natgillin/translations-raw huggingface dataset:
Det anbefales, at VFEND indgives over 1- 2 timer med en maksimal hastighed på 3 mg/ kg/ time.
It is recommended that VFEND is administered at a maximum rate of 3 mg/ kg per hour over 1 to 2 hours.
6. 6).
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).
Vfend findes også som 50 mg og 200 mg filmovertrukne tabletter og 40 mg/ ml pulver til oral suspension.
42 VFEND is also available as 50 mg and 200 mg film-coated tablets and 40 mg/ ml powder for oral suspension.
42 Brug hos voksne Behandling skal initieres med den specifikke startdosis enten som intravenøs eller oral VFEND for at opnå plasmakoncentrationer tæt på steady state på Dag 1.
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.
Detaljeret information om dosisanbefalinger ses i følgende tabel:
Detailed information on dosage recommendations is provided in the following table:
Dosisjustering Hvis patienten ikke kan tåle behandling med 4 mg/ kg 2 gange dagligt, reduceres den intravenøse dosis til 3 mg/ kg 2 gange dagligt.
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.
4. 4 og 4. 5.
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.
5. 3).
The duration of treatment with the intravenous formulation should be no longer than 6 months (see section 5.3).
Brug hos patienter med nedsat nyrefunktion Der kan hos patienter med moderat til svær nyreinsufficiens (kreatininclearance < 50 ml/ min) ses akkumulering af hjælpestoffet SBECD i intravenøst VFEND.
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.
5. 2).
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).
Hjælpestoffet SBECD i intravenøst VFEND hæmodialyseres med en clearance på 55 ml/ min.
The intravenous vehicle, SBECD, is haemodialysed with a clearance of 55 ml/ min.
Brug hos patienter med nedsat leverfunktion Dosisjustering er ikke nødvendig hos patienter med akut leverskade manifesteret ved forhøjede leverfunktionsværdier (ALAT, ASAT), (men fortsat monitorering af leverfunktionsværdierne for yderligere forhøjelser anbefales).
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).
5. 2).
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).
4. 8).
Patients with severe hepatic impairment must be carefully monitored for drug toxicity (see also section 4.8).
Initialdosis
Intravenous*
Oral eller intravenøs initialdosis kan ikke anbefales
No oral or intraveneous loading dose is recommended
Hvis pædiatriske patienter ikke kan tåle en dosis på 7 mg/ kg 2 gange dagligt, kan en dosisreduktion fra 7 mg/ kg til 4 mg/ kg overvejes, baseret på farmakokinetisk populationsanalyse og tidligere klinisk erfaring.
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.
4. 2, Brug hos voksne).
This provides equivalent exposure to 3 mg/ kg twice daily in adults (see section 4.2 use in adults).
4. 4).
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).
4. 5).
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).
Hos patienter med risikofaktorer, som f. eks. kardiotoksisk kemoterapi i anamnesen, kardiomyopati, hypokaliæmi og samtidig medicin, der kan have været medvirkende årsag, er der set sjældne tilfælde af torsades de pointes, hvis de er i behandling med voriconazol.
There have been rare cases of torsades de pointes in patients taking voriconazole who had risk factors, such as history of cardiotoxic chemotherapy, cardiomyopathy, hypokalaemia and concomitant medications that may have been contributory.
4. 2).
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).
Der er udført et klinisk studie hos raske frivillige forsøgspersoner, hvor effekten af voriconazolbehandling med enkeltdoser op til 4 gange den sædvanlige daglige dosis blev undersøgt på QT- intervallet.
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.
Infusionsrelaterede reaktioner:
Infusion-related reactions:
Infusionsrelaterede reaktioner, overvejende rødmen (” flushing ”) og kvalme, er set efter indgift af intravenøs voriconazol.
Infusion-related reactions, predominantly flushing and nausea, have been observed during administration of the intravenous formulation of voriconazole.
4. 8).
Depending on the severity of symptoms, consideration should be given to stopping treatment (see section 4.8).
Patienter der i begyndelsen, eller i løbet af behandlingen med voriconazol udvikler abnorme leverfunktionsværdier, skal rutinemæssigt monitoreres for udvikling af mere alvorlig leverskade.
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.
Nyrerelaterede bivirkninger:
45 Renal adverse events:
4. 8).
Patient being treated with voriconazole are likely to be treated concomitantly with nephrotoxic medications and have concurrent conditions that may result in decreased renal function (see section 4.8).
45 Monitorering af nyrefunktionen:
Monitoring of renal function:
Monitorering af pancreasfunktionen:
Monitoring of pancreatic function:
Derudover har VFEND i sjældne tilfælde været forbundet med lysfølsom hudreaktion især efter langtidsbehandling.
In addition VFEND has been associated with photosensitivity skin reaction especially during long term therapy.
Det anbefales, at informere patienten om, at sollys bør undgås under behandlingen.
It is recommended that patients should be informed to avoid sunlight during the treatment.
Rifabutin (potent CYP450- induktor):
Rifabutin (CYP450 inducer):
Det kan derfor være nødvendigt med en længere overvågning af respirationen.
As the half-life of alfentanil is prolonged in a four-fold manner when alfentanyl is coadministered with voriconazole, a longer respiratory monitoring period may be necessary.
Natriumindhold:
Sodium content:
Hvert hætteglas VFEND indeholder 217, 6 mg natrium.
Each vial of VFEND contains 217.6 mg of sodium.
4. 5 Interaktion med andre lægemidler og andre former for interaktion
46 4.5 Interaction with other medicinal products and other forms of interaction
46 Dette afsnit omfatter andre lægemidlers virkning på voriconazol, virkninger af voriconazol på andre lægemidler og to- vejs interaktioner.
This section addresses the effects of other medicinal products on voriconazole, the effects of voriconazole on other medicinal products and two-way interactions.
Kontraindikationer, interaktioner der kræver dosisjustering og omhyggelig klinisk og/ eller biologisk monitorering, og til sidst dem der ingen signifikant farmakokinetisk interaktion har, men som har klinisk interesse for det terapeutiske område.
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.
Effekten af samtidig administration af oral voriconazol (200 mg 2 gange dagligt) og højdosis (400 mg) og lavdosis (200 mg) oral ritonavir er undersøgt i 2 separate studier af raske frivillige forsøgspersoner.
The effect of the coadministration of oral voriconazole (200 mg twice daily) and high dose (400 mg) and low dose (100 mg) oral ritonavir (400 mg and 100 mg) was investigated in two separate studies in healthy volunteers.
Høje doser af ritonavir (400 mg 2 gange dagligt) nedsætter steady state Cmax og AUCτ af oral voriconazol med gennemsnitlig henholdsvis 66% og 82%, mens lave doser af ritonavir (100 mg 2 gange dagligt) nedsætter steady state Cmax og AUCτ af voriconazol med gennemsnitlig henholdsvis 24% og 39%.
High doses of ritonavir (400 mg twice daily) decreased the steady state Cmax and AUCτ of oral voriconazole by an average of 66% and 82%, whereas low doses of ritonavir (100 mg twice daily) decreased the Cmax and AUCτ of oral voriconazole by an average of 24% and 39% respectively.
Administration af voriconazol har ingen signifikant effekt på middel Cmax og AUCτ af ritonavir i højdosis- studiet, men der ses en lille nedsættelse af steady state Cmax og AUCτ af ritonavir med gennemsnitlig henholdsvis 25% og 13% i lavdosis ritonavir interaktionsstudiet.
Administration of voriconazole did not have a significant effect on mean Cmax and AUCτ in the high dose study although a minor decrease in steady state Cmax and AUCτ of ritonavir with an average of 25% and 13% respectively was observed in the low dose ritonavir interaction study.
Samtidig administration af voriconazol og høje doser ritonavir (400 mg og derover 2 gange dagligt) er kontraindiceret.
Coadministration of voriconazole and high doses of ritonavir (400 mg and above twice daily) is contraindicated).
4. 3 og 4. 4).
Coadministration of voriconazole and low dose ritonavir (100 mg twice daily) should be avoided unless an assessment of the benefit/ risk justifies the use of voriconazole (see section 4.3 and 4.4).
Skønt det ikke er undersøgt, er det sandsynligt, at carbamazepin eller phenobarbital vil nedsætte voriconazolkoncentrationerne signifikant.
Although not studied, carbamazepine or phenobarbital is likely to significantly decrease plasma voriconazole concentrations.
Cimetidin (400 mg 2 gange dagligt) øger voriconazols Cmax og AUCτ på henholdsvis 18% og 23%.
Cimetidine (400 mg twice daily) increased voriconazole Cmax and AUCτ by 18% and 23%, respectively.
Ranitidin (150 mg to gange dagligt) har ingen signifikant effekt på voriconazols Cmax og AUCτ.
Ranitidine (150 mg twice daily) had no significant effect on voriconazole Cmax and AUCτ.
Perikon (CYP450- induktor; P- gp- induktor):
47 St John’ s Wort (CYP450 inducer; P-gp inducer):
47 Virkninger af voriconazol på andre lægemidler
Effects of voriconazole on other medicinal products
Voriconazol hæmmer aktiviteten af cytochrom P450- isoenzymerne CYP2C19, CYP2C9 og CYP3A4.
Voriconazole inhibits the activity of cytochrome P450 isoenzymes, CYP2C19, CYP2C9 and CYP3A4.
Voriconazol bør anvendes med forsigtighed hos patienter, der samtidig tager medicin, som er kendt for at forlænge QT- intervallet.
Voriconazole should be administered with caution in patients with concomitant medication that is known to prolong QT interval.
Terfenadin, astemizol, cisaprid, pimozid og quinidin (CYP3A4 substrater):
Terfenadine, astemizole, cisapride, pimozide and quinidine (CYP3A4 substrates):
Hos stabile nyretransplaterede øger voriconazol ciclosporins Cmax og AUCτ med henholdsvis mindst 13% og 70%.
In stable, renal transplant recipients, voriconazole increased ciclosporin Cmax and AUCτ by at least 13% and 70%, respectively.
Steady state administration af oral voriconazol øger AUCτ af en enkeltdosis alfentanil 6 gange.
Steady-state administration of oral voriconazole increased the AUC∞ of a single dose of alfentanil by 6-fold.
4. 4).
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).
Tacrolimus (CYP3A4- substrat):
48 Tacrolimus (CYP3A4 substrate):
48 Orale antikoagulantia:
Oral anticoagulants:
Andre orale antikoagulantia, f. eks. phenprocoumon, acenocoumarol (CYP2C9, CYP3A4- substrater):
Other oral anticoagulants e. g. phenprocoumon, acenocoumarol (CYP2C9, CYP3A4 substrates):
Skønt det ikke er undersøgt, kan voriconazol muligvis øge plasmakoncentrationer af coumariner og dermed føre til øget protrombintid.
Although not studied, voriconazole may increase the plasma concentrations of coumarins and therefore may cause an increase in prothrombin time.
Patienter der får coumariner og voriconazol samtidig, bør have monitoreret protrombintiden med korte intervaller, og dosis af antikoagulantia bør tilsvarende justeres.
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.
Derfor skønnes det, at voriconazol kan øge benzodiazepinernes plasmaniveauer, som er metaboliseret af CYP3A4 (midazolam og triazolam) og føre til en forlænget sedativ effekt.
Therefore, voriconazole is likely to increase the plasma levels of benzodiazepines that are metabolised by CYP3A4 (e. g. midazolam and triazolam) and lead to a prolonged sedative effect.
Phenytoin (300 mg én gang dagligt) giver et fald i voriconazols Cmax og AUCτ på henholdsvis 49% og 69%.
Phenytoin (300 mg once daily)
Voriconazol (400 mg 2 gange dagligt, se pkt.
49 decreased the Cmax and AUCτ of voriconazole by 49% and 69%, respectively.
Der anbefales omhyggelig monitorering af phenytoinplasmaphenytoinniveauerne, når Phenytoin administreres samtidigt med voriconazol.
Careful monitoring of phenytoin plasma levels is recommended when phenytoin is coadministered with voriconazole.
Rifabutin (300 mg én gang dagligt) nedsatte Cmax og AUCτ af voriconazol 200 mg 2 gange dagligt med henholdsvis 69% og 78%.
Concomitant use of voriconazole and rifabutin should be avoided unless the benefit outweighs the risk. Rifabutin (300 mg once daily) decreased the Cmax and AUCτ of voriconazole at 200 mg twice daily by 69% and 78%, respectively.
Ved samtidig administration af rifabutin var Cmax og AUCτ af voriconazol 350 mg 2 gange dagligt 96% og 68% af de niveauer, der blev set, hvis der blev givet voriconazol 200 mg 2 gange dagligt alene.
During coadministration with rifabutin, the Cmax and AUCτ of voriconazole at 350 mg twice daily were 96% and 68% of the levels when administered alone at 200 mg twice daily.
Ved en dosis af voriconazol på 400 mg 2 gange dagligt var Cmax og AUCτ henholdsvis 104% og 87% højere sammenlignet med voriconazol 200 mg 2 gange dagligt alene.
At a voriconazole dose of 400 mg twice daily C max and AUCτ were 104% and 87% higher, respectively, compared with voriconazole alone at 200 mg twice daily.
4. 2).
If rifabutin coadministration with voriconazole is justified then the maintenance dose of voriconazole may be increased to 5 mg/ kg intravenously twice daily or from 200 mg to 350 mg orally, twice daily (100 mg to 200 mg orally, twice daily in patients less than 40kg) (see section 4.2).
Det forventes, at voriconazol- niveauerne vender tilbage til normalværdien under en pillefri uge.
It is expected that the voriconazole levels will return to standard levels during the pill-free week.
Orale kontraceptiva, som indeholder doser større end 1 mg norethisteron og 0, 035 mg ethinylestradiol, er ikke undersøgte.
Oral contraceptives containing doses other than 1 mg norethisterone and 0.035 mg ethinylestradiol have not been studied.
Indinavir (800 mg 3 gange dagligt) har ingen signifikant effekt på voriconazols Cmax, Cmin og AUCτ.
Indinavir (800 mg three times daily) had no significant effect on voriconazole Cmax, Cmin and AUCτ.
Voriconazol har ingen signifikant effekt på Cmax og AUCτ af indinavir (800 mg 3 gange dagligt).
Voriconazole did not have a significant effect on Cmax and AUCτ of indinavir (800 mg three times daily).
Dog kan resultater af kombinationsbehandling med voriconazol og andre HIV- proteasehæmmere ikke forudsiges hos mennesker alene på baggrund af in vitro forsøg.
50 predicted in humans only from in vitro studies.
Voriconazol
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.
50 øgede ved steady state i det samme studie steady state efavirenz Cmax og AUCτ med et gennemsnit på henholdsvis 38% og 44% hos raske forsøgspersoner.
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.
I et separat forsøg med raske forsøgspersoner gav samtidig administration af 300 mg voriconazol 2 gange dagligt og lavdosis efavirenz (300 mg 1 gang dagligt) ikke tilstrækkelig eksponering af voriconazol.
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.
Hos raske forsøgspersoner ses et fald i AUCτ på 7% og en stigning i Cmax på 23% efter samtidig administration af voriconazol 400 mg 2 gange dagligt og efavirenz 300 mg oralt 1 gang dagligt sammenlignet med voriconazol 200 mg 2 gange dagligt anvendt alene.
Following coadministration of voriconazole 400 mg twice daily with efavirenz 300 mg orally once daily, in healthy subjects, the AUCτ of voriconazole was decreased by 7% and Cmax was increased by 23%, compared to voriconazole 200 mg twice daily alone.
Det kan forårsage forbigående og reversible ændringer af synet, herunder sløret, ændret/ forøget visuel perception og/ eller fotofobi.
It may cause transient and reversible changes to vision, including blurring, altered/ enhanced visual perception
Databasen repræsenterer en heterogen population indeholdende patienter med maligne hæmatologiske sygdomme, HIV- inficerede patienter med øsofageal candidiasis og refraktære svampeinfektioner, non- neutropene patienter med candidæmi eller
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.
51 aspergillosis og raske forsøgspersoner.
Undesirable effects reported in subjects receiving voriconazole
Da størstedelen af studierne var åbne, er alle kausale bivirkninger, hvor der er en mulig årsagssammenhæng, anført efter systemorganklasse og frekvens (meget almindelig > 1/ 10, almindelig > 1/ 100 og < 1/ 10, ikke almindelig > 1/ 1000 og < 1/ 100, sjælden < 1/ 1000 og meget sjælden < 1/ 10. 000) i tabellen nedenfor.
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.
Hovedpine Svimmelhed, konfusion, tremor, agitation, paræstesi Hjerneødem, ataksi, diplopi, vertigo, hypæstesi Kramper, encephalopati, Guillain- Barre syndrom, ekstrapyramidale symptomer, søvnighed under infusion
Headache Dizziness, confusional state, tremor, agitation, paraesthesia Brain oedema, ataxia, diplopia, vertigo, hypoaesthesia Convulsion, encephalopathy, Guillain-Barre syndrome, extrapyramidal symptoms, somnolence during infusion
4. 4), kromatopsi og fotofobi)
52 Eye disorders Visual disturbances (including blurred vision (see Section Very common 4.4), chromotopsia and photophobia) Uncommon
4. 4), nystagmus, scleritis, blepharitis
Papilloedema (se Section 4.4), optic nerve disorder (including optic neuritis, see Section 4.4), nystagmus, scleritis, blepharitis
52 Luftveje, thorax og mediastinum Almindelig
Respiratory, thoracic and mediastinal disorders Common
Meget almindelig Almindelig
Gastrointestinal disorders Very common Uncommon
Nyrer og urinveje Meget almindelig Almindelig Sjælden
Renal and urinary disorders Common Uncommon Rare
Meget almindelig Almindelig
Skin and subcutaneous tissue disorders Very common Common
Almindelig Sjælden
53 Vascular disorders Common Rare
53 Lever og galdeveje Meget almindelig Almindelig Sjælden
Hepato-biliary disorders Common Uncommon
Psykiske forstyrrelser
Hepatic coma
Synsforstyrrelsen er generelt mild og resulterer sjældent i afbrydelse af behandling og har ikke været forbundet med langtidsvirkninger.
The visual disturbances were generally mild, rarely resulted in discontinuation and were not associated with long-term sequelae.
Dermatologiske reaktioner Dermatologiske reaktioner var almindelige hos patienter behandlet med voriconazol i kliniske studier, men disse patienter havde alvorlige tilgrundliggende sygdomme og fik samtidig behandling med anden medicin.
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.
Størstedelen af abnorme leverfunktionsprøver blev normale igen under behandlingen enten med eller uden dosisjustering, herunder afbrydelse af behandling.
The majority of abnormal liver function tests either resolved during treatment without dose adjustment or following
Infusionsrelaterede reaktioner Under intravenøs infusion af voriconozol hos raske frivillige forsøgspersoner er der set tilfælde af anafylaktoid- lignende reaktioner, omfattende rødmen (” flushing ”), feber, svedtendens, takykardi, trykken for brystet, dyspnø, mathedsfølelse, kvalme, kløe og udslæt.
Infusion-Related Reactions During infusion of the intravenous formulation of voriconazole in healthy subjects, anaphylactoid-type reactions, including flushing, fever, sweating, tachycardia, chest tightness, dyspnoea, faintness, nausea, pruritus and rash have occurred.
4. 4).
Symptoms appeared immediately upon initiating the infusion (see also section 4.4).
Bivirkningsprofilen er ens for de 245 pædiatriske
The adverse event profile of these 245 paediatric patients was similar to that in adults.
Lysfølsomme reaktioner (1), arytmi (1), pancreatitis (1), forhøjet serum- bilirubin (1), forhøjet antal leverenzymer (1), udslæt (1) og papilødem (1).
In the 22 patients less than 2 years old who received voriconazole in a compassionate use programme, the following adverse events (for which a relationship to voriconazole could not be excluded) were reported: photosensitivity reaction (1), arrhythmia (1), pancreatitis (1), blood bilirubin increased (1), hepatic enzymes increased (1), rash (1) and papilloedema (1).