[Pharmaceutical Intervention According to Strict Management System Can Normalize Decreased Serum Calcium Level by Denosumab and Prevent Its Aggravation].

ABSTRACT

Denosumab is a fully monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand (RANKL), and prevents skeletal-related events by bone metastasis. Hypocalcemia is the most typical adverse effect of denosumab use. We have developed a management system for the more efficient and safer management of denosumab administration, and evaluated pharmaceutical interventions for the better control of hypocalcemia. All pharmaceutical interventions in the system from April 2016 to March 2020 were retrospectively evaluated. We have also assessed the incidence of hypocalcemia in 158 patients who were administered denosumab for six months or more in the period. A total of 282 pharmaceutical interventions (7.0% of the total administration) were conducted. The most conducted intervention was regarding hypocalcemia, which involved the suspension of the injection and/or the increase of calcium and vitamin D supplement with 65% adoption and 17% temporary treatment suspensions. Other interventions were about hypercalcemia, request of laboratory examination and ordering supplements, dental consultation, and poor renal function. A total of 199 interventions (70.6%) were adopted, with 33 administrations suspended. The frequency of hypocalcemia was 27.8% with just one patient having grade 2 hypocalcemia, suggesting that there were no severe cases. Moreover, hypocalcemia was significantly normalized following pharmaceutical intervention and/or handling by physicians (p=0.02) according to the system. Conversely, the normalization rate in hypercalcemia did not differ according to the countermeasures. In conclusion, pharmaceutical interventions according to our management system benefit safe denosumab treatment, especially in severe hypocalcemia prevention.