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Fluorouracil - intravenous

Classification: C!

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.

Additional information

Since chemotherapeutic agents share some adverse effects, evaluation of a particular agent’s safety during combination chemotherapy is complicated.

Pharmacokinetics and dosing

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) [1] .

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) [2].


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 [3].

Adverse effects

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 [3].

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].

Reproductive health issues

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 [6].

For more information regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Updated: 2021-06-07

Date of litterature search: 2021-03-06


  1. Milano G, Etienne MC, Cassuto-Viguier E, Thyss A, Santini J, Frenay M et al. Influence of sex and age on fluorouracil clearance. J Clin Oncol. 1992;10(7):1171-5. PubMed
  2. Mueller F, Büchel B, Köberle D, Schürch S, Pfister B, Krähenbühl S, Froehlich TK, Largiader CR, Joerger M. Gender-specific elimination of continuous-infusional 5-fluorouracil in patients with gastrointestinal malignancies: results from a prospective population pharmacokinetic study. Cancer Chemother Pharmacol. 2013;71(2):361-70. länk
  3. Abdel-Rahman O. Impact of Sex on Chemotherapy Toxicity and Efficacy Among Patients With Metastatic Colorectal Cancer: Pooled Analysis of 5 Randomized Trials. Clin Colorectal Cancer. 2019;18(2):110-115. länk
  4. Van Cutsem E, Labianca R, Bodoky G, Barone C, Aranda E, Nordlinger B et al. Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3. J Clin Oncol. 2009;27(19):3117-25. PubMed
  5. Tejpar S, Yan P, Piessevaux H, Dietrich D, Brauchli P, Klingbiel D et al. Clinical and pharmacogenetic determinants of 5-fluorouracyl/leucovorin/irinotecan toxicity: Results of the PETACC-3 trial. Eur J Cancer. 2018;99:66-77. PubMed
  6. Fluorouracil Accord (fluorouracil). Summary of Product Characteristics. Swedish Medical Products Agency [updated 2020-12-16, cited 2021-06-03]
  7. Concise (INSIKT). Kalmar: eHälsomyndigheten. 2018 [cited 2019-03-14.] länk

Authors: Alan Fotoohi

Reviewed by: Diana Rydberg

Approved by: Karin Schenck-Gustafsson