Macrolide계 항생제와 Calcium Channel Blocker 병용시 저혈압 위험성

Abstract

Macrolide antibiotics including clarithromycin and erythromycin may potentiate the effects of 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 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 risks associated with the use of CCBs were evaluated by the 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 patients, who administered both medications over 3 days and had been received CCBs over 1 month before co-administration were incloded. They were divided into 2 groups according to the changes of the blood pressure values (Hypotension group n=24; Normal Blood Pressure 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 those in the period preceding 1 month, respectively 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 the most strongly associated risk factor of 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 55.6% of the 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.