natgillin/translations-raw huggingface dataset:
Mens den generelle risiko for nedsat nyrefunktion hos patienter med adækvat nyrefunktion er lav, er det af særlig betydning for patienter, som er udsat for risiko for eller har latent dysfunktion af nyrerne, og hos patienter, der tager lægemidler, som kan påvirke nyrefunktionen.
3 overall risk of renal impairment in patients with adequate renal function is low, this is of special importance in patients at risk of, or having underlying renal dysfunction and in patients receiving medicinal products that may affect renal function.
Det anbefales at beregne kreatininclearance for alle patienter, før behandlingen med adefovirdipivoxil påbegyndes.
It is recommended that creatinine clearance is calculated in all patients prior to initiating therapy with adefovir dipivoxil.
Patienter med normal nyrefunktion:
Patients with normal renal function:
Patienter med normal nyrefunktion bør overvåges for ændringer i serumkreatinin hver 3. måned, og deres kreatininclearance bør beregnes.
Patients with normal renal function should be monitored for changes in serum creatinine every 3 months and creatinine clearance calculated.
4. 8) med hyppigere mellemrum.
In patients at risk of renal impairment (see section 4.8), consideration should be given to more frequent monitoring of renal function.
4. 2).
The dosing interval of adefovir dipivoxil should be adjusted in these patients (see section 4.2).
Desuden skal nyrefunktionen overvåges nøje med en hyppighed, som skal tilpasses efter den individuelle patients medicinske tilstand.
In addition, renal function should be closely monitored with a frequency tailored to the individual patient’ s medical condition.
Adefovirdipivoxil anbefales ikke til patienter med en kreatininclearance på < 30 ml/ min. eller til patienter, som er i dialyse.
Adefovir dipivoxil is not recommended in patients with a creatinine clearance of < 30 ml/ min or on dialysis.
4. 2).
If treatment with adefovir dipivoxil is considered essential, then the dosing interval should be adjusted (see section 4.2).
Det tilrådes, at der udvises forsigtighed hos patienter som får andre lægemidler, der kan påvirke nyrefunktionen, eller som udskilles gennem nyrerne (f. eks. ciclosporin og tacrolimus, intravenøse aminoglykosider, amphotericin B, foscarnet, pentamidin, vancomycin, eller lægemidler, som udskilles renalt via human Organic Anion Transporter 1 (hOAT1), som f. eks. cidofovir).
Caution is advised in patients receiving other medicinal products that may affect renal function or are excreted renally (e. g. cyclosporin and tacrolimus, intravenous aminoglycosides, amphotericin B, foscarnet, pentamidine, vancomycin, or medicinal products which are secreted by the same renal transporter, human Organic Anion Transporter 1 (hOAT1), such as cidofovir).
Nyrefunktionen hos disse patienter bør overvåges nøje med en hyppighed, som skal tilpasses efter den individuelle patients medicinske tilstand.
The renal function of these patients should be closely monitored with a frequency tailored to the individual patient’ s medical condition.
4. 8.
For renal safety in patients pre- and post-transplantation with lamivudine-resistant HBV, see section 4.8.
Leverfunktion:
Hepatic function:
Spontane eksacerbationer af kronisk hepatitis B er forholdsvis almindelige og er kendetegnet ved kortvarige stigninger i serum- ALAT.
Spontaneous exacerbations in chronic hepatitis B are relatively common and are characterised by transient increases in serum ALT.
Efter opstart af antiviral terapi kan serum- ALAT stige hos nogle patienter, sideløbende med at serum- HBV- DNA- niveauer falder.
After initiating antiviral therapy, serum ALT may increase in some patients as serum HBV DNA levels decline.
4. 8).
In patients with compensated liver disease, these increases in serum ALT are generally not accompanied by an increase in serum bilirubin concentrations or hepatic decompensation (see section 4.8).
Patienter med fremskreden leversygdom eller cirrose kan være udsat for en højere risiko for leverdekompensation efter hepatitis- eksacerbation, hvilket kan være fatalt.
Patients with advanced liver disease or cirrhosis may be at a higher risk for hepatic decompensation following hepatitis exacerbation which may be fatal.
4 Se ovenfor under Nyrefunktion, hvis disse patienter udvikler nyreinsufficiens.
In the event of these patients developing renal insufficiency, see above Renal function.
Hvis det er nødvendigt at ophøre med behandlingen, bør patienter overvåges nøje i flere måneder efter behandlingens ophør, da eksacerbationer af hepatitis er sket efter seponering af 10 mg adefovirdipivoxil.
If treatment cessation is necessary, patients should be closely monitored for several months after stopping treatment as exacerbations of hepatitis have occurred after discontinuation of 10 mg adefovir
Disse eksacerbationer optrådte uden HBeAg- serokonversion og viste sig som forhøjede serum- ALAT- niveauer og stigninger i serum- HBV- DNA.
These exacerbations occurred in the absence of HBeAg seroconversion and presented as serum ALT elevations and increases in serum HBV DNA.
Stigninger i serum- ALAT, der optrådte hos patienter med kompenseret leverfunktion behandlet med 10 mg adefovirdipivoxil, var ikke ledsaget af kliniske og laboratoriebaserede ændringer forbundet med leverdekompensation.
Elevations in serum ALT that occurred in patients with compensated liver function treated with 10 mg adefovir dipivoxil were not accompanied by clinical and laboratory changes associated with liver decompensation.
De fleste post- behandlingseksacerbationer af hepatitis er blevet set inden for 12 uger efter seponering af 10 mg adefovirdipivoxil.
Most post-treatment exacerbations of hepatitis were seen within 12 weeks of discontinuation of 10 mg adefovir dipivoxil.
Lactacidosis og alvorlig hepatomegalia med steatosis:
Lactic acidosis and severe hepatomegaly with steatosis:
Disse tilfælde af lactacidosis er undertiden fatal.
Occurrences of lactic acidosis (in the absence of hypoxaemia), sometimes fatal, usually associated with severe hepatomegaly and hepatic steatosis, have been reported with the use of nucleoside analogues.
Da adefovir strukturelt er relateret til nucleosidanaloger, kan denne risiko ikke udelukkes.
As adefovir is structurally related to nucleoside analogues, this risk cannot be excluded.
Behandling med nucleosidanaloger bør seponeres, når hurtigt stigende aminotransferaseniveauer, progressiv hepatomegali eller metabolisk acidosis/ lactacidosis af ukendt ætiologi indtræder.
Treatment with nucleoside analogues should be discontinued when rapidly elevating aminotransferase levels, progressive hepatomegaly or metabolic/ lactic acidosis of unknown aetiology occur.
Godartede fordøjelsessymptomer, som f. eks. kvalme, opkastning og mavepine, kan være tegn på udviklingen af lactacidosis.
Benign digestive symptoms, such as nausea, vomiting and abdominal pain, might be indicative of lactic acidosis development.
Alvorlige tilfælde, undertiden med dødeligt udfald, blev forbundet med pancreatitis, leversvigt/ steatosis hepatis, nyresvigt og højere niveauer af serumlactat.
Severe cases, sometimes with fatal outcome, were associated with pancreatitis, liver failure/ hepatic steatosis, renal failure and higher levels of serum lactate.
Der bør udvises forsigtighed, når der ordineres nucleosidanaloger til en patient (især overvægtige kvinder) med hepatomegali, hepatitis eller andre kendte risikofaktorer for leversygdom.
Caution should be exercised when prescribing nucleoside analogues to any patient (particularly obese women) with hepatomegaly, hepatitis or other known risk factors for liver disease.
Samtidig infektion med hepatitis C eller D:
Co-infection with hepatitis C or D:
Der foreligger ingen data om virkningen af adefovirdipivoxil hos patienter, der samtidig er inficerede med hepatitis C eller hepatitis D.
There are no data on the efficacy of adefovir dipivoxil in patients co-infected with hepatitis C or hepatitis D.
Samtidig infektion med HIV:
Co-infection with HIV:
Hos patienter med kronisk hepatitis B samt infektion med HIV foreligger der kun begrænsede data om sikkerheden og virkningen af 10 mg adefovirdipivoxil.
Limited data are available on the safety and efficacy of 10 mg adefovir dipivoxil in patients with chronic hepatitis B, co-infected with HIV.
Til dato findes der ingen beviser på, at daglig dosering med 10 mg adefovirdipivoxil resulterer i fremkomsten af adefovirforbundne resistensmutationer i HIV- revers transkriptase.
To date there is no evidence that daily dosing with 10 mg adefovir dipivoxil results in emergence of adefovir-associated resistance mutations in the HIV reverse transcriptase.
Ikke desto mindre er der en potentiel risiko for at vælge HIV- stammer, som er resistente over for adefovir med mulig krydsresistens over for andre antivirale lægemidler.
Nonetheless, there is a potential risk of selection of HIV strains resistant to adefovir with possible cross-resistance to other antiviral medicinal products.
Så vidt muligt bør behandlingen af hepatitis B med adefovirdipivoxil hos en patient, som samtidig er inficeret med HIV, forbeholdes patienter, hvis HIV- RNA er under kontrol.
As far as possible, treatment of hepatitis B by adefovir dipivoxil in an HIV co-infected patient should be reserved for patients whose HIV RNA is controlled.
Behandling med 10 mg adefovirdipivoxil har ikke vist sig at være effektiv mod HIV- replikation og bør derfor ikke anvendes til at behandle HIV- infektion.
Treatment with 10 mg adefovir dipivoxil has not been shown to be effective against HIV replication and therefore should not be used to control HIV infection.
Den kliniske erfaring med patienter > 65 år er meget begrænset.
The clinical experience in patients > 65 years of age is very limited.
Ved ordinering af adefovirdipivoxil til ældre bør der udvises forsigtighed, idet man bør være opmærksom på den højere hyppighed af nedsat nyre - eller hjertefunktion hos disse patienter, samt øgning i følgesygdomme eller samtidig brug af andre lægemidler hos ældre.
Caution should be exercised when prescribing adefovir dipivoxil to the elderly, keeping in mind the greater frequency of decreased renal or cardiac function in these patients, and the increase in concomitant diseases or concomitant use of other medicinal products in the elderly.
Dette kan, i tilfælde af reduceret leverfunktion, føre til leverdekompensation med risiko for dødeligt udfald.
Resistance to adefovir dipivoxil (see section 5.1) can result in viral load rebound which may result in exacerbation of hepatitis B and, in the setting of diminished hepatic function, lead to liver decompensation and possible fatal outcome.
Hos patienter, som behandles med adefovirdipivoxil, bør den virologiske respons overvåges nøje med måling af HBV- DNA hver 3. måned.
Virological response should be closely monitored in patients treated with adefovir dipivoxil, with HBV DNA measured every 3 months.
Patienter skal underrettes om, at det ikke er påvist, at behandling med adefovirdipivoxil reducerer risikoen for at smitte andre med hepatitis B virus, og at der derfor fortsat skal anvendes hensigtsmæssige forsigtighedsregler.
Patients should be advised that therapy with adefovir dipivoxil has not been proven to reduce the risk of transmission of hepatitis B virus to others and therefore appropriate precautions should still be taken.
5 Hepsera indeholder lactosemonohydrat.
Hepsera contains lactose monohydrate.
Bør ikke anvendes til patienter med arvelig galactoseintolerans, en særlig form af hereditær lactasemangel (Lapp Lactase deficiency), eller glucose/ galactosemalabsorption.
Consequently, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.
Potentialet for CYP450- medierede interaktioner, hvor adefovir er involveret sammen med andre lægemidler, er lav, baseret på resultaterne af in vitro- forsøg, hvor adefovir ikke havde nogen indflydelse på de almindelige CYP- isoformer, som vides at være involveret i human lægemiddelstofskifte, og baseret på adefovirs kendte eliminationsvej.
The potential for CYP450 mediated interactions involving adefovir with other medicinal products is low, based on the results of in vitro experiments in which adefovir did not influence any of the common CYP isoforms known to be involved in human drug metabolism and based on the known elimination pathway of adefovir.
En klinisk undersøgelse hos levertransplanterede patienter har vist, at der ikke forekommer nogen farmakokinetisk interaktion, når adefovirdipivoxil 10 mg én gang daglig indgives samtidig med tacrolimus, som er et immunsuppressivt middel, der hovedsagelig metaboliseres via CYP450- systemet.
A clinical study in liver-transplant patients has shown that no pharmacokinetic interaction occurs when adefovir dipivoxil 10 mg once daily is administered concomitantly with tacrolimus, an immunosuppressant which is predominantly metabolised via the CYP450 system.
4. 4).
Nevertheless, given that tacrolimus and cyclosporin can affect renal function, close monitoring is recommended when either of these agents is coadministered with adefovir dipivoxil (see section 4.4).
4. 4).
Co-administration of 10 mg adefovir dipivoxil with other medicinal products that are eliminated by tubular secretion or alter tubular function may increase serum concentrations of either adefovir or the co-administered medicinal product (see section 4.4).
Der foreligger ingen data om samtidig anvendelse med andre lægemidler (herunder interferon).
No data on the concomitant use with other medicinal products (including interferon) are available.
Der foreligger ikke tilstrækkelige data om brugen af adefovirdipivoxil hos gravide kvinder.
There are no adequate data on the use of adefovir dipivoxil in pregnant women.
5. 3).
Studies in animals administered adefovir intravenously have shown reproductive toxicity (see section 5.3).
Forsøg med peroralt doserede dyr har ikke påvist teratogene eller fostertoksiske virkninger.
Studies in orally dosed animals do not indicate teratogenic or foetotoxic effects.
I betragtning af at de potentielle risici for menneskefostre under udvikling er ukendte, anbefales det, at kvinder i den fødedygtige alder, som behandles med adefovirdipivoxil, anvender effektiv antikonception.
Given that the potential risks to developing human foetuses are unknown, it is recommended that women of child-bearing potential treated with adefovir dipivoxil use effective contraception.
Det vides ikke, om adefovir udskilles i human modermælk.
It is not known whether adefovir is excreted in human milk.
Mødre bør oplyses om, at de ikke bør amme, hvis de tager adefovirdipivoxil tabletter.
Mothers should be instructed not to breast-feed if they are taking adefovir dipivoxil tablets.
Hos patienter med kompenseret leversygdom, var de hyppigst rapporterede uønskede reaktioner i løbet af 48 uger med adefovirdipivoxilbehandling asteni (13%), hovedpine (9%), mavepine (9%) og kvalme (5%).
In patients with compensated liver disease, the most frequently reported adverse reactions during 48 weeks of adefovir dipivoxil therapy were asthenia (13%), headache (9%), abdominal pain (9%) and nausea (5%).
Vurderingen af uønskede reaktioner er baseret på erfaring fra overvågningen efter markedsføring og fra tre pivotale kliniske undersøgelser hos patienter med kronisk hepatitis B:
6 Assessment of adverse reactions is based on experience from post-marketing surveillance and from three pivotal clinical studies in patients with chronic hepatitis B:
51 og 99 uger).
• two placebo-controlled studies in which 522 patients with chronic hepatitis B and compensated liver disease received double-blind treatment with 10 mg adefovir dipivoxil (n=294) or placebo (n=228) for 48 weeks. • an open-label study in which pre- (n=226) and post-liver transplantation patients (n=241) with lamivudine-resistant HBV were treated with 10 mg adefovir dipivoxil once daily, for up to 203 weeks (median 51 and 99 weeks, respectively).
Inden for hver enkelt frekvensgruppe skal bivirkningerne opstilles efter, hvor alvorlige de er.
The adverse reactions considered at least possibly related to treatment are listed below, by body system organ class, and frequency.
Hyppigheder er defineret som meget almindelige (≥ 1/ 10), almindelige (≥ 1/ 100, < 1/ 10) eller ikke kendt (identificeret fra sikkerhedsovervågning efter markedsføring og frekvensen kan ikke estimeres ud fra forhåndenværende data).
Frequencies are defined as very common (≥ 1/ 10), common (≥ 1/ 100, < 1/ 10) or not known (identified through post-marketing safety surveillance and the frequency cannot be estimated from the available data).
Almindelige (≥ 1/ 100, < 1/ 10): hovedpine.
Common (≥ 1/ 100, < 1/ 10): headache.
Almindelige (≥ 1/ 100, < 1/ 10): diarré, opkastning, mavepine, dyspepsi, kvalme, flatulens.
Common (≥ 1/ 100, < 1/ 10): diarrhoea, vomiting, abdominal pain, dyspepsia, nausea, flatulence.
Hyppighed ikke kendt: pancreatitis.
Frequency not known: pancreatitis.
Almindelige (≥ 1/ 100, < 1/ 10): udslæt, pruritus.
Common (≥ 1/ 100, < 1/ 10): rash, pruritus.
Hyppighed ikke kendt: myopati, osteomalaci (begge forbundet med proksimal renal tubulopati).
Frequency not known: myopathy, osteomalacia (both associated with proximal renal tubulopathy).
Meget almindelige (≥ 1/ 10): stigninger i kreatinin.
Very common (≥ 1/ 10): increases in creatinine.
Almindelige (≥ 1/ 100, < 1/ 10): nyresvigt, unormal nyrefunktion, hypofosfatæmi.
Common (≥ 1/ 100, < 1/ 10): renal failure, abnormal renal function, hypophosphatemia.
Fanconis syndrom, proksimal renal tubulopati.
Fanconi syndrome, proximal renal tubulopathy.
Meget almindelige (≥ 1/ 10): asteni.
Very common (≥ 1/ 10): asthenia.
4. 4).
Clinical and laboratory evidence of exacerbations of hepatitis have occurred after discontinuation of treatment with 10 mg adefovir dipivoxil (see section 4.4).
I en langvarig sikkerhedsundersøgelse med 125 HBeAg- negative patienter med kompenseret leversygdom, var den overordnede profil af uønskede hændelser uændret efter en median eksponering på 226 uger.
In a long-term safety study of 125 HBeAg negative patients with compensated liver disease, the adverse event profile was overall unchanged after a median exposure of 226 weeks.
3%, 4% og 6% af patienterne, som fik forlænget behandling.
However, mild to moderate increases in serum creatinine concentrations, hypophosphatemia and a decrease in carnitine concentrations were reported in 3%, 4% and 6% of patients, respectively, on extended treatment.
7 I en langvarig sikkerhedsundersøgelse af 65 HBeAg- positive patienter med kompenseret leversygdom (efter en median eksponering på 234 uger) var der 6 (9%) patienter, der havde bekræftede stigninger i serumkreatinin på mindst 0, 5 mg/ dl, sammenlignet med baseline, og 2 patienter ophørte med at deltage i undersøgelsen på grund af den forhøjede serumkreatinin- koncentration.
In a long-term safety study of 65 HBeAg positive patients with compensated liver disease (after a median exposure of 234 weeks), 6 patients (9%) had confirmed increases in serum creatinine of at least 0.5 mg/ dl from baseline with 2 patients discontinuing from the study due to the elevated serum creatinine concentration.
Patienter med en bekræftet stigning i kreatinin på ≥ 0, 3 mg/ dl ved uge 48 havde en statistisk signifikant højere risiko for en efterfølgende bekræftet stigning i kreatinin på ≥ 0, 5 mg/ dl.
Patients with a confirmed increase in creatinine of ≥ 0.3 mg/ dl by week 48 were at a statistically significant higher risk of a subsequent confirmed increase in creatinine of ≥ 0.5 mg/ dl.
Der blev rapporteret henholdsvis hypofosfatæmi og fald i carnitinkoncentrationer hos 3% af de patienter, som fik forlænget behandling.
Hypophosphatemia and a decrease in carnitine concentrations were reported each in 3% of patients on extended treatment.
Sikkerhed hos patienter med dekompenseret sygdom:
7 Safety in patients with decompensated disease:
Hos patienter med dekompenseret leversygdom, var de hyppigst rapportede uønskede reaktioner i løbet af op til 203 uger med adefovirdipivoxilbehandling forhøjet kreatinin (7%) og asteni (5%).
In patients with decompensated liver disease, the most frequently reported adverse reactions during up to 203 weeks of adefovir dipivoxil therapy were increased creatinine (7%) and asthenia (5%).
I kliniske undersøgelser af patienter på venteliste og post - levertransplanterede patienter, blev behandlingen med adefovirdipivoxil seponeret hos 4% (19/ 467) af patienterne på grund af uønskede hændelser i nyrerne.
In clinical studies of wait-listed and post-liver transplantation patients, four percent (19/ 467) of patients discontinued treatment with adefovir dipivoxil due to renal adverse events.
Adefovir kan fjernes ved hæmodialyse; median hæmodialyse- clearance af adefovir er 104 ml/ min.
Adefovir can be removed by haemodialysis; the median haemodialysis clearance of adefovir is 104 ml/ min.
Nukleosid - og nukleotidreverse- transkriptase- hæmmere, ATC - kode:
Nucleoside and nucleotide reverse transcriptase inhibitors, ATC code:
Adefovirdipivoxil er et peroralt prodrug af adefovir, en acyklisk nucleotidphosphonatanalog af adenosinmonophosphat, som aktivt transporteres ind i mammaliaceller, hvor det af værtsenzymer omdannes til adefovirdiphosphat.
Adefovir dipivoxil is an oral prodrug of adefovir, an acyclic nucleotide phosphonate analogue of adenosine monophosphate, which is actively transported into mammalian cells where it is converted by host enzymes to adefovir diphosphate.
Adefovirdiphosphat hæmmer virale polymeraser ved at konkurrere med det naturlige substrat (deoxyadenosintriphosphat) om den direkte binding, og udløser (efter indføjelse i viral DNA) DNA- kædeterminering.
Adefovir diphosphate inhibits viral polymerases by competing for direct binding with the natural substrate (deoxyadenosine triphosphate) and, after incorporation into viral DNA, causes DNA chain termination.
Adefovirdiphosphat hæmmer selektivt HBV- DNA - polymeraser ved koncentrationer, som er 12, 700 og 10 gange lavere end dem, som er nødvendige for at hæmme humane DNA- polymeraser, hhv. α, β og γ.
Adefovir diphosphate selectively inhibits HBV DNA polymerases at concentrations 12-, 700-, and 10-fold lower than those needed to inhibit human DNA polymerases α, β, and γ, respectively.
Adefovir er aktiv mod hepadnavirus in vitro, herunder alle almindelige former for lamivudin- resistent HBV (rtL180M, rtM204I, rtM204V, rtL180M/ rtM204V), famciclovirforbundne mutationer (rtV173L, rtP177L, rtL180M, rtT184S eller rtV207I) og hepatitis B immunoglobulin kvitterede mutationer (rtT128N og rtW153Q) samt i in vivo- dyremodeller af hepadnavirusreplikation.
Adefovir is active against hepadnaviruses in vitro, including all common forms of lamivudine-resistant HBV (rtL180M, rtM204I, rtM204V, rtL180M/ rtM204V), famciclovir-associated mutations (rtV173L, rtP177L, rtL180M, rtT184S or rtV207I) and hepatitis B immunoglobulin escape mutations (rtT128N and rtW153Q), and in in vivo animal models of hepadnavirus replication.
• HBeAg- positiv og HBeAg- negativ kronisk hepatitis B med kompenseret leversygdom
• HBeAg positive and HBeAg negative chronic hepatitis B with compensated liver disease.
I
• lamivudine-resistant HBV with either compensated or decompensated liver disease, including patients pre- and post-liver transplantation or co-infected with HIV.
8 de fleste af disse undersøgelser blev adefovirdipivoxil 10 mg føjet til igangværende lamivudinbehandling hos patienter med svigtende lamivudinterapi.
In the majority of these studies adefovir dipivoxil 10 mg was added to ongoing lamivudine treatment in patients failing lamivudine therapy.
I disse kliniske undersøgelser havde patienter aktiv viral replikation (HBV- DNA ≥ 100. 000 kopier/ ml) og forhøjede ALAT- niveauer (≥ 1, 2 x øvre grænse af normal (Upper Limit of Normal, ULN)).
In these clinical studies patients had active viral replication (HBV DNA ≥ 100,000 copies/ ml) and elevated ALT levels (≥ 1.2 x Upper Limit of Normal (ULN)).
Erfaring med patienter med kompenseret leversygdom:
Experience in patients with compensated liver disease: