Animal studies revealed evidence of embryofetal lethality and structural anomalies with the trifluridine (FTD) dose of 150 mg/kg, approximately 0.92 times the FTD exposure at the clinical dose of 35 mg/m2 twice daily. Structural anomalies observed were cleft palate, skeletal anomalies, alterations in great vessels, kinked tail, ectrodactyly, and anasarca. Male and female fertility in animals was not affected; however, dose-related increases in the corpus luteum count and implanted embryo count were observed. There are no controlled data in human pregnancy.

AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D and X are being phased out.

Use is not recommended.

AU TGA pregnancy category: D
US FDA pregnancy category: Not Assigned

Risk Summary: Based on animal data and its mechanism of action this drug can cause fetal harm. It caused embryofetal toxicity and lethality in pregnant animals when given during gestation at doses resulting in exposures lower than equivalent human exposures at the recommended dose.

Comments:
-Advise females of reproductive potential to use effective contraception during therapy and for at least 6 months after.
-Males with female partners of reproductive potential should be advised to use condoms during treatment and for at least 3 months after the final dose because of the genotoxicity potential.
-Verify negative pregnancy status in females of reproductive potential prior to initiating therapy.
-If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.

See references

Animal studies reveal levels of trifluridine (FTD)-derived radioactivity were as high as approximately 50% of the exposure in maternal plasma 1 hour after dosing and were approximately the same as those in maternal plasma for up to 12 hours following dosing. Exposure to tipiracil (TPI)-derived radioactivity was higher in milk than in maternal plasma beginning 2 hours after dosing and continuing for at least 12 hours following administration of this drug.

Use is not recommended.

Excreted into human milk: Unknown
Excreted into animal milk: Yes

Comments:
-Women should not breastfeed during therapy and for one week after.

See references