South Western Sydney Local Health District has issued the following advice about denosumab.
Denosumab 60 mg subcutaneously six-monthly (Prolia) is a monoclonal antibody which is PBS indicated in Australia for the treatment of osteoporosis.
The mechanism of action of denosumab is through inhibition of RANKL which results in the inhibition of the development and function of bone osteoclasts and thereby inhibiting the release of calcium from bone.
Denosumab (Prolia), when used for the treatment of osteoporosis can be associated with the development of hypocalcaemia which can sometimes be severe, prolonged and life-threatening. Hypocalcaemia usually occurs within the first weeks after therapy but can occur months after a dose of denosumab. If hypocalcaemia develops, the patient requires treatment with oral calcium, 25-OH vitamin D and 1,25-OH vitamin D (calcitriol) therapy and may also require immediate hospitalisation for intravenous calcium therapy.
Patient conditions that are risk factors for the development of hypocalcaemia after denosumab therapy are:
- chronic kidney disease (particularly eGFR <30 mls/min or on dialysis)
- cancer with bone metastases (for example, metastatic prostate cancer or small cell lung cancer)
- medications that increase calcium loss (for example, glucocorticoids and some anticonvulsants)
- patients that have had hypoparathyroidism, parathyroid surgery or recent thyroid surgery
- gastrointestinal malabsorption.
It is recommended that relevant specialist advice be obtained before therapy if a patient has a condition above that is risk factor for the development of hypocalcaemia.
25-OH vitamin D and/or certain electrolyte deficiencies are also risk factors for the development of hypocalcaemia and must be corrected prior to denosumab therapy. Check renal function, calcium, magnesium and 25-OH vitamin D levels
Calcium: dietary calcium intake is to be optimised. Hypocalcaemia, if present must be corrected achieving corrected calcium in the normal range using oral calcium therapy as required. Calcitriol may be required in some circumstances.
25-OH vitamin D: 25-OH vitamin D levels must be adequate (level 60 nmol/l or above achieved) using oral 25-OH vitamin D therapy as required.
Magnesium: Magnesium levels must be in the normal range using oral magnesium therapy as required.
Obtain specialist advice if there is difficulty achieving normalisation of the above parameters.
Patients should be educated regarding symptoms of hypocalcaemia and advised to immediately seek medical attention if symptoms of hypocalcaemia occur after denosumab therapy.
If an individual patient has a condition as a risk factor for the development of hypocalcaemia, serum corrected calcium and magnesium should be checked eight to 14 days post denosumab therapy or at any time if symptoms of hypocalcaemia occur.