Verapamil-Digoxin Interaction in Chronic Hemodialysis Patients

Abstract

Verapamil increases the serum-digoxin concentration (SDC) in digoxin treated normals due to a compromised renal and extrarenal clearance. In chronic hemodialysis patients (CHD-patients) treated with digoxin where the renal elimination is diminished, verapamil has been shown to cause substantial increases of SDC with risk of digoxin intoxication. The effect of verapamil treatment on SDC in 8 nearly anephric (Uvol less than 1 l/d) CHD-patients on digoxin treatment was assessed. The patients were continuously treated with verapamil for two periods of two weeks at two dosage levels, 120 mg/d and 240 mg/d, whereafter verapamil was withdrawn. SDC and serum-verapamil were measured weekly. The SDC increased from 1.1 mmol/l to 1.7 mmol/l (p less than 0.05, N = 7) during the first two weeks. Increasing the dose of verapamil to 240 mg/d did not cause a further increment in SDC; on the contrary, the mean SDC decreased. The SDC increments varied between 0 and 200% of baseline values. We conclude that verapamil treatment decreases digoxin clearance in CHD-patients and that the influence of verapamil on SDC in CHD-patients shows great interindividual variation with no close dose dependency and decreases to pretreatment level in 2-3 weeks.

Calcium Antagonists

“…Coadministration of verapamil and digoxin may result in a clinically significant elevation in digoxin concentration, According to Klein et al, [89] and Pedersen, [88] verapamil significantly increased serum digoxin concentrations, by as much as 60 to 80% according to the latter author.l 88 ] Since the process is gradual and dose-dependent, the dose of digoxin may need constant readjustment in patients who are concomitantly receiving verapamiI.l89] The potentially hazardous outcome (namely severe conduction disturbances) of the veraparnil/digoxin interaction necessitates frequent serum digoxin concentration measurements, Rendtorff et al, [86] who also found that verapamil significantly increased serum digoxin concentrations in a dose-dependent and gradual manner, attributed the process in part to reduced renal excretion without reduction in glomerular filtration, and recommended adjustment of the digoxin dose in patients concomitantly receiving veraparnil. An increase in serum digoxin concentration of 250% was described [87] in a chronic haemodialysis patient during coadministration of verapamil and digoxin, resulting in third degree AV block associated with nodal escape beats.…”