Published: 2 December 2021
Publications
Hypocalcaemia – increased risk with concomitant use of denosumab and cinacalcet
Published: 2 December 2021
Prescriber Update 42(4): 59–61
December 2021
The denosumab data sheets are being updated to include a warning for
increased risk of hypocalcaemia with concomitant use of denosumab and
cinacalcet.
Denosumab
Denosumab is a monoclonal antibody that inhibits osteoclast formation, function and survival, thereby decreasing bone resorption and increasing bone mass and strength.1,2
Denosumab is indicated to prevent skeletal-related events from osteoporosis and metastatic bone disease.3 There are two denosumab products approved and available in New Zealand: Prolia and Xgeva.
Cinacalet
Cinacalcet is a calcimimetic – a medicine that mimics the action of calcium on tissues and reduces secretion of parathyroid hormone. This action decreases the serum calcium and phosphate levels.4
Cinacalcet is indicated for treatment of secondary hyperparathyroidism in dialysis patients with end-stage renal disease, hypercalcaemia in adult patients with parathyroid carcinoma, and primary hyperparathyroidism in adult patients for whom parathyroidectomy is not a treatment option.5 Sensipar is the only cinacalcet product that is approved and available in New Zealand.
Hypocalcaemia
The clinical manifestations of hypocalcaemia depend upon the severity and chronicity of hypocalcaemia and can range from few (if any) symptoms if the hypocalcaemia is mild, to life-threatening symptoms if it is severe.6
Due to their mechanisms of action, denosumab and cinacalcet are both independently associated with hypocalcaemia. Clinical manifestations of hypocalcaemia reported following treatment with either medicine include paraesthesias, muscle stiffness, twitching, spasms and muscle cramps.1,2,5 Life-threatening events, including seizures, QT prolongation and tetany, and fatal outcomes have also been reported.1,2,5
See the respective data sheets for recommendations for reducing the risk of hypocalcaemia, including testing of serum calcium levels prior to initiation of treatment and monitoring levels during treatment:
Concomitant use of denosumab and cinacalcet may worsen the risk of hypocalcaemia. The denosumab data sheets are being updated to include this information. The cinacalcet data sheet already includes warnings about concomitant use with medicines known to lower serum calcium.
Closely monitor serum calcium levels if concomitant denosumab and cinacalcet treatment is required.
New Zealand case reports
Up to 30 June 2021, the Centre for Adverse Reactions Monitoring (CARM) had received two reports of hypocalcaemia associated with use of denosumab (CARM IDs: 128578 and 139291). There have been no reports of hypocalcaemia associated with use of cinacalcet and no reports with concomitant use of denosumab and cinacalcet.
References
- Amgen (New Zealand) Limited. 2020. Prolia New Zealand Data Sheet 5 November 2020. URL: medsafe.govt.nz/profs/datasheet/p/proliainj.pdf (accessed 15 October 2021).
- Amgen (New Zealand) Limited. 2021. Xgeva New Zealand Data Sheet 12 April 2021. URL: medsafe.govt.nz/profs/datasheet/x/xgevainj.pdf (accessed 15 October 2021).
- Laskowski LK, Goldfarb DS, et al. 2016. A RANKL wrinkle: Denosumab-induced hypocalcemia. Journal of Medical Toxicology 12(3): 305–8. DOI: 10.1007/s13181-016-0543-y (accessed 15 October 2021).
- Quarles L and Berkoben M. 2021. Management of secondary hyperparathyroidism in adult dialysis patients. In: UpToDate 15 March 2021. URL: uptodate.com/contents/management-of-secondary-hyperparathyroidism-in-adult-dialysis-patients (accessed 14 October 2021).
- Amgen (New Zealand) Limited. 2020. Sensipar New Zealand Data Sheet 5 November 2020. URL: medsafe.govt.nz/profs/Datasheet/s/Sensipartab.pdf (accessed 15 October 2021).
- Goltzman D. 2021. Clinical manifestations of hypocalcemia. In: UpToDate 12 March 2021. URL: uptodate.com/contents/clinical-manifestations-of-hypocalcemia (accessed 14 October 2021).
