Drug products: Efudix, Efudix 5% cream, Efudix cream, Efudix Meda, Efudix MEDA Pharma, Efudix MEDA Pharma GmbH, Fluorouracil Accord, Fluorouracil Sandoz, Fluorouracil Teva, Flurablastin®, Tolak
ATC code: L01BC02
Female sex is correlated with higher risk of side effects from 5-fluorouracil (5-FU). Sex differences in the pharmacokinetics of 5-FU as infusion have been noted and some studies indicate increased exposure to 5-FU in women. However, no sex-related difference in outcome has been found for 5-FU alone or in combination therapy.
Since chemotherapeutic agents share some adverse effects, evaluation of a particular agent’s safety during combination chemotherapy is complicated.
A pharmacokinetic study on patients (301 men, 79 women) showed a wide variability in the clearance rate of 5-FU (L/h/m2) among both men and women, and a significantly faster clearance rate in men (median 179; range 29-739, vs median 155; range 56-466)  .
Results of a prospective population pharmacokinetic study showed sex-specific elimination of continuous-infusional 5-FU in patients with gastrointestinal malignancies (21 men, 10 women). Men had a 26% higher elimination of 5-FU, and lower AUC of 5-FU compared to women (18 vs. 22 mg h/L) .
A pooled analysis from five5 randomized clinical trials of metastatic colorectal cancer patients (1925 men, 1298 women) who were mainly treated with FOLFOX (folinic acid, fluorouracil, and oxaliplatin)-based regimens found no difference in overall survival, or progression-free survival between men and women .
An analysis of five randomized clinical trials of metastatic colorectal cancer patients found that women had a higher rate of gastrointestinal and hematologic toxicities than men. Women were also more likely to experience alopecia, diarrhea, nausea and vomiting, anemia, and neutropenia .
Patients with stage II and stage III colon cancer were randomly allocated to receive leucovorin and fluorouracil with irinotecan biweekly (FOLFIRI, 351 men, 247 women) or without irinotecan biweekly (LV/5-FU, 340 men, 254 women) after curative surgery. Women compared to men had a higher risk for grade III-IV neutropenia in the FOLFIRI arm (OR 2.2, 95% CI: 1.8-2.8), but not in the LV/5-FU arm [4, 5].
Fetal defects and miscarriages have been reported. Women of childbearing potential and their partner should be advised against becoming pregnant and advised to use effective contraception during and 6 months after treatment with 5-FU. If the medicine is used during pregnancy or if the patient becomes pregnant while taking the medicine, she should be given complete information about the potential danger to the fetus; genetic counseling is recommended .
For more information regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2021-03-06
Reviewed by: Diana Rydberg
Approved by: Karin Schenck-Gustafsson