Hyperkalemia by eplerenone or esaxerenone in the presence or absence of clarithromycin in hypertensive patients: a retrospective observational cohort study.

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.

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