Macrolide계 항생제와 Calcium channel blocker
병용시 저혈압 위험성
 
이현정, 최지영, 김재연, 송영천, 곽혜선a
서울아산병원 약제팀, 이화여자대학교 약학대학a

The risk of hypotension following the co-prescription of
macrolide antibiotics and calcium-channel blockers

Hyun Jung Lee, Ji Young Choi, Jae Yeon Kim, Young Cheon Song, Hye Seon Kwaka

Department of Pharmacy, Asan Medical Center 388-1, Pungnab-Dong, Songpa-Gu, Seoul, Korea
College of Pharmacy, Ehwa Women's University, Daehyun-Dong, Seodaemun-gu, Seoul, Koreaa

Abstract : Macrolide antibiotics, clarithromycin and erythromycin may potentiate calcium channel blockers (CCBs) by inhibiting cytochrome P450 isoenzyme 3A4. However, this potential drug interaction is widely underestimated and its clinical consequences have not been well characterized. This study explored the risk of hypotension and consequently identified the risk factors associated with the simultaneous use of CCBs and macrolide antibiotics.
We conducted a case-crossover study involving inpatients between April 1, 2010 and March 31, 2011 at Asan Medical Center. The hypotension risk associated with the use of CCBs was evaluated by a pair-match analytic approach, comparing each patient's exposure to each macrolide antibiotic (erythromycin, clarithromycin or azithromycin) during a co-administered period (risk interval) and in the period preceding 30 days (control interval). 84 cases included patients who administered both medications over 3 days and had been received CCBs over 1 month before co-administration. They were divided into 2 groups according to the changes of the blood pressure values (Hypotension group n=24; Normal BP group n=60). We compared the data between the 2 groups and found the risk factors of hypotension. Statistical analysis was performed using the PASW Statistics version 14.0 (SPSS). A p-value of <0.05 was considered statistically significant.
A total of 84 patients with a mean (± SD, Standard Deviation) age of 66.4 (±13.7) years were studied, of whom 58 (69.0%) were male. The mean duration of the co-administration was 6.9 days. Systolic and diastolic blood pressure was reduced by 12.31±16.73 mmHg and 7.34±10.51 mmHg during the co-administration period compared to the figures in the period preceding 1 month. The incidence of hypotension defined by the International Classification of Diseases-9 (ICD-9) was 28.6%. Although other risk factors (age, sex, type of CCBs, co-administration duration, etc.) were not statistically significant, erythromycin was most strongly associated with hypotension (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.15-5.18, p=0.04). A total of 9 patients were administered erythromycin in this study, and hypotension occurred in 5 (55.6%) of 9 patients.
The frequency of hypotension, as a result of concomitant CCB and macrolide administration, appears to be small, however, we should be concerned about the risk of adverse effects that may occur. Co-administration of macrolide antibiotics and CCBs was associated with a reduction of blood pressure, particularly erythromycin. The preferential use of azithromycin should be considered when a macrolide antibiotic is required for patients already receiving a CCB. Clinicians should be aware of the potential interaction between these drugs, as well as the need for careful patient monitoring.
 
[Key words] macrolide antibiotics, calcium channel blocker, hypotension, drug interaction