FrancophonIA/ELRC3.0 huggingface dataset:
English: In another clinical trial, vemurafenib increased Cmax and AUC of a single 2 mg dose of tizanidine (CYP1A2 substrate) approximately 2.2-fold and 4.7-fold, respectively.
Danish: I et andet klinisk studie øgede vemurafenib Cmax og AUCinf af en enkelt 2 mg dosis af tizanidin (CYP1A2 substrat) henholdsvis ca. 2,2 gange og ca. 4,7 gange.
English: Sarcoidosis (1)(2)(j)
Danish: Sarcoidose (1)(2)(j)
English: Vemurafenib revealed no evidence of teratogenicity in rat or rabbit embryo/foetuses (see section 5.3).
Danish: Vemurafenib udviste ingen tegn på teratogenicitet hos rotte- eller kaninembryo/fostre (se pkt.
English: The combination of this medicine with Zelboraf is not recommended due to increased toxicity to the liver.
Danish: Det anbefales, at dette lægemiddel og Zelboraf ikke bruges samtidigt på grund af øget risiko for skadelige virkninger på leveren.
English: Patients with moderate to severe hepatic impairment may have increased exposure (see section 5.2).
Danish: Patienter med moderat til svær nedsat leverfunktion kan have øget eksponering (se pkt.
English: The safety of vemurafenib in children and adolescents has not been established.
Danish: Vermurafenibs sikkerhed hos børn og unge er ikke klarlagt.
English: Effects of vemurafenib on Drug Metabolizing Enzymes Results from an in vivo drug-drug interaction study in metastatic melanoma patients demonstrated that vemurafenib is a moderate CYP1A2 inhibitor and a CYP3A4 inducer.
Danish: Vemurafenibs virkning på enzymer, som metaboliserer lægemidler Resultater fra et in vivo lægemiddelinteraktionsstudie hos patienter med metastatisk melanom viste at vemurafenib er en moderat CYP1A2-hæmmer og en CYP3A4 induktor.
English: ● A type of severe skin reaction characterised by rash accompanied by fever and inflammation of internal organs such as liver and kidney
Danish: · En alvorlig hudreaktion kendetegnet ved udslæt sammen med feber og en betændelseslignende reaktion (inflammation) i de indre organer, såsom lever og nyre.
English: In the population pharmacokinetic analysis using data from clinical trials in patients with metastatic melanoma, increases in AST and ALT up to three times the upper limit of normal did not influence the apparent clearance of vemurafenib.
Danish: Den populationsfarmakokinetiske analyse, som brugte data fra kliniske forsøg hos patienter med metastatisk melanom, viste at stigninger i ASAT og ALAT på op til tre gange den øvre normalgrænse ikke påvirkede den tilsyneladende clearance af vemurafenib.
English: Vemurafenib has minor influence on the ability to drive and use machines.
Danish: Vemurafenib påvirker i mindre grad evnen til at føre motorkøretøj eller betjene maskiner.
English: Concomitant administration of CYP2C8 substrates with a narrow therapeutic window should be made with caution since vemurafenib may increase their concentrations.
Danish: Forsigtighed bør udvises ved samtidig anvendelse med CYP2C8 substrater med smalt terapeutisk vindue, eftersom vemurafenib kan øge koncentrationerne af disse stoffer.
English: Patients should be carefully monitored for safety and dose modifications applied if clinically indicated (see Table 1 in section 4.2).
Danish: Patienterne skal overvåges nøje i forhold til sikkerhed og dosisjusteringer, hvis det er klinisk relevant (se tabel 1 i afsnit 4.2).
English: Monitoring of these lesions occurs as outlined above for cutaneous squamous cell carcinoma.
Danish: Monitorering af disse læsioner forekommer som beskrevet ovenfor for kutant planocellulært karcinom.
English: ● It is not known whether the ingredients in Zelboraf pass into human milk.
Danish: · Det vides ikke om indholdsstofferne i Zelboraf udskilles i modermælken.
English: In the population pharmacokinetic analysis using data from clinical trials in patients with metastatic melanoma, mild and moderate renal impairment did not influence the apparent clearance of vemurafenib (creatinine clearance >40 ml/min).
Danish: Den populationsfarmakokinetiske analyse med data fra kliniske forsøg hos patienter med metastatisk melanom, viste at let og moderat nedsat nyrefunktion ikke påvirkede den tilsyneladende clearance af vemurafenib (kreatininclearance > 40 ml/min).
English: Dose reduction of the concomitant CYP1A2 substrate drug may be considered, if clinically indicated.
Danish: Dosisreduktion af det samtidig anvendte CYP1A2 substrat lægemiddel kan overvejes, hvis det er klinisk relevant.
English: No cases of overdose have been observed with vemurafenib in clinical trials.
Danish: Der er ikke observeret tilfælde af overdosering med vemurafenib i de kliniske studier.
English: Caution should be used when administering Vemurafenib with strong CYP3A4/PgP inhibitors.
Danish: Der bør udvises forsigtighed, når vemurafenib administreres sammen med kraftige CYP3A4/P-gp-hæmmere.
English: Other medicines and Zelboraf
Danish: Brug af anden medicin sammen med Zelboraf
English: Preclinical data generated in biochemical assays demonstrated that vemurafenib can potently inhibit BRAF kinases with activating codon 600 mutations (table 6).
Danish: Prækliniske data fra biokemiske analyser viser, at vemurafenib kraftigt kan hæmme BRAF-kinaser med aktiverede kodon 600-mutationer (tabel 6).
English: Effects of vemurafenib on drug transport systems In vitro studies have demonstrated that vemurafenib is an inhibitor of the efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).
Danish: Vemurafenibs påvirkning af lægemiddeltransportsystemer In vitro-studier har vist, at vemurafenib hæmmer efflux-transportørerne P-glykoprotein (P-gp) og brystkræft resistent protein (BCRP).
English: Based on these preliminary data, the concurrent administration of ipilimumab and vemurafenib is not recommended.
Danish: Baseret på disse foreløbige data anbefales det ikke at administrere ipilimumab og vemurafenib samtidigt.
English: It cannot be excluded that vemurafenib pharmacokinetics could be affected by such medicines through influence on P-gp (e.g. verapamil, cyclosporine, quinidine) or BCRP (e.g. cyclosporine, gefitinib).
Danish: Det kan ikke udelukkes, at vemurafenibs farmakokinetik kan blive påvirket af sådanne lægemidler, ved påvirkning af P-gp (f.eks. verapamil, ciclosporin, kinidin) eller BCRP (f.eks. ciclosporin, gefitinib).
English: Table 8: Overall survival in previously untreated patients with BRAF V600 mutation-positive melanoma by LDH, tumour stage and ECOG status (post hoc analysis, December 20, 2012 cutoff, censored results at time of cross over)
Danish: Tabel 8: Samlet overlevelse hos tidligere ubehandlede patienter med BRAF-V600mutationspositivt melanom udfra LDH, tumorstadie og ECOG-status (post hoc-analyse cut-off 20. december 2012, censurerede resultater på overkrydsningstidspunktet)
English: Cases of cuSCC (which include those classified as keratoacanthoma or mixed keratoacanthoma subtype) have been reported in patients treated with vemurafenib (see section 4.8).
Danish: Der er blevet rapporteret tilfælde af cuSCC (som inkluderer tilfælde klassificeret som keratoakantom eller blandet keratoakantom-undertype) hos patienter behandlet med vemurafenib (se pkt.
English: Monitoring for skin lesions should occur as outlined in section 4.4.
Danish: Monitorering for hudlæsioner bør forekomme, som beskrevet i pkt.
English: Mechanism of action and pharmacodynamic effects Vemurafenib is an inhibitor of BRAF serine-threonine kinase.
Danish: Virkningsmekanisme og farmakodynamisk virkning Vemurafenib hæmmer BRAF-serin-treonin-kinase.
English: Patients co-treated with such agents should be carefully monitored for safety and dose modifications applied if clinically indicated (see Table 1 in section 4.2).
Danish: Patienter der er i samtidig behandling med sådanne lægemidler skal overvåges nøje i forhold til sikkerhed og dosisjusteringer, hvis det er klinisk relevant (se tabel 1 i afsnit 4.2).
English: If co-administration cannot be avoided, exercise caution, as vemurafenib may increase plasma exposure of CYP1A2 substrate drugs.
Danish: Hvis samtidig anvendelse ikke kan undgås skal der udvises forsigtighed eftersom vemurafenib kan øge plasma eksponeringen af CYP1A2 substrat lægemidler.
English: Headache, dysgeusia, dizziness
Danish: Hovedpine, dysgeusi, svimmelhed
English: Data are insufficient to determine the effect of metabolic or excretory hepatic impairment on vemurafenib pharmacokinetics (see sections 4.2 and
Danish: Data er utilstrækkelige til at bestemme effekten af nedsat metaboliserings- eller udskillelses-leverfunktion på vemurafenibs farmakokinetik (se pkt.
English: Cases of radiation recall and radiation sensitization have been reported in patients treated with radiation either prior, during, or subsequent to vemurafenib treatment.
Danish: Der er rapporteret tilfælde af radiation recall syndrom og øget følsomhed for stråling hos patienter, som har fået strålebehandling enten før, under eller efter vemurafenib-behandling.
English: For photosensitivity grade 2 (intolerable) or greater, dose modifications are recommended (see section
Danish: Dosisjusteringer anbefales ved lysfølsomhed af grad 2 (uacceptabel) eller højere (se pkt.
English: ● Types of kidney injury characterized by inflammation (acute interstitial nephritis) or damage to the tubules of the kidney (acute tubular necrosis).
Danish: · Nyreskader i form af inflammation (akut interstitiel nefritis) eller skader på nyretubuli (akut tubulær nekrose).
English: Co-administration of vemurafenib increased the plasma exposure (AUC) of caffeine (CYP1A2 substrate) 2.6-fold.
Danish: Samtidig anvendelse af vemurafenib øgede plasma eksponeringen (AUC) for caffein (CYP1A2 substrat) 2,6-gange.
English: Always take Zelboraf exactly as your doctor has told you.
Danish: Tag altid Zelboraf nøjagtig efter lægens anvisning.
English: Cutaneous squamous cell carcinoma (d) (cuSCC)
Danish: Kutant planocellulært karcinom (d) (cuSCC)
English: Resume dosing at 480 mg twice daily (or discontinue permanently if the dose has already been lowered to 480 mg twice daily).
Danish: Genoptag dosering på 480 mg to gange dagligt (eller seponer permanent, hvis dosis i forvejen er blevet reduceret til 480 mg to gange dagligt).
English: A phase II single-arm, multi-centre, multinational study was conducted in 132 patients who had BRAF V600E mutation-positive metastatic melanoma according to the cobas 4800 BRAF V600 Mutation Test and had received at least one prior therapy.
Danish: Et fase II, enkelt-arm, multicenter, multinationalt studie blev udført med 132 patienter, som havde BRAF-V600E-mutationspositivt melanom vist ved cobas 4800 BRAF-V600-muationstest, og som have modtaget mindst én tidligere behandling.
English: No adjustment to the starting dose is needed for patients with hepatic impairment.
Danish: Det er ikke nødvendigt at justere startdosis for patienter med nedsat leverfunktion.
English: ● Tell your doctor if you have had, or are going to have radiotherapy, as Zelboraf may worsen radiation treatment side effects.
Danish: Reaktioner i forbindelse med strålebehandling · Fortæl lægen, hvis du har fået eller skal have strålebehandling, da Zelboraf kan forværre bivirkningerne ved strålebehandlingen
English: As vemurafenib is cleared by the liver, patients with moderate to severe hepatic impairment may have increased exposure and should be closely monitored (see sections 4.4 and 5.2).
Danish: Da vemurafenib elimineres via leveren kan patienter med moderat til svær nedsat leverfunktion have en øget eksponering og de bør monitoreres tæt (se pkt.
English: Vemurafenib might decrease the efficacy of hormonal contraceptives (see section 4.5).
Danish: Vemurafenib kan nedsætte virkningen af hormonelle præventionsmidler (se pkt.
English: However, in repeat-dose toxicity studies in rats and dogs, no histopathological findings were noted in reproductive organs in males and females (see section 5.3).
Danish: I studier af toksicitet hos rotter og hunde efter gentagne doser blev der dog ikke bemærket histopatologiske fund i forplantningsorganer hos hanner og hunner (se pkt.
English: All patients were required to have advanced melanoma with BRAF V600 mutations according to the cobas 4800 BRAF V600 Mutation Test.
Danish: Alle patienter skulle have fremskredet melanom med BRAF-V600-mutationer vist ved cobas 4800 BRAF-V600mutationstest.
English: Effects of vemurafenib on other medicinal products Vemurafenib may increase the plasma exposure of medicinal products predominantly metabolised by CYP1A2 and decrease the plasma exposure of medicines predominantly metabolised by CYP3A4.
Danish: Vemurafenib kan øge plasmaeksponeringen af lægemidler, som hovedsageligt metaboliseres af CYP1A2 og nedsætte plasmaeksponeringen af lægemidler, som hovedsageligt metaboliseres af CYP3A4.
English: Following oral dosing, the absorption rate constant for the population of metastatic melanoma patients is estimated to be 0.19 hr-1 (with 101% between patient variability).
Danish: Efter oral dosering er absorptionshastighedskonstanten for populationen af patienter med metastatisk melanom estimeret til at være 0,19 t-1 (med 101 % variabilitet mellem patienter).
English: In the event the patient develops Cutaneous Squamous Cell Carcinoma (cuSCC), it is recommended to continue the treatment without modifying the dose of vemurafenib (see sections 4.4 and 4.8).
Danish: I tilfælde af at patienten udvikler kutant planocellulært karcinom (cuSCC), anbefales det at fortsætte behandlingen uden at ændre dosis af vemurafenib (se pkt.
English: However, exposures in the embryofoetal development studies were below the clinical exposure based on AUC comparison, it is therefore difficult to define to what extent these results can be extrapolated to humans.
Danish: Eksponering i de embryoføtale udviklingsstudier var dog under den kliniske eksponering baseret på sammenligning af AUC.
English: ● If you forget a dose and it is more than 4 hours before your next dose, just take your dose as soon as you remember it. Take the next dose at the usual time.
Danish: Hvis du har glemt at tage Zelboraf · Hvis du glemmer en dosis og der er mere end 4 timer til den næste dosis, skal du tage den glemte dosis ligeså snart du kommer i tanke om det.
English: Non-cutaneous squamous cell carcinoma (non-cuSCC) Cases of non-cuSCC have been reported in patients receiving vemurafenib while enrolled in clinical trials.
Danish: Non-kutant planocellulært karcinom (non-cuSCC) Der er blevet rapporteret tilfælde af non-cuSCC hos patienter, der fik vemurafenib, mens de deltog i kliniske studier.
English: V600D
Danish: V600M
English: ● If you have any further questions, ask your doctor.
Danish: · Spørg lægen, hvis der er mere, du vil vide.
English: Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates.
Danish: Der skal udvises forsigtighed når vemurafenib anvendes samtidig med P-gp substrater.
English: These cases were managed with excision, and patients continued treatment without dose adjustment.
Danish: Disse tilfælde blev håndteret med ekscision og patienter fortsatte behandlingen uden dosisjustering.
English: Table 9 shows the overall response rate and progression-free survival in previously untreated patients with BRAF V600 mutation-positive melanoma.
Danish: Tabel 9 viser den samlede responsrate og progressionsfri overlevelse hos tidligere ubehandlede patienter med BRAF-V600-mutationspositivt melanom.
English: Table 1: Dose modification schedule based on the grade of any Adverse Events (AEs)
Danish: Tabel 1: Dosisjusteringsskema baseret på graden af enhver bivirkning
English: Cases were managed with excision and patients continued treatment without dose adjustment.
Danish: Tilfælde blev håndteret med ekscision og patienter fortsatte behandlingen uden dosisjustering.
English: No teratogenicity was observed in embryofoetal development studies in rats and rabbits at doses up to respectively 250 mg/kg/day and 450 mg/kg/day leading to exposures below the anticipated clinical exposure (based on AUC comparison).
Danish: Der blev ikke observeret teratogenicitet i embryoføtale udviklingsstudier hos rotter og kaniner ved doser på henholdsvis 250 mg/kg/døgn og 450 mg/kg/døgn førende til eksponeringer under den forventede kliniske eksponering (baseret på sammenligning af AUC).
English: Table 7: Overall survival in previously untreated patients with BRAF V600 mutation-positive melanoma by study cut-off date (N=338 dacarbazine, N=337 vemurafenib) Cut-off dates
Danish: Tabel 7: Samlet overlevelse hos tidligere ubehandlede patienter med BRAF-V600-mutationspositivt melanom ved studie cut-off dato (n=338 dacarbazin, n=337 vemurafenib)
English: Tabulated summary of adverse reactions
Danish: Tabuleret sammenfatning af bivirkninger
English: Vemurafenib was shown to be phototoxic, in vitro, on cultured murine fibroblasts after UVA irradiation, but not in vivo in a rat study at doses up to 450 mg/kg/day (at exposures below the anticipated clinical exposure (based on AUC comparison).
Danish: Vemurafenib udviste fototoksicitet in vitro på dyrkede murine fibroblaster efter UVA-bestråling, men ikke in vivo i et rottestudie ved doser på op til 450 mg/kg/døgn (ved eksponeringer under den forventede kliniske eksponering baseret på sammenligning af AUC).
English: Occasional intake of vemurafenib on an empty stomach is expected to have limited influence on steady state exposure due to the high accumulation of vemurafenib at steady state.
Danish: På grund af den høje akkumulering af vemurafenib ved steady-state forventes det, at lejlighedsvis indtagelse af vemurafenib på tom mave har begrænset indflydelse på steady-state eksponeringen.
English: There are only very limited data available in patients with moderate to severe hepatic impairment.
Danish: Der er kun meget begrænsede data tilgængelige for patienter med moderat til svær nedsat leverfunktion.
English: In a Phase I trial, asymptomatic grade 3 increases in transaminases (ALT/AST >5 x ULN) and bilirubin (total bilirubin >3x ULN) were reported with concurrent administration of ipilimumab (3 mg/kg) and vemurafenib (960 mg BID or 720 mg BID).
Danish: Asymptomatiske grad 3-stigninger i aminotransferaser (ALAT/ASAT > 5x ULN) og bilirubin (totalbilirubin > 3x ULN) er rapporteret i et fase I-studie, hvor ipilimumab (3 mg/kg) og vemurafenib (960 mg to gange dagligt eller 720 mg to gange dagligt) blev administreret samtidigt.
English: Cases reported include recall phenomenon, radiation skin injury, radiation pneumonitis, radiation esophagitis, radiation proctitis, radiation hepatitis, cystitis radiation, and radiation necrosis.
Danish: Det er rapporteret tilfælde af radiation recall syndrom, stråleskader på huden, stråle pneumonitis, stråle øsofagitis, stråle proktitis, stråle hepatitis, stråle cystitis og stråle nekrose
English: ● Medicines that could be influenced by a protein called P-gp (e.g. aliskiren, colchicine, digoxin, everolimus, fexofenadine) or a protein called BCRP (e.g. methotrexate, mitoxantrone, rosuvastatin).
Danish: · Medicin, som kan påvirkes af et protein kaldet P-gp (f.eks. aliskiren, colchicin, digoxin, everolimus, fexofenadin) eller et protein kaldet BCRP (f.eks. methotrexat, mitoxantron, rosuvastatin).
English: Mild to severe photosensitivity was reported in patients who received vemurafenib in clinical studies (see section 4.8).
Danish: Der er blevet rapporteret let til svær lysfølsomhed hos patienter, som fik vemurafenib i kliniske studier (se pkt.
English: Before taking vemurafenib, patients must have BRAF V600 mutation-positive tumour status confirmed by a validated test.
Danish: Før anvendelse af vemurafenib skal patienterne have en BRAF-V600-mutationspositiv tumorstatus bekræftet ved en valideret test (se pkt.
English: The population apparent clearance of vemurafenib in patients with metastatic melanoma is estimated to be 29.3 L/day (with 31.9% between patient variability).
Danish: Den tilsyneladende populationsclearance for vemurafenib hos patienter med metastatisk melanom er estimeret til at være 29,3 l/døgn (med 31,9 % variabilitet mellem patienter).
English: Monitoring for skin lesions should occur as outlined above for cutaneous squamous cell carcinoma.
Danish: Monitorering af hudlæsioner bør foretages, som beskrevet ovenfor for kutant planocellulært karcinom.
English: Abnormal findings should be managed according to clinical practices.
Danish: Anormale fund bør håndteres som klinisk indiceret.
English: Dose adjustments for medicinal products predominantly metabolised via CYP1A2 or CYP3A4 should be considered based on their therapeutic windows before concomitantly treating with vemurafenib (see sections 4.5 and 4.6).
Danish: Dosisjusteringer for lægemidler, der hovedsageligt metaboliseres via CYP1A2 eller CYP3A4 bør overvejes, baseret på deres terapeutiske vinduer, før samtidig behandling med vemurafenib (se pkt.
English: Arthralgia, myalgia, pain in extremity, musculoskeletal pain, back pain
Danish: Artralgi, myalgi, smerter i ekstremiteter, muskuloskeletal smerte, rygsmerter
English: Focal bone marrow necrosis was noted in one dog in a prematurely terminated 39-week BID dog study at exposures similar to the anticipated clinical exposure (based on AUC comparisons).
Danish: Fokal knoglemarvsnekrose blev bemærket i én hund i et for tidligt afsluttet 39-ugers to gange dagligt studie hos hunde ved eksponeringer tilsvarende den forventede kliniske eksponering (baseret på AUC sammenligninger).
English: Vemurafenib is indicated in monotherapy for the treatment of adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma (see section 5.1).
Danish: Vemurafenib er indiceret i monoterapi til behandling af voksne patienter med BRAF-V600mutationspositivt ikke-operabelt eller metastatisk melanom (se pkt.
English: A phase I dose-escalation study evaluating the use of vemurafenib in six adolescent patients with stage IIIC or IV BRAF V600 mutation positive melanoma was conducted.
Danish: Et fase I-dosiseskaleringsstudie undersøgte anvendelse af vemurafenib hos 6 unge patienter med stadie IIIC eller IV BRAF-V600-mutationspositivt melanom.
English: Pack-size: 56 x 1 film-coated tablets (7 blisters of 8 x 1 tablet)
Danish: Aluminium/aluminium perforeret enkeltdosis blister Pakningsstørrelse: 56 x 1 filmovertrukket tablet (7 blister á 8 x 1 tablet).
English: Cases of cuSCC were typically managed with simple excision, and patients generally continued on treatment without dose modification (see sections 4.2 and 4.4).
Danish: Tilfælde af cuSCC blev typisk håndteret med en enkel ekscision, og patienterne fortsatte generelt behandlingen uden dosisjustering (se pkt.
English: Uncommon ≥ 1/1,000 to < 1/100 Rare ≥ 1/10,000 to < 1/1,000
Danish: Sjælden ≥ 1/10.000 til < 1/1.000 Meget sjælden < 1/10.000
English: 2nd occurrence of any grade 2 or 3 AE or persistence after treatment interruption
Danish: 2. forekomst af enhver grad 2 eller 3 bivirkning eller vedvarende bivirkning efter afbrydelse af behandling
English: ● If you are allergic to vemurafenib or any of the other ingredients of this medicine (listed in section 6 of this leaflet).
Danish: Tag ikke Zelboraf: · hvis du er allergisk over for vemurafenib eller et af de øvrige indholdsstoffer i Zelboraf (angivet i punkt 6).
English: Acute kidney injury (h)
Danish: Akut nyreskade (h)
English: Resume dosing at 720 mg twice daily (or 480 mg twice daily if the dose has already been lowered).
Danish: Genoptag dosering på 720 mg to gange dagligt (eller 480 mg to gange dagligt, hvis dosis i forvejen er blevet reduceret).
English: Secondary objectives included an evaluation of the efficacy of vemurafenib using BORR in the brain of previously treated patients, duration of response (DOR), progression-free survival (PFS) and overall survival (OS) in patients with melanoma metastatic to the brain (see table 10).
Danish: Det sekundære mål inkluderede vurdering af vemurfenibs effekt ud fra den bedste samlede responsrate i hjernen hos tidligere behandlede patienter, responsvarighed, progressionfri overlevelse og samlet overlevelse hos melanompatienter med hjernemetastaser (se tabel 9).
English: ● Severe skin reactions can happen while taking Zelboraf.
Danish: Alvorlige hudreaktioner · Alvorlige hudreaktioner kan forekomme, mens du tager Zelboraf.