Denosumab — marketed as Xgeva and as Prolia — is associated with a rare but well-known risk for severe hypocalcemia (very low calcium in the blood stream). Denosumab, when give as Xgeva, is specifically indicated for the prevention of skeletal-related events in patients with bone metastases from prostate and other forms of cancer.
A recent case study reported by Muqeet Adnan et al. emphasizes the importance of patients having their serum levels of vitamin D and calcium checked prior to any initial administration of denosumab for the prevention of bone loss and other skeletal-related events. This case was observed in a patient with metastatic prostate cancer who was administered denosumab prior to any check of his vitamin D or calcium levels, and who developed severe hypocalcemia after initial treatment with denosumab. He was then found to also have low levels of vitamin D, and the authors hypothesize that this may have predisposed the patients to risk for hypocalcemia as a consequence of denosumab therapy.
The consequences of hypocalcemia can be severe. This patient required hospitalization and initial therapy with high doses of oral and intravenous calcium and vitamin D. However, he did not respond well to this type of initial therapy; as a resulst he developed hydronephrosis (fluid in the kidneys) associated with the spread of his cancer, and this led to the necessity for dialysis to manage acute renal failure and to correct the hypocalcemia.\
The prescribing information for denosumab (Xgeva) very clearly states that:
- Pre-existing hypocalcemia must be corrected prior to initiating therapy with XGEVA®(denosumab). XGEVA® can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Monitor levels more frequently when XGEVA® is administered with other drugs that can also lower calcium levels. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.
- Based on clinical trials using a lower dose of denosumab, patients with a creatinine clearance less than 30 mL/min or receiving dialysis are at greater risk of severe hypocalcemia compared to patients with normal renal function. The risk of hypocalcemia at the recommended dosing schedule of 120 mg every 4 weeks has not been evaluated in patients with a creatinine clearance less than 30 mL/min or receiving dialysis.
If your doctor advises you that you would be appropriately treated with denosumab for prevention of skeletal-related events associated with advanced forms of prostate cancer (particularly in men with metastatic disease on long-term androgen deprivation therapy), you need to be sure that your serum calcium and vitamin D levels are monitored prior to initiation of therapy.