Hypocalcaemia and hypophosphataemia following denosumab and IV ferric carboxymaltose in an older patient with normal renal function

Abstract

Background Severe hypocalcaemia and hypophosphataemia following the co‐administration of denosumab and IV ferric carboxymaltose has previously been reported in the setting of chronic kidney disease and malignancy. Despite scarce evidence, there has been growing concern amongst clinicians of a possible drug interaction between denosumab and IV iron therapies. Although electrolyte abnormalities are well known side effects of these individual therapies, it is possible that co‐administration of the agents can exaggerate these effects and result in a potentially life‐threatening interaction. Aim We present a case of profound hypocalcaemia and hypophosphataemia following same day administration of denosumab and IV ferric carboxymaltose in a hospitalised older patient. Clinical details An older female with normal renal function, serum calcium, phosphate and 25‐hydroxy‐vitamin D levels, and no history of malignancy was given denosumab 60 mg SC for secondary fracture prophylaxis following an acute osteoporotic fracture. On the same day, she received ferric carboxymaltose 1 g IV for treatment of iron‐deficiency anaemia. Outcomes Following a review of her pathology results during the inpatient hospital admission, profound hypocalcaemia and hypophosphataemia was identified 8 days after denosumab and ferric carboxymaltose administration. Despite supplementation, electrolyte abnormalities persisted for 12 days following administration. Conclusion Although the patient had no pre‐existing risk factors for developing electrolyte disturbance, profound hypocalcaemia and hypophosphatemia following denosumab and IV ferric carboxymaltose administration occurred, suggesting a possible interaction between the two therapies. Caution should be exercised by clinicians when these agents are co‐administered within a close timeframe.

Interaction between ferric carboxymaltose and denosumab causing severe hypocalcaemia and hypophosphataemia in a patient without chronic kidney disease

“…7,10 To our knowledge, only one case of such electrolyte derangements in a patient without CKD has been previously reported. 8 Although our patient demonstrated poor renal function on admission to GEM, the onset of her hypocalcaemia occurred prior to the acute decline in renal function and was likely subsequently compounded by an AKI.…”

“…Notably, the authors believed this to require an overlay of chronic kidney disease (CKD); however, a recent report suggests this interaction can occur in the presence of normal renal function. 8 We present a case of declining serum calcium and severe hypophosphataemia following denosumab injection and iron infusion in an older patient without previous CKD (as per the Kidney Disease Improving Global Outcomes definition of CKD, noting that the equation used to calculate eGFR overestimates kidney function in older patients with sarcopena) 9 and replete vitamin D levels. Notably, her creatinine clearance was low but relatively normal for her age.…”

“…Similarly, the ferric carboxymaltose–induced hypophosphataemia is thought to be compounded by the administration of denosumab and further renal phosphate wasting due to a rise in PTH secondary to hypocalcaemia. Notably, the authors believed this to require an overlay of chronic kidney disease (CKD); however, a recent report suggests this interaction can occur in the presence of normal renal function 8 . We present a case of declining serum calcium and severe hypophosphataemia following denosumab injection and iron infusion in an older patient without previous CKD (as per the Kidney Disease Improving Global Outcomes definition of CKD, noting that the equation used to calculate eGFR overestimates kidney function in older patients with sarcopena) 9 and replete vitamin D levels.…”

Intravenous iron: an update

“…41 Risk factors for hypophosphataemia following intravenous iron include baseline hypophosphataemia, repeated iron infusions, malnutrition and the use of concurrent antiresorptive therapy. 42,43 Impaired renal function is protective against iron-induced hypophosphataemia. 41 In a meta-analysis of 42 clinical trials, the pooled incidence of hypophosphataemia following ferric carboxymaltose was 47% (95% confidence interval [CI], 36-58%), compared with 4% (95% CI, 2-5%) following ferric derisomaltose.…”

“…Typically, the phosphate nadir occurs 1–2 weeks following administration, but persistence for longer than 3 months has been noted following a single infusion in patients treated with ferric carboxymaltose 41 . Risk factors for hypophosphataemia following intravenous iron include baseline hypophosphataemia, repeated iron infusions, malnutrition and the use of concurrent antiresorptive therapy 42,43 . Impaired renal function is protective against iron‐induced hypophosphataemia 41 .…”