Aminoglycosides + Verapamil - Drug Interactions

Verapamil appears to protect kidney from damage caused bygentamicin

Clinical evidence,mechanism, importance and management

In a comparative study,9 healthy subjects were given gentamicin alone (2 mg/kg loading dose, followed by doses every 8 hrs to achieve a peak concentration of 5.5 mg/L and a trough concentration of 0.5 mg/L), and 6 other subjects were given same dosage of gentamicin with sustained-release verapamil 180mg twice daily. The gentamicin AUCs of two groups were virtually same but 24-hour urinary excretion of alanine aminopeptidase (AAP) was modestly reduced, by 18%, in group given verapamil. The reduction in AAP excretion was particularly marked during first 6 days (See reference number 1). The significance of urinary AAP is that this enzyme is found primarily in brush border membranes of proximal renal tubules, and its excretion is an early and sensitive marker of renal damage. Thus it seems that verapamil may modestly protect kidneys from damage by gentamicin, but using a drug as potentially toxic as verapamil to provide this protection, when risks of renal toxicity can be minimised by carefully controlling gentamicin dosage, is unwarranted. Information about other aminoglycosides and other calcium-channel blockers seems to be lacking.

1. Kazierad DJ,Wojcik GJ, Nix DE, Goldfarb AL, Schentag JJ. The effect of verapamil on thenephrotoxic potential of gentamicin as measured by urinary enzyme excretion in healthy volunteers. J Clin Pharmacol (1995) 35, 196–201.