Tags

Type your tag names separated by a space and hit enter

Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study.
Ann Intern Med. 2013 Jun 18; 158(12):869-76.AIM

Abstract

BACKGROUND

Clarithromycin and erythromycin, but not azithromycin, inhibit cytochrome P450 isoenzyme 3A4 (CYP3A4), and inhibition increases blood concentrations of statins that are metabolized by CYP3A4.

OBJECTIVE

To measure the frequency of statin toxicity after coprescription of a statin with clarithromycin or erythromycin.

DESIGN

Population-based cohort study.

SETTING

Ontario, Canada, from 2003 to 2010.

PATIENTS

Continuous statin users older than 65 years who were prescribed clarithromycin (n = 72,591) or erythromycin (n = 3267) compared with those prescribed azithromycin (n = 68,478).

MEASUREMENTS

The primary outcome was hospitalization with rhabdomyolysis within 30 days of the antibiotic prescription.

RESULTS

Atorvastatin was the most commonly prescribed statin (73%) followed by simvastatin and lovastatin. Compared with azithromycin, coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis (absolute risk increase, 0.02% [95% CI, 0.01% to 0.03%]; relative risk [RR], 2.17 [CI, 1.04 to 4.53]) or with acute kidney injury (absolute risk increase, 1.26% [CI, 0.58% to 1.95%]; RR, 1.78 [CI, 1.49 to 2.14]) and for all-cause mortality (absolute risk increase, 0.25% [CI, 0.17% to 0.33%]; RR, 1.56 [CI, 1.36 to 1.80]).

LIMITATIONS

Only older adults were included in the study. The absolute risk increase for rhabdomyolysis may be underestimated because the codes used to identify it were insensitive.

CONCLUSION

In older adults, coprescription of clarithromycin or erythromycin with a statin that is metabolized by CYP3A4 increases the risk for statin toxicity.

PRIMARY FUNDING SOURCE

Academic Medical Organization of Southwestern Ontario.

Links

Publisher Full Text
Aggregator Full Text

Authors+Show Affiliations

Patel AM
Western University and Lawson Health Research Institute, London Health Sciences Centre, London, Ontario, Canada.
Shariff S
No affiliation info available
Bailey DG
No affiliation info available
Juurlink DN
No affiliation info available
Gandhi S
No affiliation info available
Mamdani M
No affiliation info available
Gomes T
No affiliation info available
Fleet J
No affiliation info available
Hwang YJ
No affiliation info available
Garg AX
No affiliation info available

MeSH

Acute Kidney InjuryAgedAnti-Bacterial AgentsAzithromycinCause of DeathClarithromycinCytochrome P-450 CYP3A InhibitorsDrug InteractionsErythromycinFemaleHumansHydroxymethylglutaryl-CoA Reductase InhibitorsMaleRetrospective StudiesRhabdomyolysis

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23778904

Citation

Patel, Amit M., et al. "Statin Toxicity From Macrolide Antibiotic Coprescription: a Population-based Cohort Study." Annals of Internal Medicine, vol. 158, no. 12, 2013, pp. 869-76.
Patel AM, Shariff S, Bailey DG, et al. Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study. Ann Intern Med. 2013;158(12):869-76.
Patel, A. M., Shariff, S., Bailey, D. G., Juurlink, D. N., Gandhi, S., Mamdani, M., Gomes, T., Fleet, J., Hwang, Y. J., & Garg, A. X. (2013). Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study. Annals of Internal Medicine, 158(12), 869-76. https://doi.org/10.7326/0003-4819-158-12-201306180-00004
Patel AM, et al. Statin Toxicity From Macrolide Antibiotic Coprescription: a Population-based Cohort Study. Ann Intern Med. 2013 Jun 18;158(12):869-76. PubMed PMID: 23778904.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study. AU - Patel,Amit M, AU - Shariff,Salimah, AU - Bailey,David G, AU - Juurlink,David N, AU - Gandhi,Sonja, AU - Mamdani,Muhammad, AU - Gomes,Tara, AU - Fleet,Jamie, AU - Hwang,Y Joseph, AU - Garg,Amit X, PY - 2013/6/20/entrez PY - 2013/6/20/pubmed PY - 2013/12/16/medline SP - 869 EP - 76 JF - Annals of internal medicine JO - Ann Intern Med VL - 158 IS - 12 N2 - BACKGROUND: Clarithromycin and erythromycin, but not azithromycin, inhibit cytochrome P450 isoenzyme 3A4 (CYP3A4), and inhibition increases blood concentrations of statins that are metabolized by CYP3A4. OBJECTIVE: To measure the frequency of statin toxicity after coprescription of a statin with clarithromycin or erythromycin. DESIGN: Population-based cohort study. SETTING: Ontario, Canada, from 2003 to 2010. PATIENTS: Continuous statin users older than 65 years who were prescribed clarithromycin (n = 72,591) or erythromycin (n = 3267) compared with those prescribed azithromycin (n = 68,478). MEASUREMENTS: The primary outcome was hospitalization with rhabdomyolysis within 30 days of the antibiotic prescription. RESULTS: Atorvastatin was the most commonly prescribed statin (73%) followed by simvastatin and lovastatin. Compared with azithromycin, coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis (absolute risk increase, 0.02% [95% CI, 0.01% to 0.03%]; relative risk [RR], 2.17 [CI, 1.04 to 4.53]) or with acute kidney injury (absolute risk increase, 1.26% [CI, 0.58% to 1.95%]; RR, 1.78 [CI, 1.49 to 2.14]) and for all-cause mortality (absolute risk increase, 0.25% [CI, 0.17% to 0.33%]; RR, 1.56 [CI, 1.36 to 1.80]). LIMITATIONS: Only older adults were included in the study. The absolute risk increase for rhabdomyolysis may be underestimated because the codes used to identify it were insensitive. CONCLUSION: In older adults, coprescription of clarithromycin or erythromycin with a statin that is metabolized by CYP3A4 increases the risk for statin toxicity. PRIMARY FUNDING SOURCE: Academic Medical Organization of Southwestern Ontario. SN - 1539-3704 UR - https://www.unboundmedicine.com/medline/citation/23778904/Statin_toxicity_from_macrolide_antibiotic_coprescription:_a_population_based_cohort_study_ L2 - https://www.acpjournals.org/doi/10.7326/0003-4819-158-12-201306180-00004?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -