PT  - JOURNAL ARTICLE
AU  - Li, Daniel Q.
AU  - Kim, Richard
AU  - McArthur, Eric
AU  - Fleet, Jamie L.
AU  - Bailey, David G.
AU  - Juurlink, David
AU  - Shariff, Salimah Z.
AU  - Gomes, Tara
AU  - Mamdani, Muhammad
AU  - Gandhi, Sonja
AU  - Dixon, Stephanie
AU  - Garg, Amit X.
TI  - Risk of adverse events among older adults following co-prescription of clarithromycin and statins not metabolized by cytochrome P450 3A4
AID  - 10.1503/cmaj.140950
DP  - 2015 Feb 17
TA  - Canadian Medical Association Journal
PG  - 174--180
VI  - 187
IP  - 3
4099  - http://www.cmaj.ca/content/187/3/174.short
4100  - http://www.cmaj.ca/content/187/3/174.full
SO  - CMAJ2015 Feb 17; 187
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