RT Journal Article
SR Electronic
T1 Risk of adverse events among older adults following co-prescription of clarithromycin and statins not metabolized by cytochrome P450 3A4
JF Canadian Medical Association Journal
JO CMAJ
FD Canadian Medical Association
SP 174
OP 180
DO 10.1503/cmaj.140950
VO 187
IS 3
A1 Daniel Q. Li
A1 Richard Kim
A1 Eric McArthur
A1 Jamie L. Fleet
A1 David G. Bailey
A1 David Juurlink
A1 Salimah Z. Shariff
A1 Tara Gomes
A1 Muhammad Mamdani
A1 Sonja Gandhi
A1 Stephanie Dixon
A1 Amit X. Garg
YR 2015
UL http://www.cmaj.ca/content/187/3/174.abstract
AB Background: The cytochrome P450 3A4 (CYP3A4) inhibitor clarithromycin may also inhibit liver-specific 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 all-cause 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.See also commentary on page 163 and at www.cmaj.ca/lookup/doi/10.1503/cmaj.150030