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Calcium channel blockers and Macrolides....more hypotension ,more AKI


Calcium-Channel Blocker–Clarithromycin Drug Interactions
and Acute Kidney Injury
Sonja Gandhi, BSc; Jamie L. Fleet, BHSc; David G. Bailey, BScPhm, PhD; Eric McArthur, MSc; Ron Wald, MD; Faisal Rehman, MD; Amit X. Garg, MD, PhD 


JAMA. doi:10.1001/jama.2013.282426 Published online November 9, 2013.

 Calcium-channel blockers are a popular class of antihypertensive drugs that are metabolized by the CYP3A4 enzyme. In pharmacokinetic studies, coadministration of various inhibitors of this enzyme (eg, erythromycin, antifungals, protease inhibitors, and grapefruit juice) raised plasma calcium-channel blocker concentrations by up to 500%. As a result, there is the possibility of excessive systemic calcium-channel blocker concentration and associated toxicity with concurrent use of a CYP3A4 inhibitor.

Enhanced blood pressure lowering was observed in several studies (up to 12 healthy volunteers) after a CYP3A4 inhibitor was administrated with a calcium-channel blocker.Several case reports described hospitalization with hypotension soon after a CYP3A4 inhibitor was taken with a calcium-channel blocker.Moreover, a population-based case-crossover study of older adults found a greater risk of hospitalization with hypotension when a calcium-channel blocker was coprescribed with erythromycin or clarithromycin compared with azithromycin.Currently, the US Food and Drug Administration warns that “serious adverse reactions have been reported in patients taking clarithromycin concomitantly with CYP3A4 substrates, which includes hypotension with calcium-channel blockers metabolized by CYP3A4 (eg, verapamil, amlodipine, diltiazem).”Yet calcium-channel blockers and clarithromycin continue to be frequently coprescribed in routine care.

When hypotension occurs, the kidney is particularly prone to acute ischemic injury from poor perfusion. Acute kidney injury is a clinically important event that impacts morbidity, mortality, and resource use.Despite this knowledge, the risk of acute kidney injury following coprescription of clarithromycin with a calcium-channel blocker is unknown. 

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