natgillin/translations-raw huggingface dataset:
Kombineret med andre antiretrovirale midler nedsætter CELSENTRI derfor indholdet af CCR5- tropisk hiv i patientens blod og holder det nede.
As HIV can only reproduce itself within cells, CELSENTRI, taken in combination with other antiviral medicines, reduces the level of CCR5-tropic HIV in the blood of patients, and keeps it at a low level.
CELSENTRI helbreder ikke hiv- infektion eller aids, men kan bremse den skade på immunsystemet og de infektioner og sygdomme, der er forbundet med aids.
CELSENTRI does not cure HIV infection or AIDS, but it may delay the damage to the immune system and the development of infections and diseases associated with AIDS.
Hvordan blev CELSENTRI undersøgt?
How has CELSENTRI been studied?
Virkningerne af CELSENTRI blev først afprøvet i forsøgsmodeller, inden de blev undersøgt hos mennesker.
The effects of CELSENTRI were first tested in experimental models before being studied in humans.
CELSENTRI var genstand for to hovedundersøgelser, hvori der deltog i alt 1 076 patienter med CCR5- tropisk hiv- infektion.
CELSENTRI was studied in two main studies involving a total of 1,076 patients with CCR5-tropic HIV infection.
Patienterne havde tidligere fået anden medicin mod hiv i mindst seks måneder, men medicinen virkede ikke længere.
The patients had taken other treatments for HIV for at least six months, but these had stopped working.
Virkningerne af CELSENTRI, indtaget en eller to gange dagligt, blev sammenlignet med virkningerne af placebo (virkningsløs behandling).
The effects of CELSENTRI, taken once or twice a day, were compared with those of placebo (a dummy treatment).
Alle patienterne fik desuden "optimeret baggrundsbehandling" (en kombination af andre antivirale lægemidler mod hiv, der blev valgt, så den gav hver patient størst mulig chance for at få mindsket indholdet af hiv i blodet).
All of the patients also took ‘ optimised background therapy’ (a combination of other antiviral medicines chosen for each patient as it had the best chances of reducing the levels of HIV in the blood).
Behandlingens virkning blev hovedsagelig bedømt på ændringen af hiv - indholdet i blodet efter 24 uger.
The main measure of effectiveness was the reduction in the levels of HIV in the blood (viral load) after 24 weeks.
Hvilken fordel viser undersøgelserne, at der er ved CELSENTRI?
What benefit has CELSENTRI shown during the studies?
CELSENTRI var mere effektivt end placebo til at nedsætte virusindholdet, når det blev anvendt i kombination med optimeret baggrundsbehandling.
CELSENTRI was more effective than placebo in reducing viral loads, when taken in combination with optimised background therapy.
Sammenlagt viser resultaterne af de to undersøgelser, at virusindholdet efter 24 uger i gennemsnit var faldet med 99% hos de patienter, der fik CELSENTRI som tillægsbehandling til optimeret baggrundsbehandling.
Looking at the results of the two studies taken together, viral loads had fallen by an average of 99% after 24 weeks in the patients adding CELSENTRI to optimised background therapy, compared with 90% in those adding placebo.
Den tilsvarende andel var 23% hos de patienter, der kun fik optimeret baggrundsbehandling.
The proportion of patients who had undetectable levels of HIV in their blood was about 45% when CELSENTRI was added to optimised background therapy compared with 23% of the patients receiving optimised background therapy only.
Tilsvarende resultater sås hos de patienter, der fortsatte i 48 uger med CELSENTRI, 300 mg to gange dagligt.
Similar results were also observed when looking at the patients who continued treatment with CELSENTRI 300 mg twice a day for 48 weeks.
CELSENTRI virkede lige godt, uanset om det blev givet en eller to gange dagligt.
The once- and twice-daily doses of CELSENTRI were of similar effectiveness.
Dosering to gange dagligt var dog en smule mere effektiv hos patienter, der havde risiko for nedsat virkning af hiv - behandlingen enten på grund af højt virusindhold, lav grad af immunitet eller få behandlingsmuligheder.
However, the twice- daily dose was slightly more effective in patients who were at risk of a reduced response to HIV treatment, due to high viral load, low levels of immunity or few available treatment options.
Hvilken risiko er der forbundet med CELSENTRI?
What is the risk associated with CELSENTRI?
Den almindeligste bivirkning af CELSENTRI (som ses hos flere end 1 ud af 10 patienter) er kvalme.
The most common side effect with CELSENTRI (seen in more than 1 patient in 10) is nausea (feeling sick).
Den fuldstændige liste over de indberettede bivirkninger ved CELSENTRI fremgår af indlægssedlen.
For the full list of all side effects reported with CELSENTRI, see the Package Leaflet.
CELSENTRI bør ikke anvendes hos patienter, der kan være overfølsomme (allergiske) over for maraviroc, jordnødder, soja eller andre af indholdsstofferne.
CELSENTRI should not be used in patients who may be hypersensitive (allergic) to maraviroc, peanut, soya or any of the other ingredients.
Som med anden hiv- medicin kan patienter, der er i behandling med CELSENTRI, få immunreaktiveringssyndrom (infektionslignende symptomer, der skyldes, at immunsystemet genvinder sin funktion) eller osteonekrose (knoglevævsdød).
As with other anti-HIV medicines, patients taking CELSENTRI may be at risk of immune reactivation syndrome (symptoms of infection caused by the recovering immune system) or osteonecrosis (death of bone tissue).
Patienter med leverproblemer (herunder hepatitis B eller C) kan have forhøjet risiko for leverskade, når de får CELSENTRI.
Patients who have problems with their liver (including hepatitis B or C infection) may be at an elevated risk of liver damage when taking CELSENTRI.
Hvorfor blev CELSENTRI godkendt?
Why has CELSENTRI been approved?
Udvalget for Humanmedicinske Lægemidler (CHMP) fandt, at fordelene ved CELSENTRI opvejer risiciene, når det, i kombination med andre antiretrovirale lægemidler, anvendes til behandling af behandlingserfarne voksne patienter, hos hvem kun CCR5- tropisk hiv- 1 findes i målelige mængder.
The Committee for Medicinal Products for Human Use (CHMP) decided that CELSENTRI’ s benefits are greater than its risks, in combination with other antiretroviral medicinal products, for treatment- experienced adult patients infected with only CCR5-tropic HIV-1 detectable.
Udvalget anbefalede udstedelse af markedsføringstilladelse for CELSENTRI.
The Committee recommended that CELSENTRI be given marketing authorisation.
Andre oplysninger om CELSENTRI:
Other information about CELSENTRI:
Europa- Kommissionen udstedte en markedsføringstilladelse med gyldighed i hele Den Europæiske Union for CELSENTRI til Pfizer Limited den 18. september 2007.
The European Commission granted a marketing authorisation valid throughout the European Union for CELSENTRI to Pfizer Limited on 18 September 2007.
Den fuldstændige EPAR om CELSENTRI findes her.
The full EPAR for CELSENTRI can be found here.
EU- nummer EU/ 1/ 07/ 418/ 001 EU/ 1/ 07/ 418/ 002 EU/ 1/ 07/ 418/ 003 EU/ 1/ 07/ 418/ 004 EU/ 1/ 07/ 418/ 005 EU/ 1/ 07/ 418/ 006 EU/ 1/ 07/ 418/ 007 EU/ 1/ 07/ 418/ 008 EU/ 1/ 07/ 418/ 009 EU/ 1/ 07/ 418/ 010
EU/ 1/ 07/ 418/ 001 EU/ 1/ 07/ 418/ 002 EU/ 1/ 07/ 418/ 003 EU/ 1/ 07/ 418/ 004 EU/ 1/ 07/ 418/ 005 EU/ 1/ 07/ 418/ 006 EU/ 1/ 07/ 418/ 007 EU/ 1/ 07/ 418/ 008 EU/ 1/ 07/ 418/ 009 EU/ 1/ 07/ 418/ 010
Særnavn CELSENTRI CELSENTRI CELSENTRI CELSENTRI CELSENTRI CELSENTRI CELSENTRI CELSENTRI CELSENTRI CELSENTRI
CELSENTRI CELSENTRI CELSENTRI CELSENTRI CELSENTRI CELSENTRI CELSENTRI CELSENTRI CELSENTRI CELSENTRI
Styrke 150 mg 150 mg 150 mg 150 mg 150 mg 300 mg 300 mg 300 mg 300 mg 300 mg
150 mg 150 mg 150 mg 150 mg 150 mg 300 mg 300 mg 300 mg 300 mg 300 mg
Lægemiddelform Filmovetrukken tablet Filmovetrukken tablet Filmovetrukken tablet Filmovetrukken tablet Filmovetrukken tablet Filmovetrukken tablet Filmovetrukken tablet Filmovetrukken tablet Filmovetrukken tablet Filmovetrukken tablet
Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet
Indgivelsesvej Oral anvendelse Oral anvendelse Oral anvendelse Oral anvendelse Oral anvendelse Oral anvendelse Oral anvendelse Oral anvendelse Oral anvendelse Oral anvendelse
Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use
Emballage Beholder (HDPE/ alu) Blisterpakning (PVC/ alu) Blisterpakning (PVC/ alu) Blisterpakning (PVC/ alu) Blisterpakning (PVC/ alu) Beholder (HDPE/ alu) Blisterpakning (PVC/ alu) Blisterpakning (PVC/ alu) Blisterpakning (PVC/ alu) Blisterpakning (PVC/ alu)
Bottle (HDPE/ alu) Blister (PVC/ alu) Blister (PVC/ alu) Blister (PVC/ alu) Blister (PVC/ alu) Bottle (HDPE/ alu) Blister (PVC/ alu) Blister (PVC/ alu) Blister (PVC/ alu) Blister (PVC/ alu)
Pakningsstørrelser 180 tabletter 30 tabletter 60 tabletter 90 tabletter 180 (2x90) tabletter 180 tabletter 30 tabletter 60 tabletter 90 tabletter 180 (2x90) tabletter
180 tablets 30 tablets 60 tablets 90 tablets 180 (2x90) tablets 180 tablets 30 tablets 60 tablets 90 tablets 180 (2x90) tablets
CELSENTRI 150 mg filmovertrukne tabletter.
CELSENTRI 150 mg film-coated tablets.
Hver tablet indeholder 150 mg maraviroc.
Each film-coated tablet contains 150 mg of maraviroc.
Hver 150 mg filmovertrukken tablet indeholder 0, 84 mg sojalechitin.
Excipients Each 150 mg film-coated tablet contains 0.84 mg of soya lecithin.
Blå, bikonvekse, ovale filmovertrukne tabletter, der er præget med ” Pfizer ” på den ene side og ” MVC 150 ” på den anden side.
Blue, biconvex, oval film-coated tablets debossed with “ Pfizer” on one side and “ MVC 150” on the other.
4. 2)
CELSENTRI, in combination with other antiretroviral medicinal products, is indicated for treatment- experienced adult patients infected with only CCR5-tropic HIV-1 detectable (see section 4.2).
5. 1).
This indication is based on safety and efficacy data from two double-blind, placebo-controlled trials in treatment-experienced patients (see section 5.1).
Behandling skal initieres af en læge med erfaring i behandling af HIV- infektion.
Therapy should be initiated by a physician experienced in the management of HIV infection.
Før CELSENTRI anvendes, skal det være bekræftet, at patienterne er smittet kun med HIV- 1- virus med verificeret CCR5- tropisme (dvs.
Before taking CELSENTRI it has to be confirmed that only CCR5-tropic HIV-1 is detectable (i. e.
Der skal bruges en egnet, valideret detektionsmetode på en nylig taget blodprøve.
CXCR4 or dual/ mixed tropic virus not detected) using an adequately validated and sensitive detection method on a newly drawn blood sample.
4. 4 og 5. 1).
The Monogram Trofile assay was used in the clinical studies of CELSENTRI (see sections 4.4 and 5.1).
Andre fænotype - og genotypetests er ved at blive vurderet.
Other phenotypic and genotypic assays are currently being evaluated.
På nuværende tidspunkt er der ikke dokumentation vedrørende genanvendelse af CELSENTRI til patienter, der i øjeblikket er smittet kun med HIV- 1 virus med CCR5- tropisme, men i anamnesen har haft manglende effekt af CELSENTRI (eller andre CCR5- antagonister) med en CXCR4 eller dual/ mixed tropisme.
There are currently no data regarding the reuse of CELSENTRI in patients that currently have only CCR5-tropic HIV-1 detectable, but have a history of failure on CELSENTRI (or other CCR5 antagonists) with a CXCR4 or dual/ mixed tropic virus.
Der er ikke dokumentation vedrørende skift fra et antiretroviralt produkt i en anden klasse til CELSENTRI hos virologisk supprimerede patienter.
There are no data regarding the switch from a medicinal product of a different antiretroviral class to CELSENTRI in virologically suppressed patients.
4. 5).
Adults: the recommended dose of CELSENTRI is 150 mg, 300 mg or 600 mg twice daily depending on interactions with co-administered antiretroviral therapy and other medicinal products (see Table 2 in Section 4.5).
CELSENTRI kan tages med eller uden føde.
CELSENTRI can be taken with or without food.
2 Børn:
Children:
5. 2).
CELSENTRI is not recommended for use in children due to lack of data on safety, efficacy and pharmacokinetics (see section 5.2).
Derfor bør CELSENTRI gives med forsigtighed til denne patientgruppe.
2 Elderly: there is limited experience in patients > 65 years of age (see section 5.2), therefore CELSENTRI should be used with caution in this population.
Dosisjustering er kun nødvendig ved behandling af patienter med nedsat nyrefunktion, der får potente CYP3A4- hæmmere, såsom: • proteasehæmmere (undtagen tipranavir/ ritonavir) • ketokonazol, itraconazol, clarithromycin, telithromycin.
Renal impairment: dosage adjustment is only recommended in patients with renal impairment who are receiving potent CYP3A4 inhibitors such as: • protease inhibitors (except tipranavir/ ritonavir) • ketoconazole, itraconazole, clarithromycin, telithromycin.
4. 4 og 5. 2).
CELSENTRI should be used with caution in patients with renal impairment (CLcr < 80ml/ min) who are taking potent CYP3A4 inhibitors (see sections 4.4 and 5.2).
Tabel 1 nedenfor viser retningslinjer for justering af dosisinterval baseret på simulering af stigende nedsat nyrefunktion hos patienter, der samtidigt får potente CYP3A4- hæmmere.
Table 1 below provides dose interval adjustment guidelines based on simulations of increasing renal impairment in patients being coadministered potent CYP3A4 inhibitors.
Sikkerhed og effekt af disse justeringer af dosisinterval er ikke klinisk vurderet.
The safety and efficacy of these dose interval adjustments have not been clinically evaluated.
Behandlingsrespons bør derfor følges tæt hos disse patienter.
Therefore, clinical response to treatment should be closely monitored in these patients.
4. 5 tabel 2) Anbefalet CELSENTRI dosisinterval
Dose interval adjustments based on simulations of increasing renal impairment (for dose recommendations, see Section 4.5 Table 2) Recommended CELSENTRI dose interval
Kreatininclearance (CLcr) (ml/ min)
Creatinine clearance (CLcr) (ml/ min)
50- 80 ml/ min
50- 80 ml/ min
< 50- 30 ml/ min
< 50 – 30 ml/ min
tipranavir/ ritonavir Ved samtidig administration med potente
Without potent CYP3A4 inhibitors or co- administered with tipranavir/ ritonavir If coadministered with potent CYP3A4
Justering af dosisinterval er ikke nødvendigt
No dose interval adjustment required
4. 5)
inhibitors, e. g. lopinavir/ ritonavir, darunavir/ ritonavir, atazanavir/ ritonavir, ketoconazole (see also section 4.5)
Hver 24. time
If coadministered with saquinavir/ ritonavir Every 24 hours
Hver 72. time
Every 72 hours
4. 4 og 5. 2).
Hepatic impairment: limited data are available in patients with hepatic impairment, therefore CELSENTRI should be used with caution in this population (see sections 4.4 and 5.2).
Overfølsomhed over for det aktive stof, jordnødder, soja eller over for et eller flere af hjælpestofferne.
Hypersensitivity to the active substance or to peanut or soya or to any of the excipients.
CELSENTRI bør tages som en del af en antiretroviral kombinationsbehandling.
CELSENTRI should be taken as part of an antiretroviral combination regimen.
5. 1).
CELSENTRI should optimally be combined with other antiretrovirals to which the patient's virus is sensitive (see section 5.1).
CELSENTRI bør kun anvendes hos patienter smittet kun med HIV- 1- virus med verificeret CCR5 - tropisme (dvs.
CELSENTRI should only be used when only CCR5-tropic HIV-1 is detectable (i. e.
4. 1, 4. 2 og 5. 1).
CXCR4 or dual/ mixed tropic virus not detected) as determined by an adequately validated and sensitive detection method (see sections 4.1, 4.2 and 5.1).
Monogram Trofile- assay blev benyttet i de kliniske forsøg med CELSENTRI.
The Monogram Trofile assay was used in the clinical studies of CELSENTRI.
Ændringer i viral tropisme sker over tid hos HIV- 1- smittede patienter.
Changes in viral tropism occur over time in HIV-1 infected patients.
3 Baggrundsresistens over for andre klasser af antiretrovirale produkter har vist sig at være den samme hos tidligere ikke påvist CXCR4- tropisme virus hos den lave viralpopulation, som det, der blev fundet i CCR5- tropisme virus.
Background resistance to other classes of antiretrovirals have been shown to be similar in previously undetected CXCR4-tropic virus of the minor viral population, as that found in CCR5-tropic virus.
Lægen skal sikre den nødvendige dosisjustering af CELSENTRI, når det anvendes sammen med CYP3A4- hæmmere og/ eller - induktorer, da maravirockoncentrationer og den terapeutiske effekt kan påvirkes (se pkt.
Dose adjustment: physicians should ensure that appropriate dose adjustment of CELSENTRI is made when CELSENTRI is co-administered with CYP3A4 inhibitors and/ or inducers since maraviroc concentrations and its therapeutic effects may be affected (see sections 4.2 and 4.5).
Der henvises til produktresuméerne for de antiretrovirale lægemidler, der anvendes i kombinationen.
Please also refer to the respective Summary of Product Characteristics of the other antiretroviral medicinal products used in the combination.
Patienter skal informeres om, at antiretrovirale lægemidler, herunder CELSENTRI, ikke forebygger risikoen for at overføre HIV til andre gennem seksuel kontakt eller blodkontaminering.
3 Information for patients: patients should be advised that antiretroviral therapies including CELSENTRI have not been shown to prevent the risk of transmission of HIV to others through sexual contact or contamination with blood.
De skal fortsætte med at udvise passende forsigtighed.
They should continue to use appropriate precautions.
Patienter skal også informeres om, at CELSENTRI ikke kan helbrede en HIV- 1- infektion.
Patients should also be informed that CELSENTRI is not a cure for HIV-1 infection.
I forsøg med raske frivillige forsøgspersoner, der blev behandlet med CELSENTRI i doser, der var højere end den anbefalede dosis, er tilfælde af symptomatisk ortostatisk hypotension set hyppigere end for placebo.
Postural hypotension: when CELSENTRI was administered in studies with healthy volunteers at doses higher than the recommended dose, cases of symptomatic postural hypotension were seen at a greater frequency than with placebo.
0, 5%).
However, when CELSENTRI was given at the recommended dose in HIV infected patients in Phase 3 studies, postural hypotension was seen at a similar rate compared to placebo (approximately 0.5%).
Forsigtighed tilrådes, når CELSENTRI anvendes hos patienter, der tidligere har haft ortostatisk hypotension, eller hvis de samtidigt anvender medicin, der nedsætter blodtrykket.
Caution should be used when administering CELSENTRI in patients with a history of postural hypotension or on concomitant medicinal products known to lower blood pressure.
Mulig virkning på immunitet:
Potential effect on immunity:
CCR5- antagonister kan muligvis nedsætte immunrespons ved visse infektioner.
CCR5 antagonists could potentially impair the immune response to certain infections.
Dette bør tages i betragtning, når der behandles infektioner som f. eks. aktiv tuberkulose og invasive svampeinfektioner.
This should be taken into consideration when treating infections such as active tuberculosis and invasive fungal infections.
I pivotale studier var hyppigheden af AIDS- definerede infektioner den samme for CELSENTRI og placebo.
The incidence of AIDS-defining infections was similar between CELSENTRI and placebo arms in the pivotal studies.
Der bør udvises forsigtighed, når disse patienter behandles med CELSENTRI.
Cardiovascular safety: limited data exist with the use of CELSENTRI in patients with severe cardiovascular disease, therefore special caution should be exercised when treating these patients with CELSENTRI.
Ved initiering af antiretroviral kombinationsbehandling (CART) hos HIV- inficerede patienter med svær immuninsufficiens kan der opstå en inflammatorisk reaktion på asymptomatiske eller residuale opportunistiske patogener, som kan forårsage alvorlige kliniske tilstande eller forværring af symptomer.
Immune reconstitution syndrome: in HIV infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms.
Relevante eksempler er cytomegalovirus retinitis, generaliserede og/ eller fokale mycobakterielle infektioner og pneumoni forårsaget af pneumocystis jiroveci (tidligere kendt som pneumocystis carinii).
Relevant examples are cytomegalovirus retinitis, generalised and/ or focal mycobacterial infections, and pneumonia caused by Pneumocystis jiroveci (formerly known as Pneumocystis carinii).
Alle inflammatoriske symptomer bør vurderes, og behandling påbegyndes efter behov.
Any inflammatory symptoms should be evaluated and treatment initiated when necessary.
Der er rapporteret om tilfælde af osteonekrose især hos patienter, der har fremskreden HIV- sygdom og/ eller hos patienter, som befinder sig i langvarig kombinationsbehandling med antiretrovirale lægemidler (CART).
Osteonecrosis: although the etiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV-disease and/ or long-term exposure to combination antiretroviral therapy (CART).
Sikkerhed og effekt af behandling med CELSENTRI hos patienter med alvorligt tilgrundliggende leversygdom er ikke undersøgt specifikt.
Hepatic safety: the safety and efficacy of CELSENTRI have not been specifically studied in patients with significant underlying liver disorders.
I et forsøg med raske frivillige forsøgspersoner er der rapporteret et tilfælde af mulig allergilignende levertoksicitet induceret af CELSENTRI.
A case of possible CELSENTRI-induced hepatotoxicity with allergic features has been reported in a study in healthy volunteers.
Der var dog ikke en samlet stigning i ACTG- grad 3- 4 abnormiteter af leverfunktionsprøverne (se pkt.
In addition, an increase in hepatic adverse reactions with CELSENTRI was observed during studies of treatment-experienced subjects with HIV infection, although there was no overall increase in ACTG Grade 3/ 4 liver function test abnormalities (see section 4.8).
Disse patienter bør monitoreres i henhold til gældende standardpraksis.
Patients with pre-existing liver dysfunction, including chronic active hepatitis, can have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice.
4 Seponering af behandling bør overvejes hos patienter, der viser tegn og symptomer på akut hepatitis, især ved mistænkt lægemiddelrelateret overfølsomhed eller ved stigning i levertransaminaserne kombineret med udslæt eller systemiske symptomer på mulig overfølsomhed (f. eks. kløende udslæt, eosinofili eller stigning i IgE).
Discontinuation of CELSENTRI should be considered in any patient with signs or symptoms of acute hepatitis, in particular if drug-related hypersensitivity is suspected or with increased liver transaminases combined with rash or other systemic symptoms of potential hypersensitivity (e. g. pruritic rash, eosinophila or elevated IgE).
Der bør udvises forsigtighed hos patienter med samtidig infektion med hepatitis B/ C pga. utilstrækkelig dokumentation ved behandling med CELSENTRI.
Since there are very limited data in patients with hepatitis B/ C co-infection, special caution should be exercised when treating these patients with CELSENTRI.
I tilfælde, hvor patienten tillige er i antiviralbehandling for hepatitis B og/ eller C, henvises til produktresuméerne for de relevante produkter.
In case of concomitant antiviral therapy for hepatitis B and/ or C, please refer also to the relevant product information for these medicinal products.
4. 2 og 5. 2).
4 There is limited experience in patients with reduced hepatic function, therefore CELSENTRI should be used with caution in this population (see sections 4.2 and 5.2).