Toxizität von Azathioprin

Zusammenfassung

In dieser Literaturanalyse werden die Arbeiten zur Kurz- und Langzeittoxizität von Azathioprin zusammengefasst, wobei die Häufigkeit und das Vorkommen im zeitlichen Verlauf aufgezeigt werden. 4 – 6 % der Patienten erleiden innerhalb weniger Tage eine starke Übelkeit, die zum Absetzen zwingt. Das Azathioprin-induzierte Fieber kommt bei ca. 1 – 2 % der Patienten vor. Eine Knochenmarksdepression lässt sich in einer Häufigkeit von 2 – 12 % nachweisen. In 3 % der Patienten kommt es zu einer Lebertoxizität, die teilweise dosisabhängig wie auch -unabhängig auftreten kann. Die Nebenwirkungen lassen sich nicht ausreichend durch die Bestimmung des Genotyps der Thiopurin-Methyltransferase (TPMT) vorhersagen. Die Verträglichkeit von Azathioprin ist abhängig von der zugrunde liegenden Erkrankung und ist bei Kollagenosen und Vaskulitiden höher (7 % Abbruchrate wegen Nebenwirkungen) als bei der rheumatoiden Arthritis (25 % Therapieabbruch). Die Erhöhung des Lymphomrisikos durch Azathioprin ist beim Menschen nicht belegt. Ebenso gibt es kein erhöhtes Risiko für Karzinome. Schwangerschaft und Entwicklung des Kindes sind eher von der Grunderkrankung beeinflusst als von der Azathioprin-Therapie, Fehlbildungen kommen etwa wie in der Normalbevölkerung in 3 – 5 % der Schwangerschaften vor. Insgesamt gehört Azathioprin derzeit zu den sichersten Medikamenten.

Abstract

This review summarises literature data about the prevalence of azathioprine-induced short- and long-term toxicity available from different diseases. Within a few days, about 4 – 6 % of the patients suffer from vomiting requiring discontinuation of therapy. Azathioprine-induced fever occurs in about 1 – 2 % of the patients. The prevalence of bone marrow toxicity is between 2 – 12 % and is dose-dependent. Liver toxicity is both dose-dependent and dose-independent and occurs in about 3 % of the patients. Unfortunately, the detection of the thiopurine methyltransferase (TPMT) cannot predict side effects. Tolerance to azathioprine depends on the existing disease and is higher in patients with vasculitis and connective tissue diseases compared to those with rheumatoid arthritis. There are no convincing data showing an increased risk of malignant diseases induced by azathioprine. The outcome of pregnancies is more dependent on the underlying disease of the patients, malformations of the infants are not significantly increased compared to the normal population and occur in about 3 – 5 % of the pregnancies. In conclusion, at present, azathioprine belongs to the safest drugs in rheumatology.

Azathioprin - Toxizität - Nebenwirkungen - Sicherheit

azathioprine - toxicity - side effects - safety

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