DENOSUMAB induced Hypocalcaemia in Advanced cancers at the Top End; Severity and Management (#167)
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.
- Medicines Safety Update. Denosumab and severe hypocalcaemia. Australian Prescriber 2013; 36(2):60
- Health Canada. Xgeva (denosumab) - risk of severe symptomatic hypocalcemia, including fatal cases - for health professionals. 2012.