PDG43 SAFETY EVALUATION OF ZOLEDRONIC ACID AND DENOSUMAB USING FDA ADVERSE EVENT REPORTING SYSTEM (FAERS) DATABASE 2012-2018

Abstract

Zoledronic acid and Denosumab are both indicated for the treatment of osteoporosis and skeletal related events (SRE) associated with bone metastases. The purpose of this research was 1) describe and compare the pattern of adverse drug events (ADEs) of both drugs; 2) identify potential safety signals in children19 years old due to lack of safety data. The primary data source was the public FAERS database. A retrospective time-series descriptive study was conducted with time-period from quarter 1, 2012 to quarter 2, 2018. Descriptive statistics was used to describe the trend and pattern of adverse events and number of cases over time. The annual number of ADEs, demographics and most frequently reported ADEs were identified and compared between the two drugs. The total number of ADEs for denosumab were 104,238 compared to 29,649 for zoledronate. The number of ADES of denosumab increased from 475 in 2012 to 35118 in 2017 and 24424 in the first two quarters of 2018. The mean (SD) age for denosumab and zoledronate were 71.8 (±11.89) and 65.7 (±12.57 ) respectively. Female patients were 75% for denosumab and 39% for zoledronic acid. Interestingly when evaluating the top outcome events for each drug, death ranked first in both denosumab (16776, 14.1%) and zoledronic acid (4320, 12.53%). The most frequently reported ADEs for denosumab are osteonecrosis of the jaw, fatigue, nausea, and hospitalization. While the most common ADEs for zoledronic acid are osteonecrosis of the jaw, fatigue, pain and diarrhea. Some severe adverse events not mentioned in the label included leukopenia, renal problems, and thrombocytopenia for denosumab and pneumonia, fall, and atelectasis for zoledronic acid. Regarding children, some severe ADEs associated with zoledronic acid included rhabdomyolysis, hypocalcemia, and thrombocytopenia. Therapeutic risk management is critical for both denosumab and zoledronic acid. Further studies are warranted to establish drug-ADE causal relationship.