(163) Disseminated Intravascular Coagulation after idarucizumab or andexanet alfa: a disproportional analysis and case-by-case analysis of reports from the FAERS database

Monday, August 26, 2024

8:00 AM – 6:00 PM CEST

Location: Convention Hall II

Co-Author(s)

GR

Giuseppe Roberto, PhD, PharmD

PharmD, PhD
ARS Toscana, Florence
Firenze, Italy
aF

alessandra Flaccavento

Department of Diagnostics and Public Health, University of Verona, Verona, Italy

Presenting Author(s)

Rosa Gini, PhD (she/her/hers)

Head of Unit at ARS Toscana, Florence, Italy
ARS Toscana, Florence, Italy
Florence, Italy

Co-Author(s)

AV

Alfredo Vannacci

1)Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Florence, Italy. 2)Tuscan Regional Centre of Pharmacovigilance, Florence, Italy. 3)Joint Laboratory of Technological Solutions for Clinical Pharmacology, Pharmacovigilance and Bioinformatics, University of Florence, Florence, Italy., Italy
GM

Guido Mannaioni

1)Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", Department of Neuroscience, Psychology, Drug Research and Child Health NEUROFARBA, Department of Health Sciences DSS, Università degli Studi di Firenze, Florence, Italy. 2)Azienda Ospedaliera Universitaria di Careggi, Clinical Toxicology and Poison Control Centre, Firenze, Italy., Italy
GV

Gianni Virgili

Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), Italy
MT

Marco Tuccori, PharmD, PhD

Unit of Adverse Drug Reactions Monitoring. University Hospital of Pisa; Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Pisa, Italy

Background: Idarucizumab (ID) and andexanet alfa (AA) are used for the emergency reversal of the anticoagulant effect of direct oral anticoagulant medications. ID specifically reverts dabigatran effect while AA is effective against rivaroxaban, apixaban and edoxaban. Given the recency of marketing approval and the rare utilization in clinical practice, evidence on thromboembolic safety is still poor.

Objectives: To analyze the FDA Adverse Event Reporting System (FAERS) database for the identification of possible safety signals concerning the use of idarucizumab or andexanet alfa and the occurrence of unexpected thromboembolic events

Methods: performed. Reports with ID and AA were respectively identified. Reporting Odds Ratio (ROR) and 95% confidence incidence (CI) were calculated for 434 Preferred Terms corresponding to thromboembolic events included in 3 relevant Standardized MedDRA Queries. Signals of disproportionate reporting (SDR) were drug-event pairs from ≥3 distinct reports, ROR≥1 and lower 95%CI >1. SDRs concerning drug-event pairs not currently described in medicinal product labels and literature, and with possible biological plausibility were selected. The corresponding individual case safety reports (ICSR) were requested to FDA and a case-by-case analysis was performed.

Results: A total of 11.561.146 reports were analyzed. ID and AA were listed as suspected drugs in 1463 and 399 reports, respectively. SDR were 21 and 19 for ID and AA, respectively. Among the latter, 11 ICSRs with ID and 4 with AA of disseminated intravascular coagulation (DIC) were selected for the case-by-case analysis. Two additional cases of DIC with AA reported in 2023 were found using the FAERS Public Dashboard. ICSRs received from FDA revealed 2 duplicate reports for AA and DIC. Age was reported in 10 of 11 ID cases (mean: 79 years) and in 4 of 4 cases for AA (mean: 69). Four of 11 ID cases and 3 of 4 AA cases were males. In 6 of 11 ID cases and in 3 of 4 AA cases concomitant conditions or medications that might have contributed or caused DIC occurrence were also reported. Fatal cases were 9/11 for ID and 3/4 for AA. Time-to-event was available in 5/11 ID cases (mean 24) and in 1/4 AA cases (same day). Dates of occurrence of adverse events, administration of drugs, concomitant conditions, lab tests and procedures were often removed due to anonymization issues.

Conclusions: DIC is a serious and often fatal condition that mainly occurs in critical patients like those that might need the administration of ID or AA. Nevertheless, information available in the ICSRs analyzed in this study did not allow to definitely exclude a possible role of ID and AA in the occurrence of DIC. Healthcare professionals should promptly report to pharmacovigilance systems any observed case of DIC following ID or AA.