Letters
Cancer Pharmacology
Volume 199 - Issue 4

Severe symptomatic hypocalcaemia following a single dose of denosumab

Authors:  Jennifer M McLachlan, Gavin M Marx and Margaret Bridgman

Med J Aust 2013; 199 (4): 242-243. || doi: 10.5694/mja13.10038
Published online: 2 September 2013
First-line monoclonal antibody therapy to prevent bone loss in bone-metastatic breast and prostate cancers is delivered subcutaneously, often by general practitioners who need to be aware that this treatment in patients with low vitamin D levels, impaired renal function and poor calcium absorption (all often seen in older patients) can lead to serious hypocalcaemia.
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To the Editor: Denosumab, a receptor activator of nuclear factor κ-B (RANK) ligand inhibitor, is now considered first-line therapy to prevent skeletal-related events in patients with bone metastases secondary to breast cancer and castration-resistant prostate cancer.1,2

Denosumab is administered as a subcutaneous injection, which enables it to be used in the primary care setting. This makes it important that doctors are aware of the potential toxicities.

We describe a case of severe symptomatic hypocalcaemia in a 91-year-old woman with symptomatic bone-dominant metastatic breast cancer after being treated with denosumab. She had the predisposing factor of a low baseline 25-hydroxyvitamin D level, and was treated with cholecalciferol (3000 IU daily) and calcium supplementation (600 mg twice daily) at the time of initiation of denosumab therapy. Her renal function was normal.

The patient’s general practitioner administered a single subcutaneous dose of denosumab (120 mg) with the intention of delivering monthly doses on an ongoing basis. The patient’s calcium level was monitored regularly, but at Week 7, she presented with signs of tetany, with paraesthesiae of the extremities, perioral paraesthesia and carpopedal spasm, and with a corrected serum calcium level of 1.43 mmol/L (reference interval, 2.0–2.55 mmol/L).

She required an intravenous infusion of calcium gluconate, an increase in oral calcium supplementation, and was given calcitriol at a dose of 0.5 μg twice daily in place of cholecalciferol, because of its rapid onset of action. Over the next 4 weeks, the patient was admitted to hospital three times, requiring intravenous calcium replacement in association with symptoms of tetany.

The incidence of hypocalcaemia with denosumab is reported to be 9%,1,2 and recent evidence suggests that patients at particular risk of symptomatic hypocalcaemia include those with advanced disease, low vitamin D levels, impaired renal function and poor calcium absorption;3 these features are commonly seen in older patients, as in the case we report here. Patients with severe renal impairment (creatinine clearance < 30 mL/min) are at greater risk of developing hypocalcaemia.4

There are no guidelines for the prevention of hypocalcaemia with denosumab therapy, and current practice adheres to protocols used in Phase III clinical trials.1,2 Calcium and vitamin D levels should be corrected before initiating denosumab therapy, and daily supplemental calcium (≥ 500 mg) and vitamin D (≥ 400 IU) are recommended for the duration of the treatment. Serum calcium levels should be monitored regularly.

Symptomatic or severe hypocalcaemia (corrected serum calcium level, < 1.75 mmol/L) should be corrected with 10 mL of 10% calcium gluconate infused over 10 minutes, followed by a slow intravenous infusion.5

Authors

  • Jennifer M McLachlan1
  • Gavin M Marx1
  • Margaret Bridgman1
  • 1. Sydney Adventist Hospital, Sydney, NSW.

Correspondence: jenny.clare@gmail.com

Competing interests

No relevant disclosures.

Acknowledgements

We thank the patient for allowing us to report this case.

References

View this article on Wiley Online Library