natgillin/translations-raw huggingface dataset:
EXJADE er yderligere indiceret til behandling af kronisk jernophobning, forårsaget af blodtransfusioner, i de tilfælde hvor deferoxamin- behandling er kontraindiceret eller utilstrækkelig.
EXJADE is also indicated for the treatment of chronic iron overload due to blood transfusions when deferoxamine therapy is contraindicated or inadequate in the following patient groups:
- patienter med andre anæmier,
- in patients with other anaemias,
- patienter i alderen 2 til 5 år,
- in patients aged 2 to 5 years,
- patienter med beta- thallasæmi major med jernophobning forårsaget af sjældne blodtransfusioner
- in patients with beta thalassaemia major with iron overload due to infrequent blood transfusions
(< 7 ml/ kg/ måned pakkede røde blodceller).
(< 7 ml/ kg/ month of packed red blood cells).
Behandling med EXJADE skal påbegyndes og vedligeholdes af læger med erfaring i behandling af kronisk jernophobning forårsaget af blodtransfusioner.
Treatment with EXJADE should be initiated and maintained by physicians experienced in the treatment of chronic iron overload due to blood transfusions.
Det anbefales, at behandlingen påbegyndes efter transfusion af omkring 20 enheder (cirka 100 ml/ kg) pakkede røde blodceller, eller når klinisk monitorering afdækker tegn på, at kronisk jernophobning er tilstede (f. eks. serum- ferritin > 1. 000 µg/ l).
It is recommended that treatment be started after the transfusion of approximately 20 units (about 100 ml/ kg) of packed red blood cells or when there is evidence from clinical monitoring that chronic iron overload is present (e. g. serum ferritin > 1,000 µg/ l).
Doser (i mg/ kg) skal beregnes og afrundes til nærmeste hele tabletstørrelse.
Doses (in mg/ kg) must be calculated and rounded to the nearest whole tablet size.
Målene med jernkelations- behandling er at fjerne mængden af jern, der administreres i transfusioner og, om nødvendigt, at reducere den eksisterende jernbelastning.
The goals of iron chelation therapy are to remove the amount of iron administered in transfusions and, as required, to reduce the existing iron burden.
Startdosis Anbefalet startdosis for EXJADE er 20 mg/ kg kropsvægt.
The recommended initial daily dose of EXJADE is 20 mg/ kg body weight.
En startdosis på 30 mg/ kg kan tages i betragtning for patienter, der har brug for reduktion af forhøjede jern- niveauer, og som også modtager mere end 14 ml/ kg/ måned pakkede røde blodceller (omkring > 4 enheder/ måned for en voksen).
An initial daily dose of 30 mg/ kg may be considered for patients who require reduction of elevated body iron levels and who are also receiving more than 14 ml/ kg/ month of packed red blood cells (approximately > 4 units/ month for an adult).
2 En startdosis på 10 mg/ kg kan tages i betragtning for patienter, der ikke har brug for reduktion af jern - niveauer i kroppen, og som også modtager mindre end 7 mg/ kg/ måned pakkede røde blodceller (omkring < 2 enheder/ måned for en voksen).
2 An initial daily dose of 10 mg/ kg may be considered for patients who do not require reduction of body iron levels and who are also receiving less than 7 ml/ kg/ month of packed red blood cells (approximately < 2 units/ month for an adult).
5. 1).
The patient’ s response must be monitored and a dose increase should be considered if sufficient efficacy is not obtained (see section 5.1).
Eksempelvis kan en patient, der modtager 40 mg/ kg/ dag af deferoxamin fem dage om ugen (eller tilsvarende), overføres til en daglig startdosis på 20 mg/ kg/ dag af EXJADE.
For patients already well managed on treatment with deferoxamine, a starting dose of EXJADE that is numerically half that of the deferoxamine dose could be considered (e. g. a patient receiving 40 mg/ kg/ day of deferoxamine for 5 days per week (or equivalent) could be transferred to a starting daily dose of 20 mg/ kg/ day of EXJADE).
Når dette resulterer i en daglig dosis, der er mindre end 20 mg/ kg kropsvægt, skal patientens respons monitoreres.
When this results in a daily dose less than 20 mg/ kg body weight, the patient’ s response must be monitored and a dose increase should be considered if sufficient efficacy is not obtained (see section 5.1).
5. 1).
Maintenance dose U
Vedligeholdelsesdosis Det anbefales, at serum- ferritin monitoreres hver måned, og at dosis af EXJADE justeres, hvis nødvendigt, hver 3. til 6. måned, ud fra udviklingen i serum- ferritin.
It is recommended that serum ferritin be monitored every month and that the dose of EXJADE be adjusted, if necessary, every 3 to 6 months based on the trends in serum ferritin.
Dosisjusteringer kan gøres i trin af 5 til 10 mg/ kg, og skal skræddersys til den enkelte patients respons og terapeutiske mål (vedligeholdelse eller reduktion af jernophobning).
Dose adjustments may be made in steps of 5 to 10 mg/ kg and are to be tailored to the individual patient’ s response and therapeutic goals (maintenance or reduction of iron burden).
Doser over 30 mg/ kg anbefales ikke, da der kun er begrænset erfaring med doser over dette niveau.
Doses above 30 mg/ kg are not recommended because there is only limited experience with doses above this level.
En afbrydelse af behandlingen skal overvejes, hvis serum- ferritin falder konsekvent under 500 µg/ l (se pkt.
If serum ferritin falls consistently below 500 µg/ l, an interruption of treatment should be considered (see section 4.4).
4. 4).
Preparation U
Klargøring EXJADE skal tages én gang dagligt på tom mave mindst 30 minutter før et måltid, helst på samme tidspunkt hver dag (se punkterne 4. 5 og 5. 2).
EXJADE must be taken once daily on an empty stomach at least 30 minutes before food, preferably at the same time each day (see sections 4.5 and 5.2).
Tabletterne opløses ved omrøring i et glas vand eller appelsin - eller æblejuice (100 til 200 ml), indtil en fin suspension er opnået.
The tablets are dispersed by stirring in a glass of water or orange or apple juice (100 to 200 ml) until a fine suspension is obtained.
Efter suspensionen er drukket, skal den tilbageværende rest resuspenderes i en lille mængde vand eller juice og drikkes.
After the suspension has been swallowed, any residue must be resuspended in a small volume of water or juice and swallowed.
6. 2).
The tablets must not be chewed or swallowed whole (see also section 6.2).
Ældre patienter (≥ 65 år) Dosisrekommendationer for ældre patienter er de samme som ovenfor.
Elderly patients (≥ 65 years of age) U
Pædiatriske patienter (2 til 17 år) Dosisrekommendationer for pædiatriske patienter er de samme som for ældre patienter.
The dosing recommendations for paediatric patients are the same as for adult patients.
5. 2).
In children aged between 2 and 5 years, exposure is lower than in adults (see section 5.2).
Patienter med nedsat nyrefunktion EXJADE har ikke været undersøgt hos patienter med nedsat nyrefunktion og er kontraindiceret hos patienter med estimeret kreatinin- clearance < 60 ml/ min (se pkt.
EXJADE has not been studied in patients with renal impairment and is contraindicated in patients with estimated creatinine clearance < 60 ml/ min (see sections 4.3 and 4.4).
4. 3 og 4. 4).
Patients with hepatic impairment U
Patienter med nedsat leverfunktion EXJADE har ikke været undersøgt hos patienter med nedsat leverfunktion, og skal anvendes med forsigtighed hos disse patienter.
EXJADE has not been studied in patients with hepatic impairment and must be used with caution in such patients.
De anbefalede startdoser for patienter med nedsat leverfunktion er de samme som beskrevet ovenfor.
The initial dosing recommendations for patients with hepatic impairment are the same as described above.
4. 4).
Hepatic function in all patients should be monitored before treatment then every month (see section 4.4).
4. 5).
Combination with other iron chelator therapies as the safety of such combinations has not been established (see section 4.5).
Patienter med estimeret kreatinin- clearance < 60 ml/ min.
Patients with estimated creatinine clearance < 60 ml/ min.
Nyrefunktion:
U
EXJADE har kun været undersøgt hos patienter med baseline serum- kreatinin inden for det aldersbestemte normalområde.
EXJADE has been studied only in patients with baseline serum creatinine within the age-appropriate normal range.
Forhøjelserne var på > 33% i ≥ 2 på hinanden følgende tilfælde, og nogle gange over den øvre grænse af normalområdet.
During clinical trials, increases in serum creatinine of > 33% on ≥ 2 consecutive occasions, sometimes above the upper limit of the normal range, occurred in about 36% of patients.
Disse var dosisafhængige.
These were dose- dependent.
Omkring to tredjedele af patienterne med forøget serum - kreatinin vendte tilbage til niveauet under 33% uden dosisjustering.
About two-thirds of the patients showing serum creatinine increase returned below the 33% level without dose adjustment.
Hos den sidste tredjedel reagerede forøgelsen af serum- kreatinin ikke altid på en dosisreduktion eller dosisafbrydelse.
In the remaining third the serum creatinine increase did not always respond to a dose reduction or a dose interruption.
4. 8).
Cases of acute renal failure have been reported following post-marketing use of EXJADE (see section 4.8).
Årsagerne til stigningerne i serum- kreatinin er ikke blevet klarlagt.
The causes of the rises in serum creatinine have not been elucidated.
Speciel opmærksomhed bør derfor rettes mod monitorering af serum- kreatinin hos patienter, der modtager høje doser af EXJADE og/ eller lav hyppighed af transfusioner (< 7 ml/ kg/ måned pakkede røde blodceller eller < 2 enheder/ måned for en voksen).
Particular attention should therefore be paid to monitoring of serum creatinine in patients who are receiving high doses of EXJADE and/ or low rates of transfusion (< 7 ml/ kg/ month of packed red blood cells or < 2 units/ month for an adult).
Det anbefales, at serum- kreatinin dobbeltbestemmes før påbegyndelse af behandling.
It is recommended that serum creatinine be assessed in duplicate before initiating therapy.
Efterfølgende bør monitorering finde sted månedligt.
Serum creatinine, creatinine clearance (estimated with the Cockcroft-Gault or MDRD formula in adults and with the Schwartz formula in children) and/ or plasma cystatin C levels should be monitored weekly in the first month after initiation or modification of therapy with EXJADE, and monthly thereafter.
4. 2).
For adult patients, the daily dose may be reduced by 10 mg/ kg if a rise in serum creatinine by > 33% above the average of the pre-treatment measurements and estimated creatinine clearance decreases below the lower limit of the normal range (< 90 ml/ min) are seen at two consecutive visits, and cannot be attributed to other causes (see section 4.2).
For pædiatriske patienter kan dosis reduceres med 10 mg/ kg, hvis den estimerede kreatinin- clearance falder under den nedre grænse af normalområdet (< 90 ml/ min), og/ eller serum- kreatinin- niveauer stiger over den aldersbestemte øvre grænse af det normale ved to på hinanden følgende kontrolbesøg.
For paediatric patients, the dose may be reduced by 10 mg/ kg if estimated creatinine clearance decreases below the lower limit of the normal range (< 90 ml/ min) and/ or serum creatinine levels rise above the age-appropriate upper limit of normal at two consecutive visits.
Behandlingen bør afbrydes, hvis der efter en dosisreduktion for voksne og pædiatriske patienter ses en stigning i serum- kreatinin > 33% over gennemsnittet af målingerne før behandlingen, og/ eller den beregnede kreatinin- clearance falder under den nedre grænse af normalområdet.
After a dose reduction, for adult and paediatric patients, treatment should be interrupted if a rise in serum creatinine > 33% above the average of the pre-treatment measurements is observed and/ or the calculated creatinine clearance falls below the lower limit of the normal range.
Det er de individuelle kliniske omstændigheder, der er afgørende for en eventuel genoptagelse af behandlingen.
Treatment may be reinitiated depending on the individual clinical circumstances.
Speciel opmærksomhed bør også rettes mod monitorering af serum- kreatinin hos patienter, der samtidigt modtager medicin, der nedsætter nyrefunktionen.
Particular attention should also be paid to monitoring of serum creatinine in patients who are concomitantly receiving medicinal products that depress renal function.
Der bør udføres månedlige tests for proteinuri.
Tests for proteinuria should be performed monthly.
Efter behov kan yderligere markører af nyretubulær funktion (f. eks. glucosuri hos ikke- diabetikere og lave niveauer af serum- kalium, phosphat, magnesium eller urat, phosphaturi, aminosyreuri) også monitoreres.
As needed, additional markers of renal tubular function (e. g. glycosuria in non-diabetics and low levels of serum potassium, phosphate, magnesium or urate, phosphaturia, aminoaciduria) may also be monitored.
Dosisreduktion eller afbrydelse kan overvejes, hvis der er abnormaliteter i niveauer af tubulære markører, og/ eller hvis det er klinisk indiceret.
Dose reduction or interruption may be considered if there are abnormalities in levels of tubular markers and/ or if clinically indicated.
Hvis serum- kreatinin trods dosisreduktion eller afbrydelse af behandling forbliver signifikant forhøjet, og der også er vedholdende abnormaliteter i andre markører af nyrefunktion (f. eks. proteinuri, Fanconi’ s Syndrom), bør patienten henvises til en nyrespecialist og yderligere undersøgelser (så som nyrebiopsi) kan overvejes.
If, despite dose reduction and interruption, the serum creatinine remains significantly elevated and there is also persistent abnormality in another marker of renal function (e. g. proteinuria, Fanconi’ s Syndrome), the patient should be referred to a renal specialist, and further specialised investigations (such as renal biopsy) may be considered.
4 Leverfunktion:
U U
Hos patienter i behandling med EXJADE, har der været observeret stigninger i leverfunktionstest.
Liver function test elevations have been observed in patients treated with EXJADE.
Der er efter markedsføring rapporteret tilfælde af leversvigt hos patienter behandlet med EXJADE, enkelte gange med dødelig udgang.
Postmarketing cases of hepatic failure, sometimes fatal, have been reported in patients treated with EXJADE.
4. 8).
However, the role of EXJADE as a contributing or aggravating factor cannot be excluded (see section 4.8).
Det anbefales at serum- transaminase, bilirubin og alkalin- phosphatase måles inden initiering af behandling, hver 2. uge i den første måned, og derefter månedligt Hvis der er en vedholdende og progressiv forøgelse af serum- transaminase- niveauer, der ikke kan henføres til andre årsager, bør behandling med EXJADE afbrydes.
If there is a persistent and progressive increase in serum transaminase levels that cannot be attributed to other causes, EXJADE should be interrupted.
En forsigtig genstart af behandling med lavere dosis, efterfulgt af en gradvis dosisforøgelse kan overvejes, når årsagen til leverfunktionstest- uregelmæssigheder er blevet klarlagt, eller når der igen er normale niveauer.
Once the cause of the liver function test abnormalities has been clarified or after return to normal levels, cautious re-initiation of treatment at a lower dose followed by gradual dose escalation may be considered.
EXJADE anbefales ikke hos patienter med alvorligt nedsat leverfunktion, da det ikke er undersøgt hos sådanne patienter.
EXJADE is not recommended in patients with severe hepatic impairment as it has not been studied in such patients.
Behandling har kun været påbegyndt hos patienter med niveauer for baseline lever - transaminase, der lå på op til 5 gange den øvre grænse af normalområdet.
Treatment has been initiated only in patients with baseline liver transaminase levels up to 5 times the upper limit of the normal range (see section 5.2).
Øvre gastrointestinal ulceration og blødning er rapporteret i patienter, inklusive unge og børn, som fik EXJADE.
Upper gastrointestinal ulceration and haemorrhage have been reported in patients, including children and adolescents, receiving EXJADE.
4. 8).
Multiple ulcers have been observed in some patients (see section 4.8).
Læger og patienter skal være på vagt for tegn og symptomer på gastrointestinal ulceration og blødning under behandling med EXJADE, og umiddelbart initiere yderligere undersøgelser og behandling, hvis en alvorlig gastrointestinal utilsigtet hændelse er mistænkt.
Physicians and patients should remain alert for signs and symptoms of gastrointestinal ulceration and haemorrhage during EXJADE therapy and promptly initiate additional evaluation and treatment if a serious gastrointestinal adverse event is suspected.
4. 5).
Caution should be exercised in patients who are taking EXJADE in combination with substances that have known ulcerogenic potential, such as NSAIDs, corticosteroids, or oral bisphosphonates and in patients receiving anticoagulants (see section 4.5).
Der kan forekomme hududslæt ved EXJADE- behandling.
Skin rashes may appear during EXJADE treatment.
Påbegyndelsen bør finde sted med en lavere dosis efterfulgt af en gradvis dosisforøgelse.
When interruption of treatment may be necessary, treatment may be reintroduced after resolution of the rash, at a lower dose followed by gradual dose escalation.
4. 8).
Cases of serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported in patients receiving EXJADE, with the onset of the reaction occurring in the majority of cases within the first month of treatment (see section 4.8).
Efter markedsføring har der været indberetninger af leukopeni, trombocytopeni eller pancytopeni eller forværring af disse cytopenier hos patienter behandlet med EXJADE.
There have been post-marketing reports of leukopenia, thrombocytopenia or pancytopenia, or aggravation of these cytopenias in patients treated with EXJADE.
De fleste af disse patienter havde præ- eksisterende hæmatologiske lidelser, der ofte forbindes med knoglemarvsdepression.
Most of these patients had pre- existing haematological disorders that are frequently associated with bone marrow failure.
4. 2).
Monthly monitoring of serum ferritin is recommended in order to assess the patient’ s response to therapy (see section 4.2).
Det skal overvejes at afbryde behandlingen, hvis serum- ferritin falder konsekvent under 500 µg/ l.
If serum ferritin falls consistently below 500 µg/ l, an interruption of treatment should be considered.
Resultaterne af tests for serum- kreatinin, serum- ferritin og serum- transaminaser bør registreres og vurderes regelmæssigt for tendenser.
5 The results of the tests for serum creatinine, serum ferritin and serum transaminases should be recorded and regularly assessed for trends.
Resultaterne bør også noteres i den udleverede patientfolder.
The results should also be noted in the provided patient’ s booklet.
5 I de 1- årige kliniske studier blev vækst og kønsudvikling hos pædiatriske patienter, der blev behandlet med EXJADE ikke påvirket.
In the 1-year clinical studies growth and sexual development of paediatric patients treated with EXJADE were not affected.
Som en generel forholdsregel for varetagelse af pædiatriske patienter med transfusional jernophobning bør kropsvægt, højde og kønsudvikling imidlertid monitoreres med regelmæssige intervaller (hver 12. måned).
However, as a general precautionary measure in the management of paediatric patients with transfusional iron overload, body weight, height and sexual development should be monitored at regular intervals (every 12 months).
Tabletterne indeholder lactose (1, 1 mg lactose pr. mg deferasirox).
The tablets contain lactose (1.1 mg lactose for each mg of deferasirox).
Bør ikke anvendes til patienter med arvelig galactoseintolerans, en særlig form af hereditær lactasemangel (Lapp Lactase deficiency) eller glucose/ galactosemalabsorption eller alvorlig lactasemangel.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or severe lactase deficiency should not take this medicine.
Det anbefales ikke at bruge deferasirox samtidigt med aluminiumholdige antacider.
The concomitant use of deferasirox with aluminium-containing antacid preparations is not recommended.
4. 5).
Caution should be exercised when deferasirox is combined with strong UDP- glucuronosyl transferase (UGT) inducers, or CYP2C8 substrates (see section 4.5).
Samtidig administration af EXJADE og aluminiumholdige antacidapræparater er ikke formelt undersøgt.
The concomitant administration of EXJADE and aluminium-containing antacid preparations has not been formally studied.
4. 4).
Although deferasirox has a lower affinity for aluminium than for iron, it is not recommended to take EXJADE tablets with aluminium-containing antacid preparations (see section 4.4).
EXJADE skal derfor tages på tom mave, mindst 30 minutter før et måltid og helst på samme tidspunkt hver dag (se punkterne 4. 2 og 5. 2).
EXJADE must therefore be taken on an empty stomach at least 30 minutes before food, preferably at the same time each day (see sections 4.2 and 5.2).
Deferasiroxmetabolisme afhænger af UGT- enzymer.
Deferasirox metabolism depends on UGT enzymes.
Samtidig administration af EXJADE (enkeltdosis på 30 mg/ kg) og den potente UGT- inducer, rifampicin, (gentagen dosis på 600 mg/ dag) resulterede i en nedsat eksponering for deferasirox med 44% (90% CI:
In a healthy volunteer study, the concomitant administration of EXJADE (single dose of 30 mg/ kg) and the potent UGT inducer, rifampicin, (repeated dose of 600 mg/ day) resulted in a decrease of deferasirox exposure by 44% (90% CI:
37% - 51%) i et studie hos raske frivillige.
37% - 51%).
4. 4).
Therefore, the concomitant use of EXJADE with potent UGT inducers (e. g. rifampicin, carbamazepine, phenytoin, phenobarbital, ritonavir) may result in a decrease in EXJADE efficacy (see section 4.4).
Patientens serum- ferritin bør monitoreres under og efter kombinationen, og EXJADE- dosis skal om nødvendigt justeres.
The patient ’ s serum ferritin should be monitored during and after the combination, and the dose of EXJADE adjusted if necessary.
I et studie med raske frivillige, resulterede samtidig behandling med EXJADE og midazolam (et CYP3A4 test- substrat) i et fald i eksponering for midazolam på 17% (90% CI:
In a healthy volunteer study, the concomitant administration of EXJADE and midazolam (a CYP3A4 probe substrate) resulted in a decrease of midazolam exposure by 17% (90% CI:
Derfor bør forsigtighed udvises, grundet en mulig nedsat effekt, når deferasirox kombineres med stoffer, der metabolliseres af CYP3A4 (f. eks. ciclosporin, simvastatin, hormonelle antikoceptiva, bepridil og ergotamin).
Therefore, due to a possible decrease in efficacy, caution should be exercised when deferasirox is combined with substances metabolised through CYP3A4 (e. g. ciclosporin, simvastatin, hormonal contraceptive agents, bepridil, ergotamine).
Sikkerheden af EXJADE i kombination med andre jernkelatorerer er ikke blevet klarlagt.
The safety of EXJADE in combination with other iron chelators has not been established.
4. 3).
Therefore, it must not be combined with other iron chelator therapies (see section 4.3).
Der blev ikke observeret interaktioner mellem EXJADE og digoxin hos raske voksne frivillige.
No interaction was observed between EXJADE and digoxin in healthy adult volunteers.
I et studie med raske frivillige blev det påvist, at administration af deferasirox, som moderat CYP2C8 - hæmmer (30 mg/ kg daglig) samtidig med repaglinid, et CYP2C8- substrat givet som enkeltdosis på 0, 5 mg, øgede AUC og Cmax for repaglinid med henholdsvis ca.
In a healthy volunteer study, the concomitant administration of deferasirox as a moderate CYP2C8 inhibitor (30 mg/ kg daily), with repaglinide, a CYP2C8 substrate, given as a single dose of 0.5 mg, increased repaglinide AUC and C max about 2.3-fold (90% CI [2.03-2.63]) and 1.6-fold (90% CI
2, 3 gange (90% CI [2, 03- 2, 63]) og 1, 6 gange (90% CI [1, 42- 1. 84]).
[1.42-1.84]), respectively.
Da interaktionen ikke er blevet påvist med doser højere end 0, 5 mg for repaglinid, skal samtidig brug af deferasirox og repaglinid undgås.
Since the interaction has not been established with dosages higher than 0.5 mg for repaglinide, the concomitant use of deferasirox with repaglinide should be avoided.