Precautions of Futibatinib

1 Ocular Toxicity  

Retinal Pigment Epithelial Detachment (RPED)  

Futibatinib can cause RPED, which may cause symptoms such as blurred vision.

Among 318 patients who received Futibatinib across clinical trials where  ophthalmologic monitoring did not routinely include optical coherence tomography (OCT), RPED occurred in  9% of patients. The median time to first onset of RPED was 40 days. RPED led to dose interruption of  Futibatinib in 1.3% of patients, dose reduction in 1.6% of patients, and permanent discontinuation in 0.3% of  patients.

Perform a comprehensive ophthalmological examination, including OCT of the macula, prior to initiation of  therapy, every 2 months for the first 6 months, and every 3 months thereafter. For onset of visual symptoms,  refer patients for ophthalmologic evaluation urgently, with follow-up every 3 weeks until resolution or  discontinuation of Futibatinib.

Withhold or reduce the dose of Futibatinib as recommended.

2 Hyperphosphatemia and Soft Tissue Mineralization  

Futibatinib can cause hyperphosphatemia leading to soft tissue mineralization, calcinosis, nonuremic  calciphylaxis, and vascular calcification. Increases in phosphate levels are a pharmacodynamic effect of  Futibatinib . Among 318 patients who received Futibatinib across clinical  trials, hyperphosphatemia was reported in 88% of patients based on laboratory  values above the upper limit of normal. The median time to onset of hyperphosphatemia was 5 days (range 3- 117). Phosphate binders were received by 77% of patients who received Futibatinib.

Monitor for hyperphosphatemia throughout treatment. Initiate a low phosphate diet and phosphate lowering  therapy when serum phosphate level is ≥5.5 mg/dL. For serum phosphate levels >7 mg/dL, initiate or intensify  phosphate lowering therapy and dose reduce, withhold, or permanently discontinue Futibatinib based on  duration and severity of hyperphosphatemia.

3 Embryo-Fetal Toxicity  

Based on findings in an animal study and its mechanism of action, Futibatinib can cause fetal harm when  administered to a pregnant woman. Oral administration of futibatinib to pregnant rats during the period of  organogenesis caused fetal malformations, fetal growth retardation, and embryo-fetal death at maternal  exposures lower than the human exposure at the clinical dose of 20 mg based on area under the curve (AUC).

Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential to use  effective contraception during treatment with Futibatinib and for 1 week after the last dose of Futibatinib.

Advise males with female partners of reproductive potential to use effective contraception during treatment with  Futibatinib and for 1 week after the last dose.

FDA，2022.09