Drug General Information (ID: DDIHQ5M6SL)
Drug Name			Amiodarone		Drug Info		Digitoxin		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antiarrhythmic Agents				Antiarrhythmic Agents
Structure

Mechanism of Amiodarone-Digitoxin Interaction (Severity Level: Major)
Competitive binding of plasma proteins Click to Show/Hide Mechanism Graph
Drug Name		Amiodarone				Digitoxin
Mechanism 1		Competition for plasma protein binding sites				Competition for plasma protein binding sites
Key Mechanism Factor 1
		Factor Name		Plasma protein binding
		Factor Description		Plasma protein binding refers to the degree of binding of a drug to proteins in the blood, and the lower the degree of binding, the more efficiently the drug can cross cell membranes or diffuse. Plasma protein binding alters the distribution and therapeutic characteristics of the drugs.
Mechanism Description		Increased plasma concentration of Digitoxin and Amiodarone due to competitive binding of plasma proteins
Increased risk of bradycardia Click to Show/Hide Mechanism Graph
Drug Name		Amiodarone				Digitoxin
Mechanism 2		Bradycardia				Bradycardia
Key Mechanism Factor 2
		Factor Name		Bradycardia
		Factor Description		Bradycardia is a slow heart rate in which the heart beats less than 60 times per minute. If the heart rate is very slow and the heart is not pumping enough oxygen-rich blood to the body, and you may feel dizzy, very tired or weak, and short of breath.
Mechanism Description		Increased risk of bradycardia by the combination of Amiodarone and Digitoxin

Recommended Action
Management		The need for continued digitalis therapy should be evaluated if amiodarone is prescribed to patients treated with digitalis. Empirical reduction of digitalis dosage by one-third to one-half should be considered in patients who require concomitant treatment with these drugs. Serum digitalis levels should be closely monitored and patients observed for clinical evidence of toxicity. Patients should be advised to seek medical attention if they experience signs of digitalis toxicity such as nausea, anorexia, visual disturbances, slow pulse, or irregular heartbeats.

References
1	Bajaj BP, Baig MW, Perrins EJ "Amiodarone-induced torsades de pointes: the possible facilitatory role of digoxin." Int J Cardiol 33 (1991): 335-7. [PMID: 1743800]
2	Ben-Chetrit E, Ackerman Z, Eliakim M "Amiodarone-associated hypothyroidism--a possible cause of digoxin intoxication." Am J Med Sci 289 (1985): 114-6. [PMID: 3976714]
3	Drescher S, Glaeser H, Murdter T, Hitzl M, Eichelbaum M, Fromm MF "P-glycoprotein-mediated intestinal and biliary digoxin transport in humans." Clin Pharmacol Ther 73 (2003): 223-31. [PMID: 12621387]
4	Fenster PE, White NW, Jr Hanson CD "Pharmacokinetic evaluation of the digoxin-amiodarone interaction." J Am Coll Cardiol 5 (1985): 108-12. [PMID: 3964797]
5	Freitag D, Bebee R, Sunderland B "Digoxin-quinidine and digoxin-amiodarone interactions: frequency of occurrence and monitoring in australian repatriation hospitals." J Clin Pharm Ther 20 (1995): 179-83. [PMID: 7593381]
6	Gill J, Heel RC, Fitton A "Amiodarone: an overview of its pharmacological properties, and review of its therapeutic use in cardiac arrhythmias." Drugs 43 (1992): 69-110. [PMID: 1372862]
7	Kerin NZ, Aragon E, Faitel K, Frumin H, Rubenfire M "Long-term efficacy and toxicity of high- and low-dose amiodarone regimens." J Clin Pharmacol 29 (1989): 418-23. [PMID: 2661600]
8	Klein HO, Beker B, DiSegni E, Kaplinsky E "Asystole produced by the combination of amiodarone and digoxin." Am Heart J 113 (1987): 399-400. [PMID: 3544756]
9	Koren G, Hesslein PS, MacLeod SM "Digoxin toxicity associated with amiodarone therapy in children." J Pediatr 104 (1984): 467-70. [PMID: 6707801]
10	Laer S, Scholz H, Buschmann I, Thoenes M, Meinertz T "Digitoxin intoxication during concomitant use of amiodarone." Eur J Clin Pharmacol 54 (1998): 95-6. [PMID: 9591938]
11	Marcus FI "Pharmacokinetic interactions between digoxin and other drugs." J Am Coll Cardiol 5 (1985): a82-90. [PMID: 2985676]
12	McGovern B, Garan H, Kelly E, Ruskin JN "Adverse reactions during treatment with amiodarone hydrochloride." Br Med J (Clin Res Ed) 287 (1983): 175-80. [PMID: 6409240]
13	Mingardi G "Amiodarone and plasma digoxin levels." Lancet 1 (1984): 1238. [PMID: 6144946]
14	Moysey JO, Jaggarao NS, Grundy EN, Chamberlain DA "Amiodarone increases plasma digoxin concentrations." Br Med J (Clin Res Ed) 282 (1981): 272. [PMID: 6779981]
15	Nademanee K, Kannan R, Hendrickson J, Ookhtens M, Kay I, Singh BN "Amiodarone-digoxin interaction: clinical significance, time course of development, potential pharmacokinetic mechanisms and therapeutic implications." J Am Coll Cardiol 4 (1984): 111-6. [PMID: 6736437]
16	Oetgen WJ, Sobol SM, Tri TB, Heydorn WH, Rakita L "Amiodarone-digoxin interaction: clinical and experimental observations." Chest 86 (1984): 75-9. [PMID: 6734297]
17	Product Information. Cordarone (amiodarone). Wyeth-Ayerst Laboratories, Philadelphia, PA.
18	Rodin SM, Johnson BF "Pharmacokinetic interactions with digoxin." Clin Pharmacokinet 15 (1988): 227-44. [PMID: 3056649]
19	Wilson JS, Podrid PJ "Side effects from amiodarone." Am Heart J 121 (1991): 158-71. [PMID: 1985357]