Comparing two types of macrolide antibiotics for the purpose of assessing population-based drug interactions

Abstract

ObjectiveClarithromycin strongly inhibits enzyme cytochrome P450 3A4, preventing the metabolism of some other drugs, while azithromycin is a weak inhibitor. Accordingly, blood concentrations of other drugs increase with clarithromycin coprescription leading to adverse events. These macrolide antibiotics also differ on other properties that may impact outcomes. In this study, we compared outcomes in two groups of macrolide antibiotic users in the absence of potentially interacting drugs.DesignPopulation-based retrospective cohort study.SettingOntario, Canada, from 2003 to 2010.PatientsPatients (mean 74 years) prescribed clarithromycin (n=52 251) or azithromycin (referent group, n=46 618).Main outcomesThe primary outcomes were hospital admission within 30 days of a new antibiotic prescription with any of the 12 conditions examined separately (acute kidney injury, acute myocardial infarction, neuroimaging (proxy for delirium), hypotension, syncope, hyperkalaemia, hyponatraemia, hyperglycaemia, arrhythmia, ischaemic stroke, gastrointestinal bleeding and sepsis). The secondary outcome was mortality.ResultsThe baseline characteristics of the two groups, including patient demographics, comorbid conditions, infection type and prescribing physician specialty, were nearly identical. The median daily dose was 1000 mg for clarithromycin and 300 mg for azithromycin and the median duration of dispensing antibiotics was 10 and 5 days, respectively. There was no difference between the groups in the risk of hospitalisation for any condition studied (relative risk ranged from 0.67 to 1.23). Compared with azithromycin, clarithromycin was associated with a slightly higher risk of all-cause mortality (0.46% vs 0.37%, relative risk 1.25, 95% CI 1.03 to 1.52).ConclusionsClarithromycin can be used to assess drug interactions in population-based studies with azithromycin serving as a control group. However, any differences in mortality observed between the two antibiotic groups in the setting of other drug use may be partially attributable to factors beyond the inhibition of drug metabolising enzymes and transporters, as the difference for this outcome was significant.

Drug-Drug Interactions and Acute Kidney Injury: Caveat Prescriptor

“…Interestingly, the risk of mortality also was substantially higher with clarithromycin than azithromycin coprescription with a CCB, with an NNH of 231. An earlier study 9 from this same group found that clarithromycin compared to azithromycin, not restricted to coadministration with a CCB, also was associated with a higher risk of death, but not with AKI. The extent to which the clarithromycin-alone effect confounds the findings by Gandhi et al 5 on AKI is not clear.…”

Prevalencia de potenciales interacciones farmacológicas de Azitromicina en Colombia, 2012-2013

“…El potencial riesgo de interacciones con azitromicina se presentó en el 5,1 % de los pacientes del estudio, pero se ha observado que puede darse hasta en el 21,3 % de casos de pacientes con enfermedades cardiovasculares, en ambientes hospitalarios, o en pacientes con infecciones respiratorias (21,22). Pese a que las prevalencias de potencial riesgo son mayores en otros estudios, las razones pueden ser explicadas por las diferencias en las poblaciones estudiadas, y en este caso al ser sobre una base poblacional, pueden ser muy heterogéneas, lo que hace necesario aumentar esfuerzos investigativos, para la detección de interacciones en grupos de riesgo especial (21,22).…”

Risk of adverse events among older adults following co-prescription of clarithromycin and statins not metabolized by cytochrome P450 3A4

“…10,30,31 In a previous study of provincial data, we showed that clarithromycin and azithromycin have similar indications, clinical use patterns and rates of adverse events when used independently. 32 Thus, we felt that the comparison of outcomes among older adults prescribed these antibiotics would serve as a useful model for studying drug interactions in routine clinical practice.…”