lytgobi

Important safety information

Ocular Toxicity: LYTGOBI can cause retinal pigment epithelial detachment (RPED). Perform a comprehensive ophthalmological examination including optical coherence tomography (OCT) prior to initiation of therapy, every 2 months for the first 6 months, and every 3 months thereafter and urgently at any time for visual symptoms. ( 2.3 , 5.1 ) Hyperphosphatemia and Soft Tissue Mineralization: Increases in phosphate levels can cause hyperphosphatemia leading to soft tissue mineralization, calcinosis, nonuremic calciphylaxis and vascular calcification. Monitor for hyperphosphatemia and withhold, reduce the dose, or permanently discontinue based on duration and severity of hyperphosphatemia. ( 2.3 , 5.2 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of reproductive potential of the potential risk to the fetus and to use effective contraception. ( 5.3 , 8.1 , 8.3 ) 5.1 Ocular Toxicity Retinal Pigment Epithelial Detachment (RPED) LYTGOBI can cause RPED, which may cause symptoms such as blurred vision. Among 318 patients who received LYTGOBI across clinical trials [see Adverse Reactions (6.1) ] 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 LYTGOBI 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 LYTGOBI. Withhold or reduce the dose of LYTGOBI as recommended [see Dosage and Administration (2.3) ]. Dry Eye/Corneal Keratitis Among 318 patients who received LYTGOBI across clinical trials [see Adverse Reactions (6.1) ] , dry eye occurred in 15% of patients. Treat patients with ocular demulcents as needed. 5.2 Hyperphosphatemia and Soft Tissue Mineralization LYTGOBI can cause hyperphosphatemia leading to soft tissue mineralization, calcinosis, nonuremic calciphylaxis, and vascular calcification. Increases in phosphate levels are a pharmacodynamic effect of LYTGOBI [see Clinical Pharmacology (12.2) ] . Among 318 patients who received LYTGOBI across clinical trials [see Adverse Reactions (6.1) ] , 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 LYTGOBI. 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 LYTGOBI based on duration and severity of hyperphosphatemia [see Dosage and Administration (2.3) ] . 5.3 Embryo-Fetal Toxicity Based on findings in an animal study and its mechanism of action, LYTGOBI 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 LYTGOBI and for 1 week after the last dose of LYTGOBI. Advise males with female partners of reproductive potential to use effective contraception during treatment with LYTGOBI and for 1 week after the last dose [see Use in Specific Populations (8.1 , 8.3) ] .