Drug Interactions between futibatinib and Vilevev MB

MONITOR CLOSELY: The following interaction applies only to products containing sodium biphosphate that are used for bowel cleansing. It does not apply to products containing sodium biphosphate that are used for other, non-laxative related purposes.

Coadministration with agents that affect renal function or perfusion such as diuretics, ACE inhibitors, angiotensin receptor blockers, and nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of acute phosphate nephropathy associated with the use of bowel-cleansing phosphate solutions. The risk and/or severity of fluid and electrolyte disturbances may also be increased, which can lead to serious adverse events including cardiac arrhythmias, seizures, and renal impairment. Acute phosphate nephropathy is a rare adverse event that presents as acute renal failure with minimal proteinuria and a bland urine sediment. Renal biopsy findings are consistent with nephrocalcinosis and include acute and/or chronic renal tubular injury, calcium-phosphate crystal deposition in the distal tubules and collecting ducts, and no other pattern of histological injury. The risk of acute phosphate nephropathy stems from the large phosphate load, fluid shifts, and decreased intravascular volume, which can be exacerbated in the presence of medications that affect renal perfusion or function. In reported cases, acute renal failure was typically diagnosed within two to five months of colonoscopy. These cases often resulted in permanent impairment of renal function, some requiring long-term dialysis.

MANAGEMENT: Caution is advised when bowel-cleansing phosphate preparations are prescribed in patients treated with agents that affect renal function or perfusion, particularly if they are frail or elderly. Bowel-cleansing phosphate preparations should not be used in patients who have impaired renal function or perfusion, dehydration, or uncorrected electrolyte abnormalities. In patients at risk for acute phosphate nephropathy, baseline and postprocedure labs including serum electrolytes, calcium, phosphate, BUN, and creatinine should be performed. Patients should be advised not to exceed the recommended dosage of their bowel-cleansing preparation and to drink sufficient quantities of clear fluids during before, during, and after bowel cleansing. Limited data suggest that administration of an electrolyte rehydration solution may attenuate the electrolyte abnormalities and hypovolemia. Hospitalization and intravenous fluid hydration may be appropriate for frail or elderly patients who may be unable to drink an adequate volume of fluid.

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.