Advice for healthcare professionals:
- cases of clinically significant hypercalcaemia (rebound hypercalcaemia) have been reported up to 9 months after discontinuation of denosumab treatment for giant cell tumour of bone
- monitor patients for signs and symptoms of hypercalcaemia after discontinuation, consider periodic assessment of serum calcium, and re-evaluate the patient’s calcium and vitamin D supplementation requirements
- advise patients to report symptoms of hypercalcaemia (see list in main text)
- denosumab is not recommended in patients with growing skeletons
- report any suspected adverse reactions to denosumab or other medicines on a Yellow Card
Cases of rebound hypercalcaemia
Cases of clinically significant hypercalcaemia requiring hospitalisation and complicated by acute renal injury have been reported in a clinical trial of adults and skeletally mature adolescents with giant cell tumour of bone. Cases of rebound hypercalcemia were reported up to 9 months after discontinuation of denosumab (for description of selected cases see article). Cases have also been through some national adverse drug reaction reporting schemes. No Yellow Cards have been received of this suspected adverse drug reaction with denosumab in the UK, but continued vigilance is recommended.
The Summary of Product Characteristics for Xgeva has been updated to include risk of hypercalcaemia following discontinuation of treatment for giant cell tumour of the bone. This adverse event is thought to occur uncommonly, with an estimated frequency of occurring in fewer than 1 in every 100 patients receiving denosumab.
Symptoms of hypercalcaemia include excessive thirst, fatigue, drowsiness, confusion, loss of concentration, depression, nausea, vomiting, constipation, and muscle and/or bone pain.
Clinically significant hypercalcaemia is a known risk after stopping denosumab treatment in patients with growing skeletons; denosumab is not recommended in this patient group.
Denosumab 120 mg (Xgeva▼) is indicated for the treatment of adults and skeletally mature adolescents with giant cell tumour of bone that is unresectable or where surgical resection is likely to result in severe morbidity. See Summary of Product Characteristics.
Denosumab 120 mg is also indicated for the prevention of skeletal-related events with advanced malignancies involving bone (see June 2018 Drug Safety Update on risk of new primary malignancy.
Denosumab is also associated with the risk of hypocalcaemia usually occurring in the first weeks of treatment, although it can occur later (see Drug Safety Update articles from September 2014 and October 2012).
Denosumab 60 mg (Prolia) is indicated for the treatment of osteoporosis and bone loss. For full indication see Summary of Product Characteristics.
Report any suspected adverse drug reactions
The Medicines and Healthcare products Regulatory Agency continually monitors the safety of all medicines. All suspected adverse reactions associated with Xgeva▼, including after stopping treatment, should be reported to the Yellow Card Scheme.
Article citation: Drug Safety Update volume 11, issue 11; June 2018: 2.