Lonsurf Use In Pregnancy & Lactation

Pregnancy: Risk Summary: Based on animal data and its mechanism of action [see Pharmacology: Mechanism of Action under Actions], Lonsurf can cause fetal harm. Lonsurf caused embryo-fetal lethality and embryo-fetal toxicity in pregnant rats when given during gestation at doses resulting in exposures lower than or similar to human exposures at the recommended clinical dose (see Data as follows). There are no available data on Lonsurf use in pregnant women. Advise pregnant women of the potential risk to a fetus.
Data: Animal Data: Trifluridine/tipiracil was administered orally once daily to female rats during organogenesis at dose levels of 15, 50, and 150 mg/kg [trifluridine (FTD) equivalent]. Decreased fetal weight was observed at FTD doses ≥50 mg/kg (approximately 0.33 times the FTD exposure at the clinical dose of 35 mg/m² twice daily). At the FTD dose of 150 mg/kg (approximately 0.92 times the FTD exposure at the clinical dose of 35 mg/m² twice daily), embryolethality and structural anomalies (kinked tail, cleft palate, ectrodactyly, anasarca, alterations in great vessels, and skeletal anomalies) were observed.
Lactation: Risk Summary: There are no data on the presence of trifluridine, tipiracil or its metabolites in human milk or its effects on the breastfed child or on milk production. In nursing rats, trifluridine and tipiracil or their metabolites were present in breast milk (see Data as follows). Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Lonsurf and for 1 day following the final dose.
Data: Radioactivity was excreted in the milk of nursing rats dosed with trifluridine/tipiracil containing ¹⁴C-FTD or ¹⁴C-tipiracil (TPI). Levels of FTD-derived radioactivity were as high as approximately 50% of the exposure in maternal plasma an hour after dosing with trifluridine/tipiracil and were approximately the same as those in maternal plasma for up to 12 hours following dosing. Exposure to 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 trifluridine/tipiracil.
Females and Males of Reproductive Potential: Pregnancy Testing: Verify pregnancy status in females of reproductive potential prior to initiating Lonsurf [see Pregnancy as previously mentioned].
Contraception: Lonsurf can cause fetal harm when administered to a pregnant woman. [See Pregnancy as previously mentioned.]
Females: Advise females of reproductive potential to use effective contraception during treatment with Lonsurf and for at least 6 months after the final dose.
Males: Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use condoms during treatment with Lonsurf and for at least 6 months after the final dose. [See Pharmacology: Toxicology: Nonclinical Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility under Actions.]