A new study leveraging the FDA Adverse Event Reporting System (FAERS) database has shed light on potential adverse events (AEs) associated with avatrombopag, a thrombopoietin receptor agonist used to treat thrombocytopenia. The disproportionality analysis, published in Scientific Reports, revealed both previously known and novel AEs, emphasizing the need for vigilant monitoring during avatrombopag therapy.
Identification of Novel Adverse Events
The study identified common AEs consistent with previous research, including thrombosis, headache, contusion, petechiae, and gingival bleeding. Notably, the analysis also uncovered previously unreported AEs such as liver function abnormalities, photopsia, and ear discomfort. The association between avatrombopag and liver function abnormalities remains unclear, although hepatotoxicity has been noted with eltrombopag, another TPO-RA drug. Researchers recommend regular monitoring of liver function during treatment. The study also noted that photopsia and ear discomfort require further clinical investigation to understand the potential associations and mechanisms.
Thrombotic Risk and Platelet Monitoring
The analysis highlighted abnormal platelet counts as a significant AE signal. Previous studies have indicated that excessive increases in platelet count with avatrombopag overdose can lead to thrombotic or thromboembolic complications. The current study reported thrombotic events, including renal vein thrombosis (n=4), portal vein thrombosis (n=10), cerebral venous sinus thrombosis (n=3), embolism (n=6), deep vein thrombosis (n=16), pulmonary embolism (n=20), and thrombosis (n=17). The authors suggest enhanced platelet testing during avatrombopag use, recommending weekly platelet counts until a stable count of ≥ 50 × 10^9/L is achieved, followed by monthly monitoring. Platelet counts should also be checked weekly for at least four weeks after discontinuing avatrombopag.
Timing of Adverse Events
The study found that many AEs occurred within 30 days of drug administration, with a median time to onset of one day for non-serious AEs. This suggests that healthcare professionals should be particularly alert for adverse events soon after initiating avatrombopag treatment. The difference in time to onset between serious and non-serious AEs may be related to continued medication use and disease progression, warranting vigilance for serious AEs with ongoing treatment.
Methodology and Limitations
The study employed four algorithms—ROR, PRR, BCPNN, and MGPS—to analyze the FAERS data. AEs were considered statistically significant signals when all disproportionality measures crossed the significance threshold. The authors acknowledge limitations inherent to the FAERS database, including spontaneous reporting bias, underreporting, and inaccuracies. The database also lacks information to calculate the incidence of AEs. Disproportionality analyses provide only an estimate of signal strength and do not establish causality. Despite these limitations, the study provides valuable insights into the post-marketing safety profile of avatrombopag, supporting further clinical studies to confirm causal relationships between the drug and the identified adverse events. The comprehensive characterization of AE signals may guide safer and more effective use of avatrombopag in clinical practice.
