Fix-sequenzielle Folsäuresupplementierung bei Methotrexat-Therapie

Zusammenfassung

Im Abwägen zwischen Folinsäure und Folsäure ergeben sich klare Vorteile für die Folsäure. Diskret höhere MTX-Dosen in den Folsäure-MTX-Gruppen können nötig sein, um die volle MTX-Wirkung zu erhalten, obwohl in der Literatur keine klinisch relevanten Publikationen vorliegen und die Hinweise darauf eher indirekter Natur sind. Es ist aber auch möglich, dass höhere (effektivere) MTX-Dosen erst durch Folsäuregabe realisierbar sind. Die mg-Unterschiede sind zudem marginal (2 bis 4 mg/Woche) und stellen bei gleichzeitiger sicherer Reduzierung der MTX-induzierten unerwünschten Wirkungen einen akzeptablen Kompromiss dar. Ein wöchentliches Folsäure-zu-MTX-Verhältnis von 0,45 : 1,0 bis zu 2,85 : 1,0 reduziert UAW signifikant. Der zeitliche Rahmen, in dem Folsäure im Verhältnis zu MTX gegeben wurde, reichte von 4 Tagen vor bis zu 24 Stunden nach der MTX-Gabe. Folsäure zeigt ein deutlich weiteres „zeitliches Applikationsfenster” als Folinsäure. Folsäure beeinträchtigt unter diesen Dosis- bzw. Zeitverhältnissen die MTX-Wirkung nicht. Folsäure erfüllte die Forderung, unerwünschte Arzneimittelwirkungen zu reduzieren und die MTX-Wirkung nicht zu nivellieren in drei doppelblinden, zwei prospektiven offenen Studien und einer Metaanalyse.

Abstract

When comparing folinic acid with folic acid, clear advantages for folic acid are apparent. Discretely higher doses of MTX may be necessary in the folic acid-MTX group in order to retain the full activity of MTX although no clinically relevant reports are available in the literature and all indications are thus of an indirect nature. However, it is also possible that higher (more effective) doses of MTX may be achievable by means of administration of folic acid. The mg differences are however marginal (2 to 4 mg/week) and - with a concomitant and certain reduction of MTX-induced adverse effects - represent an acceptable compromise. A weekly folic acid to MTX ratio of from 0.45:1.0 up to 2.85:1.0 significantly reduces the adverse events. The time period within which folic acid can be administered in relation to MTX ranges from 4 days before to 24 hours after the administration of MTX. Thus, folic acid exhibits and markedly wider “administration window” than folinic acid. At these doses and timepoints folic acid does not negatively influence the action of MTX. Folic acid has fulfilled the requirements to reduce adverse drug reactions and not to flatten the efficacy of MTX in three double-blind studies, two prospective open studies and a meta-analysis.

Schlüsselwörter

Folsäuresupplementierung - Methotrexat-Therapie - Folinsäure - Folsäure - unerwünschten Wirkungen - zeitliche Applikationsfenster - Folsäure zu MTX-Verhältnis

Key words

Folic acid supplementation - methotrexate therapy - folinic acid - folic acid - adverse events - administration window - folic acid to MTX ratio

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