Pharmacovigilance Analysis Of FDA Adverse Event Reporting System (FAERS) Events For Inclisiran

Background: Inclisiran is a first-in-class, cholesterol-lowering small interfering RNA based therapy for treatment of atherosclerosis or familial hypercholesterolemia as an adjunct to maximally tolerated statin therapy. Since approval by FDA in December 2021, it is getting increasingly popular due to biannual regimen. During trials and upon review for FDA approval, it exhibited injection site reaction, arthralgia, urinary tract infection, diarrhea, and dyspnea. Objective: In view of increased usage, it is important to establish a side effect profile of inclisiran in general population since the ORION 9, 10 and 11 trials. Methods: We explored reported adverse events (AEs) of inclisiran using FDA Adverse Event Reporting System (FAERS). A total of 472 AEs were reported until September 2022. 44.49% AEs were reported by healthcare professionals (HCPs), which were further analyzed. AEs were analyzed in men (35.2%) vs women (45.2%) and in three age groups of 18-64, 65-85, and >85 years. Results: A total of 100 (47%) events were serious including 38% hospitalization and 14% deaths. The most frequently reported AE was surprisingly dyspnea in conjunction with cough (21.9%) followed by myalgia (15.2%), injection site pain (5.2%), arthralgia (4.3%), diarrhea (4.3%), rash (3.3%) and fatigue (2.4%). Most AEs were consistent with ORION trial except elevated LDL (8.2%), acute myocardial infarction (AMI) (7.6%), hyponatremia (6.6%), acute kidney injury (AKI) (3.3%) and headache (2.4%). It was reported more in women of age group 65-85 years. Discussion: The events of death and hospitalization after initiating inclisiran could have been associated with AMI, AKI and hyponatremia that are newly reported since the trial, however the temporality and mechanisms are unknown. Even though the trial has shown that this drug is relatively safe, physicians must be vigilant about the new developments to avoid decompensation in vulnerable patients. Its use in patients with pulmonary disease can worsen dyspnea. Conclusion: With the current increasing use of inclisiran, there is a need for more data on safety profile. In future, further randomized trials are required to better assess the safety profile focusing on temporality and mechanisms of AMI and AKI in relation to inclisiran.