Hyperkalemia by eplerenone or esaxerenone in the presence or absence of clarithromycin in hypertensive patients: a retrospective observational cohort study. Issue 4 (19th April 2023)

• Record Type: Journal Article
• Authors: Hirai, Toshinori; Ueda, Shun; Ogura, Toru; Katayama, Kan; Dohi, Kaoru; Hosohata, Keiko; Aoyama, Takahiko; Matsumoto, Yoshiaki; Iwamoto, Takuya
• Is Part Of: Journal of hypertension. Volume 41:Issue 4(2023)
• Page Start: 580
• Page End: 586
• Publication Date: 2023-04-19
• Subjects: cytochrome P450 3A4 -- drug–drug interaction -- eplerenone -- esaxerenone -- potassium; Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/HJH.0000000000003372
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: Mineralocorticoid receptor antagonists (MRAs), eplerenone and esaxerenone, cause hyperkalemia dose-dependently. We investigated the cytochrome P450 3A4-mediated drug−drug interaction between the MRAs and clarithromycin. Methods: This retrospective observational study included adult hypertensive patients with MRA plus clarithromycin or MRA alone with a propensity score matching (1:1). The difference in serum potassium level (ΔK, maximum level – baseline level) between groups was compared using the Mann–Whitney U -test. Linear regression analysis was used to detect variables that correlated with ΔK in patients with MRA plus clarithromycin. Results: After propensity score matching (each nine patients), serum potassium level was elevated after treatment with MRA plus clarithromycin [4.3 (3.5 to 5.1) meq/l to 4.9 (4.0 to 5.5) meq/l, P = 0.0234] and MRA alone [4.3 (4.0 to 4.7) meq/l to 4.6 (4.4 to 5.2) meq/l, P = 0.0469]. Although there was no significant difference in ΔK between groups [MRA plus clarithromycin: 0.5 (0.1 to 1.1) meq/l vs. MRA alone: 0.3 (0.1 to 1.2) meq/l, P = 0.7231], ΔK was significantly higher in esaxerenone plus clarithromycin than in esaxerenone alone [0.6 (0.5 to 1.1) meq/l vs. 0.1 (0.1 to 0.2) meq/l, P = 0.0495]. Conversely, clarithromycin did not show a significant effect on ΔK in patients with eplerenone [0.4 (−0.2 to 1.2) meq/l vs. 0.8 (0.1 to 1.3) meq/l, P = 0.5745]. A positive correlation was found between ΔK and age in patients with MRA plus clarithromycin ( y = 0.03 × x − 1.38, r = 0.71, P = 0.0336). Conclusion: The drug–drug interaction between MRAs and clarithromycin was evident, particularly in esaxerenone. Serum potassium levels should be closely monitored in older patients. Abstract :