Drug Interactions between ferric pyrophosphate and futibatinib

MONITOR: Coadministration of agents that can increase serum phosphate levels during treatment with fibroblast growth factor receptor (FGFR) inhibitors may lead to elevated serum phosphate levels. The mechanism appears to be related to the pharmacodynamic effects of FGFR inhibition, which has been shown to lead to an increase in serum phosphate levels, including hyperphosphatemia. Hyperphosphatemia can cause precipitation of calcium-phosphate crystals which over time can lead to hypocalcemia, soft tissue mineralization such as cutaneous calcification and calcinosis, secondary hyperparathyroidism, anemia, muscle cramps, seizures, QT prolongation, and arrhythmias. Soft tissue mineralization, including cutaneous calcification, calcinosis, and non-uremic calciphylaxis have been observed during treatment with other FGFR inhibitors.

MANAGEMENT: Close monitoring of serum phosphate levels is recommended throughout treatment with FGFR inhibitors, including futibatinib and pemigatinib, particularly at the start of therapy and if used concomitantly with agents that may increase serum phosphate levels. Agents that may increase serum phosphate levels include potassium phosphate supplements, vitamin D supplements, antacids, phosphate-containing enemas or laxatives, and medications known to have phosphate as an excipient. In the event of hyperphosphatemia, dose adjustment of the FGFR inhibitor, use of phosphate-lowering therapy, dietary phosphate restriction, and/or temporary or permanent cessation of the FGFR inhibitor may be required, depending on the duration and severity of the hyperphosphatemia. The manufacturer's product labeling should be consulted for further information and dosage adjustment guidance.