Vol.72 No.3 May 2024

Investigation of Kounis syndrome with suspect antimicrobials using national and international databases of adverse drug reactions

Ichiro Nakakura¹⁾, Kota Sakakura¹⁾, Shoko Amano¹⁾, Tomohito Wakabayashi¹⁾, Mai Sakamoto¹⁾, Kazuya Nakano¹⁾, Tomoko Ueno¹⁾ and Kazuyoshi Kawabata¹⁾

¹⁾Department of Pharmacy, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shinmachi, Suita, Osaka, Japan

Abstract

Kounis syndrome refers to "acute coronary syndrome associated with allergic reactions" caused by drugs or other causes. In drug-induced Kounis syndrome, involvement of antimicrobials is well known. Although there have previously been reports on Kounis syndrome using the database of adverse drug event, there are few reports of Kounis syndrome induced by antimicrobials. In this study, we report on the Kounis syndrome induced by antimicrobials and the suspect antimicrobials, using based on the Japanese Adverse Drug Event Report database (JADER) and FDA Adverse Event Reporting System (FAERS) database. Among the reported cases of Kounis syndrome in the JADER and FAERS databases, there were 37 and 775 cases with suspected involvement of antimicrobials, respectively.
In JADER, 9 suspect antimicrobials were identified, and clarithromycin was the most frequently implicated antimicrobial (12 cases). In FAERS, 33 suspect antimicrobials were identified, with clavulanic acid/amoxicillin was the most frequently implicated antimicrobial (133 cases). In all, 8 antimicrobials in JADER and 29 antimicrobials in FAERS were found to have safety signals. In this report, antimicrobials that have not been reported to cause Kounis syndrome in previous reports were identified as suspect drugs. Among the antimicrobials with safety signals, "shock,""anaphylaxis," and "acute coronary syndrome associated with allergic reaction" were not listed as adverse drug reactions in the package insert for metronidazole. Therefore, the possibility of Kounis syndrome must be considered even for drugs for which there are no reports of shock or anaphylaxis.

Key word

antimicrobial, adverse effect, Kounis syndrome

Received

October 25, 2023

Accepted

December 21, 2023

Jpn. J. Chemother. 72 (3): 322-330, 2024