DENOSUMAB induced Hypocalcaemia in Advanced cancers at the Top End; Severity and Management — ASN Events

DENOSUMAB induced Hypocalcaemia in Advanced cancers at the Top End; Severity and Management (#167)

Lauren James 1 , Alison Buete 1 , Narayan Karanth 1
  1. Royal Darwin Hospital, Tiwi, NT, Australia

Background: Denosumab is a human monoclonal antibody to the receptor activator of nuclear factor-kB (RANK-L), indicated for osteoporosis and prevention of skeletal related events in patients with bone metastases from solid tumours. Hypocalcaemia is a known adverse effect of denosumab, commonly occurring within the first 6 months of treatment.1  As a result of post-marketing analysis the product information has been updated to reflect that severe symptomatic hypocalcaemia has been reported, and recommends that all patients take daily oral calcium and vitamin D supplementation.2  However there are no guidelines available for treating hypocalcaemia occurring as a result of denosumab.

Methods: A retrospective chart review was conducted to determine the incidence and severity of hypocalcaemia at the Alan Walker Cancer Centre & RDH following the introduction of denosumab.

Results: Since first dispensing in December 2011, 20 patients were treated, with a total of 100 doses. Despite all patients receiving prophylactic calcium, 15 patients (75%) had a reduction in corrected calcium from baseline, with a mean change of 0.214 mmol/L. Of these patients 4 (20%) suffered severe hypocalcaemia requiring interruption or cessation of treatment. The lowest case of corrected calcium was 1.44mmol/L, which required hospital admission and IV therapy. Hypocalcaemia in this patient is still persistent 3 months post denosumab, despite ongoing calcium and calcitriol therapy.

Conclusion: RANK-L inhibition can lead to severe and prolonged hypocalcaemia. RDH has since developed an algorithm for a step-wise approach for the management and treatment of hypocalcaemia due to denosumab, which is now being used to treat these patients.

  1. Medicines Safety Update. Denosumab and severe hypocalcaemia. Australian Prescriber 2013; 36(2):60
  2. Health Canada. Xgeva (denosumab) - risk of severe symptomatic hypocalcemia, including fatal cases - for health professionals. 2012.