Antiarrhythmic Agents

Drug Interactions of Clinical Significance

Abstract

The management of cardiac arrhythmias has grown more complex in recent years. Despite the recent focus on nonpharmacological therapy, most clinical arrhythmias are treated with existing antiarrhythmics. Because of the narrow therapeutic index of antiarrhythmic agents, potential drug interactions with other medications are of major clinical importance.

As most antiarrhythmics are metabolised via the cytochrome P450 enzyme system, pharmacokinetic interactions constitute the majority of clinically significant interactions seen with these agents. Antiarrhythmics may be substrates, inducers or inhibitors of cytochrome P450 enzymes, and many of these metabolic interactions have been characterised. However, many potential interactions have not, and knowledge of how antiarrhythmic agents are metabolised by the cytochrome P450 enzyme system may allow clinicians to predict potential interactions.

Drug interactions with Vaughn-Williams Class II (β-blockers) and Class IV (calcium antagonists) agents have previously been reviewed and are not discussed here. Class I agents, which primarily block fast sodium channels and slow conduction velocity, include quinidine, procainamide, disopyramide, lidocaine (lignocaine), mexiletine, flecainide and propafenone. All of these agents except procainamide are metabolised via the cytochrome P450 system and are involved in a number of drug-drug interactions, including over 20 different interactions with quinidine. Quinidine has been observed to inhibit the metabolism of digoxin, tricyclic antidepressants and codeine. Furthermore, cimetidine, azole antifungals and calcium antagonists can significantly inhibit the metabolism of quinidine. Procainamide is excreted via active tubular secretion, which may be inhibited by cimetidine and trimethoprim. Other Class I agents may affect the disposition of warfarin, theophylline and tricyclic antidepressants. Many of these interactions can significantly affect efficacy and/or toxicity.

Of the Class III antiarrhythmics, amiodarone is involved in a significant number of interactions since it is a potent inhibitor of several cytochrome P450 enzymes. It can significantly impair the metabolism of digoxin, theophylline and warfarin. Dosages of digoxin and warfarin should empirically be decreased by one-half when amiodarone therapy is added.

In addition to pharmacokinetic interactions, many reports describe the use of antiarrhythmic drug combinations for the treatment of arrhythmias. By combining antiarrhythmic drugs and utilising additive electrophysiological/pharmacodynamic effects, antiarrhythmic efficacy may be improved and toxicity reduced. As medication regimens grow more complexwith the aging population, knowledge of existing and potential drug-drug interactions becomes vital for clinicians to optimise drug therapy for every patient.

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References

  1. 1.

    Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide or placebo - the Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991; 324: 781–8

    PubMed  CAS  Google Scholar 

  2. 2.

    Kuck K-H, Schluter M. Junctional tachycardia and the role of catheter ablation. Lancet 1993; 341: 1386–91

    PubMed  CAS  Google Scholar 

  3. 3.

    Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med 1996; 335: 1933–40

    PubMed  CAS  Google Scholar 

  4. 4.

    The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997; 337: 1576–83

    Google Scholar 

  5. 5.

    Prystowsky EN, Benson W, Fuster V, et al. Management of patients with atrial fibrillation. A statement for healthcare professionals from the subcommittee on electrocardiography and electrophysiology, American Heart Association. Circulation 1996; 93: 1262–77

    PubMed  CAS  Google Scholar 

  6. 6.

    Ommen SR, Odell JA, Stanton MS. Atrial arrhythmias after cardiothoracic surgery. N Engl J Med 1997; 336: 1429–34

    PubMed  CAS  Google Scholar 

  7. 7.

    Daoud EG, Strickberger SA, Man KC, et al. Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery. N Engl J Med 1997; 337: 1785–91

    PubMed  CAS  Google Scholar 

  8. 8.

    Sherrid MV, Pearle G, Gunsburg DZ. Mechanism of benefit of negative inotropes in obstructive hypertrophic cardiomyopathy. Circulation 1998; 97: 41–7

    PubMed  CAS  Google Scholar 

  9. 9.

    Singh BN. Amiodarone: the expanding antiarrhythmic role and how to follow a patient on chronic therapy. Clin Cardiol 1997; 20: 608–18

    PubMed  CAS  Google Scholar 

  10. 10.

    Benet LZ, Kroetz DL, Sheiner L. Pharmacokinetics: the dynamics of drug absorption, distribution, and elimination. In: Hardman JG, Limbird LE, editors. Goodman & Gillman’s the pharmacologic basis of therapeutics. New York (NY): McGraw-Hill, 1996: 3–28

    Google Scholar 

  11. 11.

    Lévy S. Combination therapy for cardiac arrhythmias. Am J Cardiol 1988; 61: 95A–101A

    PubMed  Google Scholar 

  12. 12.

    Duff HJ, Roden D, Primm RK, et al. Mexiletine in the treatment of resistant ventricular arrhythmias: enhancement of efficacy and reduction of dose-related side effects by combination with quinidine. Circulation 1983; 67: 1124–8

    PubMed  CAS  Google Scholar 

  13. 13.

    Blitzer M, Costeas C, Kassotis J, et al. Rhythm management in atrial fibrillation - with a primary emphasis on pharmacological therapy: Part 1. PACE 1998; 21: 590–602

    PubMed  CAS  Google Scholar 

  14. 14.

    Rendic S, Di Carlo FJ. Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab Rev 1997; 29 (1 & 2): 413–580

    PubMed  CAS  Google Scholar 

  15. 15.

    Michalets EL. Update: clinically significant cytochrome P-450 drug interactions. Pharmacotherapy 1998; 18 (1): 84–112

    PubMed  CAS  Google Scholar 

  16. 16.

    Slaughter RL, Edwards DJ. Recent advances: the cytochrome P450 enzymes. Ann Pharmacother 1995; 29: 619–24

    PubMed  CAS  Google Scholar 

  17. 17.

    Lennard MS. Genetically determined adverse drug reactions involving metabolism. Drug Saf 1993; 9 (1): 60–77

    PubMed  CAS  Google Scholar 

  18. 18.

    Funck-Brentano C. Genetically determined drug interactions of antiarrhythmic drugs. Cardiology 1992; 6Suppl. 2: 11–4

    Google Scholar 

  19. 19.

    Vaughn Williams EM. A classification of antiarrhythmic actions reassessed after a decade of new drugs. J Clin Pharmacol 1984; 24: 129–47

    Google Scholar 

  20. 20.

    Task Force of the Working Group of Arrhythmias of European Society of Cardiology. The Sicilian gambit: a new approach to classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms. Circulation 1991; 84:1831–51

    Google Scholar 

  21. 21.

    Blaufarb I, Pfeifer TM, Frishman WH. β-Blockers. Drug interactions of clinical significance. Drug Saf 1995; 13 (6): 359–70

    PubMed  CAS  Google Scholar 

  22. 22.

    Rosenthal T, Ezra D. Calcium antagonists. Drug interactions of clinical significance. Drug Saf 1995; 13 (3): 157–87

    PubMed  CAS  Google Scholar 

  23. 23.

    Magnani B, Malini PL. Cardiac glycosides. Drug Interactions of clinical significance. Drug Saf 1995; 12 (2): 97–109

    PubMed  CAS  Google Scholar 

  24. 24.

    Marcus FI. Drug interactions with amiodarone. Am Heart J 1983; 106: 9924–30

    Google Scholar 

  25. 25.

    Tartini R, Kappenberger L, Steinbrunn W, et al. Dangerous interaction between amiodarone and quinidine. Lancet 1982; I (8285): 1327–9

    Google Scholar 

  26. 26.

    Saal AK, Werner JA, Greene HL, et al. Effect of amiodarone on serum quinidine and procainamide levels. Am J Cardiol 1984; 53 (9): 1264–7

    PubMed  CAS  Google Scholar 

  27. 27.

    Baker BJ, Gammill J, Massengill J, et al. Concurrent use of quinidine and disopyramide: evaluation of serum concentrations and electrocardiographic effects. Am Heart J 1983; 105 (1): 12–5

    PubMed  CAS  Google Scholar 

  28. 28.

    Munafo A, Buclin T, Tuto D, et al. The effect of a low dose of quinidine on the disposition of flecainide in healthy volunteers. Eur J Clin Pharmacol 1992; 43 (4): 441–3

    PubMed  CAS  Google Scholar 

  29. 29.

    Broly F, Vandamme N, Caron J, et al. Single-dose quinidine treatment inhibits mexiletine oxidation in extensive metabolizers of debrisoquine. Life Sci 1991; 48: 123–8

    Google Scholar 

  30. 30.

    Hughes B, Dyer JE, Schwartz AB. Increased procainamide plasma concentrations caused by quinidine: a new drug interaction. Am Heart J 1987; 114: 908–9

    PubMed  CAS  Google Scholar 

  31. 31.

    Klein RC, Huang SK, Marcus FI, et al. Efficacy of propafenone when used in combination with procainamide or quinidine. Am Heart J 1987; 114 (3): 551–8

    PubMed  CAS  Google Scholar 

  32. 32.

    Funck-Brentano C, Kroemer HK, Pavlou H, et al. Genetically-determined interaction between propafenone and low dose quinidine: role of active metabolites in modulating net drug effect. Br J Clin Pharmacol 1989; 27 (4): 435–44

    PubMed  CAS  Google Scholar 

  33. 33.

    Morike KE, Roden DM. Quinidine-enhanced beta-blockade during treatment with propafenone in extensive metabolizer human subjects. Clin Pharmacol Ther 1994; 55 (1): 28–34

    PubMed  CAS  Google Scholar 

  34. 34.

    Cooke CE, Sklar GE, Nappi JM. Possible pharmacokinetic interaction with quinidine: ciprofloxacin or metronidazole? Ann Pharmacother 1996; 30 (4): 364–6

    PubMed  CAS  Google Scholar 

  35. 35.

    Spinler SA, Cheng JW, Kindwall KE, et al. Possible inhibition of hepatic metabolism of quinidine by erythromycin. Clin Pharmacol Ther 1995; 57 (1): 89–94

    PubMed  CAS  Google Scholar 

  36. 36.

    Lin JC, Quasny HA. QT prolongation and development of torsades de pointes with the concomitant administration of oral erythromycin base and quinidine. Pharmacotherapy 1997; 17 (3): 626–30

    PubMed  CAS  Google Scholar 

  37. 37.

    Kaukonen KM, Olkkola KT, Neuvonen PJ. Itraconazole increases plasma concentrations of quinidine. Clin Pharmacol Ther 1997; 62: 10–7

    Google Scholar 

  38. 38.

    McNulty RM, Lazor JA, Sketch M. Transient increase in plasma quinidine concentrations during ketoconazole-quinidine therapy. Clin Pharmacol 1989; 8 (3): 222–5

    CAS  Google Scholar 

  39. 39.

    Posicor Product Information. Nutley(NJ): Roche Laboratories, June 1997

  40. 40.

    Farringer JA, Green JA, O’Rourke RA, et al. Nifedipine-induced alterations in serum quinidine concentrations. Am Heart J 1984; 108: 1570–2

    PubMed  CAS  Google Scholar 

  41. 41.

    Van Lith RM, Appleby DH. Quinidine-nifedipine interaction. Drug Intell Clin Pharmacol 1985; 19: 829–31

    Google Scholar 

  42. 42.

    Green JA, Clementi WA, Porter C, et al. Nifedipine-quinidine interaction. Clin Pharmacol 1983; 2: 461–5

    CAS  Google Scholar 

  43. 43.

    Munger MA, Jarvis RC, Nair R, et al. Elucidation of the nifedipine-quinidine interaction. Clin Pharmacol Ther 1989; 45: 411–6

    PubMed  CAS  Google Scholar 

  44. 44.

    Oates NS. Influence of quinidine on nifedipine plasma pharmaco-kinetics. Br J Pharmacol 1988; 25: 675

    Google Scholar 

  45. 45.

    Schellens JH, Ghabrial H, van der wart H-HF, et al. Differential effects of quinidine on the disposition of nifedipine, sparteine, and mephenytoin in humans. Clin Pharmacol Ther 1991; 50: 520–8

    PubMed  CAS  Google Scholar 

  46. 46.

    Bowles SK, Reeves RA, Cardozo L, et al. Evaluation of the pharmacokinetic and pharmacodynamic interaction between quinidine and nifedipine. J Clin Pharmacol 1993; 33: 727–31

    PubMed  CAS  Google Scholar 

  47. 47.

    Bailey DG, Freeman DJ, Melendez LJ, et al. Quinidine interaction with nifedipine and felodipine: pharmacokinetic and pharmacodynamic evaluation. Clin Pharmacol Ther 1993; 53: 354–9

    PubMed  CAS  Google Scholar 

  48. 48.

    Maisel AS, Motulsky HJ, Insel PA. Hypotension after quinidine plus verapamil: possible additive competition at alpha-adrenergic receptors. N Engl J Med 1984; 312: 167–70

    Google Scholar 

  49. 49.

    Lavoie R. The effect of verapamil on quinidine pharmaco-kinetics in man [abstract]. Drug Intell Clin Pharmacol 1986; 20: 457

    Google Scholar 

  50. 50.

    Trohman RG, Estes DM, Castellanos A, et al. Increased quinidine plasma concentrations during administration of verapramil: a new quinidine-verapramil interaction. Am J Cardiol 1986; 57 (8): 706–7

    PubMed  CAS  Google Scholar 

  51. 51.

    Edwards DJ, Lavorie R, Beckman H, et al. The effect of coadministration of verapramil on the pharmacokinetics and metabolism of quinidine. Clin Pharmacol Ther 1987; 41: 68–73

    PubMed  CAS  Google Scholar 

  52. 52.

    Laganiere S, Davies RF, Carignan G, et al. Pharmacokinetic and pharmacodynamic interactions between diltiazem and quinidine. Clin Pharmacol Ther 1996; 60 (3): 255–64

    PubMed  CAS  Google Scholar 

  53. 53.

    Matera MG, De Santis D, Vacca C, et al. Quinidine-diltiazem: pharmacokinetic interaction in humans. Curr Ther Res 1986; 40: 653–6

    CAS  Google Scholar 

  54. 54.

    Data JL, Wilkinson GR, Nies AS. Interaction of quinidine with anticonvulsant drugs. N Engl J Med 1976; 294: 699–702

    PubMed  CAS  Google Scholar 

  55. 55.

    Urbano AM. Phenytoin-quinidine interactions in a patient with recurrent ventricular tachyarrhythmias [letter]. N Engl J Med 1983; 308 (4): 225

    PubMed  CAS  Google Scholar 

  56. 56.

    Twum-Barima Y, Carruthers SG. Quinidine-rifampin interaction. N Engl J Med 1981; 304 (24): 1466–9

    PubMed  CAS  Google Scholar 

  57. 57.

    Bussey HI, Merritt GJ, Hill EG. The influence of rifampin on quinidine and digoxin. Arch Intern Med 1984; 144 (5): 1021–3

    PubMed  CAS  Google Scholar 

  58. 58.

    Schwartz A, Brown JR. Quinidine-rifampin interaction. Am Heart J 1984; 107 (4): 789–90

    PubMed  CAS  Google Scholar 

  59. 59.

    Chapron DJ, Mumford D, Pitegoff GI. Apparent quinidine-induced digoxin toxicity after withdrawal of pentobarbital: a case of sequential drug interactions. Arch Intern Med 1979; 139 (3): 363–5

    PubMed  CAS  Google Scholar 

  60. 60.

    Rodgers GC, Blackman MS. Quinidine interaction with anticonvulsants. Drug Intell Clin Pharmacol 1983; 17 (11): 819–20

    CAS  Google Scholar 

  61. 61.

    Grogano AW. Anesthesia for atrial fibrillation. Effect of quinidine on muscle relaxation. Lancet 1963; II: 1039–40

    Google Scholar 

  62. 62.

    Kornfeld P, Horowitz SH, Genkins G, et al. Myasthenia gravis unmasked by antiarrhythmic agents. Mt Sinai J Med 1976; 43: 10–4

    PubMed  CAS  Google Scholar 

  63. 63.

    Hardy BG, Schentag JJ. Lack of effect of cimetidine on the metabolism of quinidine: effect on renal clearance. Int J Clin Pharmacol Ther 1988; 26: 388–91

    CAS  Google Scholar 

  64. 64.

    Fruncillo RJ, DiGregorio GJ, Soll A. Effect of cimetidine on the pharmacokinetics of quinidine and lidocaine in the rat. J Pharm Sci 1983; 72 (7): 826–8

    PubMed  CAS  Google Scholar 

  65. 65.

    Hardy BG, Zador IT, Golden L, et al. Effect of cimetidine on the pharmacokinetics and pharmacodynamics of quinidine. Am J Cardiol 1983; 52 (1): 172–5

    PubMed  CAS  Google Scholar 

  66. 66.

    Farringer JA, McWay-Hess K, Clementi WA. Cimetidine-quinidine interaction. Clin Pharmacol 1984; 3 (1): 81–3

    CAS  Google Scholar 

  67. 67.

    Kolb KW, Garnett WR, Small RE, et al. Effect of cimetidine on quinidine clearance. Ther Drug Monitor 1984; 6 (3): 306–13

    CAS  Google Scholar 

  68. 68.

    Sindrup SH, Brosen K, Bjerring P, et al. Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine. Clin Pharmacol Ther 1990; 48 (6): 686–93

    PubMed  CAS  Google Scholar 

  69. 69.

    Sindrup SH, Arendt-Nielsen L, Brosen K, et al. The effect of quinidine on the analgesic effect of codeine. Eur J Clin Pharmacol 1992; 42 (6): 587–91

    PubMed  CAS  Google Scholar 

  70. 70.

    Zhang Y, Britto MR, Valderhaug KL, et al. Dextromethorphan: enhancing its systemic availability by way of low-dose quinidine-mediated inhibition of cytochrome P4502D6. Clin Pharmacol Ther 1992; 51 (6): 647–55

    PubMed  CAS  Google Scholar 

  71. 71.

    Leahey EB, Reiffel JA, Giradina EGV, et al. The effect of quinidine and other oral antiarrhythmic drugs on serum digoxin: a prospective study. Ann Intern Med 1980; 92: 605–8

    PubMed  Google Scholar 

  72. 72.

    Koren G, MacLeod SM. Characteristics of the digoxin-quinidine and digoxin-verapramil interactions in the rat kidney. Res Commun Chem Pathol Pharmacol 1984; 45 (1): 3–18

    PubMed  CAS  Google Scholar 

  73. 73.

    Bigger JT, Leahey EB. Quinidine and digoxin: an important interaction. Drugs 1982; 24: 229–39

    PubMed  CAS  Google Scholar 

  74. 74.

    Fichtl B, Doering W. The quinidine-digoxin interaction in perspective. Clin Pharmacokinet 1983; 8: 137–54

    PubMed  CAS  Google Scholar 

  75. 75.

    Gessman L, Danilo P, Rosen MR. An electrophysiologic study of the quinidine-digoxin interaction. J Clin Pharmacol 1983; 23: 16–23

    PubMed  CAS  Google Scholar 

  76. 76.

    Su SF, Huang JD. Inhibition of the intestinal digoxin absorption and exsorption of quinidine. Drug Metab Dispos 1996; 24 (2): 142–7

    PubMed  CAS  Google Scholar 

  77. 77.

    Zhou H-H, Anthony LB, Roden DM, et al. Quinidine reduces clearance of (+) propranolol more than (−) propranolol through marked reduction in 4-hydroxylation. Clin Pharmacol Ther 1990; 457: 686–93

    Google Scholar 

  78. 78.

    Leemann T, Dayer P, Meyer UA. Single-dose quinidine treatment inhibits metoprolol oxidation in extensive metabolizers. Eur J Clin Pharmacol 1986; 29 (6): 739–41

    PubMed  CAS  Google Scholar 

  79. 79.

    Kessler KM, Humphries Jr WC, Black M, et al. Quinidine pharmaco-kinetics in patients with cirrhosis or receiving propranolol. Am Heart J 1978; 96 (5): 627–35

    PubMed  CAS  Google Scholar 

  80. 80.

    Fenster P, Perrier D, Mayersohn M, et al. Kinetic evaluation of the propranolol-quinidine combination. Clin Pharmacol Ther 1980; 27 (4): 450–3

    PubMed  CAS  Google Scholar 

  81. 81.

    Rey AM, Gums JG. Altered absorption of digoxin, sustained-release quinidine, and warfarin with sucralfate. Drug Intell Clin Pharm 1991; 25 (7-8): 745–6

    CAS  Google Scholar 

  82. 82.

    Brosen K, Gram LF. Quinidine inhibits the 2-hydroxylation of imipramine and desipramine but not the demethylation of imipramine. Eur J Clin Pharmacol 1989; 37 (2): 155–60

    PubMed  CAS  Google Scholar 

  83. 83.

    Steiner E, Dumont E, Spina E, et al. Inhibition of desipramine 2-hydroxylation by quinidine and quinine. Clin Pharmacol Ther 1998; 43 (5): 577–81

    Google Scholar 

  84. 84.

    Damkier, Hansen LL, Brosen K. Effect of fluvoxamine on the pharmacokinetics of quinidine. Eur J Clin Pharmacol 1999; 55 (6): 451–6

    PubMed  CAS  Google Scholar 

  85. 85.

    Gazzaninga AB, Stewart DR. Possible quinidine induced hemorrhage in a patient with warfarin sodium [letter]. N Engl J Med 1969; 280: 711

    Google Scholar 

  86. 86.

    Sylven C, Anderson P. Evidence that disopyramide does not interact with warfarin [letter]. BMJ 1983 Apr 9; 286: 1181

    PubMed  CAS  Google Scholar 

  87. 87.

    Koch-Weser j. Quinidine-induced hypoprothrombinemic hemorrhage in patients with chronic warfarin therapy. Ann Intern Med 1968; 68: 511–7

    PubMed  CAS  Google Scholar 

  88. 88.

    Gerhardt RE, Knouss RF, Thyrum PT, et al. Quinidine excretion in aciduria and alkaluria. Ann Intern Med 1969; 71 (5): 927–33

    PubMed  CAS  Google Scholar 

  89. 89.

    Romankiewicz JA, Reidenberg M, Drayer D, et al. The noninterference of aluminum hydroxide gel with quinidine sulfate absorption: an approach to control quinidine-induced diarrhea. Am Heart J 1978; 96 (4): 518–20

    PubMed  CAS  Google Scholar 

  90. 90.

    Mauro VF, Mauro LS, Fraker Jr TD, et al. Effect of aluminum hydroxide gel on quinidine gluconate absorption. Drug Intell Clin Pharm 1990; 24 (3): 252–4

    CAS  Google Scholar 

  91. 91.

    Windle J, Prystowsky EN, Miles WM, et al. Pharmaco-kinetic and electrophysiologic interactions of amiodarone and procainamide. Clin Pharmacol Ther 1987; 41 (6): 603–10

    PubMed  CAS  Google Scholar 

  92. 92.

    Saal AK, Werner JA, Greene HL, et al. Effect of amiodarone on serum quinidine and procainamide levels. Am J Cardiol 1984; 53 (9): 1264–7

    PubMed  CAS  Google Scholar 

  93. 93.

    Kosoglou T, Rocci Jr ML, Vlasses PH. Trimethoprim alters the disposition of procainamide N-acetylprocainamide. Clin Pharmacol Ther 1988; 44 (4): 467–77

    PubMed  CAS  Google Scholar 

  94. 94.

    Vlasses PH, Kosoglou T, Chase SL, et al. Trimethoprim inhibition of the renal clearance of procainamide and N-acetylprocainamide. Arch Intern Med 1989; 149 (6): 1350–3

    PubMed  CAS  Google Scholar 

  95. 95.

    Martin DE, Shen J, Griener J, et al. Effects of ofloxacin on the pharmacokinetics and pharmacodynamics of procainamide. J Clin Pharmacol 1996; 36 (1): 85–91

    PubMed  CAS  Google Scholar 

  96. 96.

    Ochs HR, Carstens G, Roberts GM, et al. Metoprolol or propranolol does not alter the kinetics of procainamide. J Cardiovasc Pharmacol 1983; 5 (3): 392–5

    PubMed  CAS  Google Scholar 

  97. 97.

    Christian DC, Meredith CG, Speeg KV. Cimetidine inhibits renal procainamide clearance. Clin Pharmacol Ther 1984; 36: 221–7

    PubMed  CAS  Google Scholar 

  98. 98.

    Bauer LA, Black D, Gensler A. Procainamide-cimetidine drug interaction in elderly male patients. J Am Geriatr Soc 1990; 38 (4): 467–9

    PubMed  CAS  Google Scholar 

  99. 99.

    Rodvold KA, Paloucek FP, Jung D, et al. Interaction of steady-state procainamide with H2-receptor antagonists cimetidine and ranitidine. Ther Drug Monit 1987; 9 (4): 378–83

    PubMed  CAS  Google Scholar 

  100. 100.

    Martin BK. Effect of ranitidine on procainamide disposition. Br J Clin Pharmacol 1985; 19 (6): 858–60

    PubMed  CAS  Google Scholar 

  101. 101.

    Somogyi A, Bochner F. Ranitidine and procainamide absorption. Br J Clin Pharmacol 1985; 20 (2): 182–3

    PubMed  CAS  Google Scholar 

  102. 102.

    Rocci Jr ML, Kosoglou T, Ferguson RK, et al. Ranitidine-induced changes in the renal and hepatic clearances of procainamide are correlated. J Pharmacol Exp Ther 1989; 248 (3): 923–8

    PubMed  CAS  Google Scholar 

  103. 103.

    Teichman SL, Fisher JD, Matos JA, et al. Disopyramide-pyridostigmine: report of a beneficial drug interaction. J Cardiovasc Pharmacol 1985; 7: 108–13

    PubMed  CAS  Google Scholar 

  104. 104.

    Wilcox RG, Hampton JR, Rowley JM. Randomised placebo controlled trial comparing oxprenolol with disopyramide phosphate in immediate treatment of suspected myocardial infarction. Lancet 1980; II: 765–9

    Google Scholar 

  105. 105.

    Cumming AD, Robertson D. Interaction between disopyramide and practolol. BMJ 1979; 2: 1264

    PubMed  CAS  Google Scholar 

  106. 106.

    Bonde J, Bodtker S, Angelo HR, et al. Atenolol inhibits the elimination of disopyramide. Eur J Clin Pharmacol 1985; 28: 41–3

    PubMed  CAS  Google Scholar 

  107. 107.

    Aitio ML, Mansury L, Tula E, et al. The effect of enzyme induction on the metabolism of disopyramide in man. Br J Clin Pharmacol 1981; 11: 279–85

    PubMed  CAS  Google Scholar 

  108. 108.

    Staum JM. Enzyme induction: rifampin-disopyramide interaction. Drug Intell Clin Pharm 1990; 24 (7-8): 701–3

    CAS  Google Scholar 

  109. 109.

    Aitio ML, Vuoremma T. Enhanced metabolism and diminished efficacy of disopyramide by enzyme induction. Br J Clin Pharmacol 1980; 9: 149–52

    PubMed  CAS  Google Scholar 

  110. 110.

    Kessler JM, Keys PN, Stafford RW. Disopyramide and phenytoin interaction. Br JClin Pharm 1982; 1: 263–4

    CAS  Google Scholar 

  111. 111.

    Kapil RP, Axelson JE, Mansfield IL, et al. Disopyramide pharmaco-kinetics and metabolism: effects of inducers. Br J Clin Pharmacol 1987; 24: 781–91

    PubMed  CAS  Google Scholar 

  112. 112.

    Ragosta M, Weihl AC, Rosenfeld LE. Potentially fatal interaction between erythromycin and disopyramide. Am J Med 1989; 86 (4): 465–6

    PubMed  CAS  Google Scholar 

  113. 113.

    Iida H, Morita T, Suzuki E, et al. Hypoglycemia induced by interaction between clarithromycin and disopyramide. Jpn Heart J 1999; 40 (1): 91–6

    PubMed  CAS  Google Scholar 

  114. 114.

    Jou MJ, Huang SC, Kiang FM, et al. Comparison of the effects of cimetidine and ranitidine on the pharmacokinetics of disopyramide in man. J Pharm Pharmacol 1997; 49 (11): 1072–5

    PubMed  CAS  Google Scholar 

  115. 115.

    Fruncillo RJ, Kozin SH, Digregorio GJ. Effect of amiodarone on the pharmacokinetics of phenytoin, quinidine, and lidocaine in the rat. Res Commun Chem Pathol Pharmacol 1985; 50 (3): 451–4

    PubMed  CAS  Google Scholar 

  116. 116.

    Siegmund JB, Wilson JH, Imhoff TE. Amiodarone interaction with lidocaine. J Cardiovasc Pharmacol 1993; 21 (4): 513–5

    PubMed  CAS  Google Scholar 

  117. 117.

    Ochs HR, Carstens G, Greenblatt DJ. Reduction in lidocaine clearance during continuous infusion and by coadministration of propranolol. N Engl J Med 1980; 303: 373–7

    PubMed  CAS  Google Scholar 

  118. 118.

    Nies AS, Shand DG, Wilkinson GR. Altered hepatic blood flow and drug disposition. Clin Pharmacokinet 1976; 1 (2): 135–55

    PubMed  CAS  Google Scholar 

  119. 119.

    Bax NDS, Tucker GT, Lennard MS, et al. The impairment of lignocaine clearance by propranolol - major contribution from enzyme inhibition. Br J Clin Pharmacol 1985; 19: 597–603

    PubMed  CAS  Google Scholar 

  120. 120.

    Conrad KA, Byers JM, Finley PR, et al. Lidocaine elimination: effects of metoprolol and of propranolol. Clin Pharmacol Ther 1983; 33 (2): 133–8

    PubMed  CAS  Google Scholar 

  121. 121.

    Bosch J. Medical treatment of portal hypertension. Digestion 1998; 59: 547–55

    PubMed  CAS  Google Scholar 

  122. 122.

    Sekiyama T, Komeichi H, Nagano T, et al. Effects of the α-/β-blocking agent carvedilol on hepatic and systemic hemodynamics in patients with cirrhosis and portal hypertension. Arzneimittel Forschung/Drug Res 1997; 47: 353–5

    CAS  Google Scholar 

  123. 123.

    Stenson RE, Constantino RT, Harrison DC. Interrelationships of hepatic blood flow, cardiac output, and blood levels of lidocaine in man. Circulation 1971; 43: 205–11

    PubMed  CAS  Google Scholar 

  124. 124.

    Feely J, Wilkinson GR, McAllister CB, et al. Increased toxicity and reduced clearance of lidocaine by cimetidine. Ann Intern Med 1982; 96: 592–4

    PubMed  CAS  Google Scholar 

  125. 125.

    Berk SI, Gal P, Bauman JL, et al. The effect of oral cimetidine on total and unbound serum lidocaine concentration in patients with suspected myocardial infarction. Int J Cardiol 1987; 14: 91–4

    PubMed  CAS  Google Scholar 

  126. 126.

    Powell JR, Foster JR, Patterson JH, et al. Effect of duration of lidocaine infusion and route of cimetidine administration on lidocaine pharmacokinetics. Clin Pharm 1986; 5: 993–8

    PubMed  CAS  Google Scholar 

  127. 127.

    Li AP, Rasmussen A, Xu L, et al. Rifampicin induction of lidocaine metabolism in cultured human hepatocytes. J Pharmacol Exp Ther 1995; 274 (2): 673–7

    PubMed  CAS  Google Scholar 

  128. 128.

    Perucca E, Richens A. Reduction of oral bioavailability of lignocaine by induction of first pass metabolism in epileptic patients. Br J Clin Pharmacol 1979; 8 (1): 21–31

    PubMed  CAS  Google Scholar 

  129. 129.

    Bruckner J, Thomas Jr KC, Bikhazi GB, et al. Neuromuscular drug interactions of clinical importance. Anesth Analg 1980; 59 (9): 678-82

    Google Scholar 

  130. 130.

    Fukuda S, Wakuta K, Ishikawa T, et al. Lidocaine modifies the effect of succinylcholine on muscle oxygen consumption in dogs. Anesth Analg 1987; 66 (4): 325–8

    PubMed  CAS  Google Scholar 

  131. 131.

    Pentikainen PJ, Koivula IH, Hiltunen HA. Effect of rifampicin treatment on the kinetics of mexiletine. Eur J Clin Pharmacol 1982; 23 (3): 261–6

    PubMed  CAS  Google Scholar 

  132. 132.

    Begg EJ, Chinwah PM, Webb C, et al. Enhanced metabolism of mexiletine after phenytoin administration. Br J Clin Pharmacol 1982; 14 (2): 219–23

    PubMed  CAS  Google Scholar 

  133. 133.

    Katz A, Buskila D, Sukenik S. Oral mexiletine-theophylline interaction. Int J Cardiol 1987; 17 (2): 227–8

    PubMed  CAS  Google Scholar 

  134. 134.

    Kessler KM, Interian Jr A, Cox M, et al. Proarrhythmia related to a kinetic and dynamic interaction of mexiletine and theophylline. Am Heart J 1989; 117 (4): 964–6

    PubMed  CAS  Google Scholar 

  135. 135.

    Stanley R, Comer T, Taylor JL, et al. Mexiletine-theophylline interaction. Am J Med 1989; 86 (6 Pt 1): 733–4

    PubMed  CAS  Google Scholar 

  136. 136.

    Ueno K, Miyai K, Seki T, et al. Interaction between theophylline and mexiletine. DICP 1990; 24 (5): 471–2

    PubMed  CAS  Google Scholar 

  137. 137.

    Stoysich AM, Mohiuddin SM, Destache CJ, et al. Influence of mexiletine on the pharmacokinetics of theophylline in healthy volunteers. J Clin Pharmacol 1991; 31 (4): 354–7

    PubMed  CAS  Google Scholar 

  138. 138.

    Loi CM, Wei XX, Vestal RE. Inhibition of theophylline metabolism by mexiletine in young male and female nonsmokers. Clin Pharmacol Ther 1991; 49 (5): 571–80

    PubMed  CAS  Google Scholar 

  139. 139.

    Hurwitz A, Vacek JL, Botteron GW, et al. Mexiletine effects on theophylline disposition. Clin Pharmacol Ther 1991; 50 (3): 299–307

    PubMed  CAS  Google Scholar 

  140. 140.

    Ueno K, Miyai K, Kato M, et al. Mechanism of interaction between theophylline and mexiletine. Drug Intell Clin Pharmacol 1991; 25 (7-8): 727–30

    CAS  Google Scholar 

  141. 141.

    Nemeroff CB, DeVane L, Pollock BG. Newer antidepressants and the cytochrome P450 system. Am J Psychol 1996; 153: 311–20

    CAS  Google Scholar 

  142. 142.

    Funck-Bretano C, Jacqz-Aigrain E, Leenhardt A, et al. Influence of amiodarone on genetically determined drug metabolism in humans. Clin Pharmacol Ther 1991; 50: 259–66

    Google Scholar 

  143. 143.

    Funck-Bretano C, Becquemont L, Kroemer HK, et al. Variable disposition kinetics and electrocardiographic effects of flecainide during repeat dosing in humans: contribution of genetic factors, dose-dependent clearance, interaction with amiodarone. Clin Pharmacol Ther 1994; 55 (3): 256–69

    Google Scholar 

  144. 144.

    Tjandra-Maga TB, Van Hecken A, Van Melle P, et al. Altered pharmacokinetics of oral flecainide by cimetidine. Br J Clin Pharmacol 1986; 22: 108–10

    PubMed  CAS  Google Scholar 

  145. 145.

    Holtzman JL, Weeks CE, Kvam DC, et al. Identification of drug interactions by meta-analysis of pre-marketing trials; the effect of smoking on the pharmacokinetics and dosage requirements for flecainide acetate. Clin Pharmacol Ther 1989; 46: 1–8

    PubMed  CAS  Google Scholar 

  146. 146.

    Tjandramaga TB, Verbesselt A, Hecken A, et al. Oral digoxin pharmacokinetics during multiple-dose flecainide treatment. Arch Int Pharmacodynamic Ther 1982; 260: 302–3

    CAS  Google Scholar 

  147. 147.

    Lewis GP, Holtzman JL. Interaction of flecainide with digoxin and propranolol. Am J Cardiol 1984; 53: 52B–7B

    PubMed  CAS  Google Scholar 

  148. 148.

    Weeks C, Conrad G, Kvam D, et al. The effect of flecainide acetate, a new antiarrhythmic, on plasma digoxin level. J Clin Pharmacol 1986; 26: 27–31

    PubMed  CAS  Google Scholar 

  149. 149.

    Muhiddin KA, Johnston A, Turner P. The influence of urinary pH on flecainide excretion and its serum pharmacokinetics. Br J Clin Pharmacol 1984; 17 (4): 447–51

    PubMed  CAS  Google Scholar 

  150. 150.

    Johnston A, Warrington S, Turner P. Flecainide pharmacokinetics in healthy volunteers: the influence of urinary pH. Br J Clin Pharmacol 1985; 20 (4): 333–8

    Google Scholar 

  151. 151.

    Kowey PR, Kirsten EB, Chau-Hwei JF, et al. Interaction between propranolol and propafenone in healthy volunteers. J Clin Pharmacol 1989; 29 (6): 512–7

    PubMed  CAS  Google Scholar 

  152. 152.

    Spes CH, Angermann CE, Horn K, et al. Ciclosporin-propafenone [letter]. Klin Wochenschr 1990; 68 (17): 872

    PubMed  CAS  Google Scholar 

  153. 153.

    Tjandra-Maga TB, Van Hecken A, Van Melle P, et al. Altered pharmacokinetics of oral flecainide by cimetidine. Br J Clin Pharmacol 1986; 22: 108–10

    PubMed  CAS  Google Scholar 

  154. 154.

    Palumbo E, Svetoni N, Casini M, et al. Digoxin-propafenone interactions: values and limitations of plasma determination of the two drugs. Antiarrhythmic effectiveness of propafenone [in Italian]. G Ital Cardiol 1986; 16: 855–62

    PubMed  CAS  Google Scholar 

  155. 155.

    Nolan PE, Marcus FI, Erstad Bl, et al. Effects of coadministration of propafenone on the pharmacokinetics of digoxin in healthy volunteer subjects. J Clin Pharmacol 1989; 29: 46–52

    PubMed  CAS  Google Scholar 

  156. 156.

    Castel JM, Cappiello E, Leopaldi D, et al. Rifampicin lowers plasma concentrations of propafenone and its antiarrhythmic effect. Br J Clin Pharmacol 1990; 30 (1): 155–6

    PubMed  CAS  Google Scholar 

  157. 157.

    Dilger K, Greiner B, Fromm MF, et al. Consequences of rifampicin treatment on propafenone disposition in extensive and poor metabolizers of CYP2D6. Pharmacogenetics 1999; 9 (5): 551–9

    PubMed  CAS  Google Scholar 

  158. 158.

    Lee BL, Dohrmann ML. Theophylline toxicity after propafenone treatment: evidence for drug interaction. Clin Pharmacol Ther 1992; 51 (3): 353–5

    PubMed  CAS  Google Scholar 

  159. 159.

    Spinler SA, Gammaitoni A, Charland SL, et al. Propafenonetheophylline interaction. Pharmacotherapy 1993; 13 (1): 68–71

    PubMed  CAS  Google Scholar 

  160. 160.

    Kates RE, Yee Y-G, Kirsten EB. Interaction between warfarin and propafenone in healthy volunteer subjects. Clin Pharmacol Ther 1987; 42: 305–11

    PubMed  CAS  Google Scholar 

  161. 161.

    Laer S, Neumann J, Scholz H. Interaction between sotalol and an antacid preparation. Br J Clin Pharmacol 1997; 43 (3): 269–72

    PubMed  CAS  Google Scholar 

  162. 162.

    Lesko LJ. Pharmacokinetic drug interactions with amiodarone. Clin Pharmacokinet 1989; 17 (2): 130–40

    PubMed  CAS  Google Scholar 

  163. 163.

    Marcus FI. Drug Interactions with amiodarone. Am Heart J 1983; 106: 9924–30

    Google Scholar 

  164. 164.

    Lee TH, Friedman PL, Goldman L, et al. Sinus arrest and hypotension with combined amiodarone-diltiazem therapy. Am Heart J 1986; 109: 163–4

    Google Scholar 

  165. 165.

    Mamprin F, Mullins P, Graham T, et al. Amiodarone-cyclosporine interaction in cardiac transplantation. Am Heart J 1992; 123 (6): 1725–6

    PubMed  CAS  Google Scholar 

  166. 166.

    Nicolau DP, Uber WE, Crumbley AJ 3rd, et al. Amiodarone-cyclosporine interaction in a heart transplant patient. J Heart Lung Transplant 1991; 11 (3 Pt 1): 564–8

    Google Scholar 

  167. 167.

    Chitwood KK, Abdul-Haqq AJ, Heim-Duthoy KL. Cyclosporine-amiodarone interaction. Ann Pharmacother 1993; 27 (5): 569–71

    PubMed  CAS  Google Scholar 

  168. 168.

    Moysey JO, Jaggarao NS, Grundy EN, et al. Amiodarone increases plasma digoxin concentrations. BMJ 1981; 282: 272

    PubMed  CAS  Google Scholar 

  169. 169.

    Furlanello E, Inama G, Ferrari M, et al. Digoxin-amiodarone: a further example of digoxin-antiarrhythmic agents interaction [in Italian]. G Ital Cardiol 1981; 11: 1725–8

    PubMed  CAS  Google Scholar 

  170. 170.

    Oetgen WJ, Sobol SM, Tri TB, et al. Amiodarone-digoxin interaction, clinical and experimental observations. Chest 1984; 86: 75–9

    PubMed  CAS  Google Scholar 

  171. 171.

    Nedemanee K, Kannan R, Hendrickson J, et al. Amiodaronedigoxin interaction: clinical significance, time course of development, potential pharmacokinetic mechanisms and therapeutic implications. J Am Coll Cardiol 11984; 4: 111–6

  172. 172.

    Fenster PE, White NW, Hanson CD. Pharmacokinetic evaluation of the digoxin-amiodarone interaction. J Am Coll Cardiol 1985; 5: 108–12

    Google Scholar 

  173. 173.

    Krusteva E. Changes in the plasma levels and basic pharmaco-kinetic parameters of digoxin used in combination with gentamicin, amiodarone and spironolactone. Fol Med 1992; 34 (20): 24–8

    CAS  Google Scholar 

  174. 174.

    Liberman BA, Teasdale SJ. Anaesthesia and amiodarone. Can Anaesth Soc J 1985; 32 (6): 629–38

    PubMed  CAS  Google Scholar 

  175. 175.

    Navalgund AA, Alifimoff JK, Jakymec AJ, et al. Amiodarone-induced sinus arrest successfully treated with ephedrine and isoproterenol. Anesth Analg 1986; 65 (4): 414–6

    PubMed  CAS  Google Scholar 

  176. 176.

    Koblin DD, Romanoff ME, Martin DE, et al. Anesthetic management of the patient receiving amiodarone. Anesthesiology 1987; 66 (4): 551–3

    PubMed  CAS  Google Scholar 

  177. 177.

    Nolan PE, Marcus FI, Hoyer GL, et al. Pharmacokinetics interaction between intravenous phenytoin and amiodarone in healthy volunteers. Clin Pharmacol Ther 1989; 46: 43–50

    PubMed  CAS  Google Scholar 

  178. 178.

    Nolan PE, Erstad BL, Hoyer GL, et al. Steady-state interaction between amiodarone and phenytoin in normal subjects. Am J Cardiol 1990; 65: 1252–7

    PubMed  CAS  Google Scholar 

  179. 179.

    Doecke CJ, Veronese ME, Pond SM, et al. Relationship between phenytoin and tolbutamide hydroxylations in human liver microsomes. Br J Clin Pharmacol 1991; 31: 125–30

    PubMed  CAS  Google Scholar 

  180. 180.

    Nolan Jr PE, Marcus FI, Karol MD, et al. Effect of phenytoin on the clinical pharmacokinetics of amiodarone. J Clin Pharmacol 1990; 30 (12): 1112–9

    PubMed  Google Scholar 

  181. 181.

    Soto J, Sacristan JA, Arellano F, et al. Possible theophylline-amiodarone interaction [abstract]. Drug Intell Clin Pharm 1990; 24 (11): 1115

    CAS  Google Scholar 

  182. 182.

    Heimark LD, Wienkers L, Kunze KJ, et al. The mechanism of the interaction between amiodarone and warfarin in humans. Clin Pharmacol Ther 1992; 51: 398–407

    PubMed  CAS  Google Scholar 

  183. 183.

    O’Reilly RA, Trager WF, Rettie AE, et al. Interaction of amiodarone with racemic warfarin and its separated enantiomorphs in humans. Clin Pharmacol Ther 1987; 42: 290–4

    PubMed  Google Scholar 

  184. 184.

    Almog S, Shafran N, Halkin H, et al. Mechanism of warfarin potentiation by amiodarone: dose- and concentration-dependent inhibition of warfarin elimination. Eur J Clin Pharmacol 1985; 28: 257–61

    PubMed  CAS  Google Scholar 

  185. 185.

    Martinowitz U, Rabinowici J, Goldfarb D, et al. Interaction between warfarin sodium and amiodarone. N Engl J Med 1981; 304 (11): 671–2

    PubMed  CAS  Google Scholar 

  186. 186.

    Kerin NZ, Blevins RD, Goldman L, et al. The incidence, magnitude, and time course of the amiodarone-warfarin interaction. Arch Intern Med 1988; 148: 1779–81

    PubMed  CAS  Google Scholar 

  187. 187.

    Cropp JS, Antal EG, Talbert RL. Ibutilide: a new class III antiarrhythmic agent. Pharmacotherapy 1997; 17 (1): 1–9

    PubMed  CAS  Google Scholar 

  188. 188.

    Lenz TL, Hilleman DE. Dofetilide, a new class III antiarrhythmic agent. Pharmacotherapy 2000; 20 (7): 776–86

    PubMed  CAS  Google Scholar 

  189. 189.

    Porter RS. Adenosine: supplementary considerations about activity and use. Clin Pharm 1990; 9: 163–4

    Google Scholar 

  190. 190.

    Lai WT, Lee CS, Wu JC, et al. Effects of verapramil, propranolol, and procainamide on adenosine-induced negative dromotropism. Am Heart J 1996; 132 (4): 76–5

    Google Scholar 

  191. 191.

    Biaggioni I, Onrot J, Hollister AS, et al. Cardiovascular effects of adenosine infusion in man and their modulation by dipyridamole. Life Sci 1986; 39 (23): 2229–36

    PubMed  CAS  Google Scholar 

  192. 192.

    Watt AH, Bernard MS, Webster J, et al. Intravenous adenosine in the treatment of supraventricular tachycardia: a dose-ranging study and interaction with dipyridamole. Br J Clin Pharmacol 1986; 21 (2): 227–30

    PubMed  CAS  Google Scholar 

  193. 193.

    Conradson TB, Dixon CM, Clarke B, et al. Cardiovascular effects of infused adenosine in man: potentiation by dipyridamole. Acta Physiol Scand 1987; 129 (3): 387–91

    PubMed  CAS  Google Scholar 

  194. 194.

    German DC, Kredich NM, Bjornsson TD. Oral dipyridamole increases plasma adenosine levels in human beings. Clin Pharmacol Ther 1989: 45 (1): 80–4

    PubMed  CAS  Google Scholar 

  195. 195.

    Maxwell DL, Fuller RW, Conradson TB, et al. Contrasting effects of two xanthines, theophylline and enprofylline, on the cardio-respiratory stimulation of infused adenosine in man. Acta Physiol Scand 1987: 131 (3): 459–65

    PubMed  CAS  Google Scholar 

  196. 196.

    Smits P, Lenders JW, Thien T. Caffeine and theophylline attenuate adenosine-induced vasodilation in humans. Clin Pharmacol Ther 1990; 48 (4): 410–8

    PubMed  CAS  Google Scholar 

  197. 197.

    Biaggioni I, Paul S, Puckett A, et al. Caffeine and theophylline as adenosine receptor antagonists in humans. J Pharmacol Exp Ther 1991; 258 (2): 588–93

    PubMed  CAS  Google Scholar 

  198. 198.

    Campbell TJ. Subclassification of Class I antiarrhythmic drugs: enhanced relevance after CAST. Cardiovasc Drugs Ther 1992; 6: 519–28

    PubMed  CAS  Google Scholar 

  199. 199.

    Grace AA, Camm AJ. Quinidine. N Engl J Med 1998; 338: 35–45

    PubMed  CAS  Google Scholar 

  200. 200.

    Kim SG, Felder SD, Waspe LE, et al. Electrophysiologic effects and clinical efficacy of mexiletine used alone or in combination with Class IA agents for refractory recurrent ventricular tachycardias or ventricular fibrillation. Am J Cardiol 1986; 485–90

    Google Scholar 

  201. 201.

    Giardina E-GV, Wechsler ME. Low dose quinidine-mexiletine combination therapy versus quinidine monotherapy for treatment of ventricular arrhythmias. J Am Coll Cardiol 1990; 15: 1138–45

    PubMed  CAS  Google Scholar 

  202. 202.

    Greenspan AM, Speilman SR, Webb CR, et al. Efficacy of combination therapy with mexiletine and a type IA agent for inducible ventricular tachyarrhythmias secondary to coronary artery disease. Am J Cardiol 1985; 56: 277–84

    PubMed  CAS  Google Scholar 

  203. 203.

    Bonavita GJ, Pires LA, Wagshal AB, et al. Usefulness of oral quinidine-mexiletine combination therapy for sustained ventricular tachyarrhythmias as assessed by programmed electrical stimulation when quinidine monotherapy has failed. Am Heart J 1994; 127: 847–51

    PubMed  CAS  Google Scholar 

  204. 204.

    Sheldon RS, Duff HJ, Mitchell LB, et al. Effect of oral combination therapy with mexiletine and quinidine on left and right ventricular function. Am Heart J 1988; 115: 1030–6

    PubMed  CAS  Google Scholar 

  205. 205.

    Kim SG, Mercndo AD, Tam S, et al. Combination of disopyramide and mexiletine for better tolerance and additive effects for treatment of ventricular arrhythmias. J Am Coll Cardiol 1989; 13: 659–64

    PubMed  CAS  Google Scholar 

  206. 206.

    Poole JE, Werner JA, Bardy GH, et al. Intolerance and ineffectiveness of mexiletine in patients with serious ventricular arrhythmias. Am Heart J 1986; 112: 322–6

    PubMed  CAS  Google Scholar 

  207. 207.

    Widerhorn J, Sager PT, Rahimtoola SH, et al. The role of combination therapy with mexiletine and procainamide in patients with inducible sustained ventricular tachycardia refractory to intravenous procainamide. PACE 1991; 14: 420–6

    PubMed  CAS  Google Scholar 

  208. 208.

    Foster MT, Peters RW, Froman D, et al. Electrophysiologic effects and predictors of success of combination therapy with class Ia and Ib antiarrhythmic drugs for sustained ventricular arrhythmias. Am J Cardiol 1996; 78: 47–50

    PubMed  CAS  Google Scholar 

  209. 209.

    Khalighi K, Peters RW, Feliciano Z, et al. Comparison of class Ia/Ib versus Class III antiarrhythmic drugs for the suppression of inducible sustained ventricular tachycardia associated with coronary artery disease. Am J Cardiol 1997; 80: 591–4

    PubMed  CAS  Google Scholar 

  210. 210.

    Reiffel JA, Reiter MJ, Blitzer M. Antiarrhythmic drugs and devices for the management of ventricular tachyarrhythmia in ischemic heart disease. Am J Cardiol 1998; 82: 31I–40I

    PubMed  CAS  Google Scholar 

  211. 211.

    Mendes L, Podrid PJ, Fuchs T, et al. Role of combination drug therapy with a Class IC antiarrhythmic agent and mexiletine for ventricular tachycardia. J Am Coll Cardiol 1991; 17: 1396–402

    PubMed  CAS  Google Scholar 

  212. 212.

    Yeung-Lai-Wah JA, Murdock CJ, Boone J, et al. Propafenone-mexiletine combination for the treatment of sustained ventricular tachycardia. J Am Coll Cardiol 1992; 20: 547–51

    PubMed  CAS  Google Scholar 

  213. 213.

    Sager PT. Modulation of antiarrhythmic drug effects by beta-adrenergic sympathetic stimulation. Am J Cardiol 1998; 82: 20I–30I

    PubMed  CAS  Google Scholar 

  214. 214.

    Friehling TD, Lipshutz H, Marinchak RA, et al. Effectiveness of propranolol added to a Type I antiarrhythmic agent for sustained ventricular tachycardia secondary to coronary artery disease. Am J Cardiol 1990; 65: 1328–33

    PubMed  CAS  Google Scholar 

  215. 215.

    Brodsky MA, Chough SP, Allen BJ, et al. Adjuvant metoprolol improves efficacy of class I antiarrhythmic drugs in patients with inducible sustained monomorphic ventricular tachycardia. Am Heart J 1992; 124: 629–35

    PubMed  CAS  Google Scholar 

  216. 216.

    Myerburg RJ, Kessler KM, Cox MM, et al. Reversal of proarrhythmic effects of flecainide acetate and encainide hydrochloride by propranolol. Circulation 1989; 80: 1571–9

    PubMed  CAS  Google Scholar 

  217. 217.

    Kennedy HL, Brooks MM, Barker AH, et al. Beta-blocker therapy in the Cardiac Arrhythmia Suppression Trial. Am J Cardiol 1994; 74: 674–80

    PubMed  CAS  Google Scholar 

  218. 218.

    Reiffel JA, Hahn E, Hartz V, et al. Sotalol for ventricular tachyarrhythmias: beta-blocking and class III contributions, and relative efficacy versus class I drugs after prior drug failure. Am J Cardiol 1997; 79: 1048–53

    PubMed  CAS  Google Scholar 

  219. 219.

    Boissel J-P, Boutitie F, Bernard C, et al. Synergy between amiodarone and β-blockers after myocardial infarction [abstract]. Circulation 1998; Suppl. 98: 470

    Google Scholar 

  220. 220.

    Channer KS, MacConell JT, Rees JR. β-Adrenoceptor blockers in atrial fibrillation: the importance of partial agonist activity. Br J Clin Pharmacol 1994; 37: 53–7

    PubMed  CAS  Google Scholar 

  221. 221.

    Lawson-Matthew P, McLean KA, Dent M, et al. Xamoterol improves the control of chronic atrial fibrillation in elderly patients. Age Ageing 1995; 24: 321–5

    PubMed  CAS  Google Scholar 

  222. 222.

    Van Gelder IC, Brugemann J, Crijns HJGM. Current treatment recommendations in antiarrhythmic therapy. Drugs 1998; 55: 331–46

    PubMed  Google Scholar 

  223. 223.

    Reiffel JA. Selecting an antiarrhythmic agent for atrial fibrillation should be a patient-specific, data-driven decision. Am J Cardiol 1998; 82: 72N–81N

    PubMed  CAS  Google Scholar 

  224. 224.

    Toivonen L, Kadish A, Morady F. A prospective comparison of Class IA, B, and C antiarrhythmic agents in combination with amiodarone in patients with inducible, sustained ventricular tachycardia. Circulation 1991; 84: 101–8

    PubMed  CAS  Google Scholar 

  225. 225.

    Jung W, Mletzko R, Manz M, et al. Efficacy and safety of combination therapy with amiodarone and Type I agents for treatment of inducible ventricular tachycardia. PACE 1993; 16: 778–88

    PubMed  CAS  Google Scholar 

  226. 226.

    Nademanee K. The amiodarone-class I agent combination increases refractoriness, conduction, and the number of electrophysiologic studies. But does it increase survival rate? Circulation 1991; 84: 429–31

    PubMed  CAS  Google Scholar 

  227. 227.

    Fenrich AL, Perry JC, Friedman RA. Flecainide and amiodarone: combined therapy for refractory tachyarrhythmias in infancy. J Am Coll Cardiol 1995; 25: 1195–8

    PubMed  Google Scholar 

  228. 228.

    Dorian P, Newman D, Berman N, et al. Sotalol and type IA drugs in combination prevent recurrences of sustained ventricular tachycardia. J Am Coll Cardiol 1993; 22: 106–13

    PubMed  CAS  Google Scholar 

  229. 229.

    Lee SD, Newman D, Ham M, et al. Electrophysiologic mechanisms of antiarrhythmic efficacy of a sotalol and class Ia drug combination: elimination of reverse use dependence. J Am Coll Cardiol 1997; 29: 100–5

    PubMed  CAS  Google Scholar 

  230. 230.

    Zehender M, Hohnloser S, Muller B, et al. Effects of amiodarone versus quinidine and verapamil in patients with chronic atrial fibrillation: results of a comparative study and a 2-year follow-up. J Am Coll Cardiol 1992; 19: 1054–9

    PubMed  CAS  Google Scholar 

  231. 231.

    Reiter MJ, Feiffel JA. Importance of beta blockade in the therapy of serious ventricular arrhythmias. Am J Cardiol 1998; 82: 9I–19I

    PubMed  CAS  Google Scholar 

  232. 232.

    Zipes DP, Wellens HJ. Sudden cardiac death. Circulation 1998; 98: 2334–51

    PubMed  CAS  Google Scholar 

  233. 233.

    De Ponti F, Poluzzi E, Montanaro N. QT-interval prolongation by non-cardiac drugs: lessons to be learned from recent experience. Eur J Clin Pharmacol 2000; 56: 1–18

    PubMed  Google Scholar 

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Trujillo, T.C., Nolan, P.E. Antiarrhythmic Agents. Drug-Safety 23, 509–532 (2000). https://doi.org/10.2165/00002018-200023060-00003

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Keywords

  • Digoxin
  • Amiodarone
  • Quinidine
  • Sotalol
  • Disopyramide