Tegafur + Uracil is a fixed-dose oral fluoropyrimidine combination used primarily in the treatment of gastrointestinal cancers. Tegafur is a prodrug of 5-fluorouracil (5-FU), and uracil competitively inhibits the enzyme dihydropyrimidine dehydrogenase (DPD), which degrades 5-FU, thereby prolonging its half-life and enhancing its antitumor activity. This combination allows for convenient oral administration with a more favorable pharmacokinetic profile compared to intravenous 5-FU.
Adult: Standard dose: Tegafur 300-400 mg/m²/day (in divided doses) + Uracil in a fixed 1:4 molar ratio. Common regimen: 2 capsules of Tegafur 100mg + Uracil 224mg, taken orally three times daily (total 600 mg tegafur/day) for 28 days, followed by a 7-day rest period (35-day cycle). Dose is based on body surface area (BSA).
Note: Take capsules with a full glass of water, within 1 hour after a meal to reduce gastrointestinal upset. Do not crush or chew. Doses should be spaced evenly throughout the day (e.g., every 8 hours).
Tegafur is a prodrug that is converted hepatically to the active metabolite 5-fluorouracil (5-FU). 5-FU exerts its cytotoxic effect through two primary mechanisms: 1) Inhibition of thymidylate synthase (TS) by its metabolite fluorodeoxyuridine monophosphate (FdUMP), which disrupts DNA synthesis. 2) Incorporation of its metabolites (FUTP, FdUTP) into RNA and DNA, leading to dysfunctional nucleic acid synthesis and cell death. Uracil, a natural pyrimidine base, competitively inhibits the enzyme dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme in 5-FU catabolism. This inhibition results in sustained plasma and tumor tissue concentrations of 5-FU, enhancing its efficacy.
Pregnancy: Category D: Positive evidence of human fetal risk. Can cause fetal harm. Contraindicated. Women of childbearing potential must use effective contraception during and for at least 6 months after therapy.
Driving: May cause dizziness, fatigue, or visual disturbances. Patients should be cautioned about operating machinery or driving until they know how the medication affects them.
| Warfarin and other Coumarin Anticoagulants | Increased anticoagulant effect and risk of bleeding due to protein binding displacement and possible reduced metabolism. | Major |
| Phenytoin | Increased phenytoin levels and risk of toxicity. Tegafur may inhibit CYP2C9. | Major |
| Leucovorin (Calcium Folinate) | Potentiates the cytotoxic effect of 5-FU by stabilizing the ternary complex with thymidylate synthase. Used therapeutically but requires careful monitoring for increased toxicity. | Moderate |
| Allopurinol | May decrease the efficacy of 5-FU by interfering with its activation pathway. Generally not co-administered. | Moderate |
| Live Vaccines (e.g., MMR, Varicella, Yellow Fever) | Risk of disseminated vaccine-induced infection due to immunosuppression. Contraindicated. | Major |
| CYP2A6 Inhibitors (e.g., Methoxsalen, Tranylcypromine) | May decrease conversion of tegafur to 5-FU, reducing efficacy. | Moderate |
| CYP2A6 Inducers (e.g., Rifampicin) | May increase conversion of tegafur to 5-FU, potentially increasing toxicity. | Moderate |
Same composition (Tegafur (100mg) + Uracil (224mg)), different brands: