Drug reference

fluorouracil

pyrimidine analogue, antimetabolite · anticancer

pyrimidine analogue, antimetaboliteanticancer

CDSCO approved

EXCRETION

—

not curated

INTERACTIONS

12 major

SEVERE in our sources

PREGNANCY

—

not curated

Top interactionssee all 12 →

AdalimumabSevereDatabaseDDInter
AnisindioneSevereDatabaseDDInter
BaricitinibSevereDatabaseDDInter
CertolizumabSevereDatabaseDDInter

Mechanism

5-Fluorouracil requires enzymatic conversion (ribosylation and phosphorylation) to the nucleotide form to exert its cytotoxic activity. Fluorodeoxyuridine monophosphate (FdUMP) inhibits thymidylate synthase (TS), blocking the synthesis of deoxythymidine triphosphate (dTTP). As triphosphate (FUTP), the drug is incorporated into RNA. FdUTP and dUTP can be incorporated into DNA, leading to strand breakage and affects on RNA processing and functions.

Indications

metastatic colon carcinomas (produces partial responses in 10-20% of patients, rarely used as single agent)upper GI tract carcinomasbreast carcinomasadjuvant therapy for colorectal cancers (in combination with leucovorin and oxaliplatin or irinotecan)premalignant keratoses of the skin (topical application)multiple superficial basal cell carcinomas (topical application)cancers of the esophagus (with radiation)stomach (with radiation)pancreas (with radiation)cervix (with radiation)anus (with radiation)head and neck (with radiation)Colon cancerRectum cancerStomach cancerPancreas cancerLiver cancerUrinary bladder cancerHead and neck cancersSuperficial basal cell carcinoma (topical)Actinic keratosis (topical)

Pharmacokinetics

Onset

not specified

Peak effect

not specified

Bioavailability

28 (0–80)%

Protein binding

not specified

Metabolism

inactivated by reduction of the pyrimidine ring by dihydropyrimidine dehydrogenase (DPD); liver dysfunction does not require dose modification due to sufficient extrahepatic degradation

Excretion

<10%

Side effects

Common

anorexianauseastomatitisdiarrheamyelosuppression (with bolus-dose regimens, leukopenia nadir 9-14 days)thrombocytopeniaanemialoss of hair (alopecia)nail changesdermatitisincreased pigmentationatrophy of the skinhand-foot syndrome (occurs more often with infusional regimens)acute chest pain (with evidence of ischemia in ECG due to coronary artery vasospasms)MyelosuppressionMucositisDiarrhoeaVomitingPeripheral neuropathy ('hand-foot syndrome')

Serious