FrancophonIA/ELRC3.0 huggingface dataset:
English: Inhibitors of OATP1B1/3 such as eltrombopag or gemfibrozil may result in increases in simeprevir plasma concentrations.
Danish: Hæmmere af OATP1B1/3, for eksempel eltrombopag og gemfibrozil, kan medføre stigning i plasmakoncentrationen af simeprevir.
English: In vitro experiments with human liver microsomes indicated that simeprevir primarily undergoes oxidative metabolism by the hepatic CYP3A4 system.
Danish: Eksperimenter in vitro med humane levermikrosomer har indikeret, at simeprevir fortrinsvis gennemgår oxidativ metabolisme via CYP3A4-systemet i leveren.
English: Detailed information on this medicinal product is available on the website of the European Medicines
Danish: Yderligere information om dette lægemiddel findes på Det Europæiske Lægemiddelagenturs
English: Simeprevir in combination with sofosbuvir
Danish: Simeprevir i kombination med sofosbuvir
English: Substitutions such as D168V or A, and R155K were usually associated with large reductions in susceptibility to simeprevir in vitro (FC in EC50 > 50), whereas other substitutions such as Q80K or R, S122R, and D168E displayed in vitro low level resistance (FC in EC50 between 2 and 50).
Danish: Substitutioner såsom D168V eller A samt R155K var normalt forbundet med stærkt nedsat følsomhed for simeprevir in vitro (FC i EC50 > 50), hvorimod andre substitutioner såsom Q80K eller R, S122R og D168E udviste et lavt resistensniveau (FC i EC50 mellem 2 og 50) in vitro.
English: In 2% and 0.3% of the simeprevir-treated patients grade 3 or 4 ‘blood bilirubin increased' was reported, respectively (pooled phase 3 studies).
Danish: Hos henholdsvis 2% og 0,3% af de simeprevir -behandlede patienter blev der indberettet forhøjet blodbilirubin af grad 3 eller 4 (puljede fase 3-studier).
English: Please refer to section 4.5 for information on interactions with medicinal products.
Danish: 4.5 indeholder information om interaktioner med andre lægemidler.
English: In vitro experiments with human Caco-2 cells indicated that simeprevir is a substrate of P-gp.
Danish: Eksperimenter in vitro med humane Caco-2-celler indikerede, at simeprevir er substrat for
English: In study HPC2014 (OSIRIS), patients received simeprevir + sofosbuvir for 8 weeks (patients without cirrhosis) or 12 weeks (patients with or without cirrhosis) (see table 11).
Danish: I studie HPC2014 (OSIRIS) fik patienterne simeprevir + sofosbuvir i 8 uger (patienter uden cirrose) eller 12 uger (patienter med eller uden cirrose) (se tabel 11).
English: There are no safety and efficacy data of OLYSIO in patients over the age of 75 years.
Danish: Der findes ingen data vedrørende OLYSIOs sikkerhed og virkning hos patienter over 75 år.
English: Simeprevir does not induce CYP1A2 or CYP3A4 in vitro.
Danish: Simeprevir inducerer ikke CYP1A2 eller CYP3A4 in vitro.
English: Dose adjustment of the PDE-5 inhibitor may be required when OLYSIO is co-administered with sildenafil or tadalafil administered chronically at doses used for the treatment of pulmonary arterial hypertension.
Danish: Justering af dosis af PDE-5-hæmmeren kan være nødvendig, når OLYSIO administreres sammen med kronisk dosering af sildenafil eller tadalafil til behandling af pulmonal arteriel hypertension.
English: The safety and efficacy of OLYSIO in children aged below 18 years have not yet been established.
Danish: Pædiatrisk population OLYSIOs sikkerhed og virkning hos børn under 18 år er endnu ikke klarlagt.
English: Compared to intake without food, administration of simeprevir with food to healthy subjects increased the AUC by 61% after a high-fat, high-caloric (928 kcal) and 69% after a normal caloric (533 kcal) breakfast, and delayed the absorption by 1 hour and 1.5 hours, respectively.
Danish: Sammenlignet med indtagelse uden føde medførte administration af simeprevir sammen med mad til raske studiedeltagere en stigning i AUC med 61% efter fedtholdig, kalorierig (928 kcal) morgenmad og med 69% efter morgenmad med normalt kalorieindhold (533 kcal).
English: OLYSIO 150 mg hard capsules
Danish: OLYSIO 150 mg hårde kapsler
English: Co-administration of OLYSIO with ciclosporin is not recommended as this leads to significantly higher exposure of simeprevir (see section 4.5).
Danish: Samtidig administration af OLYSIO og ciclosporin anbefales ikke, da dette giver signifikant højere eksponering for simeprevir (se pkt.
English: The daily dose of ribavirin is weight based (< 75 kg = 1,000 mg and ≥ 75 kg = 1,200 mg) and administered orally in two divided doses with food; also refer to the Summary of Product Characteristics of ribavirin.
Danish: Den daglige dosis af ribavirin er vægtbaseret (< 75 kg: 1.000 mg; ≥ 75 kg: 1.200 mg) og administreres oralt fordelt på to doser sammen med mad.
English: The most frequently reported adverse reactions (incidence ≥ 5% following 12 or 24 weeks of treatment) were rash, pruritus, constipation and photosensitivity reaction (see section 4.4).
Danish: De hyppigst indberettede bivirkninger (frekvens ≥ 5% efter 12 eller 24 ugers behandling) var udslæt, kløe, obstipation og lysfølsomhedsreaktion (se pkt.
English: Efficacy in patients with HCV genotype 1
Danish: Effekt hos patienter med HCV-genotype 1
English: Studies in animals have shown reproductive effects (see section 5.3).
Danish: Dyrestudier har påvist reproduktionstoksicitet (se pkt.
English: Compared to healthy subjects with normal hepatic function, the mean steady-state AUC of simeprevir was 2.4-fold higher in non-HCV infected subjects with moderate hepatic impairment (Child-Pugh B) and 5.2-fold higher in non-HCV infected subjects with severe hepatic impairment (Child-Pugh C).
Danish: Sammenlignet med raske personer med normal leverfunktion var den gennemsnitlige AUC for simeprevir ved steady state 2,4 gange højere hos ikke-HCV-inficerede personer med moderat leverinsufficiens (Child-Pugh B) og 5,2 gange højere hos ikke-HCV-inficerede personer med svær leverinsufficiens (Child-Pugh C).
English: No meaningful changes in QTc interval were observed with either the recommended dose of 150 mg once daily or the supratherapeutic dose of
Danish: Der blev ikke observeret nogen betydningsfulde ændringer i QTc-intervallet hverken ved den anbefalede dosis på 150 mg én gang dagligt eller den supraterapeutiske dosis på 350 mg én gang dagligt.
English: Women must use an effective method of contraception during treatment with OLYSIO.
Danish: Prævention Kvinder skal bruge en sikker præventionsmetode under behandling med OLYSIO.
English: Simeprevir-resistant variants studied remained susceptible to representative HCV nucleoside and non-nucleoside polymerase inhibitors, and NS5A inhibitors.
Danish: De undersøgte simeprevir-resistente varianter forblev følsomme for repræsentative HCV-nukleosid og -nonnukleosid polymerasehæmmere samt NS5A-hæmmere.
English: During the first 12 weeks of treatment, the most frequently reported adverse reactions (incidence ≥ 5%) were nausea, rash, pruritus, dyspnoea, blood bilirubin increase and photosensitivity reaction
Danish: I løbet af de første 12 ugers behandling var de hyppigst indberettede bivirkninger (forekomst ≥ 5%) kvalme, udslæt, kløe, dyspnø, stigning i bilirubin i blodet og lysfølsomhedsreaktion (se pkt.
English: One patient (3.2%) receiving 24 weeks of treatment experienced a grade 4 ‘blood bilirubin increased' event.
Danish: En enkelt patient (3,2%), som fik 24 ugers behandling, fik grad 4 forhøjet bilirubin i blodet.
English: Superior versus historical control rate (historical SVR rates of approved combination treatments of direct acting antivirals with peginterferon alfa and ribavirin).
Danish: Superioritet vs. historisk kontrolrate (historiske SVR-rater for godkendte kombinationsbehandlinger med direkte virkende antivirale midler plus peginterferon alfa og ribavirin).
English: Warnings and precautions related to these medicinal products also apply to their use in OLYSIO combination treatment.
Danish: Advarslerne og forsigtighedsreglerne for disse lægemidler gælder også for deres anvendelse i kombinationsbehandling med OLYSIO.
English: - The other ingredients are sodium lauryl sulfate, magnesium stearate, colloidal anhydrous silica, croscarmellose sodium, lactose monohydrate, gelatin, titanium dioxide (E171), iron oxide black (E172) and shellac (E904).
Danish: - Øvrige indholdsstoffer: natriumlaurilsulphat, magnesiumstearat, kolloid vandfri silica, croscarmellosenatrium, lactosemonohydrat, gelatine, titandioxid (E 171), sort jernoxid (E 172)
English: Increased simeprevir exposures have been observed in individuals with severe renal impairment.
Danish: Der er observeret forhøjet eksponering for simeprevir hos personer med alvorlig nyreinsufficiens.
English: The dosing recommendation is applicable to the recommended dose of simeprevir 150 mg once daily.
Danish: Doseringsanbefalingen gælder for den anbefalede dosis af simeprevir på 150 mg én gang dagligt.
English: Excess exposure to sun and use of tanning devices during treatment with OLYSIO should be avoided.
Danish: Langvarigt ophold i solen og anvendelse af solarium bør undgås under behandling med OLYSIO.
English: Because OLYSIO must be co-administered with other medicinal products, for the treatment of CHC, the contraindications and warnings applicable to those medicinal products also apply to their use in combination treatment with OLYSIO (see section 4.3).
Danish: Da OLYSIO skal indgives sammen med andre lægemidler til behandling af CHC, gælder de samme kontraindikationer og advarsler for disse præparater også for deres anvendelse i kombinationsbehandling med OLYSIO (se pkt.
English: Simeprevir must be taken with food (see section 4.2).
Danish: Simeprevir skal tages sammen med mad (se pkt.
English: Name and address of the manufacturer responsible for batch release
Danish: Navn og adresse på den fremstiller, der er ansvarlig for batchfrigivelse Janssen Cilag SpA
English: The safety profile of OLYSIO 150 mg in combination with peginterferon alfa and ribavirin in a phase 3 study conducted in Asian patients in China and South-Korea is comparable to non-Asian patients from a pooled phase 3 population from global studies, except for higher frequencies for ‘blood bilirubin increased' events (see table 8).
Danish: Sikkerhedsprofilen for OLYSIO 150 mg i kombination med peginterferon alfa og ribavirin i et fase 3studie, der blev gennemført med asiatiske patienter i Kina og Sydkorea, er sammenlignelig med sikkerhedsprofilen for ikke-asiatiske patienter fra en samlet fase 3-population fra globale studier, bortset fra de højere frekvenser for bivirkningen ‘forhøjet bilirubin i blodet' (se tabel 8).
English: The contraindications and warnings regarding pregnancy and contraception requirements applicable to the co-administered medicinal products also apply to their use in OLYSIO combination treatment.
Danish: De kontraindikationer og advarsler vedrørende graviditet og de krav til kontraception, som gælder for de lægemidler, der indgives samtidigt, gælder også for deres anvendelse ved kombinationsbehandling med OLYSIO.
English: Treatment stopping rules for HCV therapy were used to ensure that patients with inadequate on-treatment virologic response discontinued treatment in a timely manner.
Danish: Der blev brugt regler for seponering af HCV-behandlingen for at sikre, at behandlingen blev seponeret rettidigt hos patienter med utilstrækkeligt virologisk respons under behandlingen.
English: Short term monotherapy data of simeprevir from studies C201 (genotype 1) and C202 (genotype 2, 3, 4, 5 and 6) in patients receiving 200 mg once daily simeprevir for 7 days is presented in table 9.
Danish: Data fra korttids-monoterapi med simeprevir fra studie C201 (genotype 1) og C202 (genotype 2, 3, 4, 5 og 6) hos patienter, der fik 200 mg simeprevir én gang dagligt i 7 dage, vises i tabel 9.
English: Table 23: Treatment outcome in HCV genotype 4 infected patients (study HPC3011)
Danish: Tabel 23: Behandlingsresultat hos HCV-genotype 4-inficerede patienter (studie HPC3011)
English: There are no clinical data on the efficacy of simeprevir in patients with a history of exposure to the NS3/4A PIs telaprevir or boceprevir.
Danish: Der findes ingen kliniske data vedrørende effekten af simeprevir hos patienter med tidligere eksponering for NS3/4A-PI'erne telaprevir eller boceprevir.
English: Relapsers after prior interferon-based therapy.
Danish: Patienter med recidiv efter tidligere interferon-baseret behandling.
English: - OLYSIO contains the active substance ‘simeprevir'.
Danish: - OLYSIO indeholder det aktive stof simeprevir.
English: The long-term clinical impact of the emergence or persistence of simeprevir-resistance-associated
Danish: Den langsigtede kliniske betydning af fremkomst eller varighed af substitutioner, der er forbundet med
English: Caution is warranted and therapeutic drug monitoring for these antiarrhythmics and/or clinical monitoring (ECG etc.) when orally administered are recommended.
Danish: Der skal udvises forsigtighed, og terapeutisk monitorering af disse antiarytmika og/eller klinisk monitorering (ekg osv.) anbefales, hvis de indgives oralt.
English: Most of the photosensitivity reactions were of mild severity (grade 1); grade 2 photosensitivity reactions were reported in two patients (0.7%) receiving 12 weeks of treatment.
Danish: De fleste lysfølsomhedsreaktioner var lette i styrke (grad 1); lysfølsomhedsreaktion af grad 2 blev indberettet hos 2 patienter (0,7%), der fik 12 ugers behandling.
English: It is not recommended to co-administer OLYSIO with systemic erythromycin.
Danish: Det anbefales ikke at administrere OLYSIO sammen med systemisk erythromycin.
English: No dose adjustment is required when OLYSIO is co-administered with doses of sildenafil, vardenafil, or tadalafil indicated for the treatment of erectile dysfunction.
Danish: Dosisjustering er ikke nødvendig, når OLYSIO administreres sammen med sildenafil, vardenafil eller tadalafil ved doser til behandling af erektil dysfunktion.
English: The one patient with on-treatment failure discontinued treatment early due to an adverse event.
Danish: Den ene patient med manglende effekt under behandlingen afbrød behandlingen før det planlagte tidspunkt på grund
English: The efficacy of simeprevir (150 mg once daily) as part of an interferon-free regimen (sofosbuvir, 400 mg once daily) was evaluated in patients with HCV genotype 1 or 4 infection, who were treatment-naïve or treatment-experienced patients (following prior interferon-based therapy) (table 11).
Danish: Effekten af simeprevir (150 mg én gang dagligt) som en del af et interferonfrit regime (sofosbuvir, 400 mg én gang dagligt) blev undersøgt hos patienter med HCV-genotype 1- eller 4-infektion, der var behandlingsnaive eller behandlingserfarne (efter tidligere interferon-baseret behandling) (tabel 11).
English: Refer to table 3 for treatment stopping rules based on HCV RNA levels at weeks 4, 12 and 24 for patients receiving treatment with OLYSIO, peginterferon alfa and ribavirin.
Danish: Tabel 3 viser reglerne for behandlingsophør baseret på HCV-RNA-niveauerne i uge 4, 12 og 24 for patienter, der får OLYSIO, peginterferon alfa og ribavirin.
English: In patients with HCV genotype 1a with a baseline Q80K amino acid substitution an emerging R155K substitution was observed most frequently at failure.
Danish: Ved manglende effekt hos patienter med HCV-genotype 1a med en Q80K-aminosyresubstitution ved baseline blev der hyppigst observeret en opstået R155K-substitution.
English: If a dose of OLYSIO is missed by more than 12 hours after the usual dosing time, the patient should not take the missed dose of OLYSIO and should resume dosing of OLYSIO with food at the regularly
Danish: Hvis en dosis af OLYSIO glemmes i mere end 12 timer efter det sædvanlige doseringstidspunkt, må patienten ikke tage den manglende dosis, men skal genoptage doseringen af OLYSIO sammen med mad på det sædvanlige, planlagte tidspunkt.
English: Alternative therapy should be considered for patients infected with HCV genotype 1a with the Q80K polymorphism or in cases where testing is not accessible.
Danish: Anden behandling bør overvejes for patienter, der er inficerede med HCV-genotype 1a med Q80K-polymorfisme, og i tilfælde, hvor det ikke er muligt at teste.
English: In healthy adult subjects receiving single doses up to 600 mg or once daily doses up to 400 mg for 5 days, and in HCV infected adult patients receiving 200 mg once daily for 4 weeks, adverse reactions were consistent with those observed in clinical studies at the recommended dose (see section 4.8).
Danish: Hos raske voksne personer, der har fået enkelte doser på op til 600 mg eller doser på op til 400 mg én gang dagligt i 5 dage, og hos HCV-inficerede voksne patienter, der har fået 200 mg én gang dagligt i 4 uger, var bivirkningerne de samme som dem, der blev observeret i kliniske studier med den anbefalede dosis (se pkt.
English: Simeprevir exposure is significantly increased in patients with severe hepatic impairment (see section 5.2).
Danish: Eksponeringen for simeprevir er signifikant forhøjet hos patienter med alvorlig leverinsufficiens (se pkt.
English: No dose adjustment of daclatasvir or OLYSIO is required.
Danish: Dosisjustering af daclatasvir eller OLYSIO ikke nødvendig
English: It is not recommended to co-administer OLYSIO with delavirdine, etravirine or nevirapine.
Danish: Det anbefales ikke at administrere OLYSIO sammen med delavirdin, etravirin eller nevirapin.
English: Open-label, randomised, except for studies HPC3018 and HPC3021 which were single arm, and study HPC2014 which
Danish: Åbent, randomiseret, bortset fra studierne HPC3018 og HPC3021, der havde en enkelt behandlingsarm, og studie HPC2014, som var delvist randomiseret.
English: Therefore, co-administration of OLYSIO with substances that moderately or strongly inhibit or induce CYP3A4 is not recommended.
Danish: Samtidig administration af OLYSIO og stoffer, der hæmmer eller inducerer CYP3A4 moderat eller kraftigt, anbefales derfor ikke.
English: Most of the rash and pruritus events in simeprevir-treated patients were of mild or moderate severity
Danish: De fleste tilfælde af udslæt og kløe hos simeprevir-behandlede patienter var lette eller moderate i
English: Simeprevir in combination with peginterferon alfa and ribavirin There were no differences in haemoglobin, neutrophils or platelets between both treatment groups.
Danish: Simeprevir i kombination med peginterferon alfa og ribavirin Der var ingen forskelle i hæmoglobin, neutrofiler eller trombocytter i de 2 behandlingsgrupper.
English: Variants carrying amino-acid substitutions conferring reduced susceptibility to NS5A inhibitors (L31F/V, Y93C/H), nucleoside polymerase inhibitors (S282T) and non-nucleoside polymerase inhibitors (C316N, M414I/L, P495A) remained susceptible to simeprevir in vitro.
Danish: Varianter, der bærer aminosyresubstitutioner, som giver nedsat følsomhed for NS5A-hæmmere (L31F/V, Y93C/H), nukleosidpolymerase-hæmmere (S282T) og non-nukleosidpolymerase-hæmmere (C316N, M414I/L, P495A), forblev følsomme for simeprevir in vitro.
English: A higher incidence of anaemia in patients with advanced fibrosis receiving simeprevir in combination with peginterferon alfa and ribavirin has been reported.
Danish: En højere incidens af anæmi hos patienter med fremskreden fibrose, der fik simeprevir i kombination med peginterferon alfa og ribavirin, er rapporteret.
English: The median simeprevir EC50 and EC90 values against a HCV genotype 1b replicon were 9.4 nM (7.05 ng/ml) and 19 nM (14.25 ng/ml), respectively.
Danish: De mediane EC50- og EC90-værdier for simeprevir i forhold til et HCV-genotype 1b-replikon var henholdsvis 9,4 nM (7,05 ng/ml) og 19 nM (14,25 ng/ml).
English: OLYSIO in combination with sofosbuvir: HCV/HIV-1 co-infected patients should be treated for the same duration as HCV mono-infected patients.
Danish: OLYSIO i kombination med sofosbuvir: Hos patienter med HCV/HIV 1-coinfektion er behandlingsvarigheden den samme som for HCV-monoinficerede patienter.
English: The interaction between simeprevir and the medicinal product was evaluated in a pharmacokinetic study in opioid-dependent adults on stable methadone maintenance therapy.
Danish: Interaktionen mellem simeprevir og lægemidlet blev undersøgt i et farmakokinetisk studie med opioidafhængige voksne i stabil vedligeholdelsesbehandling med methadon.
English: Note, substitutions at NS3 position 43 and 156 associated with reduced simeprevir activity in vitro were not observed at
Danish: Bemærk, at substitutioner ved NS3-position 43 og 156, forbundet med nedsat aktivitet af simeprevir in vitro, blev ikke observeret på tidspunktet for manglende behandlingseffekt.
English: In studies HPC3017 (OPTIMIST-1) and HPC3018 (OPTIMIST-2), patients received simeprevir + sofosbuvir for 8 weeks (HPC3017 only) or 12 weeks (HPC3017 and HPC3018) (see table 11).
Danish: I studierne HPC3017 (OPTIMIST-1) og HPC3018 (OPTIMIST-2) fik patienterne simeprevir + sofosbuvir i 8 uger (kun HPC3017) eller 12 uger (HPC3017 og HPC3018) (se tabel 11).
English: nelfinavir, nevirapine, ritonavir, saquinavir or tipranavir to treat HIV infection - atorvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin or simvastatin to lower cholesterol
Danish: nelfinavir, nevirapin, ritonavir, saquinavir eller tipranavir til behandling af HIV-infektion - atorvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin eller simvastatin til sænkning af
English: Co-administration of OLYSIO with medicinal products that are primarily metabolised by CYP3A4 may result in increased plasma concentrations of such medicinal products (see table 4).
Danish: Samtidig administration af OLYSIO og lægemidler, der primært metaboliseres af CYP3A4, kan medføre forhøjede plasmakoncentrationer af sådanne lægemidler (se tabel 4).
English: Eighty percent (28/35), 90% (18/20), 40% (4/10) and 49% (19/39) of simeprevir-treated treatment-naïve patients, prior relapsers, prior partial responders and prior null responders, respectively, had undetectable HCV RNA at week 4.
Danish: Henholdsvis 80% (28/35), 90% (18/20), 40% (4/10) og 49% (19/39) af de simeprevir-behandlede behandlingsnaive patienter og patienter med tidligere recidiv, tidligere delvist respons og tidligere nul respons havde udetekterbart HCV-RNA ved uge 4.
English: Cases of bradycardia have been observed when OLYSIO is used in combination with sofosbuvir and concomitant amiodarone.
Danish: Der er observeret tilfælde af bradykardi, når OLYSIO blev anvendt i kombination med sofosbuvir og samtidig amiodaron.
English: In patients receiving 24 weeks simeprevir with sofosbuvir, no grade 2 or 3 adverse reactions were reported; one patient (3.2%) experienced a grade 4 adverse reaction (‘blood bilirubin increased').
Danish: Hos patienter, der fik 24 ugers behandling med simeprevir sammen med sofosbuvir, blev der ikke indberettet bivirkninger af grad 2 eller 3; en enkelt patient (3,2%) havde en bivirkning af grad 4 (forhøjet bilirubin i blodet).
English: You may experience a rash during treatment with OLYSIO.
Danish: Du kan få udslæt under behandling med OLYSIO.
English: The pharmacokinetic properties of simeprevir have been evaluated in healthy adult subjects and in adult HCV infected patients.
Danish: De farmakokinetiske egenskaber for simeprevir er blevet undersøgt hos raske, voksne studiedeltagere og hos voksne HCV-inficerede patienter.
English: 12 weeks SMV + peg-IFN-alfa + RBV, followed by 12 or 36 weeks peg-IFN-alfa + RBV control group: 48 weeks placebo + peg-IFN-alfa + RBV
Danish: 12 ugers SMV + peg-IFN-alfa + RBV efterfulgt af 12 eller 36 ugers peg-IFN-alfa + RBV kontrolgruppe: 48 ugers placebo + peg-IFN-alfa + RBV
English: Increased concentrations of
Danish: Let forhøjede koncentrationer af
English: Laboratory testing during treatment with OLYSIO, peginterferon alfa and ribavirin HCV RNA levels should be monitored at weeks 4 and 12 and as clinically indicated (see also guidelines for treatment duration and stopping rules; section 4.2).
Danish: Laboratorietest under behandling med OLYSIO, peginterferon alfa og ribavirin HCV-RNA-niveauet skal kontrolleres i uge 4 og 12 og efter klinisk behov (se også retningslinjerne for behandlingsvarighed og regler for behandlingsophør, pkt.