LONSURF

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LONSURF (LONSURF).

How it works

LONSURF (trifluridine and tipiracil) is a combination of the thymidine-based nucleoside analogue trifluridine and the thymidine phosphorylase inhibitor tipiracil. Trifluridine incorporates into DNA and inhibits cell proliferation, while tipiracil increases trifluridine exposure by inhibiting its degradation by thymidine phosphorylase.

What the body does with it

Metabolism	Trifluridine is primarily metabolized by thymidine phosphorylase (TP) to inactive metabolites (trifluorothymine), while tipiracil is a potent TP inhibitor that prevents degradation of trifluridine. Following oral administration, tipiracil is minimally metabolized, primarily by aldehyde oxidase and xanthine oxidase, and is excreted mainly in feces.
Excretion	Primarily renal: tipiracil is excreted unchanged in urine (approximately 50% of dose); trifluridine is eliminated via metabolism and renal excretion (as metabolites and unchanged drug). Fecal elimination accounts for <3% of total clearance.
Half-life	Trifluridine: terminal half-life approximately 1.4-2.1 hours; tipiracil: terminal half-life approximately 2-3 hours. Clinical context: short half-lives necessitate twice-daily dosing on Days 1-5 and 8-12 of a 28-day cycle.
Protein binding	Trifluridine: <1% bound to plasma proteins; tipiracil: approximately 31% bound, primarily to human serum albumin.
Volume of Distribution	Trifluridine: Vd approximately 0.6-0.8 L/kg; tipiracil: Vd approximately 0.4-0.5 L/kg. Indicates distribution into total body water and some tissue binding.
Bioavailability	Oral: trifluridine absolute bioavailability is approximately 60-80%; tipiracil bioavailability is approximately 90% (relative to oral solution).
Onset of Action	Oral administration: time to peak plasma concentration (Tmax) for trifluridine is about 2 hours; tipiracil Tmax about 2-3 hours. Clinical effect (anti-tumor) occurs after multiple cycles, typically assessed after 2-3 cycles.
Duration of Action	Duration of therapeutic effect is continuous throughout the dosing cycle; drug levels decline rapidly after last dose, but antiproliferative effect on cancer cells persists over the treatment cycle.

Classification & Brands

Dosing & administration

Adults: 35 mg/m2 orally twice daily on days 1-5 and 8-12 of each 28-day cycle.

Dosage form	TABLET
Renal impairment	CrCl 30-59 mL/min: Reduce dose to 20 mg/m2 twice daily on same schedule. CrCl 15-29 mL/min: Not recommended. CrCl <15 mL/min: Not recommended.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B: Not recommended. Child-Pugh C: Not recommended.
Pediatric use	Safety and efficacy not established. No approved pediatric dosing.
Geriatric use	No specific dose adjustment required; monitor for increased toxicity due to age-related renal function decline.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LONSURF (LONSURF).

Breastfeeding	Unknown if excreted in human breast milk. Due to potential for serious adverse reactions in nursing infants (e.g., myelosuppression, gastrointestinal toxicity), breastfeeding is not recommended during LONSURF therapy and for at least 1 week after the last dose. M/P ratio: not reported.
Teratogenic Risk	FDA Pregnancy Category D. Has potential to cause fetal harm. Trimester 1: High risk of teratogenicity (based on animal studies showing embryo-fetal mortality and malformations). Trimester 2 & 3: Risk of fetal growth restriction, low birth weight, and developmental abnormalities. Avoid use in pregnant women unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

WARNING: SEVERE MYELOSUPPRESSION. LONSURF causes severe myelosuppression (neutropenia, anemia, thrombocytopenia). Withhold or permanently discontinue LONSURF based on severity. Do not start LONSURF until absolute neutrophil count is at least 1500/mm^3, platelets at least 100,000/mm^3, and hemoglobin at least 9 g/dL. Monitor blood counts at least every 2 weeks during treatment.

Side Effect Profile

Serious Effects

Absolute Contraindications

None. No absolute contraindications listed in prescribing information; use with caution in patients with severe renal impairment (creatinine clearance <30 mL/min) and moderate-to-severe hepatic impairment.

Clinical Precautions

Precautions

["Severe myelosuppression: Monitor blood counts frequently; dose modifications required for neutropenia, anemia, thrombocytopenia","Gastrointestinal toxicity: Nausea, vomiting, diarrhea, and dehydration; antiemetic therapy recommended","Increased risk of infections: Monitor for signs/symptoms; manage promptly","Fertility impairment: May impair female and male fertility","Embryo-fetal toxicity: Can cause fetal harm; advise females of reproductive potential of effective contraception"]

Clinical Tips & Counseling

Drug interactions

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LONSURF

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LONSURF (LONSURF).

How it works

What the body does with it

Metabolism	Trifluridine is primarily metabolized by thymidine phosphorylase (TP) to inactive metabolites (trifluorothymine), while tipiracil is a potent TP inhibitor that prevents degradation of trifluridine. Following oral administration, tipiracil is minimally metabolized, primarily by aldehyde oxidase and xanthine oxidase, and is excreted mainly in feces.
Excretion	Primarily renal: tipiracil is excreted unchanged in urine (approximately 50% of dose); trifluridine is eliminated via metabolism and renal excretion (as metabolites and unchanged drug). Fecal elimination accounts for <3% of total clearance.
Half-life	Trifluridine: terminal half-life approximately 1.4-2.1 hours; tipiracil: terminal half-life approximately 2-3 hours. Clinical context: short half-lives necessitate twice-daily dosing on Days 1-5 and 8-12 of a 28-day cycle.
Protein binding	Trifluridine: <1% bound to plasma proteins; tipiracil: approximately 31% bound, primarily to human serum albumin.
Volume of Distribution	Trifluridine: Vd approximately 0.6-0.8 L/kg; tipiracil: Vd approximately 0.4-0.5 L/kg. Indicates distribution into total body water and some tissue binding.
Bioavailability	Oral: trifluridine absolute bioavailability is approximately 60-80%; tipiracil bioavailability is approximately 90% (relative to oral solution).
Onset of Action	Oral administration: time to peak plasma concentration (Tmax) for trifluridine is about 2 hours; tipiracil Tmax about 2-3 hours. Clinical effect (anti-tumor) occurs after multiple cycles, typically assessed after 2-3 cycles.
Duration of Action	Duration of therapeutic effect is continuous throughout the dosing cycle; drug levels decline rapidly after last dose, but antiproliferative effect on cancer cells persists over the treatment cycle.

Classification & Brands

Dosing & administration

Adults: 35 mg/m2 orally twice daily on days 1-5 and 8-12 of each 28-day cycle.

Dosage form	TABLET
Renal impairment	CrCl 30-59 mL/min: Reduce dose to 20 mg/m2 twice daily on same schedule. CrCl 15-29 mL/min: Not recommended. CrCl <15 mL/min: Not recommended.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B: Not recommended. Child-Pugh C: Not recommended.
Pediatric use	Safety and efficacy not established. No approved pediatric dosing.
Geriatric use	No specific dose adjustment required; monitor for increased toxicity due to age-related renal function decline.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LONSURF (LONSURF).

Breastfeeding	Unknown if excreted in human breast milk. Due to potential for serious adverse reactions in nursing infants (e.g., myelosuppression, gastrointestinal toxicity), breastfeeding is not recommended during LONSURF therapy and for at least 1 week after the last dose. M/P ratio: not reported.
Teratogenic Risk	FDA Pregnancy Category D. Has potential to cause fetal harm. Trimester 1: High risk of teratogenicity (based on animal studies showing embryo-fetal mortality and malformations). Trimester 2 & 3: Risk of fetal growth restriction, low birth weight, and developmental abnormalities. Avoid use in pregnant women unless benefit outweighs risk.