Tamoxifen [Novaldex]: Ungünstige Wechselwirkung mit SSRIs (Serotonin-Wiederaufnahmehemmern)

13. Mai 2010 – Wie das Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM)  mitteilt, wurde in einer kanadischen Kohortenstudie gezeigt, dass der Serotonin-Wiederaufnahmehemmer (SSRI) Paroxetin die Wirkung von Tamoxifen in der Hormonbehandlung eines Mammakarzinoms herabsetzen kann (BMJ 2010; 340:c693). Bei gleichzeitiger Verabreichung von Tamoxifen und Paroxetin ergab sich eine Erhöhung der Brustkrebssterblichkeit.

Sowohl Tamoxifen als auch SSRIs wie Paroxetin werden über das P450-System der Leber metabolisiert. Das „Prodrug“ Tamoxifen wird mit Hilfe des Enzyms CYP2D6 in seine aktiven Metaboliten umgewandelt. Paroxetin hemmt irreversibel in starkem Maße das Enzym CYP2D6. Auch für den SSRI Fluoxetin gibt es noch zu bestätigende Hinweise auf diese mögliche Wechselwirkung.

Die Gabe von SSRIs in Kombination mit Tamoxifen spielt in Deutschland eine zunehmende Rolle. Zum einen treten Depressionen während einer Hormontherapie und generell bei onkologischen Patienten gehäuft auf. Zum anderen werden SSRIs nicht bestimmungsgemäß (Off-Label-Gebrauch) bei Hitzewallungen unter einer Tamoxifentherapie angewendet.

Das BfArM weist auf die aktuelle Diskussion auf EU-Ebene hin, in der sowohl potentielle Wechselwirkungen von Tamoxifen mit CYP2D6-Enzymhemmern als auch der potentielle Effekt von CYP2D6 Genvarianten (Allelische Varianten) auf das klinische Ansprechen von Brustkrebspatientinnen auf die Tamoxifentherapie wissenschaftlich diskutiert werden. Sobald Ergebnisse dieser Diskussion vorliegen, wird das BfArM darüber informieren.

Tamoxifen ist in Deutschland unter anderem als Novaldex, Tamax, Taxofen, und Tamofen auf dem Markt. Paroxetin ist unter anderem als Paroxat, Paroxemis, und verschiedenen Varianten des Namens Paroxetin erhältich.

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About the Author
Joseph Gut - thasso Professor in Pharmakologie und Toxikologie. Experte in theragenomischer und personalisierter Medizin und individualisierter Arzneimittelsicherheit. Experte in Pharmako- und Toxiko-Genetik. Experte in der klinischen Sicherheit von Arzneimitteln, Chemikalien, Umweltschadstoffen und Nahrungsinhaltsstoffen.

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