Can Efudix (fluorouracil) be used during pregnancy?

Efudix (Fluorouracil) is Contraindicated During Pregnancy

Fluorouracil cream (Efudix) must not be used during pregnancy as it is contraindicated due to potential teratogenic effects and risk of fetal harm. 1

Evidence for Contraindication

The FDA drug label for topical fluorouracil explicitly states that:

1. Fluorouracil cream may cause fetal harm when administered to pregnant women 1
2. It is contraindicated in women who are or may become pregnant during therapy 1
3. Patients should be informed of the potential hazard to the fetus if pregnancy occurs during treatment 1

Documented Risks

The contraindication is based on several concerning findings:

• One case of cleft lip and palate has been reported in a newborn when fluorouracil cream was used as recommended 1
• One case of ventricular septal defect and cases of miscarriage have been reported when applied to mucous membrane areas 1
• Multiple birth defects have been reported in a fetus of a patient treated with intravenous fluorouracil 1

Mechanism of Teratogenicity

While the amount of fluorouracil absorbed systemically after topical administration is typically minimal, the drug has demonstrated significant teratogenic potential:

• Animal studies show teratogenicity in mice, rats, and hamsters when given at doses equivalent to human intravenous doses 1
• Maximum teratogenicity was observed in mice with single intraperitoneal injections on specific days of gestation 1
• The drug can cause increased resorptions or embryolethality in animal models 1

Additional Considerations

Systemic Absorption Risk

Though topical application typically results in minimal systemic absorption, there are documented cases of serious systemic effects from topical 5-fluorouracil:

• A case report documented severe neutropenia in a patient after just 14 applications of topical 5-fluorouracil 2
• Patients with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency are at particularly high risk for systemic toxicity, as this enzyme is responsible for catabolizing fluorouracil 1

Alternative Approaches

For patients requiring treatment during pregnancy:

• Treatment should be deferred until after pregnancy whenever possible
• For conditions requiring immediate treatment, consultation with maternal-fetal medicine specialists and dermatologists is essential to identify safer alternative treatments

Clinical Decision Making

When considering treatment for dermatological conditions during pregnancy:

• Always check pregnancy status before prescribing Efudix
• Counsel women of childbearing potential about the need for effective contraception during treatment
• If pregnancy is detected during treatment, discontinue Efudix immediately and refer for maternal-fetal medicine consultation

The evidence is clear that the risks of fluorouracil use during pregnancy outweigh any potential benefits, and safer alternatives should be sought for pregnant patients requiring treatment for dermatological conditions.