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Intravenous (IV) dose: 4mg
Onset of effect: <4 days
Maximum effect: 4 to 7 days
Duration of effect: 4 weeks
Intravenous (IV) dose: 30 to 90mg
Onset of effect: <3 days
Maximum effect: 5 to 7 days
Duration of effect: 2.5 weeks
Denosumab is a human monoclonal antibody that binds to RANKL, a receptor activator of osteoclasts. It is used primarily in preventing skeletal related events in patients with bone metastases of some solid tumours however recent small trial studies have shown it to be effective in treating hypercalcaemia in resistant cases.
Denosumab is administered as a subcutaneous injection. Side effects include osteonecrosis of the jaw, dyspnoea and diarrhoea. It is more expensive than bisphosphonate therapy hence further economic review is warranted. It does not cause renal toxicity therefore may be useful for patients with renal impairment who may not be able to receive bisphosphonates.
Calcitonin should only be used in exceptional circumstances when the corrected calcium level is extremely high and there is a clinical indication for the rapid reduction of the calcium level e.g. symptomatic cardiac arrhythmias.
Calcitonin should be given in addition to a bisphosphonate. It reduces the calcium level rapidly whilst the slower acting bisphosphonate will take longer to work but have a longer lasting effect. The dose is 100 IU every 6-8 hours to a maximum of 400IU in 24 hours. It is administered as a subcutaneous or intramuscular injection. It is highly emetogenic; an antiemetic should be coprescribed.
The role of steroids in severe hypercalcaemia is confined to haematological tumours that respond to the cytostatic effects of steroids including myeloma, leukaemia and lymphoma.
Effective but not used in clinical practice in the UK.
Subcutaneous administration of bisphosphonates
For some patients, it is not appropriate for or too burdensome for them to have intravenous therapy of bisphosphonates. It is possible to consider a subcutaneous route instead for administration of therapy. There are case reports (level 4 evidence) available describing administration of subcutaneous bisphosphonates, although these are mostly using clodronate which is not routinely available in the UK (1,2). It is important to note that this must be conducted alongside adequate hydration.
Pamidronate disodium: 90mg diluted in 1 litre of sodium chloride 0.9% over 12-24 hours
Zolendronic acid: There are no published guidelines for administration but this guideline would like to reference the case report from Mountbattern Hospice ‘Zoledronic acid was typically added to 500mL of sodium chloride 0.9% and infused subcutaneously under gravity using a ‘BD Safe- Tintima’ subcutaneous cannula over approximately 12 hours’ (3).
Disclaimer
These Guidelines are intended for use by healthcare professionals and the expectation is that they will use clinical judgement, medical, and nursing knowledge in applying the general principles and recommendations contained within. They are not meant to replace the many available texts on the subject of palliative care.
Some of the management strategies describe the use of drugs outside their licensed indications. They are, however, established and accepted good practice. Please refer to the current BNF for further guidance.
Whilst SPAGG takes every care to compile accurate information , we cannot guarantee its correctness and completeness, and it is subject to change. We do not accept responsibility for any loss, damage or expense resulting from the use of this information.