natgillin/translations-raw huggingface dataset:
For at nedsætte risikoen for kvalme og/ eller opkastning forbundet med indgivelse af probenecid, bør patienterne tilskyndes til at spise før hver probeneciddosis.
In order to reduce the potential for nausea and/ or vomiting associated with administration of probenecid, patients should be encouraged to eat food prior to each dose of probenecid.
Hos patienter, som udvikler allergiske eller overfølsomhedssymptomer over for probenecid (f. eks. udslæt, feber, kuldegysninger og anafylaksi), bør den profylaktiske eller terapeutiske brug af et passende antihistamin og/ eller paracetamol overvejes.
In patients who develop allergic or hypersensitivity symptoms to probenecid (e. g., rash, fever, chills and anaphylaxis), prophylactic or therapeutic use of an appropriate antihistamine and/ or paracetamol should be considered.
Cidofovir er kontraindiceret til patienter, der ikke kan behandles med probenecid pga. klinisk signifikant overfølsomhed overfor det aktive stof eller overfor andre sulfapræparater.
Cidofovir administration is contraindicated in patients unable to receive probenecid because of a clinically significant hypersensitivity to the active substance or medicinal product or to other sulfa- containing medicines.
Et probenecid desensibiliseringsprogram anbefales ikke.
A probenecid desensitisation program is not recommended for use.
Udover probenecid skal patienterne indgives ialt 1 liter 0, 9% (normal) natriumchlorid infusionsvæske intravenøst umiddelbart før hver cidofovirinfusion.
In addition to probenecid, patients must receive a total of one litre of 0.9% (normal) saline solution intravenously immediately prior to each infusion of cidofovir.
Patienter, som kan tolerere yderligere væskemængde, kan indgives op til ialt 2 liter 0, 9% natriumchlorid infusionsvæske intravenøst med hver cidofovir- dosis.
Patients who can tolerate the additional fluid load may receive up to a total of 2 litres of 0.9% saline intravenously with each dose of cidofovir.
Hvis endnu 1 liter er nødvendig, skal denne infunderes i løbet af 1 - 3 timer og påbegyndes samtidig med eller umiddelbart efter cidofovir- infusionen.
The first litre of saline solution should be infused over a 1 hour period immediately before the cidofovir infusion, and the second litre, if given, infused over a 1-3 hour period beginning simultaneously with the cidofovir infusion or starting immediately after the infusion of cidofovir.
Behandlingen med cidofovir bør afbrydes og intravenøs hydrering tilrådes, hvis serumkreatinin stiger med ≥44 µmol/ l (≥0, 5 mg/ dl) eller hvis der udvikles vedvarende proteinuri ≥2+.
Cidofovir therapy should be discontinued and intravenous hydration is advised if serum creatinine increases by ≥ 44 µmol/ l (≥ 0.5 mg/ dl), or if persistent proteinuria ≥ 2+ develops.
Hos patienter, der har proteinuri ≥2+, bør der foretages intravenøs hydrering og testen bør gentages.
In patients exhibiting ≥ 2+ proteinuria, intravenous hydration should be performed and the test repeated.
Hvis der stadig ses proteinuri ≥2+ efter hydrering, bør cidofovir behandlingen stoppes.
If following hydration, a ≥ 2+ proteinuria is still observed, cidofovir therapy should be discontinued.
Fortsat indgift af cidofovir til patienter med vedvarende proteinuri ≥2+ efter intravenøs hydrering kan resultere i yderligere tegn på proximal tubulær beskadigelse inklusiv glycosuri, fald i serum phosphat, urinsyre og bicarbonat og stigning i serumkreatinin.
Continued administration of cidofovir to patients with persistent ≥ 2+ proteinuria following intravenous hydration may result in further evidence of proximal tubular injury, including glycosuria, decreases in serum phosphate, uric acid and bicarbonate, and elevations in serum creatinine.
Fordele og ulemper ved at genoptage cidofovirbehandlingen af patienter, der er fuldt restituerede efter cidofovirrelateret nephrotoksicitet, er endnu ikke blevet fastslået.
For those patients who fully recover from cidofovir associated renal toxicity, the benefits-risk balance of reintroducing cidofovir has not yet been evaluated.
Patientmonitorering Proteinuri synes at være en tidlig og følsom indikator for cidofovirinduceret nephrotoksicitet.
Patient Monitoring Proteinuria appears to be an early and sensitive indicator of cidofovir-induced nephrotoxicity.
4. 8).
Differential white blood cell counts should also be performed prior to each dose of cidofovir (see section 4.8).
Øjenpåvirkning Patienter, der får cidofovir, bør regelmæssigt få foretaget øjenundersøgelser, for at påvise evt. uveitis/ iritis og okulær hypertoni.
Ocular Events Patients receiving cidofovir should be advised to have regular follow-up ophthalmologic examinations for possible occurrence of Uveitis/ Iritis and Ocular Hypotony.
Desuden bør cidofocir seponeres ved tilbagevendende uveitis/ iritis efter succesfuld behandling.
In case of Uveitis/ Iritis cidofovir should be discontinued if there is no response to treatment with a topical corticosteroid or the condition worsens, or if iritis/ uveitis reoccurs after successful treatment.
5. 3).
4 Other Cidofovir should be considered a potential carcinogen in humans (see section 5.3 Preclinical safety data).
4 Cidofovir bør anvendes med forsigtighed, ved behandling af patienter med diabetes mellitus, pga. den potentielt forøgede risiko for udvikling af okulær hypotoni.
Caution should be applied when considering cidofovir treatment of patients with diabetes mellitus due to the potential increased risk of developing ocular hypotony.
Der bør fortsat anvendes prævention for at forhindre overførsel af HIV.
Appropriate precautions should continue to be employed to prevent transmission of HIV.
For beskrivelse af andre nukleosidanalog- reverstranskriptase- inhibitorer (NRTI) anvendt sammen med probenecid henvises til de relevante produktbeskrivelser.
For other NRTI drugs administered concomitantly with probenecid, reference should be made to their respective prescribing information for any appropriate recommendations.
HCV og HBV- relateret hepatitis, er ikke blevet undersøgt i kliniske forsøg.
Interactions of cidofovir/ probenecid and anti-HIV drugs or drugs used to treat common chronic viral infections in this population, such as HCV and HBV-related hepatitis, have not been investigated in clinical trials.
Probenecid er kendt for at øge tilgængeligheden af mange lægemidler (f. eks. paracetamol, aciclovir, angiotensin- converterende enzyminhibitorer, aminosalicylsyre, barbiturater, benzodiazepiner, bumetanid, clofibrat, methotrexat, famotidin, furosemid, NSAID, teofyllin og zidovudin).
Probenecid is known to increase the exposure of many substances (e. g., paracetamol, acyclovir, angiotensin-converting enzyme inhibitors, aminosalicyclic acid, barbiturates, benzodiazepines, bumetanide, clofibrate, methotrexate, famotidine, furosemide, nonsteroidal anti-inflammatory agents, theophylline, and zidovudine).
Når cidofovir og probenecid udskrives sammen med anden medicin, er det vigtigt, at lægen rådfører sig med gældende produktresumé (eller anden passende reference) for probenecid, og tilsvarende produktinformation for det andet produkt for komplet information om interaktioner og andre vigtige forhold for det enkelte produkt.
Therefore, when co-prescribing cidofovir/ probenecid with other agents, it is important for prescribers to consult the current probenecid SPC (or an appropriate drug reference source) and the respective prescribing information of the other co-administered products for full information regarding drug interactions and other features of that product.
Cidofovir er embryotoksisk hos rotter og kaniner ved subterapeutiske doser.
Cidofovir is embryotoxic in rats and rabbits at subtherapeutic dose levels.
En signifikant forøget føtal incidens af eksterne bløddels - og skeletanomalier forekom hos kaniner ved 1, 0 mg/ kg/ dag, hvilket også var toksisk for moderen.
A significantly increased foetal incidence of external, soft tissue and skeletal anomalies occurred in rabbits at 1.0 mg/ kg/ day, which was also maternally toxic.
Graviditet Der findes ingen undersøgelser af cidofovir indgift til gravide kvinder.
Pregnancy There are no studies of cidofovir in pregnant women.
VISTIDE bør ikke anvendes under graviditet.
VISTIDE should not be used during pregnancy.
Kvinder i den fødedygtige alder bør anbefales at bruge effektiv prævention under og efter behandling med cidofovir.
Women of childbearing potential should be advised to use effective contraception during and after treatment with cidofovir.
Amning Det vides ikke, om cidofovir udskilles i modermælken.
Lactation It is not known whether cidofovir is excreted in human milk.
Da mange lægemidler udskilles i modermælken, skal ammende mødre instrueres i at ophøre med cidofovir eller indstille amningen, hvis de fortsat får cidofovir.
Because many substances are excreted in human milk, nursing mothers should be instructed to discontinue cidofovir or discontinue nursing if they continue to receive cidofovir.
Passage af placentabarrieren af beslægtede stoffer er observeret hos drægtige rotter.
Passage of the placenta barrier of cidofovir-related compound was observed in pregnant rats.
Udskillelse af cidofovir- relateret materiale i mælken hos lakterende dyr er ikke undersøgt.
Excretion of cidofovir-related material into milk of lactating animals was not examined.
4. 4.
Refer to section 4.4 for further information
5 4. 7 Virkninger på evnen til at føre motorkøretøj eller betjene maskiner
5 4.7 Effects on ability to drive and use machines
Lægen rådes til at diskutere dette med patienten og at give sin anbefaling i hvert enkelt tilfælde på grundlag af sygdomstilstand og tolerance overfor lægemidlet.
The physician is advised to discuss this issue with the patient, and based upon the condition of the disease and the tolerance of medication, give his recommendation in the individual case.
Frekvenser er anført: meget almindelig (≥ 1/ 10), almindelig (≥ 1/ 100 til < 1/ 10), ikke almindelig (≥ 1/ 1. 000 til < 1/ 100) eller ikke kendt (kan ikke estimeres ud fra forhåndenværende data).
Frequencies are defined as: very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10), uncommon (≥ 1/ 1000 to < 1/ 100) or not known (cannot be estimated from the available data).
Systemorganklasser Blod og lymfesystem
System Organ Class Blood and lymphatic system disorders
Meget almindelig Nervesystemet
Very common Nervous system disorders
Meget almindelig Øjne
Very common Eye disorders
Almindelig Øre og labyrint
Common Ear and labyrinth disorders
4. 4)
Iritis, uveitis, hypotony of the eye (see Section 4.4)
Ikke kendt
Not known Respiratory, thoracic and mediastinal disorders
Luftveje, thorax og mediastinum Almindelig Mave- tarmkanalen
Common Gastrointestinal disorders
Meget almindelig Ikke kendt Hud og subkutane væv
Very common Not known Skin and subcutaneous tissue disorders
Kvalme, opkast Pancreatitis
Nausea, Vomiting Pancreatitis
Meget almindelig Nyrer og urinveje
Very common Renal and urinary disorders
Meget almindelig Almindelig Ikke almindelig
Very common
Proteinuri; forhøjet kreatinin (se pkt.
Proteinuria, blood creatinine increased (see Section 4.4)
4. 4).
Common Uncommon
Nyresvigt Fanconis syndrom
Renal failure Fanconi syndrome acquired
Almene symptomer og reaktioner på administrationsstedet Meget almindelig Almindelig
General disorders and administration site conditions Very common Common
Nogle af dem var fatale.
Reports of renal failure (plus events possibly caused by renal failure, e. g. blood creatinine increased, proteinuria, glycosuria) received during post-marketing surveillance include some which were fatal.
Ved tilfælde af glykosuri, proteinuri/ aminoaciduria, hypourikæmi, hypophosphatæmi og/ eller hypokaliæmi bør cidofovir- relateret Fanconis syndrom overvejes.
The finding of any glycosuria, proteinuria/ aminoaciduria, hypouricemia, hypophosphatemia and/ or hypokalemia, should prompt for the consideration of cidofovir-related Fanconi syndrome.
I nedenstående tabel er bivirkninger, der sandsynligvis eller muligvis kan relateres til probenecid, baseret på kliniske forsøg:
6 The following table lists adverse reactions possibly or probably related to probenecid based on clinical trial experience:
Systemorganklasser Nervesystemet
System Organ Class Nervous system disorders
Almindelig
Common Gastrointestinal disorders
6 Mave- tarmkanalen Meget almindelig Hud og subkutane væv
Very common Skin and subcutaneous tissue disorders
Kvalme, opkast
Nausea, vomiting
Feber Asteni, kulderystelser
Fever Asthenia, chills
Ud over de her anførte bivirkninger kan probenecid også give andre bivirkninger herunder appetitløshed, tandkødssmerter, rødmen, alopeci, svimmelhed, anæmi og pollakiuri.
In addition probenecid may also cause other adverse
Der er forekommet overfølsomhedsreaktioner såsom dermatitis, pruritus, urticaria, og sjældent anafylaksi og Stevens- Johnsons syndrom.
Hypersensitivity reactions, with dermatitis, pruritus, urticaria and, rarely, anaphylaxis, and Stevens-Johnson syndrome have occurred.
Hæmolytisk anæmi er også set og kan være forbundet med G6DP - mangel.
Haemolytic anaemia has also occurred, and may be associated with G6DP deficiency.
Når cidofovir og probenecid udskrives samtidig, er det derfor vigtigt, at lægen rådfører sig med gældende produktresumé (eller anden passende reference) for probenecid for komplet information om sikkerhedsprofil og andre vigtige forhold for produktet.
Therefore, when co- prescribing probenecid with cidofovir, it is important for prescribers to consult the current probenecid SmPC (or an appropriate drug reference source) for full information on the safety profile and other features of that product.
Der er rapporteret to tilfælde af cidofovir overdosering.
Two cases of cidofovir overdose have been reported.
En patient fik en enkelt dosis på 16, 4 mg/ kg, og den anden patient fik en enkelt dosis på 17, 3 mg/ kg.
One patient received a single dose of 16.4 mg/ kg and the other patient received a single dose of 17.3 mg/ kg.
4. 4).
One of these patients experienced a minor transient change in renal function, while the other patient had no change in renal function (see section 4.4).
Antiviralt middel til systemisk brug, ATC kode:
Antiviral for systemic use, ATC Code:
J05AB12
J05AB12
Generelt Cidofovir er en cytidinanalog med in vitro og in vivo - aktivitet over for human cytomegalovirus (HCMV).
General Cidofovir is a cytidine analogue with in vitro and in vivo activity against human cytomegalovirus (HCMV).
Virkningsmekanisme Cidofovir undertrykker HCMV- replikation ved selektiv hæmning af virus DNA- syntese.
Mechanism of action Cidofovir suppresses HCMV replication by selective inhibition of viral DNA synthesis.
Biokemiske data understøtter selektiv hæmning af HSV- 1, HSV- 2 og HCMV DNA- polymeraser af cidofovirdi - phosphat, der er cidoforvirs aktive intracellulære metabolit.
Biochemical data support selective inhibition of HSV-1, HSV-2 and HCMV DNA polymerases by cidofovir diphosphate, the active intracellular metabolite of cidofovir.
Cidofovirdiphosphat hæmmer disse viruspolymeraser ved koncentrationer, som er 1/ 8 til 1/ 600 af dem, der er nødvendige for at hæmme humane cellers DNA- polymeraser alfa, beta og gamma.
Cidofovir diphosphate inhibits these viral polymerases at concentrations that are 8- to 600-fold lower than those needed to inhibit human cellular DNA polymerases alpha, beta, and gamma.
Optagelse af cidofovir i virus- DNA medfører fald i virus- DNA syntesens hastighed.
Incorporation of cidofovir into viral DNA results in reductions in the rate of viral DNA synthesis.
Cidofovir trænger ind i celler ved hjælp af væskefase endocytose og phosphoryleres til cidofovirmonophosphat og derefter til cidofovirdiphosphat.
Cidofovir enters cells by fluid-phase endocytosis and is phosphorylated to cidofovir monophosphate and subsequently to cidofovir diphosphate.
Ydermere har cidofovirphosphatcholinerne en halveringstid på 87 timer.
Prolonged antiviral effects of cidofovir are related to the half-lives of its metabolites; cidofovir diphosphate persists inside cells with a half-life of 17-65 hours and a cidofovir phosphate-choline adduct has a half-life of 87 hours.
7 Antivirusaktivitet In vitro er cidofovir aktiv over for HCMV, som er et medlem af herpes viridae- familien.
7 Antiviral activity Cidofovir is active in vitro against HCMV, a member of the herpesviridae family.
Antivirus aktivitet er blevet iagttaget i koncentrationer, som er signifikant mindre end dem, der medfører celledød.
Antiviral activity is seen at concentrations significantly below those which cause cell death.
In vitro følsomheden over for cidofovir er vist i følgende tabel.
The in vitro sensitivity to cidofovir is shown in the following table:
Cidofovirhæmning af virus- multiplikation i celle kultur Virus IC50( µM) Vildtype CMV- isolater Ganciclovirresistente CMV - isolater Foscarnetresistente CMV- isolater
Virus wild-type CMV isolates ganciclovir-resistant CMV isolates foscarnet-resistant CMV isolates
0, 7 (±0, 6) 7, 5 (±4, 3) 0, 59 (±0, 07)
IC50 (µM) 0.7 (± 0.6) 7.5 (± 4.3) 0.59 (± 0.07)
In vivo aktivitet over for HCMV blev bekræftet i kontrollerede kliniske undersøgelser af cidofovir, hvor AIDS- patienter med CMV- retinitis blev behandlet.
In vivo activity against HCMV was confirmed with controlled clinical studies of cidofovir for the treatment of CMV retinitis in patients with AIDS, which demonstrated statistically significant delays in time to CMV retinitis progression for patients on cidofovir when compared to control patients.
Disse undersøgelser viste statistisk signifikant forlængelse af tid til CMV- retinitis progression hos patienter, der fik cidofovir i sammenligning med kontrolpatienter.
The median times to retinitis progression in the two efficacy studies (GS-93-106 and GS-93-105), were 120 days and not reached for the treatment arms vs.
I studie GS- 93- 107 udført med patienter, som havde fået tilbagefald efter behandling med andre midler, var mediantiden for retinitis progression 115 dage.
In study GS-93-107 conducted in patients who had relapsed after treatment with other agents, the median time to retinitis progression was 115 days.
Virus resistens Efter in vitro selektion af ganciclovirresistente HCMV- isolater, blev der iagttaget krydsresistens mellem ganciclovir og cidofovir med ganciclovirselekterede mutationer i HCMV DNA- polymerase - genet, men ikke med mutationer i UL97- genet.
Viral resistance Following in vitro selection of ganciclovir-resistant HCMV isolates, cross-resistance between ganciclovir and cidofovir was seen with ganciclovir-selected mutations in the HCMV DNA polymerase gene but not with mutations in the UL97 gene.
Der blev ikke iagttaget krydsresistens mellem foscarnet og cidofovir med foscarnet- selekterede mutanter.
No cross-resistance between foscarnet and cidofovir was seen with foscarnet-selected mutants.
Cidofovir selekterede mutanter fik en mutation i DNA- polymerase- genet og var krydsresistente over for ganciclovir, men var modtagelige over for foscarnet.
Cidofovir-selected mutants had a mutation in the DNA polymerase gene and were cross-resistant to ganciclovir, but susceptible to foscarnet.
Hos patienter med normal nyrefunktion blev 80 til 100% af den intravenøse dosis genfundet i urinen som uomdannet cidofovir indenfor 24 timer.
In patients with normal renal function, 80 to 100% of the intravenous dose was recovered in the urine over 24 hours as unchanged cidofovir.
Ved afslutningen af en infusion over 1 time af cidofovir 5 mg/ kg, indgivet samtidig med oral probenecid, var den gennemsnitlige (±SD) cidofovir- serumkoncentration 19, 6 (±7, 18) μg/ ml.
At the end of a one-hour infusion of cidofovir 5 mg/ kg administered with concomitant oral probenecid, the mean (± SD) serum concentration of cidofovir was 19.6 (± 7.18) mcg/ ml.
138 (±36) ml/ time/ kg, 388 (±125) ml/ kg og 2, 2 (±0, 5) time.
The mean values of total serum clearance, volume of distribution at steady-state and terminal elimination half-life were 138 (± 36) ml/ hr/ kg, 388 (± 125) ml/ kg and 2.2 (±0.5) hour, respectively.
Der blev vist dosisuafhængig kinetik med enkeltdoser af cidofovir, der blev givet i dosisområdet 3 til 7, 5 mg/ kg.
Dose-independent kinetics were demonstrated with single doses of cidofovir given over the dose range 3 to 7.5 mg/ kg.
In vitro- proteinbinding In vitro- proteinbinding af cidofovir til plasma eller serumprotein var 10% eller mindre i cidofovirs koncentrationsområde fra 0, 25 til 25 μg/ ml.
In vitro protein binding In vitro protein binding of cidofovir to plasma or serum protein was 10% or less over the cidofovir concentration range 0.25 to 25 mcg/ ml.
Prækliniske dyrestudier viste, at nephrotoksicitet var cidofovirs vigtigste dosisbegrænsende toksicitet.
Preclinical animal studies demonstrated that nephrotoxicity was the major dose-limiting toxicity of cidofovir.
1 gang ugentligt med 1 g oral probenecid.
Evidence for a nephroprotective effect for probenecid was shown in a 52-week study conducted in cynomolgus monkeys administered cidofovir 2.5 mg/ kg once weekly intravenously with 1 g of probenecid given orally.
8 Carcinogenese I en 26 ugers intravenøs toksicitetsundersøgelse blev der iagttaget en signifikant stigning i forekomsten af mammaadenocarcinomer hos hunrotter og af Zymbals kirtelcarcinomer hos han - og hunrotter ved subterapeutiske plasmaniveauer af cidofovir.
Carcinogenesis In a 26-week intravenous toxicity study, a significant increase in incidence of mammary adenocarcinomas was seen in female rats and of Zymbal’ s gland carcinomas in male and female rats at subtherapeutic plasma levels of cidofovir.
I en særskilt undersøgelse medførte subkutane injektioner af cidofovir 1 gang om ugen i 19 på hinanden følgende uger, mammaadenocarcinomer hos hunrotter ved doser på ned til 0, 6 mg/ kg/ uge.
In a separate study, once weekly subcutaneous injections of cidofovir for 19 consecutive weeks resulted in mammary adenocarcinomas in female rats at doses as low as 0.6 mg/ kg/ week.
Der blev ikke iagttaget tumorer i cynomolgus aber, der fik cidofovir intravenøst 1 gang ugentlig i 52 uger ved doser op til 2, 5 mg/ kg/ uge.
No tumours were observed in cynomolgus monkeys administered cidofovir intravenously once weekly for 52 weeks at doses up to 2.5 mg/ kg/ week.
Mutagenicitet og reproduktionstoksikologi Undersøgelser har vist, at cidofovir er klastogenetisk in vitro ved 100 μg/ ml og embryotoksisk hos rotter og kaniner.
Mutagenicity and reproductive toxicology Studies have shown that cidofovir is clastogenic in vitro at 100 µg/ ml and is embryotoxic in rats and rabbits.
Cidofovir fremkaldte ingen mutagen reaktion ved dosisniveauer på op til 5 mg/ plade ved tilstedeværelsen af og uden metabolisk aktivering med rottelever S- 9 fraktion i mikrobiologiske assays, der omfatter Salmonellea typhimurium til basepar substitutioner eller frameshift mutationer (Ames) og Escherichia coli til omvendte mutationer.
No mutagenic response was elicited by cidofovir at dose levels up to 5 mg/ plate, in the presence and absence of metabolic activation by rat liver S-9 fraction, in microbial assays involving Salmonella typhimurium for base pair substitutions or frameshift mutations (Ames) and Escherichia coli for reverse mutations.
Der blev iagttaget en forøgelse i dannelsen af mikronucleerede polykromatiske erytrocytter in vivo hos mus, der fik en høj toksisk cidofovirdosis intraperitonealt (≥2000 mg/ kg).
An increase in formation of micronucleated polychromatic erythrocytes was observed in vivo in mice receiving a high, toxic intraperitoneal dose of cidofovir (≥ 2000 mg/ kg).
Cidofovir inducerede kromosomafvigelser i humane perifere blodlymfocytter in vitro uden metabolisk aktivering (S- 9 fraktion).
Cidofovir induced chromosomal aberrations in human peripheral blood lymphocytes in vitro without metabolic activation (S-9 fraction).
På de 4 cidofovirniveauer (12, 5 til 100 µg/ ml), der blev undersøgt, forøgedes procentdelen af beskadigede metafaser og antallet af afvigelser pr. celle på en koncentrationsafhængig måde.
At the 4 cidofovir levels (12.5 to 100 µg/ ml) tested, the percentage of damaged metaphases and number of aberrations per cell increased in a concentration-dependent manner.