LYTGOBI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LYTGOBI (LYTGOBI).
Futibatinib is a selective, irreversible inhibitor of fibroblast growth factor receptor (FGFR) 1-4. It binds covalently to the ATP-binding pocket of FGFR, inhibiting downstream signaling and reducing tumor cell proliferation and angiogenesis.
| Metabolism | Primarily metabolized by CYP3A4 and to a lesser extent by CYP2D6 and CYP2C9. |
| Excretion | Primarily fecal (approximately 81% of administered dose) with renal excretion accounting for <1% as unchanged drug. Biliary excretion contributes to fecal elimination. |
| Half-life | Terminal elimination half-life is approximately 9 hours (range 6–12 hours) following oral administration, supporting twice-daily dosing. |
| Protein binding | ≥99.7% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution (Vd/F) is approximately 1000 L (≈14 L/kg for a 70 kg patient), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is not determined; absolute bioavailability unknown. Absorption is rapid with Tmax 2–4 hours; food does not significantly affect absorption. |
| Onset of Action | Oral: Peak plasma concentrations (Tmax) occur at 2–4 hours; clinical antitumor effect observed within 2–4 weeks of continuous dosing. |
| Duration of Action | Durable target inhibition with continuous dosing; treatment continued until disease progression or unacceptable toxicity. Duration variable based on individual response. |
4 mg orally once daily, taken on an empty stomach (at least 1 hour before or 2 hours after food), until disease progression or unacceptable toxicity.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min). For severe renal impairment (eGFR 15-29 mL/min), reduce dose to 3 mg once daily. Not recommended in end-stage renal disease (eGFR <15 mL/min) or on dialysis. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose to 3 mg once daily. Child-Pugh C: Not recommended. |
| Pediatric use | Safety and efficacy have not been established in pediatric patients; no specific dosing guidelines available. |
| Geriatric use | No specific dose adjustment recommended; monitor renal function and tolerability due to potential age-related decline in organ function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LYTGOBI (LYTGOBI).
| Breastfeeding | There are no data on the presence of futibatinib in human milk, its effects on the breastfed infant, or its effects on milk production. Because of the potential for serious adverse reactions in breastfed infants from LYTGOBI, advise women not to breastfeed during treatment and for at least 1 week after the last dose. M/P ratio is unknown. |
| Teratogenic Risk | LYTGOBI (futibatinib) is an FGFR inhibitor. Based on its mechanism of action and animal studies, it is expected to cause fetal harm when administered to a pregnant woman. In animal reproduction studies, oral administration of futibatinib to pregnant rats during organogenesis resulted in embryo-fetal mortality and structural anomalies at maternal exposures below the human exposure at the recommended dose. There are no adequate and well-controlled studies in pregnant women. Advise pregnant women of the potential risk to the fetus. First trimester: highest risk of major congenital malformations; second and third trimesters: risk of fetal growth restriction and fetal demise. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Concurrent use with strong or moderate CYP3A4 inducers"]
| Precautions | ["Retinal pigment epithelial detachment (RPED) and other ocular toxicities","Hyperphosphatemia due to FGFR inhibition","Embryo-fetal toxicity","May cause QT prolongation"] |
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| Fetal Monitoring | Monitor pregnancy status in women of reproductive potential. Perform pregnancy testing prior to initiation of LYTGOBI. During treatment, monitor for signs of fetal distress via standard obstetric ultrasound and fetal growth assessments if pregnancy is suspected or confirmed. Also monitor for maternal toxicities including hyperphosphatemia, nail toxicity, and ocular toxicity as per prescribing information, which may indirectly affect fetal well-being. |
| Fertility Effects | Based on findings in animals, LYTGOBI may impair fertility in females and males of reproductive potential. In female rats, effects on fertility included decreased corpora lutea and implantation sites at clinically relevant exposures. In male rats, there were no effects on mating or fertility but testicular degeneration was observed. The reversibility of these effects is unknown. |