Background: After kidney transplantation, calcineurin inhibitors (CNIs, cyclosporine, tacrolimus) are key components of immunosuppression but have multiple potential drug interactions. Macrolide antibiotics are often used for atypical infections. Clarithromycin and erythromycin inhibit the metabolism of CNIs through CYP3A4, thereby increasing the risk of CNI toxicity, such as nephrotoxicity. In contrast, azithromycin does not affect CNI metabolism.

Objective: To determine the frequency of CNI-macrolide co-prescriptions, the proportion who receive post-prescription monitoring, and the risk of adverse drug events in kidney transplant recipients.

Methods: We conducted a retrospective study using linked databases in Alberta, Canada to follow kidney transplant recipients (2008-2015). We identified recipients on continuous CNI who were co-prescribed either clarithromycin, erythromycin, or azithromycin. We compared outcomes in those who received clarithromycin/erythromycin vs. azithromycin. The primary outcome was a composite of all-cause hospitalization, acute kidney injury (creatinine increase ≥26.5 umol/L or 1.5-times baseline), and death within 30 days of the macrolide prescription.

Results: At the time of the macrolide prescription, the 293 recipients who were co-prescribed a CNI and a macrolide had a mean age of 55 years and an estimated glomerular filtration rate of 55 mL/min/1.73 m². Almost 40% (n=112) of recipients were prescribed clarithromycin/erythromycin while the remainder were prescribed azithromycin (n=181). Compared to azithromycin users, clarithromycin/erythromycin users were less likely to have outpatient serum creatinine monitoring post-prescription (56% vs. 69%, p=0.03). There was no significant difference in the primary outcome between the two groups (17% vs. 11%, p=0.11); however, the risk of all-cause hospitalization was higher in the clarithromycin/erythromycin group (10% vs. 3.3%, p=0.02).

Conclusion: Despite drug interactions, clarithromycin/erythromycin were frequently prescribed in kidney transplant recipients on CNIs. Compared to azithromycin, clarithromycin/erythromycin users were less likely to have post-prescription monitoring of kidney function and were at higher risk of hospitalization. Further research is needed to improve safe prescribing practices in kidney transplant recipients.

CITATION INFORMATION: Jeong R., Quinn R., Ravani P., Lentine K., Lloyd A., Hemmelgarn B., Wen K., Braam B., Gourishankar S., Wong A., Lam N. Calcineurin Inhibitors, Macrolides, and the Risk of Adverse Drug Events in Kidney Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

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