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ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS › ANTINEOPLASTIC AGENTS › ANTIMETABOLITES › Pyrimidine analogues
tegafur, combinations
L01BC53
Forms & Strengths
- Oral capsules: tegafur 20 mg / gimeracil 5.8 mg / oteracil potassium 19.6 mg (TS-1)
Adult Dosing
- Gastric cancer: 25 mg/m² (based on tegafur) twice daily for 28 consecutive days followed by 14 days of rest; repeat every 6 weeks
- Head and neck cancer: 25-30 mg/m² twice daily for 14 consecutive days followed by 7 days of rest
- Colorectal cancer: 30-35 mg/m² twice daily for 21 consecutive days followed by 7 days of rest
Pediatric Dosing
- Safety and efficacy in pediatric patients have not been established
Indications
- Advanced gastric cancer
- Colorectal cancer
- Head and neck cancer
- Non-small cell lung cancer
Mechanism of Action
- Tegafur is a prodrug of 5-fluorouracil (5-FU), which inhibits thymidylate synthase and incorporates into RNA/DNA
- Gimeracil is a competitive inhibitor of dihydropyrimidine dehydrogenase (DPD), maintaining high 5-FU plasma concentrations
- Oteracil potassium localizes in the gastrointestinal tract to reduce the phosphorylation of 5-FU, decreasing GI toxicity
Contraindications
- Severe hypersensitivity to tegafur, gimeracil, oteracil, or 5-fluorouracil
- Severe bone marrow suppression (leukocytes < 3,000/mcL or platelets < 75,000/mcL)
- Severe renal impairment (creatinine clearance < 30 mL/min)
- Severe hepatic impairment
- Pregnancy and lactation
- Concomitant use with other fluoropyrimidine therapies or sorivudine analogues
Adverse Reactions
- Bone marrow suppression (neutropenia, thrombocytopenia, anemia)
- Gastrointestinal toxicity (diarrhea, nausea, vomiting, stomatitis, anorexia)
- Fatigue and asthenia
- Pigmentation disorders and rash
- Elevated liver enzymes and bilirubin
- Lacrimation increased
Drug Interactions
- Sorivudine and brivudine: potentially fatal pharmacokinetic interaction due to irreversible inhibition of DPD by metabolites
- Other fluoropyrimidines: increased risk of severe cumulative toxicity
- Phenytoin: increased plasma concentrations and toxicity of phenytoin due to CYP2C9 inhibition
- Warfarin: increased INR and bleeding risk due to inhibition of warfarin metabolism
Curated Content: Needs Vetting Before Put to Clinical Use