"Risk of adverse events among older adults following co-prescription of" by Daniel Q. Li, Richard Kim et al.
 

Paediatrics Publications

Document Type

Article

Publication Date

2-17-2015

Journal

CMAJ

Volume

187

Issue

3

First Page

174

Last Page

180

URL with Digital Object Identifier

10.1503/cmaj.140950

Abstract

Background: The cytochrome P450 3A4 (CYP3A4) inhibitor clarithromycin may also inhibit liverspecific organic anion-transporting polypeptides (OATP1B1 and OATP1B3). We studied whether concurrent use of clarithromycin and a statin not metabolized by CYP3A4 was associated with an increased frequency of serious adverse events. Methods: Using large health care databases, we studied a population-based cohort of older adults (mean age 74 years) who were taking a statin not metabolized by CYP3A4 (rosuvastatin [76% of prescriptions], pravastatin [21%] or fluvastatin [3%]) between 2002 and 2013 and were newly prescribed clarithromycin (n = 51 523) or azithromycin (n = 52 518), the latter an antibiotic that inhibits neither CYP3A4 nor OATP1B1 and OATP1B3. Outcomes were hospital admission with a diagnostic code for rhabdomyolysis, acute kidney injury or hyperkalemia, and allcause mortality. All outcomes were assessed within 30 days after co-prescription. Results: Compared with the control group, patients co-prescribed clarithromycin and a statin not metabolized by CYP3A4 were at increased risk of hospital admission with acute kidney injury (adjusted relative risk [RR] 1.65, 95% confidence interval [CI] 1.31 to 2.09), admission with hyperkalemia (adjusted RR 2.17, 95% CI 1.22 to 3.86) and all-cause mortality (adjusted RR 1.43, 95% CI 1.15 to 1.76). The adjusted RR for admission with rhabdomyolysis was 2.27 (95% CI 0.86 to 5.96). The absolute increase in risk for each outcome was small and likely below 1%, even after we considered the insensitivity of some hospital database codes. Interpretation: Among older adults taking a statin not metabolized by CYP3A4, co-prescription of clarithromycin versus azithromycin was associated with a modest but statistically significant increase in the 30-day absolute risk of adverse outcomes.

Plum Print visual indicator of research metrics
PlumX Metrics
  • Citations
    • Citation Indexes: 51
    • Policy Citations: 1
  • Usage
    • Downloads: 15
  • Captures
    • Readers: 87
  • Mentions
    • News Mentions: 1
  • Social Media
    • Shares, Likes & Comments: 15
see details

Share

COinS