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. |
| Molecular Weight | 480.5 |
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 | Based on animal studies and its mechanism of action (FGFR inhibitor), LYTGOBI (futibatinib) can cause fetal harm when administered to a pregnant woman. There are no adequate human studies in first trimester. Advise pregnant women of potential risk to fetus. |
| 2nd trimester | Same as first trimester. Animal studies show teratogenicity and embryofetal toxicity. Avoid use unless maternal benefit outweighs fetal risk. |
| 3rd trimester | Potential for fetal harm, including possible oligohydramnios and fetal renal impairment due to FGFR inhibition in development. Use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for LYTGOBI (LYTGOBI).
| Placental transfer | Based on molecular weight (less than 500 Da) and lipophilicity, likely crosses placenta. Animal studies confirm fetal exposure and toxicity. |
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or effects on milk production. Due to potential for serious adverse reactions in breastfed infant, advise women not to breastfeed during treatment and for 1 week after last dose. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to futibatinib or any excipients
| Precautions | Retinal pigment epithelial detachment (RPED) and other ocular toxicities, Hyperphosphatemia due to FGFR inhibition, Embryo-fetal toxicity, May cause QT prolongation |
| Food/Dietary | Avoid grapefruit, grapefruit juice, and Seville oranges as they are strong CYP3A4 inhibitors and can increase futibatinib exposure. No other specific food interactions are documented. For hyperphosphatemia management, dietary phosphate restriction may be recommended. |
| Clinical Pearls |
Loading safety data…
| Lactation Rating | L5 (Contraindicated) |
| 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. |
| 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. |
| LYTGOBI (futibatinib) is a fibroblast growth factor receptor (FGFR) inhibitor. Monitor for hyperphosphatemia, as FGFR inhibition disrupts FGF23 signaling; initiate phosphate-lowering therapy if serum phosphate >5.5 mg/dL. Check ophthalmologic exams for retinal pigment epithelial detachment (RPED) due to FGFR inhibition in the retina. Avoid concomitant use with strong CYP3A4 inhibitors or inducers; adjust dose accordingly. |
| Patient Advice | Take LYTGOBI exactly as prescribed, typically once daily with or without food. · You will need regular blood tests to monitor phosphate levels; high phosphate can be managed with medications or dietary changes. · Report any visual changes such as blurred vision, floaters, or sudden loss of vision immediately. · Avoid grapefruit, grapefruit juice, and Seville oranges during treatment. · Inform your doctor about all medications, including over-the-counter drugs and supplements, to avoid interactions. · Use effective contraception during treatment and for at least 1 week after the last dose if you or your partner can become pregnant. |