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TumorDiagnostik & Therapie 2012; 33(01): 29-33
DOI: 10.1055/s-0031-1281866
Originalarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Eisenchelat-Therapie mit Deferasirox: Therapiebeginn und Dosisoptimierung

Iron chelaton therapy with Deferasirox: Optimizing dosage and therapy initiation
A. Giagounidis
1   Medizinische Klinik II, Katholisches Klinikum Duisburg, St.-Johannes-Hospital, Duisburg
,
H. Al-Ali
2   Medizinische Klinik und Poliklinik II, Universitätsklinikum Leipzig
,
A. Mohr
3   Schwerpunktpraxis „Onkologie Lerchenfeld“, Hamburg
,
D. Haase
4   Abteilung Hämatologie und Onkologie, Universitätsmedizin Göttingen
,
W. K. Hofmann
5   III. Medizinische Klinik, Hämatologie und internistische Onkologie, Universitätsmedizin Mannheim
,
K. A. Kreuzer
6   Klinik I für Innere Medizin, Universitätsklinikum Köln
,
N. Gattermann
7   Klinik für Hämatologie, Onkologie und Klinische Immunologie, Universitätsklinikum Düsseldorf
› Author Affiliations
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Publication History

Publication Date:
02 February 2012 (online)

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Zusammenfassung

Der orale Eisenchelator Deferasirox (Exjade®) wird zur Behandlung der transfusionsbedingten Eisenüberladung eingesetzt. Die empfohlene Startdosis beträgt 20 mg/kg Körpergewicht (KG)/Tag, wobei die Dosis je nach Therapieziel und Ausmaß der Eisenzufuhr in Schritten von 5 – 10 mg/kg KG/Tag angepasst werden kann. Dosierungen ≥ 30 mg/kg KG/Tag werden insbesondere bei Patienten mit schwerer Eisenüberladung empfohlen. Deferasirox kann zu Nebenwirkungen führen, die von Patienten als belastend empfunden werden. Dazu zählt insbesondere eine teilweise schlagartig eintretende Diarrhö, die in der Regel nach 2 – 4 Wochen sistiert. Diese Phase kann durch ein Nebenwirkungsmanagement mit symptomatischer Therapie der Diarrhö, Verschieben der Einnahme auf den Zeitpunkt vor dem Zubettgehen oder ggf. durch Reduktion oder Unterbrechung der Deferasirox-Therapie überwunden werden. In der Praxis hat sich zuletzt ein einschleichender Beginn der Behandlung mit Deferasirox bewährt, der gegenüber einer schnellen Therapieeinleitung mit höheren Dosen Vorteile beim Nebenwirkungsmanagement hat. Die klinische Erfahrung zeigt, dass das schrittweise Auftitrieren von Deferasirox bis zur Zieldosis von den Patienten besser angenommen wird und die Compliance sehr hoch ist. Die Dosis wird dabei innerhalb der ersten 4 Wochen im Rahmen der wöchentlichen Kontrolluntersuchungen in Schritten von 5 – 10 mg/kg KG/Tag gesteigert.

Therapieerfolg und Therapietreue können mit der Bestimmung verschiedener Parameter überprüft werden. Die Bestimmung des Serumferritinspiegels ist die einfachste und kostengünstigste, wenn auch nicht exakteste Möglichkeit des Therapiemonitorings. Eine weitere Möglichkeit, die zurzeit etabliert wird, ist die Messung des labilen Plasmaeisens (labile plasma iron, LPI) im Serum. Die LPI-Messung kann frühzeitig das Erreichen des Akutziels einer Reduktion des redoxaktiven Eisens dokumentieren und so die Effektivität der Behandlung nachweisen. Auch können die Patienten den Nutzen der Behandlung früher und überzeugender verfolgen und so die Compliance verbessern. In Zukunft sind weitere Fortschritte in Richtung individualisierter Therapiekonzepte durch die Berücksichtigung pharmakogenetischer Daten zu erwarten.

Abstract

Administration of the oral iron chelator deferasirox (Exjade®) is indicated for the treatment of transfusional iron overload. The recommended initial dose is 20 mg/kg body weight (BW)/day, that can be adjusted in steps of 5 – 10 mg/kg BW/day according to treatment goals and iron intake. Doses ≥ 30 mg/kg BW/day are recommended in particular for those patients with severe iron overload. Patients may suffer from side effects of deferasirox treatment, in particular from sudden-onset diarrhea, which usually resolves within 2 – 4 weeks. During this period, side effect management may consist of symptomatic treatment of diarrhea, postponing taking deferasirox just before bedtime, dose reduction or temporary suspension of deferasirox treatment. In practice, at treatment initiation a gradual dose increase has proved to be effective, offering advantages in terms of side effect management compared to abrupt onset of treatment with higher deferasirox doses. Clinical experience shows, that a stepwise uptitration of deferasirox to the target dose is not only tolerated better by the patients but also results in high adherence. The dose is increased in steps of 5 – 10 mg/kg BW/day within the first 4 weeks along with weekly therapy monitoring.

Therapeutic success and adherence can be monitored through various parameters: The determination of serum ferritin levels is most simple and economical, but lacks accuracy. Another option now being established is the measurement of labile plasma iron (LPI) in serum. It allows to record the desired acute reduction of redox active iron at an early time point and thus documents treatment success. In addition, patients can see the treatment benefit earlier and more convincingly and thus improve adherence. By taking account of pharmacogenetic data, further progress towards personalized treatment can be expected.

Schlüsselwörter

Eisenüberladung - Deferasirox - Dosierung - Verträglichkeit - Diarrhö - Compliance

Key words

iron overload - deferasirox - dosing - tolerability - diarrhea - adherence
 

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