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TOMUDEX (raltitrexed) is indicated for use as a palliative treatment of advanced colorectal cancer where 5-fluorouracil and folinic acid based regimens are either not tolerated or inappropriate1.

TOMUDEX was first authorised for use in the UK in 2000 for use in advanced colorectal cancer1

TOMUDEX Mode of Action

TOMUDEX is a folate analogue belonging to the family of anti-metabolite chemotherapy medicines and has potent inhibitory activity against the enzyme thymidylate synthase (TS). Compared to other antimetabolites such as 5-fluorouracil or methotrexate, raltitrexed acts as a direct and specific TS inhibitor1

TS is a key enzyme in the de novo synthesis of thymidine triphosphate (TTP), a nucleotide required exclusively for deoxyribonucleic acid (DNA) synthesis. Inhibition of TS leads to DNA fragmentation and cell death. TOMUDEX is transported into cells via a reduced folate carrier (RFC) and is then extensively polyglutamated by the enzyme folyl polyglutamate synthetase (FPGS) to polyglutamate forms that are retained in cells and are even more potent inhibitors of TS1

TOMUDEX polyglutamation* enhances TS inhibitory potency and increases the duration of TS inhibition in cells which may improve antitumour activity. Polyglutamation could also contribute to increased toxicity due to drug retention in normal tissues1.


  1. TOMUDEX® Summary of Product Characteristics