natgillin/translations-raw huggingface dataset:
c. Analysen (ved dyb sekventering) omfattede NS5A-polymorfismer forbundet med resistens, der gav >2,5 gange ændring i EC50 (K24G/N/R, M28A/G/T, Q30E/G/H/L/K/R/T, L31I/F/M/V, P32L, S38F, H58D, A92K/T og Y93C/F/H/N/S for genotype 1a HCV-infektion og L31I/F/M/V, P32L, P58D, A92K og Y93C/H/N/S for genotype 1b HCV-infektion).
c. Analysis (by deep sequencing) included NS5A resistance-associated polymorphisms that conferred > 2.5-fold change in EC50 (K24G/N/R, M28A/G/T, Q30E/G/H/L/K/R/T, L31I/F/M/V, P32L, S38F, H58D, A92K/T, and Y93C/F/H/N/S for genotype 1a and L31I/F/M/V, P32L, P58D, A92K, and Y93C/H/N/S for genotype 1b HCV infection).
Tabel 13 viser recidivrater med det 12-ugers regime (med eller uden ribavirin) for udvalgte undergrupper (se også tidligere pkt.
Table 13 presents relapse rates with the 12-week regimens (with or without ribavirin) for selected subgroups (see also previous section “Effect of baseline HCV resistance-associated variants on treatment outcome”).
Sikkerheden af Harvoni er ikke blevet undersøgt hos patienter med svært nedsat nyrefunktion (estimeret glomulær filtrationshastighed [eGFR] <30 ml/min/1,73 m2) eller nyresygdom i slutstadiet (ESRD), der kræver hæmodialyse.
The safety of Harvoni has not been assessed in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2) or end stage renal disease (ESRD) requiring haemodialysis.
Tabel 9: Demografi og baselinekarakteristika i studie ION-1 Patientdisposition
Table 9: Demographics and baseline characteristics in study ION-1 Patient disposition
Site-directed mutagenese af Y93H-substitutionen i både genotype 1a og 1b samt Q30R- og L31M-substitutionen i genotype 1a tildelte høje niveauer af nedsat følsomhed over for ledipasvir (interval på 544 til 1.677 gange større ændring i EC50).
and L31M substitution in genotype 1a conferred high levels of reduced susceptibility to ledipasvir (fold-change in EC50 ranging from 544-fold to 1,677-fold).
NS5A-RAVs blev set på tidspunktet for recidiv hos 11/13 patienter (for genotype 1a: Q30R alene [n = 2], Y93C [n = 1], Y93H/C [n = 2], Q30R + H58D [n = 1], M28T + Q30H [n = 1]; for genotype 1b: Y93H [n = 3], Y93H/C [n = 1]).
NS5A RAVs were seen at the time of relapse in 11/13 patients (for genotype 1a: Q30R alone [n = 2], Y93C [n = 1], Y93H/C [n = 2], Q30R + H58D [n = 1], M28T + Q30H [n = 1]; for genotype 1b: Y93H [n = 3], Y93H/C [n = 1]).
Ledipasvir/sofosbuvirs potentiale in vitro for at påvirke andre lægemidler Ved koncentrationer, der blev opnået i klinikken, er ledipasvir ikke en hæmmer af levertransportere, herunder OATP 1B1 eller 1B3, BSEP, OCT1, OCT2, OAT1, OAT3, multidrug- og toksisk stofekstrusion (MATE) 1-transporter, multidrug resistance protein (MRP) 2 eller MRP4.Sofosbuvir og GS-331007 er ikke hæmmere af lægemiddeltransporterne P-gp, BCRP, MRP2, BSEP, OATP1B1, OATP1B3, OCT1 og GS-331007 er ikke en hæmmer af OAT1, OCT2 og MATE1.
In vitro potential for ledipasvir/sofosbuvir to affect other medicinal products At concentrations achieved in the clinic, ledipasvir is not an inhibitor of hepatic transporters including the OATP 1B1 or 1B3, BSEP, OCT1, OCT2, OAT1, OAT3, multidrug and toxic compound extrusion (MATE) 1 transporter, multidrug resistance protein (MRP) 2 or MRP4.
Harvoni indeholder:
What Harvoni contains
Indehaver af markedsføringstilladelsen Gilead Sciences International Ltd. Cambridge
Marketing Authorisation Holder Gilead Sciences International Ltd. Cambridge
Hos behandlingserfarne patienter havde tidligere behandling med PEG-IFN + ribavirin ± en HCV-proteasehæmmer eller sofosbuvir + ribavirin ± PEG-IFN svigtet.
Treatment-experienced patients had failed prior treatment with PEG-IFN + ribavirin ± an HCV protease inhibitor or sofosbuvir +
Harvoni + ribavirin i 12 uger (se pkt.
Harvoni + ribavirin for 12 weeks (see section 5.1).
Sikkerhedsprofilen for ledipasvir/sofosbuvir sammen med ribavirin i 12 eller 24 uger hos patienter med dekompenseret leversygdom og/eller patienter efter levertransplantation blev vurderet i et åbent studie (SOLAR-1).
Patients with decompensated cirrhosis and/or who are awaiting liver transplant or post-liver transplant The safety profile of ledipasvir/sofosbuvir with ribavirin for 12 or 24 weeks in patients with decompensated liver disease and/or those post-liver transplant was assessed in an open-label study (SOLAR-1).
Der er iagttaget tilfælde af svær bradykardi og hjerteblok ved anvendelse af Harvoni samtidig med amiodaron og/eller andre hjertefrekvenssænkende lægemidler (se pkt.
Cases of severe bradycardia and heart block have been observed when Harvoni is used with concomitant amiodarone and/or other drugs that lower heart rate (see sections 4.4 and 4.5).
ORALE ANTIKONTRACEPTIVA Norgestimat/ ethinylestradiol (norgestimat 0,180 mg/ 0,215 mg/ 0,25 mg/ ethinylestradiol 0,025 mg)/ ledipasvir (90 mg én gang dagligt)d
ORAL CONTRACEPTIVES Norgestimate/ ethinyl estradiol (norgestimate 0.180 mg/ 0.215 mg/ 0.25 mg/ ethinyl estradiol 0.025 mg)/ ledipasvir (90 mg once daily)
Tabel 6: Demografi og baselinekarakteristika i studie ION-3 Patientdisposition
Table 6: Demographics and baseline characteristics in study ION-3 Patient disposition
Ingen dosisjustering af Harvoni eller ciclosporin er nødvendig.
No dose adjustment of Harvoni or ciclosporin is required.
Samtidig administration bør ikke anvendes.
Co-administration is not recommended.
LÆGEMIDLETS NAVN Harvoni 90 mg/400 mg filmovertrukne tabletter ledipasvir/sofosbuvir
NAME OF THE MEDICINAL PRODUCT Harvoni 90 mg/400 mg film-coated tablets ledipasvir/sofosbuvir
Harvoni er kontraindiceret sammen med carbamazepin, phenobarbital og phenytoin, potente P-gp-inducere i tarmen (se pkt.
Harvoni is contraindicated with carbamazepine, phenobarbital and phenytoin, potent intestinal P-gp inducers (see section 4.3).
anvendes til at behandle hiv-infektion
Use with certain HIV antiretroviral regimens
Ingen dosisjustering af Harvoni eller tacrolimus er nødvendig.
No dose adjustment of Harvoni or tacrolimus is required.
c/ sofosbuvir (400 mg enkeltdosis)c,d
c/ sofosbuvir (400 mg once daily)c, d
c. Patienter med manglende cirrose-status blev ekskluderet fra denne undergruppeanalyse.
c. Patients with missing cirrhosis status were excluded from this subgroup analysis.
d. Patienter med manglende cirrose-status blev ekskluderet fra denne undergruppeanalyse.
d. Patients with missing cirrhosis status were excluded from this subgroup analysis.
b. Patienter med manglende cirrose-status blev ekskluderet fra denne undergruppeanalyse.
b. Patients with missing cirrhosis status were excluded from this subgroup analysis.
Sikkerheden af ledipasvir/sofosbuvir er ikke blevet undersøgt hos patienter med svært nedsat nyrefunktion (estimeret glomulær filtrationshastighed [eGFR] <30 ml/min/1,73 m2) eller nyresygdom i slutstadiet (ESRD, end stage renal disease), der kræver hæmodialyse (se pkt.
The safety of ledipasvir/sofosbuvir has not been assessed in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2) or end stage renal disease (ESRD) requiring haemodialysis (see section 5.2).
c. Andet omfatter patienter, der ikke opnåede SVR og ikke opfyldte kriterierne for virologisk svigt (f.eks. lost to follow-up).
c. Other includes patients who did not achieve SVR and did not meet virologic failure criteria (e.g. lost to follow-up).
Ledipasvir/sofosbuvirs virkning er ikke blevet undersøgt hos HCV-genotype 5- og 6-inficerede patienter med dekompenseret cirrose, og/eller som venter på levertransplantation eller har gennemgået en levertransplantation.
Patients with decompensated cirrhosis and/or who are awaiting liver transplant or post-liver transplant The efficacy of ledipasvir/sofosbuvir in genotype 5 and genotype 6 HCV-infected patients with decompensated cirrhosis and/or who are awaiting liver transplant or post-liver transplant has not been investigated.
også kaldet ”E110”, før du tager denne medicin.
before taking this medicine.
Det skal du vide, før du begynder at tage Harvoni Tag ikke Harvoni
What you need to know before you take Harvoni
• Fortæl det til lægen, hvis du er overfølsom over for sunset yellow FCF aluminiumpigment,
• Tell your doctor if you are allergic to sunset yellow FCF aluminium lake, also called “E110”
Resultat for patienter uden SVR Virologisk svigt under behandling Recidiv b
Outcome for patients without SVR On-treatment virologic failure Relapse b
ANTIMYKOBAKTERIELLE MIDLER Rifampicin (600 mg én gang dagligt)/ ledipasvir (90 mg enkeltdosis)d
ANTIMYCOBACTERIALS Rifampicin (600 mg once daily)/ ledipasvir (90 mg single dose)
Kan ikke fortolkes a. En patient i behandlingsarmen med 24 ugers LDV/SOF og en patient i behandlingsarmen med 24 ugers LDV/SOV+RBV havde oplevet svigt af en tidligere behandling med et non-pegyleret interferonbaseret regimen.
a. One patient in the LDV/SOF 24-week treatment arms and one patient in the LDV/SOF+RBV 24-week treatment arm were prior treatment failures of a non-pegylated interferon based regimen.
b. Andet omfatter patienter, der ikke opnåede SVR og ikke opfyldte kriterierne for virologisk svigt (f.eks. lost to follow-up).
b. Other includes patients who did not achieve SVR and did not meet virologic failure criteria (e.g. lost to follow-up).
Tacrolimus (5 mg enkeltdosis)/ sofosbuvir (400 mg enkeltdosis)
Tacrolimus (5 mg single dose)/ sofosbuvir (400 mg single dose)
Norgestimat/ ethinylestradiol (norgestimat 0,180 mg/ 0,215 mg/ 0,25 mg/ ethinylestradiol 0,025 mg)/ sofosbuvir (400 mg én gang dagligt)
Norgestimate/ ethinyl estradiol (norgestimate 0.180 mg/ 0.215 mg/ 0.25 mg/ ethinyl estradiol 0.025 mg)/ sofosbuvir (400 mg once daily)d
Resultat for patienter uden SVR Virologisk svigt under behandling
Outcome for patients without SVR On-treatment virologic failure
Lægemidler, der er potente P-gp-inducere (rifampicin, rifabutin, prikbladet perikon, carbamazepin, phenobarbital og phenytoin), kan nedsætte plasmakoncentrationerne af ledipasvir og sofosbuvir signifikant og føre til en reduceret terapeutisk virkning af ledipasvir/sofosbuvir.
Medicinal products that are potent P-gp inducers (rifampicin, rifabutin, St. John's wort, carbamazepine, phenobarbital and phenytoin) may significantly decrease ledipasvir and sofosbuvir plasma concentrations leading to reduced therapeutic effect of ledipasvir/sofosbuvir and thus are contraindicated with Harvoni (see section 4.3).
Efter behandling med ledipasvir/sofosbuvir sammen med ribavirin i 12 uger hos patienter med dekompenseret sygdom (uanset levertransplantationsstatus) var der 3/7 patienter med NS5A-RAV ved baseline, der gav >100 gange nedsat følsomhed for ledipasvir, som recidiverede, sammenlignet med 4/68 af patienterne uden baseline-RAVs eller -RAVs, der gav ≤100 gange nedsat følsomhed for ledipasvir.
Following treatment with ledipasvir/sofosbuvir with ribavirin for 12 weeks in patients with decompensated disease (irrespective of liver transplantation status), 3/7 patients with baseline NS5A RAVs conferring > 100-fold reduced susceptibility to ledipasvir relapsed, as compared to 4/68 in those without any baseline RAVs or RAVs conferring ≤ 100-fold reduced susceptibility to ledipasvir.
Patienter, der venter på levertransplantation og efter levertransplantation - SOLAR-1 SOLAR-1 er et åbent, multicenterstudie, der evaluerer 12 og 24 ugers behandling med ledipasvir/sofosbuvir + ribavirin hos patienter med genotype 1 eller 4 CHC, der har fremskreden leversygdom og/eller som har gennemgået en levertransplantation.
SOLAR-1 is an open-label, multicentre study evaluating 12 and 24 weeks of treatment with ledipasvir/sofosbuvir + ribavirin in patients with genotype 1 or 4 CHC who have advanced liver disease and/or who have undergone liver transplantation.
Tabel 13: Recidivrater for udvalgte undergrupper i studie ION-2 LDV/SOF
Table 13: Relapse rates for selected subgroups in study ION-2 LDV/SOF
Raltegravir (400 mg to gange dagligt)/ sofosbuvir (400 mg én gang dagligt)d
Raltegravir (400 mg twice daily)/ sofosbuvir (400 mg once daily)
HIV ANTIVIRALE STOFFER: INTEGRASEHÆMMERE Raltegravir (400 mg to gange dagligt)/ ledipasvir (90 mg én gang dagligt)d
HIV ANTIVIRAL AGENTS: INTEGRASE INHIBITORS Raltegravir (400 mg twice daily)/ ledipasvir (90 mg once daily)
Harvoni indeholder sunset yellow FCF aluminiumpigment (E110)
Harvoni contains sunset yellow FCF aluminium lake (E110)
ANGIVELSE AF AKTIVT STOF/AKTIVE STOFFER Hver filmovertrukken tablet indeholder 90 mg ledipasvir og 400 mg sofosbuvir.
STATEMENT OF ACTIVE SUBSTANCE(S) Each film-coated tablet contains 90 mg ledipasvir and 400 mg sofosbuvir.
Ciclosporin (600 mg enkeltdosis)/ sofosbuvir (400 mg enkeltdosis)
Ciclosporin (600 mg single dose)/ sofosbuvir (400 mg single dose)
Indeholder lactose og sunset yellow FCF aluminiumpigment (E110).
LIST OF EXCIPIENTS Contains lactose and sunset yellow FCF aluminium lake (E110).
skyldtes den systemiske eksponering næsten udelukkende udgangsstoffet (>98 %).
Following a single dose of 90 mg [14C]-ledipasvir, systemic exposure was almost exclusively due to the parent drug (> 98%).
b. Benævnelsen for recidiv er antallet af patienter med HCV-rna < LLOQ ved deres seneste vurdering under behandling.
b. The denominator for relapse is the number of patients with HCV RNA < LLOQ at their last on-treatment assessment.
Ændring i MELD-score (model for end stage liver disease): 53 % (72/135) og 21 % (28/135) havde hhv. en forbedring eller ingen ændring i MELD-score fra baseline til uge 4 efter behandlingen.
Change in MELD score: 53% (72/135) and 21% (28/135) had an improvement or no change of MELD score from baseline to post-treatment week 4, respectively; of the 35 patients whose MELD score was ≥ 15 at baseline, 63% (22/35) had a MELD score < 15 at post-treatment week 12.
24 uger (n = 217)
24 weeks (n = 217)
Tabel 10: Responsrater i ION-1-studiet LDV/SOF
Table 10: Response rates in study ION-1 LDV/SOF
Harvoni + ribavirin i 24 uger (se pkt.
Harvoni + ribavirin for 24 weeks (see sections 4.4 and 5.1).
Efter en enkelt 90 mg dosis af [14C]-ledipasvir hos raske personer, var forholdet af [14C]-radioaktivitet mellem blod og plasma fra
After a single 90 mg dose of [14C]-ledipasvir in healthy subjects, the blood to plasma ratio of [
a. Nævneren for recidiv er antallet af patienter med HCV-rna <LLOQ ved deres seneste vurdering under behandling.
a. The denominator for relapse is the number of patients with HCV RNA < LLOQ at their last on-treatment assessment.
↑ AUC 1,50 (1,42; 1,59)
↑ Cmin 1.15 (0.90, 1.46)
Tabel 12: Responsrater i studie ION-2 LDV/SOF
Table 12: Response rates in study ION-2 LDV/SOF
Efter behandling med ledipasvir/sofosbuvir sammen med ribavirin i 12 uger hos levertransplanterede patienter med kompenseret leversygdom (SOLAR-1) var der ikke nogen (n = 8) af patienterne med NS5A-RAVs ved baseline, der gav >100 gange nedsat følsomhed for ledipasvir, som recidiverede.
Following treatment with ledipasvir/sofosbuvir with ribavirin for 12 weeks in post-liver transplant patients with compensated liver disease (SOLAR-1), none (n = 8) of the patients with baseline NS5A RAVs conferring a ledipasvir fold-change of > 100 relapsed.
Virkning og anvendelse
Treatment and duration
Elvitegravir/ cobicistat/ emtricitabin/ tenofovirdisoproxilfumarat (150 mg/ 150 mg/ 200 mg/ 300 mg én gang dagligt)/ ledipasvir (90 mg én gang dagligt)c/ sofosbuvir (400 mg én gang dagligt)
Elvitegravir/ cobicistat/ emtricitabine/ tenofovir disoproxil fumarate (150 mg/ 150 mg/ 200 mg/ 300 mg once daily)/ ledipasvir (90 mg once daily)
H2-receptorantagonister Famotidin (40 mg enkeltdosis)/ ledipasvir (90 mg enkeltdosis)c/ sofosbuvir (400 mg enkeltdosis)
Famotidine (40 mg single dose)/ ledipasvir (90 mg single dose)c/ sofosbuvir (400 mg single dose)
Median (interval)a
Median (range)
12 uger (n = 217)
12 weeks (n = 217)
Den højeste dokumenterede dosis af ledipasvir og sofosbuvir var hhv. 120 mg to gange dagligt i 10 dage, og en enkeltdosis på 1.200 mg. I disse studier med raske frivillige blev der ikke dokumenteret nogen uønskede virkninger ved disse dosisniveauer, og bivirkningerne var sammenlignelige med hensyn til hyppighed og sværhedsgrad med dem, der blev rapporteret i placebogrupperne.
In these healthy volunteer studies, there were no untoward effects observed at these dose levels, and adverse reactions were similar in frequency and severity to those reported in the placebo groups.
Recidiv b
Relapse b
5.1 for detaljer om dette studie).
(listed in section 6 of this leaflet).
Ændring i CPT: 59 % (79/133) og 34 % (45/133) havde hhv. en forbedring eller ingen ændring af CPT-scores fra baseline til uge 12 efter behandlingen.
Change in CPT: 59% (79/133) and 34% (45/133) had an improvement or no change of CPT scores from baseline to post-treatment week 12, respectively; of the 39 patients who had CPT C cirrhosis at baseline, 56% (22/39) had CPT B cirrhosis at post-treatment week 12; of the 99 patients who had CPT B cirrhosis at baseline, 29% (27/92) had CPT A cirrhosis at post-treatment week 12.
SVR Resultat for patienter uden SVR Virologisk svigt under behandling
SVR Outcome for patients without SVR On-treatment virologic failure a
Harvoni er kontraindiceret sammen med rifabutin, en kraftig P-gp-inducer i tarmen (se pkt.
Harvoni is contraindicated with rifabutin, a potent intestinal P-gp inducer (see section 4.3).
Harvoni er kontraindiceret sammen med rifampicin, en kraftig P-gp-inducer i tarmen (se pkt.
Harvoni is contraindicated with rifampicin, a potent intestinal P-gp inducer (see section 4.3).
Når Harvoni anvendes i kombination med ribavirin, henvises også til produktresuméet for ribavirin for patienter med kreatininclearance (CrCl) <50 ml/min (se pkt.
Product Characteristics for ribavirin for patients with creatinine clearance (CrCl) < 50 mL/min (see section 5.2).
Famotidin (40 mg enkeltdosis)/ ledipasvir (90 mg enkeltdosis)
H2-receptor antagonists Famotidine (40 mg single dose)/ ledipasvir (90 mg single dose)
0,51 til 0,66.
C]-radioactivity ranged between 0.51 and 0.66.
In vitro data indikerer, at ledipasvir kan være en svag inducer af metaboliserende enzymer, såsom
In vitro data indicate that ledipasvir may be a weak inducer of metabolising enzymes such as CYP3A4, CYP2C and UGT1A1.
Emtricitabin ↔ Cmax 1,02 (0,98; 1,06) ↔ AUC 1,05 (1,02; 1,08) ↔ Cmin 1,06 (0,97; 1,15)
Emtricitabine ↔ Cmax 1.02 (0.96, 1.08) ↔ AUC 1.04 (1.00, 1.08) ↔ Cmin 1.03 (0.97, 1.10)
↑ Cmin 1,47 (1,38; 1,57) Ledipasvir ↑ Cmax 1,68 (1,54; 1,84)
Ledipasvir ↑ Cmax 1.68 (1.54, 1.84)
Abacavir/ lamivudin (600 mg/ 300 mg én gang dagligt)/ ledipasvir (90 mg én gang dagligt)c/ sofosbuvir (400 mg én gang dagligt)c,d
Abacavir/ lamivudine (600 mg/ 300 mg once daily)/ ledipasvir (90 mg once daily)
Samtidig administration af lægemidler, der er potente P-glykoprotein (P-gp)-inducere i tarmen (rifampicin, rifabutin, perikon [Hypericum perforatum], carbamazepin, phenobarbital og phenytoin) vil nedsætte plasmakoncentrationerne af ledipasvir og sofosbuvir signifikant og kan medføre manglende virkning af Harvoni (se pkt.
Medicinal products that are potent P-glycoprotein (P-gp) inducers in the intestine (rifampicin, rifabutin, St. John's wort [Hypericum perforatum], carbamazepine, phenobarbital and phenytoin).
HIV ANTIVIRALE STOFFER: HIV PROTEASEHÆMMERE Atazanavir boostet med ritonavir (300 mg/ 100 mg én gang dagligt)/ ledipasvir (90 mg én gang dagligt)c/ sofosbuvir (400 mg én gang dagligt)c,d
HIV ANTIVIRAL AGENTS: HIV PROTEASE INHIBITORS Atazanavir boosted with ritonavir (300 mg/ 100 mg once daily)/ ledipasvir (90 mg once daily)
Famotidin doseret sammen med Harvonid
Omeprazole dosed simultaneously with Harvoni
GS-331007 ↓ Cmax 0,73 (0,65; 0,83) ↔ AUC 1,04 (0,89; 1,22) IMMUNOSUPPRIMERENDE MIDLER Ciclosporin g
GS-331007 ↓ Cmax 0.73 (0.65, 0.83) ↔ AUC 1.04 (0.89, 1.22)
HIV ANTIVIRALE STOFFER: REVERS TRANSKRIPTASEHÆMMERE Efavirenz/ emtricitabin/ tenofovirdisoproxilfumarat (600 mg/ 200 mg/ 300 mg/ én gang dagligt)/ ledipasvir (90 mg én gang dagligt)c/ sofosbuvir (400 mg én gang dagligt)c,d
HIV ANTIVIRAL AGENTS: REVERSE TRANSCRIPTASE INHIBITORS Efavirenz/ emtricitabine/ tenofovir disoproxil fumarate (600 mg/ 200 mg/ 300 mg/ once daily)/ ledipasvir (90 mg once daily)
Amning
Pravastating
Stabile replikoner NS5B transitoriske replikoner
NS5B transient replicons Median (range)
Tabel 7: Responsrater i ION-3-studiet LDV/SOV
Table 7: Response rates in study ION-3 LDV/SOF
Atazanavir ↔ Cmax 1,07 (0,99; 1,14)
Emtricitabine ↔ Cmax 1.08 (0.97, 1.21)
↑ Dabigatran ↔ Ledipasvir ↔ Sofosbuvir
↑ Ledipasvir ↔ Sofosbuvir
Ledipasvir ↓ Cmax 0,65 (0,56; 0,76) ↓ AUC 0,41 (0,36; 0,48)
Ledipasvir ↓ Cmax 0.65 (0.56, 0.76)
Ledipasvir ↑ Cmax 1,81 (1,69; 2,94) ↑ AUC 1,92 (1,77; 2,07)
Ledipasvir ↑ Cmax 1.81 (1.69, 2.94)
Ledipasvir ↑ Cmax 1,63 (1,51; 1,75) ↑ AUC 1,78 (1,64; 1,94) ↑ Cmin 1,91 (1,76; 2,08)
Tenofovir ↑ Cmax 1.64 (1.54, 1.74) ↑ AUC 1.50 (1.42, 1.59) ↑ Cmin 1.59 (1.49, 1.70)
↔ AUC 1,09 (0,87; 1,37)
↔ Cmin 1.07 (0.89, 1.28)
Protonpumpehæmmere Omeprazol (20 mg én gang dagligt)/ ledipasvir (90 mg enkeltdosis)
Proton pump inhibitors Omeprazole (20 mg once daily)/ ledipasvir (90 mg single dose)c/ sofosbuvir (400 mg single dose)
↑ Cmin 1,63 (1,45; 1,84) Ritonavir ↔ Cmax 0,86 (0,79; 0,93)
↔ Cmin 1.06 (0.97, 1.15) Rilpivirine ↔ Cmax 0.97 (0.88, 1.07)
Behandlingsnaive voksne med eller uden cirrose - ION-1 (studie 0102) - genotype 1 ION-1 var et randomiseret, åbent studie der undersøgte 12 og 24 ugers behandling med ledipasvir/sofosbuvir med eller uden ribavirin hos 865 behandlingsnaive patienter med CHC foråsaget af infektion med HCV af genotype 1, herunder patienter med cirrose (randomiseret 1:1:1:1).
ION-1 was a randomised, open-label study that evaluated 12 and 24 weeks of treatment with ledipasvir/sofosbuvir with or without ribavirin in 865 treatment-naïve patients with genotype 1 CHC
↔ Cmin 1,08 (0,98; 1,20) Ritonavir ↔ Cmax 1,17 (1,01; 1,35)
↔ Cmin 1.12 (1.05, 1.20) Ledipasvir ↔ Cmax 1.10 (1.01, 1.19)
↔ AUC 0,94 (0,67; 1,33)
↔ Cmin 0.97 (0.86, 1.10)
Træthed
Relapse
Sikkerheden af disse vacciner bør fortsat overvåges nøje.
The safety of these vaccines should continue to be carefully monitored.
Størstedelen af indberetningerne om POTS kom fra et center i Danmark (Brinth et al, 2015)1.
The vast majority of POTS reports came from a centre in Denmark (Brinth et al, 2015)1.
Over 80 mio. piger og kvinder verden over har nu fået disse vacciner, som i nogle europæiske lande er blevet givet hos 90 % af den aldersgruppe, som vaccination anbefales for.
More than 80 million girls and women worldwide have now received these vaccines, and in some European countries they have been given to 90% of the age group recommended for vaccination.
Den 9. juli 2015 iværksatte Europa-Kommissionen derfor en procedure i henhold til artikel 20 i forordning (EF) nr. 726/2004 som et resultat af lægemiddelovervågningsdata, og anmodede EMA om at vurdere disse betænkeligheder.
On 09 July 2015 the European Commission therefore triggered a procedure under Article 20 of Regulation (EC) No 726/2004 resulting from pharmacovigilance data, and requested the EMA to assess these concerns.
Disse syndromer er tidligere gentagne gange blevet gennemgået af PRAC.
These syndromes have been subject to previous repeated review by PRAC.
• Udvalget For Risikovurdering inden for Lægemiddelvurdering (PRAC) behandlede proceduren i henhold til artikel 20 af forordning (EF) nr. 726/2004 for HPV-vacciner
• The Pharmacovigilance Risk Assessment Committee (PRAC) considered the procedure under Article 20 of Regulation (EC) No 726/2004 for HPV vaccines.
I denne forbindelse kommenterede CHMP, at man ved sådanne sammenholdelser bør tage den formentlig stigende viden om disse syndromer i betragtning for at sikre korrekt fortolkning af nye data.
In this respect, the CHMP commented that these comparisons should take into account likely increasing awareness of these syndromes to ensure appropriate interpretation of emerging data.
Vacciner mod humant papillomavirus (HPV) har været godkendt i EU siden 2006 til forebyggelse af cervixcancer og forskellige andre cancerformer, der skyldes infektion med HPV.
Human papillomavirus (HPV) vaccines have been authorised in the European Union since 2006 for the prevention of cervical and various other cancers caused by HPV infection.
Der blev ikke konstateret tilfælde i Cervarix- eller sammenligningsgruppen.
No cases were identified in the Cervarix and comparator cohorts.