Tamoxifen: Wechselwirkung mit SSRIs (Serotonin-Wiederaufnahmehemmern)

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21.  März 2010 – In einer kanadischen Kohortenstudie wurde gezeigt, dass der Serotonin-Wiederaufnahmehemmer (SSRI) Paroxetin die Wirkung von Tamoxifen in der Hormonbehandlung eines Mammakarzinoms herabsetzen kann.  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.

Das deutsche Bundesintitut für Arzneimittel und Medizinalproduckte (BfArM) stellt fest, dass die Gabe von SSRIs in Kombination mit Tamoxifen in Deutschland eine zunehmende Rolle spielt. Zum einen treten Depressionen während einer Hormontherapie und generell bei onkologischen Patienten gehäuft auf.  Zum anderen werden SSRIs nicht bestimmungsgemäß (d.h. im sogenannten Off-Label-Gebrauch) bei Hitzewallungen unter einer Tamoxifentherapie angewendet wird.

Das BfArM weist im weiteren 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 auf das klinische Ansprechen von Brustkrebspatientinnen auf die Tamoxifentherapie wissenschaftlich diskutiert werden. Sobald Ergebnisse dieser Diskussion vorliegen, wird das BfArM darüber informieren.

Lesen sie auch die Originalatudie unter folgender Referenz: BMJ (2010) 340, c693.

Paroxetin, Fluoxetin, und Tamoxifen sind in Deutschland unter diversen Produkte- und Handelsnamen auf dem Markt erhältlich. Weitere Infomationen zu diesen Produkten sind bei PharmNet.Bund und dem zugehörigen Suchportal leicht zugänglich.

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thassodotcom 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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