| Summary: | 碩士 === 高雄醫學大學 === 藥學系碩士在職專班 === 103 === Background: Previous case reports revealed that concomitant therapy with calcium channel blockers and macrolides resulted in hypotension. In 2012, the U.S. FDA issued a warning to remind physicians that the combination of clarithromycin and calcium channel blockers may cause severe hypotension. Drug-drug interactions not only affect the effectiveness, but also cause adverse effects, especially in cardiovascular drugs. Because a lot of cardiovascular drugs are metabolized by cytochrome P450 enzyme systems, simultaneous use with CYP 3A4 inhibitors or inducers, will lead to fluctuations of therapeutic levels, and further resulted in some adverse effects. Contrary to azithromycin, erythromycin and clarithromycin have inhibitory activity of cytochrome P450 3A4 (CYP 3A4). Therefore, co-administration with some calcium channel blockers which are the substrates of CYP 3A4 system will increase the risk of hypotension. Consequently, while hypotension occurs, poor kidney perfusion may also be a concern.
Objective: We conducted a population-based cohort study to investigate the incidence of acute kidney injury, hypotension and shock from the possible drug-drug interaction of calcium channel antagonists-macrolides.
Methods: The study used the 2005 National Health Insurance Research Database (NHIRD) from 2000 to 2012. We identified patients who had concurrent usage of calcium channel blockers and macrolides in 2002~2012. According to CYP 3A4 inhibitor activity, users of erythromycin/clarithromycin were in the treatment group, and azithromycin users were the control group. The incidences of hypotension, shock, and acute kidney injury after concurrent usage were identified. The propensity scores (PS) weighting were adapted in the statistical analysis.
Results: In the period between 2000~2012, those combinations at the same prescription,were frequently prescribed by internists, accounting for 59.37%% of all, and it had more frequency of occurrence in local community hospitals (60.53%) than in the clinic. We also identified 1,774 patients who received a coprescription with calcium channel blockers and macrolides in the period between 2002~2012, including 1,407 patients in erythromycin/clarithromycin group and 367 patients in azithromycin group. The incidence of acute kidney injury in azithromycin group (7.08%) was higher than in erythromycin/ clarithromycin group (3.20%) with odds ratio (OR) of 0.43 (95% CI: 0.26~0.71). But the incidence of hypotension or shock was not statistical significance from the two groups (OR: 0.55, 95% CI: 0.29~1.05). However, in azithromycin group, there were more comorbidities, and more renal disease patients. Therefore, propensity score was used to balance the two groups. In those who had underlying disease with renal disease, the incidence of acute kidney injury outcome in erythromycin/ clarithromycin group was 14.52%, and in azithromycin group was 12.70% (p= 0.73, weighted OR: 1.77, 95% CI: 0.98~3.18). Similarly, incidences of hypotension or shock were respectively 3.23%, 6.35% (p= 0.45, weighted OR: 1.50, 95% CI: 0.61~3.69). Furthermore, in our study, older age, multiple comorbidities, chronic renal disease, and the longer length of combinated days seemed to relate between acute kidney injury in erythromycin/clarithromycin group.
Conclusions: The finding did not support the theory that combination with azithromycin would be more risk than erythromycin/clarithromycin group. There was no statistical significance in incidences of hypotension or shock between two groups in 18 years older Taiwanese.
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