5-Fluorouracil (5-FU) — Drug Monograph

Brand names: Adrucil, Efudex (topical), Fluoroplex (topical)

Drug class: Antimetabolite

Mechanism of Action

Fluorinated pyrimidine analog metabolized intracellularly to FdUMP, which inhibits thymidylate synthase (TS), depleting dTTP for DNA synthesis (S-phase specific). Also incorporated into RNA as FUTP, disrupting RNA processing. Leucovorin (folinic acid) enhances FdUMP-TS binding 100-fold by stabilizing the ternary complex.

FDA Indications

• Palliative management of carcinoma of the colon, rectum, breast, stomach, and pancreas

Common Side Effects

• Mucositis/stomatitis (especially with bolus schedules)
• Nausea, vomiting, diarrhea
• Myelosuppression (more with bolus)
• Hand-foot syndrome/palmar-plantar erythrodysesthesia (more with CI)
• Alopecia
• Photosensitivity
• Elevated liver enzymes

Clinical Pearl

Cardiotoxicity from 5-FU is underrecognized. Any patient developing chest pain during infusion should have infusion stopped immediately and ECG obtained. Calcium channel blockers and nitrates are used for treatment; rechallenging with 5-FU is very high risk — capecitabine substitution may also cause cardiotoxicity (same mechanism). DPYD genotyping is becoming standard practice in Europe and is endorsed by CPIC. Uridine triacetate (Vistogard) is the emergency antidote for 5-FU (or capecitabine)…

Related Therapies & Mechanisms

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