Sakemm mhux speċifikat mod ieħor, l- istudji dwar l- interazzjoni tal- mediċina saru fuq suġġetti maskili b' saħħithom billi ntuża dożaġġ multiplu għal stat stabbli b' voriconazole orali f' doża ta '200 mg darbtejn kuljum.
These results are relevant to other populations and routes of administration.
Dawn ir- riżultati huma rilevanti għal popolazzjonijiet u rotot oħra ta 'amministrazzjoni.
6 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 interactions for the first two sections are presented in the following order: contraindications, those requiring dosage adjustment and careful clinical and/ or biological monitoring and finally those that have no significant pharmacokinetic interaction but may be of clinical interest in this therapeutic field.
L- interazzjonijiet għall - ewwel żewġ sezzjonijiet huma ppreżentati fl- ordni segwenti: kontra- indikazzjonijiet, dawk li jeħtieġu aġġustament tad- dożaġġ u monitoraġġ kliniku u/ jew bijoloġiku attent u fl- aħħarnett dawk li m' għandhomx interazzjoni farmakokinetika sinifikanti iżda li jistgħu jkunu ta 'interess kliniku f' dan il - qasam terapewtiku.
Effects of other medicinal products on voriconazole Voriconazole is metabolised by cytochrome P450 isoenzymes, CYP2C19, CYP2C9 and CYP3A4.
Voriconazole huwa metabolizzat mill- isoenzimi taċ- ċitokromu P450, CYP2C19, CYP2C9 u CYP3A4.
Inhibitors or inducers of these isoenzymes may increase or decrease voriconazole plasma concentrations respectively.
L- inibituri jew indutturi ta 'dawn l- isoenzimi jistgħu jnaqqsu jew iżidu rispettivament il - konċentrazzjonijiet ta' voriconazole fil- plasma.
Rifampicin (CYP450 inducer):
Rifampicin (induttur ta 'CYP450):
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 93% 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.
Coadministration of voriconazole and rifampicin is contraindicated (see section 4.3).
L- amministrazzjoni ta 'voriconazole ma' rifampicin hija kontra- indikata (ara sezzjoni 4. 3).
The effect of the coadministration of oral 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 orali (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 fi stat 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.
One outlier subject with raised voriconazole levels was identified in each of the ritonavir interaction studies.
Kien identifikat suġġett iżolat b' livelli ogħla ta 'voriconazole f' kull studju ta' l- interazzjoni b' 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 to the patient 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 għall- pazjent ma tiġġustifikax l- użu ta' voriconazole (ara sezzjoni 4. 3 u 4. 4).
Carbamazepine and phenobarbital (potent CYP450 inducers):
Carbamazepine u phenobarbital (indutturi qawwija ta 'CYP450):
Although not studied, carbamazepine or phenobarbital are 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.
Coadministration of voriconazole with carbamazepine and phenobarbital is contraindicated (see section 4.3).
L- amministrazzjoni ta 'voriconazole u carbamazepine flimkien hija kontra - indikata (ara sezzjoni 4. 3).
Cimetidine (non-specific CYP450 inhibitor and increases gastric pH):
7 Cimetidine (inibitur mhux speċifiku ta 'CYP450 u jżid il- pH gastriku):
Cimetidine (400 mg twice daily) increased voriconazole Cmax and AUCτ by 18% and 23%, respectively.
Cimetidine (400 mg darbtejn kuljum) żied Cmax u AUC ta 'voriconazole bi 18% u 23%, rispettivament.
No dosage adjustment of voriconazole is recommended.
Ma huwa rakkomandat ebda aġġustament fid- doża ta 'voriconazole.
Ranitidine (increases gastric pH):
Ranitidine (iżid il- pH gastriku):
Ranitidine (150 mg twice daily) had no significant effect on voriconazole Cmax and AUCτ.
Ranitidine (150 mg darbtejn kuljum) ma kellux effett sinifikanti fuq Cmax u AUC ta 'voriconazole.
Macrolide antibiotics:
Antibijotiċi macrolide:
Erythromycin (CYP3A4 inhibitor; 1 g twice daily) and azithromycin (500 mg once daily) had no significant effect on voriconazole Cmax and AUCτ.
Erythromycin (inibitur ta 'CYP3A4; 1g darbtejn kuljum) u azithromycin (500 mg darba kuljum) ma kellhomx effett sinifikanti fuq Cmax u AUC ta' voriconazole.
St John’ s Wort (CYP450 inducer; P-gp inducer):
John’ s Wort (fexfiex) (inibitur CYP450, u induttur P- gp):
In a clinical study in healthy volunteers, St John’ s Wort exhibited a short initial inhibitory effect followed by induction of voriconazole metabolism.
Wara ġimagħtejn ta ’ kura b’ St.
After 15 days of treatment with St John’ s Wort (300 mg three times daily), plasma exposure following a single 400 mg dose of voriconazole decreased by 40-60%.
John’ s Wort (300mg tliet darbiet kuljum), l- ammont fil- plażma wara doża waħda ta ’ voriconazole 400mg naqset bejn 40% u 60%.
Therefore, concomitant use of voriconazole with St John’ s Wort is contraindicated (see section 4.3).
John’ s Wort huwa kontraindikat.
Effects of voriconazole on other medicinal products 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.
Therefore there is potential for voriconazole to increase the plasma levels of substances metabolised by these CYP450 isoenzymes.
Għalhekk hemm il- possibbilta 'li voriconazole jżid il- livelli fil- plasma ta' sustanzi metabolizzati minn dan l- isoenzimi CYP450.
7 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 below and 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 taħt u sezzjoni 4. 3).
Terfenadine, astemizole, cisapride, pimozide and quinidine (CYP3A4 substrates):
Terfenadine, astemizole, cisapride, pimozide and quinidine (sostratt ta 'CYP3A4):
Although not studied, coadministration of voriconazole with terfenadine, astemizole, cisapride, pimozide, or quinidine is contraindicated, since increased plasma concentrations of these medicinal products can lead to QTc prolongation and rare occurrences of torsades de pointes (see section 4.3).
Għalkemm mhix studjata, l- amministrazzjoni ta 'voriconazole ma' terfenadine, astemizole, cisapride, pimozide, jew quinidine hija kontra- indikata, billi konċentrazzjonijiet akbar fil- plasma ta 'dawn il- prodotti mediċinali jistgħu jwasslu għal titwil tal- QTc u okkorrenzi rari ta' torsades de pointes (ara sezzjoni 4. 3).
Sirolimus (CYP3A4 substrate):
Sirolimus (sostratt ta 'CYP3A4):
Voriconazole increased sirolimus (2 mg single dose) Cmax and AUCτ by 556% and 1014%, respectively.
Voriconazole żied Cmax u AUC ta 'sirolimus (2 mg doża waħda)  b' 556% u 1014%, rispettivament.
Coadministration of voriconazole and sirolimus is contraindicated (see section 4.3).
L- amministrazzjoni ta 'voriconazole ma' sirolimus hija kontra - indikata (ara sezzjoni 4. 3).
Ergot alkaloids (CYP3A4 substrates):
Alkalojdi ta 'l- ergotina (sostratti ta' CYP3A4):
Although not studied, voriconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) and lead to ergotism.
Għalkemm mhux studjat, voriconazole jista 'jżid il - konċentrazzjonijiet ta' alkalojdi ta 'l- ergotina (ergotamine u dihydroergotamine) fil- plasma u jwassal għal ergotiżmu.
Coadministration of voriconazole with ergot alkaloids is contraindicated (see section 4.3).
L- amministrazzjoni ta 'voriconazole ma' alkalojdi ta 'l- ergotina hija kontra- indikata (ara sezzjoni 4. 3).
Ciclosporin (CYP3A4 substrate):
Ciclosporin (sostratt ta 'CYP3A4):
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.
When initiating voriconazole in patients already receiving ciclosporin it is recommended that the ciclosporin dose be halved and ciclosporin level carefully monitored.
Meta jinbeda voriconazole f' pazjenti li diġa 'jkunu qegħdin jirċievu ciclosporin, huwa rakkomandat li d- doża ta' ciclosporin titnaqqas bin - nofs u l- livell ta 'ciclosporin jiġi mmonitorjat b' attenzjoni.
Increased ciclosporin levels have been associated with nephrotoxicity.
Livelli akbar ta 'ciclosporin ġew assoċjati ma' nefrotossiċità.
When voriconazole is discontinued, ciclosporin levels must be carefully monitored and the dose increased as necessary.
Meta voriconazole jiġi mwaqqaf, il- livelli ta 'ciclosporin iridu jiġu mmonitorjati bir- reqqa u d- doża miżjuda kif meħtieġ.
Methadone (CYP3A4 substrate):
Methadone (sostratt ta 'CYP3A4):
In subjects receiving a methadone maintenance dose (32-100 mg once daily) coadministration of oral voriconazole (400 mg twice daily for 1 day, then 200 mg twice daily for four days) increased the Cmax and AUC of pharmacologically active R-methadone by 31% and 47%, respectively, whereas the Cmax and AUC of the S-enantiomer increased by approximately 65% and 103%, respectively.
F' suġġetti li jkunu qegħdin jirċievu doża ta 'manteniment tal - methadone (32- 100 mg darba kuljum), l- amministrazzjoni konġunta ta' voriconazole orali (400 mg darbtejn kuljum għal ġurnata, imbagħad 200 mg darbtejn kuljum għal erbat ijiem) żiedet Cmax u AUC ta 'R- methadone attiv b' mod farmakoloġiku b' 31% u 47% rispettivament, filwaqt li l- Cmaxu AUC ta' S- enantiomer żdiedu b' madwar 65% u 103%, rispettivament.
Voriconazole plasma concentrations during coadministration of methadone were comparable to voriconazole levels (historical data) in healthy subjects without any comedication.
Monitoraġġ frekwenti għal
Frequent monitoring for adverse events and toxicity related to increased plasma concentrations of methadone, including QT prolongation, is recommended during coadministration.
8 episodji avversi u tossiċità marbuta ma 'konċentrazzjonijiet akbar ta' methadone fil- plasma, fosthom titwil tal- QT, huwa rakkomandat waqt amministrazzjoni flimkien.
Dose reduction of methadone may be needed.
Jista 'jkun meħtieġ tnaqqis fid- doża tal- methadone.
Short Acting Opiates (CYP3A4 substrate):
Opiates li jaħdmu fuq qasir żmien (sustratt CYP3A4):
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- AUCτ 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.
Tacrolimus (CYP3A4 substrate):
Tacrolimus (sostratt ta 'CYP3A4):
Voriconazole increased tacrolimus (0.1 mg/ kg single dose) Cmax and AUCt (area under the plasma concentration time curve to the last quantifiable measurement) by 117% and 221%, respectively.
Voriconazole żied Cmax u AUCt (l- arja taħt il- kurva tal - konċentrazzjonijiet fil- plasma mal- ħin sa l- aħħar kejl kwantifikabbli) ta 'tacrolimus (doża waħda ta' 0. 1 mg/ kg) b' 117% u 221%, rispettivament.
When initiating voriconazole in patients already receiving tacrolimus, it is recommended that the tacrolimus dose be reduced to a third of the original dose and tacrolimus level carefully monitored.
Meta jinbeda voriconazole f' pazjenti li diġa 'jkunu qegħdin jieħdu tacrolimus, huwa rakkomandat li d- doża ta' tacrolimus titnaqqas għal terz tad- doża oriġinali u l- livell ta 'tacrolimus jiġu mmonitorjat b' attenzjoni.
Increased tacrolimus levels have been associated with nephrotoxicity.
Livelli akbar ta 'tacrolimus ġew assoċjati ma' nefrotossiċità.
When voriconazole is discontinued, tacrolimus levels must be carefully monitored and the dose increased as necessary.
Meta voriconazole jiġi mwaqqaf, il- livelli ta 'tacrolimus iridu jiġu mmonitorjati bir- reqqa u d- doża miżjuda kif meħtieġ.
Oral anticoagulants:
Sustanzi orali kontra l- koagulazzjoni tad- demm:
Warfarin (CYP2C9 substrate):
Warfarin (sostratt ta 'CYP2C9):
Coadministration of voriconazole (300 mg twice daily) with warfarin (30 mg single dose) increased maximum prothrombin time by 93%.
L- amministrazzjoni ta 'voriconazole (300 mg darbtejn kuljum) ma' warfarin (doża waħda ta '30 mg) żiedet il- ħin massimu li jieħu d- demm biex jagħqad bi 93%.
Close monitoring of prothrombin time is recommended if warfarin and voriconazole are coadministered.
Huwa rakkomandat monitoraġġ mill- qrib tal- ħin li jieħu d- demm biex jagħqad jekk warfarin u voriconazole jiġu amministrati flimkien.
8 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):
Although not studied, voriconazole may increase the plasma concentrations of coumarins and therefore may cause an increase in prothrombin time.
Għalkemm mhux studjat, voriconazole jista 'jżid il- konċentrazzjonijiet ta' coumarins fil- plasma u għalhekk jista 'jikkawża żieda fil- ħin li jieħu d- demm biex jagħqad.
If patients receiving coumarin preparations are treated simultaneously with voriconazole, the prothrombin time should be monitored at close intervals and the dosage of anticoagulants adjusted accordingly.
Jekk il - pazjenti li jkunu qegħdin jirċievu preparazzjonijiet tal- coumarin jiġu kkurati fl- istess ħin b' voriconazole, il- ħin li jieħu d- demm biex jagħqad għandu jiġi mmonitorjat f' intervalli viċin u d - dożaġġ tas- sustanzi kontra l- koagulazzjoni tad- demm jiġu aġġustati kif meħtieġ.
Sulphonylureas (CYP2C9 substrates):
Sulphonylureas (sostratti ta 'CYP2C9):
Although not studied, voriconazole may increase the plasma levels of sulphonylureas (e. g. tolbutamide, glipizide, and glyburide) and therefore cause hypoglycaemia.
Għalkemm mhux studjat, voriconazole jista 'jżid il- livelli ta' sulphonylureas (eż. tolbutamide, glipizide, u glyburide) fil- plasma u b' hekk jikkawża ipogliċemija.
Careful monitoring of blood glucose is recommended during coadministration.
Huwa rakkomandat monitoraġġ attent tal- glukosju fid- demm waqt amministrazzjoni flimkien.
Statins (CYP3A4 substrates):
Statins (sostratti ta 'CYP3A4):
Although not studied clinically, voriconazole has been shown to inhibit lovastatin metabolism in vitro (human liver microsomes).
Għalkemm mhux klinikament studjat, voriconazole nstab li jimpedixxi l- metaboliżmu ta 'lovastatin in vitro (mikrosomi tal- fwied uman).
Therefore, voriconazole is likely to increase plasma levels of statins that are metabolised by CYP3A4.
Għalhekk, voriconazole huwa probabbli li jżid il- livelli fil- plasma ta 'l- istatins li jiġu metabolizzati minn CYP3A4.
It is recommended that dose adjustment of the statin be considered during coadministration.
Huwa rakkomandat li jiġi kkunsidrat aġġustament fid- doża ta 'l- istatins waqt amministrazzjoni flimkien.
Increased statin levels have been associated with rhabdomyolysis.
Livelli akbar ta 'statins kienu assoċjati ma' rhabdomyolysis.
Benzodiazepines (CYP3A4 substrates):
Benzodiazepines (sostratti ta 'CYP3A4):
Although not studied clinically, voriconazole has been shown to inhibit midazolam metabolism in vitro (human liver microsomes).
Għalkemm mhux studjat klinikament, voriconazole nstab li jimpedixxi l- metaboliżmu ta 'midazolam in vitro (mikrosomi tal- fwied uman).
Therefore, voriconazole is likely to increase the plasma levels of benzodiazepines that are metabolised by CYP3A4 (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 (midazolam u triazolam) u jwassal għal effett sedattiv fit- tul.
It is recommended that dose adjustment of the benzodiazepine be considered during coadministration.
Huwa rakkomandat li jiġi kkunsidrat aġġustament fid- doża tal- bezodiazepine waqt amministrazzjoni konġunta.
Vinca Alkaloids (CYP3A4 substrates):
Alkalojdi Vinca (sostratti ta 'CYP3A4):
Although not studied, voriconazole may increase the plasma levels of the vinca alkaloids (e. g. vincristine and vinblastine) and lead to neurotoxicity.
Għalkemm mhux studjat, voriconazole jista 'jżid il- livelli fil - plasma ta' l- alkalojdi vinca (eż. vincristine u vinblastine) u jwassal għal newrotossiċità.
Prednisolone (CYP3A4 substrate):
Prednisolone (sostratt ta 'CYP3A4):
Voriconazole increased Cmax and AUCτ of prednisolone (60 mg single dose) by 11% and 34%, respectively.
Voriconazole żied Cmax u AUC ta 'prednisolone (doża waħda ta' 60 mg) bi 11% u 34%, rispettivament.
No dosage adjustment is recommended.
Mhux rakkomandat aġġustament fid- dożaġġ.
Digoxin (P-glycoprotein mediated transport):
9 Digoxin (trasport medjat bil- gyloproteina- P):
Voriconazole had no significant effect on Cmax and AUCτ of digoxin (0.25 mg once daily).
Voriconazole ma kellux effett sinifikanti fuq Cmax u AUC ta 'digoxin (0. 25 mg darba kuljum).
Mycophenolic acid (UDP-glucuronyl transferase substrate):
Aċidu mikofenoliku (UDP- glucuronyl transferase substrate):
Voriconazole had no effect on the Cmax and AUCt of mycophenolic acid (1 g single dose).
Voriconazole ma kellux effett fuq Cmax u AUCt ta 'l- aċidu mikofenoliku (doża waħda ta' 1 g).
Non-Steroidal Anti-Inflammatory Drugs (CYP2C9 substrates):
Mediċini anti- infjammatorji non- sterojdali (sostratti ta ’ CYP2C9):
Voriconazole increased Cmax and AUC of ibuprofen (400 mg single dose) by 20% and 100%, respectively.
Voriconazole żied Cmax u AUC ta ’ ibuprofen (400 mg doża waħdanija) b’ 20% u 100%, rispettivament.
Voriconazole increased Cmax and AUC of diclofenac (50 mg single dose) by 114% and 78%, respectively.
Voriconazole żied Cmax u AUC ta ’ diclofenac (50 mg doża waħdanija) b’ 114% u 78%, rispettivament.
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.
Two-way interactions
Interazzjonijiet miż- żewġ naħat
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 jekk il- vantaġġ ma jkunx akbar mir- riskju.
Phenytoin (300 mg once daily) decreased the Cmax and AUCτ of voriconazole by 49% and 69%, respectively.
Phenytoin (300 mg darba kuljum) naqqas Cmax u AUC ta 'voriconazole b' 49% u 69%, rispettivament.
Voriconazole (400 mg twice daily, see section 4.2) increased Cmax and AUCτ of phenytoin (300 mg once daily) by 67% and 81%, respectively.
Voriconazole (400 mg darbtejn kuljum, ara sezzjoni 4. 2) żied Cmax u AUCta 'phenytoin (300 mg darba kuljum) b' 67% u 81%, rispettivament.
Careful monitoring of phenytoin plasma levels is recommended when phenytoin is coadministered with voriconazole.
Huwa rakkomandat monitoraġġ attent tal- livelli ta 'phenytoin fil- plasma meta phenytoin jiġi amministrat flimkien ma' voriconazole.
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.
Rifabutin (CYP450 inducer):
Rifabutin (induttur ta 'CYP450 induce):
Concomitant use of voriconazole and rifabutin should be avoided unless the benefit outweighs the risk.
L- użu f' daqqa ta 'voriconazole u rifabutin għandu jiġi evitat sakemm il- vantaġġ ma jkunx akbar mir- riskju.
During coadministration with
Rifabutin (300 mg darba kuljum) naqqas Cmax u AUC ta 'voriconazole f' doża ta' 200 mg darbtejn kuljum b' 69% u 78%, rispettivament.
9 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 Cmax 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.
Voriconazole at 400 mg twice daily increased Cmax and AUCτ of rifabutin by 195% and 331%, respectively.
Voriconazole f' doża ta '400 mg darbtejn kuljum żied Cmax u AUC ta' rifabutin b' 195% u 331%, rispettivament.
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 40 kg) (see section 4.2).
(100 mg għal 200 mg b' mod orali, darbtejn kuljum fil- każ ta 'pazjenti li jiżnu anqas minn 40 kg) (ara sezzjoni 4. 2).
Careful monitoring of full blood counts and adverse events to rifabutin (e. g. uveitis) is recommended when rifabutin is coadministered with voriconazole.
Huwa rakkomandat monitoraġġ bir- reqqa ta 'l- għadd sħiħ ta' ċelloli bojod u ħomor fid - demm u ta 'l- episodji avversi għal rifabutin (ngħidu aħna uveite) meta rifabutin jiġi amministrat flimkien ma' voriconazole.
Omeprazole (CYP2C19 inhibitor; CYP2C19 and CYP3A4 substrate):
Omeprazole (inibitur ta 'CYP2C19; sostratt ta' CYP2C19 u CYP3A4):
Omeprazole (40 mg once daily) increased voriconazole Cmax and AUCτ by 15% and 41%, respectively.
Omeprazole (40 mg darba kuljum) żied Cmax u AUC ta 'omeprazole bi 15% u 41%, rispettivament.
Voriconazole increased omeprazole Cmax and AUCτ by 116% and 280%, respectively.
Voriconazole żied Cmax u AUC ta 'omeprazole b' 116% u 280%, rispettivament.
When initiating voriconazole in patients already receiving omeprazole, it is recommended that the omeprazole dose be halved.
Meta jinbeda voriconazole f' pazjenti li diġa 'jkunu qegħdin jirċievu omeprazole, huwa rakkomandat li d- doża ta' omeprazole titnaqqas bin- nofs.
The metabolism of other proton pump inhibitors which are CYP2C19 substrates may also be inhibited by voriconazole.
Il- metaboliżmu ta 'proton pump inhibitors oħra li jkunu sostratti ta' CYP2C19 jista 'wkoll jiġi mwaqqaf minn voriconazole.
Oral Contraceptives:
Kontraċettivi Orali:
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 AUCτ 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.
It is expected that the voriconazole levels will return to standard levels during the pill-free week.
Huwa mistenni li l- livelli ta 'voriconazole jerġgħu lura għal- livelli normali fil- ġimgħa li ma jitteħdux pilloli.
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 10 kontraċettiva tagħhom probabbli ma tkunx affettwata.
Although no increase in the incidence of hormonal related adverse events was observed in the clinical interaction study, higher estrogen and progestagen levels may cause notably nausea and menstrual disorders.
Għalkemm ma kienet osservata l- ebda żieda fl - inċidenza ta 'episodji avversi relatati ma' l- ormoni fl- istudju kliniku ta 'l- interazzjoni, livelli ogħla ta' estroġenu u proġestoġenu jistgħu jikkawżaw notevolment dardir u disturbi mestrwali.
Oral contraceptives containing doses other than 1 mg norethisterone and 0.035 mg ethinylestradiol have not been studied.
Kontraċettivi orali li fihom dożi oħra għajr 1 mg norethisterone u 0. 035 mg ethinylestradiol ma kinux studjati.
Antiretroviral Agents:
Aġenti antiretrovirali:
Indinavir (CYP3A4 inhibitor and substrate):
Indinavir (inibitur u sostratt ta 'CYP3A4):
Indinavir (800 mg three times daily) had no significant effect on voriconazole Cmax, Cmin and AUCτ.
Indinavir (800 mg tliet darbiet kuljum) ma kellux effett sinifikanti fuq Cmax, Cmin u AUC ta 'voriconazole.
Voriconazole did not have a significant effect on Cmax and AUCτ of indinavir (800 mg three times daily).
Voriconazole ma kellux effett sinifikanti fuq Cmax u AUCta 'indinavir (800 mg tliet darbiet kuljum).
Other HIV protease inhibitors (CYP3A4 inhibitors):
Inibituri oħra tal- protease ta 'l- HIV (inibituri ta' CYP3A4):
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 (p. e. saquinavir, amprenavir u nefinavir).
In vitro studies also show that the metabolism of voriconazole may be inhibited by HIV protease inhibitors.
L- istudji in vitro juru wkoll li l- metaboliżmu ta 'voriconazole jista' jiġi mwaqqaf mill- inibituri tal- protease ta 'l- HIV.
However results of the combination of voriconazole with other HIV protease inhibitors cannot be predicted in humans only from in vitro studies.
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.
Patients should be carefully monitored for any occurrence of drug toxicity and/ or loss of efficacy during the co-administration of voriconazole and HIV protease inhibitors.
Il- pazjenti għandhom jiġu mmonitorjati b' attenzjoni għal kwalunkwe okkorrenza ta 'tossiċità bil - mediċina u/ jew telf ta' l- effikaċja waqt l- amministrazzjoni flimkien ta 'voriconazole u inibituri tal - protease ta' l- HIV.
Efavirenz (a non-nucleoside reverse transcriptase inhibitor) (CYP450 inducer; CYP3A4 inhibitor and substrate):
Efavirenz (non- nucleoside reverse transcriptase inhibitor) (induttur ta 'CYP450; inibitur u sostratt ta' CYP3A4):
Standard doses of voriconazole and standard doses of efavirenz must not be coadministered 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 the same study voriconazole at steady state increased the steady state Cmax and AUCτ of efavirenz by an average of 38% and 44% respectively, in healthy subjects.
Fl- istess studju, voriconazole stabbli żied l- Cmax u AUCstabbli ta 'efavirenz b' medja ta' 38% u 44% rispettivament, f' suġġetti adulti.
In a separate study in healthy subjects, voriconazole dose of 300mg 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
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.
(The AUCτ of efavirenz was increased by 17% and Cmax was equivalent compared to efavirenz 600 mg once daily alone).
AUC ta 'efavirenz żdied bi 17% u l- Cmax kien ekwivalenti meta mqabbel ma' efavirenz 600 mg darba kuljum waħdu.
These differences were not considered to be clinically significant.
Dawn id- differenzi ma kinux meqjusa bħala klinikament sinifikanti.
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 (ara sezzjoni 4. 2).
Non-nucleoside reverse transcriptase inhibitors (NNRTI) (CYP3A4 substrates, inhibitors or CYP450 inducers):
Non- nucleoside reverse transcriptase inhibitors (NNRTI) (sostratti u inibituri ta 'CYP3A4 jew indutturi ta' CYP450):
In vitro studies show that the metabolism of voriconazole may be inhibited by delavirdine.
Studji in vitro juru li l- metaboliżmu ta 'voriconazole jista' jiġi mwaqqaf minn delavirdine.
Although not studied, the metabolism of voriconazole may be induced by nevirapine.
Għalkemm mhux studjat, il- metaboliżmu ta 'voriconazole jista' jiġi indott minn nevirapine.
An in-vivo study showed that voriconazole inhibited the metabolism of efavirenz.
Studju in- vivo wera li voriconazole waqqaf il- metaboliżmu ta 'efavirenz.
Voriconazole may also inhibit the metabolism of NNRTIs besides efavirenz.
Voriconazole jista 'wkoll iwaqqaf il- metaboliżmu ta' NNRTIs apparti efavirenz.
Patients should be carefully monitored for any occurrence of drug toxicity and/ or lack of efficacy during the coadministration of voriconazole and NNRTIs.
Il- pazjenti għandhom jiġu mmonitorjati b' attenzjoni għal kwalunkwe okkorrenza ta 'tossiċità bil- mediċina u/ jew telf ta' l - effikaċja waqt l- amministrazzjoni flimkien ta 'voriconazole u NNRTIs.
Dose adjustments are required when voriconazole is co-administered with efavirenz (see sections 4.2 and 4.4).
Aġġustamenti fid- dożi huma neċessarji meta voriconazole huwa mogħti ma efavirenz (ara sezzjonijiet 4. 2. u 4. 4).
4.6 Pregnancy and lactation
11 4. 6 Tqala u Treddigħ
Pregnancy There are no adequate data from the use of VFEND in pregnant women.
Tqala M' hemmx tagħrif adegwat mill- użu ta 'VFEND f' nisa tqal.
VFEND must not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the foetus.
VFEND m' għandux jintuża waqt it- tqala sakemm il- benefiċċju għall- omm ma jisboqx b' mod ċar ir - riskju potenzjali għall- fetu.
Women of child-bearing potential Women of child-bearing potential must always use effective contraception during treatment.
Nisa li jistgħu jinqabdu tqal In- nisa li jistgħu jinqabdu tqal iridu dejjem jużaw kontraċezzjoni effettiva waqt il- kura.
Lactation The excretion of voriconazole into breast milk has not been investigated.
Treddigħ It- tneħħija ta 'voriconazole fil- ħalib tas- sider ma ġietx investigata.
Breast-feeding must be stopped on initiation of treatment with VFEND.
It- treddigħ għandu jiġi mwaqqaf malli tinbeda l- kura b' VFEND.
VFEND may have a moderate influence on the ability to drive and use machines.
VFEND jista 'jkollu effett moderat fuq il- ħila biex issuq u tħaddem magni.
It may cause transient and reversible changes to vision, including blurring, altered/ enhanced visual perception and/ or photophobia.
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.
The safety profile of voriconazole is based on an integrated safety database of more than 2000 subjects (1655 patients in therapeutic trials).
Il- profil tas- sigurtà ta 'voriconazole huwa bbażat fuq database integrata tas- sigurtà ta' aktar minn 2000 suġġett (1655 pazjent f' testijiet terapewtiċi).
This represents a heterogeneous population, containing patients with haematological malignancy, HIV infected patients with oesophageal candidiasis and refractory fungal infections, non-neutropenic patients with candidaemia or aspergillosis and healthy volunteers.
Din tirrappreżenta popolazzjoni eteroġenea, li tinkludi pazjenti b' tumuri ematoloġiċi, pazjenti infettati bl- HIV b' candidiasis esofagali u infezzjonijiet fungali refrettarji, pazjenti mhux newtropeniċi b' candidaemia jew asperġillosi u voluntiera b' saħħithom.
Five hundred and sixty one patients had a duration of voriconazole therapy of greater than 12 weeks, with 136 patients receiving voriconazole for over 6 months.
Ħames mija u wieħed u sittin pazjent ħadu terapija b' voriconazole li damet aktar minn 12- il ġimgħa, b' 136 pazjent jirċievu voriconazole għal aktar minn 6 xhur.
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,
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.
11 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.
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa għandhom jitniżżlu skond is- serjetà tagħhom.
The most commonly reported adverse events were visual disturbances, pyrexia, rash, vomiting, nausea, diarrhoea, headache, peripheral oedema and abdominal pain.
L- aktar episodji avversi rrapportati b' mod komuni kienu disturbi fil- vista, deni, raxx, rimettar, dardir, dijarea, uġigħ ta 'ras, edema periferali u uġigħ fl - addome.
The severity of the adverse events was generally mild to moderate.
Is- severità ta 'l- episodji avversi kienet ġeneralment ħafifa għal moderata.
No clinically significant differences were seen when the safety data were analysed by age, race, or gender.
Ebda differenzi klinikament sinifikanti ma kienu jidhru meta d- data tas- sigurtà ġiet analizzata skond l- età, razza jew sess.
Undesirable effects reported in subjects receiving voriconazole:
12 Effetti mhux mixtieqa rrapportati f' suġġetti li kienu qegħdin jirċeivu voriconazole
System Organ Class Investigations
Sistema tal- Klassifika ta 'l- Organi Stħarriġ
Elevated liver function tests (including ASAT, ALAT, alkaline phosphatase, GGT, LDH, bilirubin), blood creatinine increased
Testijiet tal- funzjoni elevata tal- fwied (fosthom ASAT, ALAT, alkaline phosphatase, GGT, LDH, bilirubin), żieda tal- kreatinina fid- demm