Drug Interactions between acetaminophen / caffeine / magnesium salicylate / phenyltoloxamine and erdafitinib

MONITOR CLOSELY: Coadministration with agents that can alter serum phosphate levels may affect the initial dosage determination of erdafitinib. The mechanism appears to be related to the pharmacodynamic effects of fibroblast growth factor receptor (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. In clinical trials with erdafitinib, hyperphosphatemia (all grades) was reported as an adverse event in 76% of erdafitinib-treated patients, with a median onset time of 20 days, requiring phosphate binder therapy in 32% of patients. During these clinical trials, agents known to increase serum phosphate levels (e.g., potassium phosphate supplements, vitamin D supplements, some antacids, phosphate-containing enemas or laxatives, and medications known to have phosphate as an excipient) were prohibited with erdafitinib therapy unless no alternative was available; however, phosphate binders were permitted to treat increases in serum phosphate levels.

MANAGEMENT: The manufacturer of erdafitinib advises avoiding concomitant use with agents that may alter serum phosphate levels before its initial dose increase period, which is between 14 to 21 days of starting erdafitinib therapy and is based on serum phosphate levels. This includes agents that may decrease serum phosphate levels, such as phosphate binders, or increase serum phosphate levels, such as potassium phosphate supplements, vitamin D supplements, antacids, phosphate-containing enemas or laxatives, and medications known to have phosphate as an excipient. In addition, close monitoring of serum phosphate levels is recommended throughout treatment with erdafitinib, particularly if used concomitantly with agents that may increase serum phosphate levels. In the event of hyperphosphatemia, dose adjustment of erdafitinib, use of phosphate-lowering therapy, dietary phosphate restriction, and/or temporary or permanent treatment cessation of erdafitinib may be required according to the duration and severity of the hyperphosphatemia. The manufacturer's product labeling should be consulted for further information and dosage adjustment guidance.

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