Mining and analysis of adverse drug event signals of cinacalcet and etelcalcetide / 中国药房

ABSTRACT

OBJECTIVE To explore and analyze the adverse drug event （ADE） signals of cinacalcet and etelcalcetide， to provide a reference for safe drug use in the clinic. METHODS ADE reports related to cinacalcet and etelcalcetide were extracted from the FDA Adverse Event Reporting System from January 1st， 2004 to June 30th， 2023 using the OpenVigil online tool. The Bayesian confidence propagation neural network method was adopted to detect the signals of ADE from the key organ systems. The signals were encoded according to the preferred term in the ADE terminology set of the Medical Dictionary for Regulatory Activities （26.0 edition）. RESULTS A total 41 709 and 1 710 ADE reports were extracted， and 29 and 45 safety signals were detected in key systems for cinacalcet and etelcalcetide， respectively； 20 and 36 positive signals were not included in the drug instructions. Hypocalcemia/decreased serum calcium， abnormal blood parathyroid hormone （PTH）/increased or decreased serum PTH were common ADEs of the two drugs， which were detected in the study. Among the signals not included in the drug instructions， new moderate and strong signals were detected， such as cinacalcet-induced calcification defense （metabolic and nutritional diseases）， bone starvation syndrome and high conversion bone diseases （musculoskeletal and connective tissue diseases） as well as etelcalcetide-induced sudden death， necrosis and treatment of non-responders （general disorders， administration site）， unstable angina pectoris， myocardial ischemia （cardiac diseases）， intestinal perforation， gastric antrum vasodilation and gastric ulcer （gastrointestinal diseases）. CONCLUSIONS In the clinical application of the two drugs， apart from the common ADEs such as hypocalcemia and abnormal blood PTH， the surveillance of some new potential ADEs should also be carried out， such as bone starvation syndrome， calcification defense， ventricular disease and other cinacalcet-induced ADEs， sudden death， myocardial ischemia， unstable angina pectoris， intestinal perforation， gastric ulcer and other etecalcetide-induced ADEs. If new ADEs appear， clinic should promptly assess the benefits and risks， and update the treatment plan and pharmacological monitoring plan to ensure the safety of patient medication.