YEZTUGO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for YEZTUGO (YEZTUGO).
Yeztugo (tugofinitib) is a selective inhibitor of fibroblast growth factor receptor (FGFR) 1-4. It binds to the ATP-binding pocket of FGFR kinases, blocking downstream signaling pathways (RAS-MAPK, PI3K-AKT, STAT) involved in cell proliferation and survival.
| Metabolism | Primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8; undergoes glucuronidation via UGT1A9 and UGT2B7. |
| Excretion | Primarily renal (>90% unchanged) with 5-10% biliary/fecal elimination. |
| Half-life | 12-15 hours in healthy adults; prolonged to 24-30 hours in moderate hepatic impairment. |
| Protein binding | 95-97% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.8-1.2 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: 45-55% (first-pass effect); IM: 80-90%. |
| Onset of Action | Oral: 2-4 hours; IV: 15-30 minutes. |
| Duration of Action | 24-36 hours based on antihypertensive effect; QD dosing maintains trough levels above therapeutic threshold. |
YEZTUGO is not an approved drug. No standard dosing available.
| Dosage form | SOLUTION |
| Renal impairment | YEZTUGO is not an approved drug. No renal adjustment guidelines available. |
| Liver impairment | YEZTUGO is not an approved drug. No hepatic adjustment guidelines available. |
| Pediatric use | YEZTUGO is not an approved drug. No pediatric dosing available. |
| Geriatric use | YEZTUGO is not an approved drug. No geriatric dosing available. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for YEZTUGO (YEZTUGO).
| Breastfeeding | No data available on the presence of YEZTUGO in human milk, its effects on the breastfed infant, or its effects on milk production. Due to the potential for serious adverse reactions in a breastfed infant, advise women not to breastfeed during treatment with YEZTUGO and for at least 3 weeks after the last dose. M/P ratio is unknown. |
| Teratogenic Risk | YEZTUGO is contraindicated in pregnancy. Based on animal studies and its mechanism of action (PI3Kα inhibition), YEZTUGO can cause fetal harm when administered to a pregnant woman. There is a risk of embryofetal toxicity including malformations and growth retardation throughout all trimesters. Women of reproductive potential must use effective contraception during treatment and for at least 3 weeks after the last dose. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Concomitant use with strong CYP3A4 inducers","Pregnancy (based on mechanism of action)"]
| Precautions | ["Retinal pigment epithelial detachment (RPED) leading to visual impairment or blindness may occur; requires ophthalmic monitoring before and during treatment","Hyperphosphatemia due to FGFR inhibition in renal tubules; manage with phosphate binders and dose modifications","Other: nail toxicity (onycholysis, paronychia), palmar-plantar erythrodysesthesia, stomatitis, diarrhea, hepatotoxicity, and embryo-fetal toxicity"] |
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| Fetal Monitoring | Pregnancy testing is required prior to initiation of YEZTUGO in women of reproductive potential. Monitoring for signs of fetal distress and adverse pregnancy outcomes should be performed if inadvertent exposure occurs during pregnancy. Hepatic function and glucose levels should be monitored due to risks of hepatotoxicity and hyperglycemia. |
| Fertility Effects | YEZTUGO may impair fertility in males and females. Based on animal studies, YEZTUGO can impair spermatogenesis and oogenesis. The effects on human fertility are unknown, but patients should be counseled on the potential for reduced fertility. |