A possible interaction between felodipine and digoxin was studied in 23 patients with congestive heart failure before and after 8 weeks treatment with both drugs.
A modest, non-significant increase in serum digoxin level 2 h postdose (+15%) was found in the felodipine group (n=11) compared to placebo (n=12), with no change in the trough and 6 h postdose levels.
There was a bimodal distribution of the observed changes in serum digoxin level 2 h postdose: a significant increase (p<0.001) was observed only in patients with a high plasma felodipine level, which may have been caused by changes in the absorption rate in those patients. Changes in the elimination of digoxin after felodipine therapy appeared unlikely, since the trough and 6 h post-dose levels were unchanged.
Analysis of the clinical characteristics, haemodynamics and laboratory values revealed no significant differences between the subgroups. The observed increase in serum digoxin warrants monitoring the trough and peak levels digoxin in patients with congestive heart failure who are also being treated with felodipine.
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Schwartz JB, Keefe D, Kates RE (1982) Acute and chronic pharmacodynamic interaction of verapamil and digoxin in patients with atrial fibrillation. Circulation 65: 1163–1170
Pedersen KE, Dorph-Pedersen A, Hvidt S, Klitgaard NA, Nielsen-Kudsk F (1981) Digoxin-verapamil interaction. Clin Pharmacol Ther 30: 311–316
Klein HO, Lang R, Weiss E, De Segni E, Libhaber C, Guerrero J, Kaplinsky E (1982) The influence of verapamil on digoxin concentration. Circulation 65: 998–1003
Pedersen KE, Dorph-Pedersen A, Hvidt S, Klitgaard NA, Pedersen KK (1982) The long-term effect of verapamil on plasma digoxin concentration and renal digoxin clearnance in healthy subjects. Eur J Clin Pharmacol 22: 123–127
Doering W (1983) Effects of coadministration of verapamil and quinidine on serum digoxin concentration. Eur J Clin Pharmacol 25: 517–521
Rameis H, Mayometschnigg D, Ganzinger W (1984) The diltiazem digoxin interaction. Clin Pharmacol Ther 36: 183–189
Yoshida A, Fujita M, Kurosawa N, Nioka M, Shichinohe T, Arakuwa M, Fakuda R, Owada E, Ito K (1984) Effects of diltiazem on plasma level and urinary excretion of digoxin in healthy subjects. Clin Pharmacol Ther 35: 681–685
Schwartz JB, Migliore PhJ (1984) Effects of nifedipine on serum digoxin concentrations and renal digoxin clearance. Clin Pharmacol Ther 36: 19–24
Schwartz JB, Raizner A, Akers S (1984) The effect of nifedipine on serum digoxin concentration in patients. Am Heart J 1077: 669
Kuhlmann J (1985) Effects of nifedipine and diltiazem on plasma levels and renal excretion of beta-acetyldigoxin. Clin Pharmacol Ther 37: 150–156
De Cesaris R, Balestruzzi M, Chiarappa R, Ranieri G (1983) Increase of serum digoxin levels after combined administration of calcium antagonists and beta-methyl digoxin. G Ital Cardiol 13: 188–191
Belz GG, Doering W, Munkes R, Matthews J (1983) Interaction between digoxin and calcium antagonists and antiarrhythmic drugs. Clin Pharmacol Ther 33: 410–417
Pedersen KE, Dorph-Pedersen A, Hvidt S, Klitgaard NA, Kjaer K, Nielsen-Kudsk F (1982) Effect of nifedipine on digoxin kinetics in healthy subjects. Clin Pharmacol Ther 32: 562
Zylber-Katz E, Koren G, Levy M (1984) Pharmacokinetic study of digoxin and nifedipine coadministration (abstr). Clin Pharmacol Ther 36: 19–24
Kirch W, Hutt HJ, Dylewicz P, Graf KJ, Ohnhaus EE (1986) Dose-dependence of the nifedipine-digoxin interaction? Clin Pharmacol Ther 39: 35–39
Schwartz JB (1985) Digoxin and nifedipine. Am J Cardiol 55: 31E-34E
Ahnoff M (1984) Determination of felodipine in plasma by gas chromatography with electron capture detection. J Pharm Biomed Anal 2: 519–526
Schaumann W (1978) Beta-methyl digoxin, a new lipophilic digoxin derivative. In: Bodem G, Dengler HJ (eds) Cardiac glycosides. Springer, Berlin Heidelberg New York, pp 93–104
Antman EM, Smith TW (1985) Drug interactions with digitalis glycosides. In: Smith TW (ed) Digitalis glycosides. Grune & Stratton, Orlando, pp 65–82
Jelliffe RW (1986) An improved method of digoxin therapy. Ann Intern Med 69: 703–717
Halkin H, Sheiner LB, Peck CC, Melmon KL (1975) Determinants of the renal clearance of digoxin. Clin Pharmacol Ther 1: 385–394
Steiness E (1984) Renal tubular secretion of digoxin. Circulation 50: 103–107
Rietbrock N, Woodcock BG (1981) Pharmacokinetics of digoxin and derivatives. In: Greeff K (ed) Handbook of experimental pharmacology. Springer, Berlin Heidelberg New York, pp 31–56
Cogan JJ, Humphreys MH, Carlson CJ, Benowitz NL, Rappaport E (1981) Acute vasodilator therapy increases renal clearance of digoxin in patients with congestive heart failure. Circulation 64: 973–976
Hansen PB, Buch J, Rasmussen O, Waldorff S, Steiness E (1984) Influence of atenolol and nifedipine on digoxin-induced inotropism in humans. Br J Clin Pharmacol 18: 817–822
Ljung B (1980) Vascular versus myocardial selectivity in vitro of H 154/82, a new dihydropyridine. Blood Vessels 17: 154
Dunselman PHJM, Kuntze CEE, van Bruggen A, Hamer H, Wesseling H, Lie KI (1987) Felodipine in heart failure: A double-blind placebo-controlled study in 23 patients. Circulation 76 [Suppl 4], abstract 710
Kramer WG, Kobilash AJ, Lewis RP, Bathala MS, Viscont JA, Reunig RH (1979) Pharmacokinetics of digoxin: Relationship between response intensity and predicted compartmental drug levels in man. J Pharmacokinet Biopharm 7: 47–61
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Dunselman, P.H.J.M., Scaf, A.H.J., Kuntze, C.E.E. et al. Digoxin-felodipine interaction in patients with congestive heart failure. Eur J Clin Pharmacol 35, 461–465 (1988). https://doi.org/10.1007/BF00558239
- drug interaction
- congestive heart failure