Name: Lirafugratinib (Lyrfigtu) in Previously treated FGFR2 fusion or rearrangement-positive cholangiocarcinoma: Effects of Lirafugratinib on other drugs
Published: 2026-09-27T09:44:05-04:00

Product information and disease description Product description Product information Drug/Drug, drug/disease interactions

Effects of Lirafugratinib on other drugs

4 evidence topics · 3 sources

P-gp, BCRP, OATP1B1, and OATP1B3 substrates

“Monitor for increased adverse reactions for P-gp, BCRP, OATP1B1, and/or OATP1B3 substrates in which minimal concentration changes may lead to serious adverse reactions. Follow the recommended dosage modifications in the approved prescribing information for these substrates.” (opens the prescribing information at this quote)
“Lirafugratinib inhibits P-gp, BCRP, OATP1B1, and OATP1B3 in-vitro. Lirafugratinib may increase exposure of drugs that are substrates of P-gp, BCRP, OATP1B1, or OATP1B3, which may increase the risk of adverse reactions of these substrates [see Clinical Pharmacology (12.3)].” (opens the prescribing information at this quote)
“Lirafugratinib inhibits P-gp,MATE1, MATE2-K, OCT1, OCT2, OATP1B1, OATP1B3, BCRP, and BSEP, but does not inhibit OAT1 or OAT3.” (opens the prescribing information at this quote)

Cytochrome P450 substrates

“No clinically significant differences in the pharmacokinetics of the following drugs are predicted when used concomitantly with lirafugratinib: repaglinide (CYP2C8 substrate), tolbutamide (CYP2C9 substrate), omeprazole (CYP2C19 substrate), desipramine (CYP2D6 substrate), midazolam (CYP3A substrate), and caffeine (CYP1A2 substrate).” (opens the prescribing information at this quote)
“Lirafugratinib both induces and inhibits CYP2B6.” (opens the prescribing information at this quote)

Required clinical drug interaction trial with a P-gp and BCRP substrate

“Conduct a clinical pharmacokinetic trial to assess a serious potential risk of increased drug toxicity by evaluating the effect of repeat doses of lirafugratinib on the single dose pharmacokinetics of a sensitive P-gp and BCRP substrate and inform appropriate management strategies for clinically relevant drug interactions.” (opens the source at this quote in a new tab)

Preclinical inhibition of ABCG2 (BCRP)-mediated efflux

“Our findings reveal that lirafugratinib, at concentrations that do not impair cell viability, restores sensitivity to ABCG2-substrate chemotherapeutic drugs and enhances apoptosis in ABCG2-overexpressing nonsmall cell lung cancer cells.” (opens the source at this quote in a new tab)
“Mechanistically, lirafugratinib impedes the efflux capability of ABCG2 without altering its protein expression.” (opens the source at this quote in a new tab)
“Submicromolar concentrations of lirafugratinib (100–500 nM) markedly reduced the IC50 values of the ABCG2 substrate drugs mitoxantrone, SN-38, and topotecan” (opens the source at this quote in a new tab)
“In contrast, lirafugratinib had no effect on the cytotoxicity of the non-ABCG2 substrate cisplatin, used as a negative control (Fig. 2D, H, L). Notably, lirafugratinib did not enhance the efficacy of chemotherapeutic agents in ABCB1-overexpressing models (data not shown), further supporting its selectivity toward ABCG2.” (opens the source at this quote in a new tab)
“At 1 μM, lirafugratinib significantly increased intracellular PhA fluorescence in H460-MX20 (Fig. 4A), A549-Bec150 (Fig. 4B), and ABCG2-transfected HEK293 cells (Fig. 4C), to an extent comparable” (opens the source at this quote in a new tab)
“These findings indicate that ABCG2 overexpression does not measurably influence lirafugratinib cytotoxicity and support the conclusion that lirafugratinib is not efficiently transported by ABCG2 at cytotoxic concentrations.” (opens the source at this quote in a new tab)

ABCG2 substrate, resistant cell line	IC50 without lirafugratinib, nM (FR)	IC50 with lirafugratinib 0.5 μM, nM (FR)	IC50 with Ko143 1.0 μM, nM (FR)
Mitoxantrone, H460-MX20	“127.47 ± 19.02 (1.0)”	“5.26 ± 0.54*** (24.2)”	“5.10 ± 0.55*** (25.0)”
SN-38, H460-MX20	“287.93 ± 57.81 (1.0)”	“10.49 ± 2.03** (27.4)”	“5.74 ± 1.26** (50.2)”
Topotecan, H460-MX20	“476.00 ± 135.61 (1.0)”	“30.23 ± 6.11** (15.7)”	“26.77 ± 7.41** (17.8)”
Mitoxantrone, A549-Bec150	“177.86 ± 29.58 (1.0)”	“8.07 ± 0.99*** (22.0)”	“16.10 ± 2.49*** (11.0)”
SN-38, A549-Bec150	“550.15 ± 62.74 (1.0)”	“16.04 ± 2.44*** (34.3)”	“12.54 ± 1.26*** (43.9)”
Topotecan, A549-Bec150	“386.80 ± 105.85 (1.0)”	“38.02 ± 6.68** (10.2)”	“39.51 ± 8.09** (9.8)”