ISSN 1214-0287 (on-line)
ISSN 1214-021X (printed)

Volume 1 (2003), No 3, p 127-139

Amiodarone - excellent antiarrhythmic drug? (Happy end after 40 years of problems)

Petr Petr, Miroslav Verner, Chris J. Van Wyk, Hendrik A. Koeleman, Pavel Svitil, Hana Kalova

Address: Petr Petr, Faculty of Medical and Social Studies, B. Nemcove 54, 370 87 Ceske Budejovice, Czech Republic

Received 15th April 2003.
Published online 9th July 2003.

Full text article (pdf)

Amiodarone, discovered forty years ago and in general use as an anti-anginal drug, has become a wide-spectrum anti-arrhythmic, used as the drug of preference in cardiac failure and after myocardial infarction, where it is the only drug (besides some betablockers) which does not increase overall mortality. It is successfully used in therapy and prophylaxis for life threatening arrhythmias, even when electro physiological testing has failed to disclose the detailed mechanism of arrhythmia. In cases of myocardial infarction it should be regarded as the anti-arrhythmic drug of first choice. Amiodarone is a drug which is capable with high probability of anticipating arrhythmias, combining, in an exclusive exceptional entity, beneficial effects on cardiac electrophysiology, neurochemical parameters, coronary flow and haemodynamics with a unique local antithyroid effect. A detailed survey of the current experimental and clinical basis for practical use is given, based on 93 cited sources from the last 30 years.

anti-arrhythmic drug; electrophysiology; indications; interactions; adverse effects

Bartalena L, Bogazzi F, Martino E: Amiodarone induced thyrotoxicosis: a difficult diagnostic and therapeutic challenge. Clin Endocrinol 56:33-38, 2002.

Biran I, Steiner I: Coital headaches induced by amiodarone. Neurology 58:501-502, 2002.

Bogazzi F, Bartalena L, Gasperi M, Braverman LE, Martino E: The various effects of amiodarone on thyroid function. Thyroid 1:511-519, 2001.

Brembilla-Perrot B, Claudon O, Houriez P, Beurrier D, Suty-Selton C: Absence of change of signal - averaged electrocardiogram identifies patients with ventricular arrhytmias who are non responders to amiodarone. Int J Cardiol 83:47-55, 2002.

Brilakis ES, Friedman PA, Gersh BJ, Shen WK: Oral amiodarone and atrial fibrillation. Lancet 358:47-149, 2001.

Bytesnik J: Indication for the Amiodaron medication considering new findings. (In Czech). VI. Congress of Internal Medicine for Doctors in Practice with an International Participation, Zlín 1999.

Bytesnik J: Management of arrhythmias with amiodarone in the light of new knowledge (In Czech). 42:193-199, 2000.

Carlson BO, Singh BN, Temciuc M, Nilsson S, Li Y-L, Wellin Ch, Malm J: Synthesis and preliminary characterisation of a novel anti-arrhythmic compound KB 13 00 15. J Med Chem 45:623-630, 2002.

Caron MF, Kluger J, White CM: Amiodarone in the new AHA guidelines for ventricular tachyarrhythmias Ann Pharmacother 45:1248-1254, 2001.

Chopra IJ, Baber K: Use of oral cholecystographic agents in the treatment of amiodarone induced hyperthyroidism. J Clin Endocrinol Metabol 86:4707-4710, 2001.

Chouri N, Langin T, Lantuejoul S, Coulomb M, Brambilla C: Pulmonary nodules with CT halo sign. Respiration 69:103-106, 2002.

Chung WH, Bennett BM, Racz WJ, Brien JF, Massey TE: Induction of c-jun and TGF-beta 1 Fischer 344 rats during amiodaroneinduced pulmonary fibrosis. Amer J Physiol 28l:110-118, 2001.

David I: Perioperative tachyarrhythmia (In Czech). Cas Lek Ces 13:403-410, 2002.

Dorian P, Cas D, Schwartz B, Cooper R, Gelaznikas R, Barr A: Amiodarone as compared with lidocaine for shock resistant ventricular fibrillation. New Engl J Med 346:884-890, 2002.

Dubin AM, Van Hare GF, Collins KK, Bernstein D, Rosenthal DN: Survey of current practices in use of amiodarone and implatable cardio verter Defibrillators in paediatrics patients with end-stage heart failure. American J Cardiol 88:809-810, 2001.

Eaton SEM, Euinton HA, Newman CM, Weetman AP, Bennet W: Clinical experience of amiodarone-induced therotoxicosis over a 3-year period: role of colour-flow Doppler sonography. Clin Endocrinol 56:33-38, 2002.

Fejfar Z, Dvorak J, Pidrmann V: Workshop on Cardiology (In Czech). Session of Czech Medical Society of J. E. Purkyne, Zlin 1980.

Galperin J, Elizari MV, Chiale PA, Molina RT, Ledesma R, Scapin AO, Vazquez Blanco M: Efficacy of amiodarone for the termination of chronic atrial fibrillation and maintenance of normal sinus rhythm: a prospective, multicenter, randomised, controlled, double blind trial. J Cardiovasc Pharmacol Ther 6:341-350, 2001.

Gough IR, Gough J: Surgical management of amiodarone-associated thyrotoxicosis. Med J Austral 176:128-129, 2002.

Grupcheva C, McGhee CNJ: In vivo confocal microscopy of patients with amiodarone-inducen keratopathy. Cornea 21:430-432, 2002.

Ha HR, Kozlik P, Stieger B, Bigler L, Follath F: Metabolism of amiodarone. High performance liquid chromatography assay for mono-N-desethylamiodarone hydroxylation in liver microsomes. J Chromat.757:309-315, 2001.

Haan CK, Geraci SA: Role of amiodarone in reducing atrial fibrillation after cardiac surgery inj adults. Ann Thor Surg 73:1665-1669, 2002.

Herold M: Sudden death and implantable cardioverters-defibrillators (In Czech)., pp. 16-17.

High WA, Weiss SD: Images in clinical medicine, Pigmentation related to amiodarone. New Engl J Med 345:1464, 2001.

Hilleman DE, Spinler SA: Conversion of recent- onset atrial fibrillation with intravenous amiodarone: a meta-analysis of randomized controlled trials. Pharmacotherapy 22:66-74, 2002.

Ikaheimo K, Kettunen R, Mantyjarvi M: Visual functions and adverse ocular effects in patients with amiodarone medication. Acta Ophtalmol Scand 80:59-63, 2002.

James PR, Barrera GC: Intravenous amiodarone in intensive care: time for a reappraisal? Inten Care Med 8:1433, 2001.

Jiráskova M: Phototoxicity and photoallergy as side effects of drugs from a dermatologist's point of view (In Czech). Remedia 1:271-276, 2001.

Jun AS, Brocks DR: High-performance liquid chromatography assay of amiodarone in rat plasma. J Pharm Pharmaceut Sci 3:263-368, 2001.

Kaushik S, Hussain A, Clarke P, Lazar HL: Acute pulmonary toxicity after low-dose amiodarone therapy. Ann Cardiothor Surg 72:1760-1761, 2001.

Kaye DM, Dart AM, Jennings GL, Esler MD: Antiadrenergic effect of chronic amiodarone therapy in human heart failure. Journal of the Amer Coll Cardiol 33:1533-1539, 1999.

Kharabseh S, Abendroth C, Kozak M: Fatal pulmonary toxicity occurring within two weeks of initiation of amiodarone. Amer J Cardiol 89:896-898, 2002.

Kerin NZ, Faitel K, Kerin IA, Quinones L, Stomel RJ: Efficacy of low - dose amiodarone in the prevention of paroxysmal atrial fibrillation resistant to type I A anti-arrhythmic drugs. Amer J Ther 7:245-250, 2000.

Kim MH, Rachwal W, McHale C, Bruckman D, B.F. Decena, P. Rusman, F. Morady, K.A. Eagle: Effect of amiodarone, diltiazem, beta-blocker on frequency of atrial fibrillation, length of hospitalisation and hospital costs after coronary artery bypass grafting. Amer J Cardiol 89:1126-1128, 2002.

Kontoyannis DA, Anastasiou MI, Kontoyannis SA, Zaga AK, Nanas JN: Intravenous amiodarone decreases the duration of atrial fibrillation associated with acute myocardial infarction. Cardiovasc Drugs Ther 15:155-160, 2001.

Kovoor P, Eipper V, Byth K, Cooper MJ, Ross DL: Comparison of sotalol with amiodarone for long- term treatment of spontaneous sustained ventricular tachy-arrhythmia based on coronary artery disease. Eur Heart J 20:364-374, 1999.

Lau W, Newman D, Dorian P: Can anti-arrhythmic agents be selected based on mechanism of action? Drugs 60:1315-1328, 2000.

Leung PM, Quinn ND, Belchetz PE: Amiodarone-induced thyrotoxicosis: not a benign condition. Int J Clin Pract 56:4-6, 2002.

Levy S: Pharmacologic management of atrial fibrillation: current therapeutic strategies. Amer Heart J 141:15-21, 2001.

Levy S, Ricard P: Using the right drug: a treatment algorithm for regular supraventricular taxhycardia. European Heart Journal 18:27-32, 1997.

Lullmann H, Mohr K, Wehling M: Pharmacology and Toxikology (In Czech). Avicenum/Grada Publishing, Praha 2002, pp. 694.

Macaluso DC, Shults WT, Fraunfelder FT: Features of amiodarone-induced optic neuropathy. American Journal of Ophtalmology. 127:610-612, 1999.

Malik M, Camm AJ, Janse MJ, Julian DG, Frangin GA, Schwartz PJ: Depressed Heart Rate Variability Identifies Post infarction Patients Who Might Benefit From prophylactic Treatment With Amiodarone. A sub study of EMIAT (The European Myocardial Infarction Amiodarone Trial) J Amer Coll Cardiol 35:1263-1275, 2003.

Manolis AG, Katsivas AG, Vassilopoulos C, Tsatiris CG: Electrical storms in an ICD-recipient with 429 delivered appropriate shocks: therapeutic management with anti-arrhythmic drug combination. J Interven Card Electrophysiol 6:91-94, 2002.

Marek J (ed.): Pharmacotherapy of Internal Diseases (In Czech). Avicenum/Grada Publ., Praha 1998, pp. 743.

Matsuyama T, Tanno K, Kobayashi Y, Obara C, Ryu S, Adachi T, Ezumi H, Asano T, Miyata A, Koba S, Baba T, Katagiri T: T wave alternant for predicting adverse effects of amiodarone in a patient with dilated cardiomyopathy. J Circ J 65:468-470, 2001.

Medicamenta Nova (In Czech), Symposium LS JEP, Praha 1983.

Mendez M, Parera V, Enriquez de Salamanca R, Battle A: Amiodarone is a pharmacologically safe drug for porphyries, Gen Pharmacol 32:259-263, 1999.

Meng X, Mojaverian P, Doedee M, Lin E, Weinryb I, Chiang ST, Kowey PR: Bioavailability of amiodarone tablets administered with and without food in healthy subjects. Amer J Cardiol 87:432-435, 2001.

Micuda S, Hodac M, Sispera L, Parizek P, Pleskot M, Zimova G, German J, Martinkova J, Pidrman V: Influence of amiodarone on urinary excretion of betahydrocortisol in humans. Physiol Res 50:191-196, 2001.

Moorthy RS, Valluri S: Ocular toxicity associated with systemic drug therapy. Curr Opin Ophtalmol 10:438-446, 1999.

Mutschler E: Arzneimittel - Wirkungen, Pharmakology and Toxikology textbook Wisentschaftliche Verlaggesellschaft mbH. Stuttgart 1991, pp. 879.

Nagele H, Schomburg R, Petersen B, Rodiger W: Dual chamber pacing in patients with severe heart failure on beta blocker and amiodarone treatment: preliminary results of a randomised study. Heart 87:566-567, 2002.

Naganuma M, Shiga T, Nishikata K, Tsuchiya T, Kasanuki H, Fujii E: Role of desethylamiodarone in the antikoagulant effect of concurrent amiodarone and warfarin therapy, J Cardiovasc Pharmacol Ther 6:363-367, 2001.

Nakajima K, Yamazaki K, Yamada E, Kanaji Y, Kosaka S, Sato K, Takano K: Amiodarone stimulates interleukin-6 production in cultured human thyrocytes, exerting cytotoxic effects on thyroid follicles in suspension culture. Thyroid 11:101-109, 2001.

Neuzil P, Taborsky M, Sediva L, Niederle P: Radiofrequency ablation of auricular flutter in patients with long-term treatment of auricular fibrillation with amiodarone: application of hybrid therapy (In Czech). Prakt Lek 81:208-211, 2001.

Noble SL, Reploge WH, Dickey SR: Amiodarone for the treatment of persistent atrial fibrillation. J Fam Pract 48:34-335, 1999.

Opincariu M, Varro A, Iost N, Virag L, Hala O, Szolnoki J, Szecsi J, Bogats G, Szenohradszky P, Matyus P, Papp JG: The cellular electro physiologic effect of GYKI 16638, a new anti-arrhythmic compound. Curr Med Chem 9:41-46, 2002.

Osman F, Franklyn JA, Sheppard MC, Gammage MD: Succesfull treatment of amiodarone-induced thyrotoxicosis. Circulation 105:1275-1277, 2002.

Petr P: Final Report on Clinical Testing of Cordarone (amiodarone) Krka inj. in Patients ith AMI (In Czech), Clinical Research Report Series, Novo Mesto, Yugoslavia, 1986.

Pitsiavas V, Smerdely P, Boyages SC: Amiodarone compared with iodine exhibits a potent and persistent inhibitory effect on TSHstimulated CAMP production in vitro: a possible mechanism to explain amiodarone-induced hypothyroidism. Eur J Endocrinol 140:241-249, 1999.

Pleskot M, Parizek P, Hodac M, Haman L, Stastek J, Cervinka P, Tauchman M: Ventricular fibrillation in chronic heart disease (In Czech). Vn Lek 46:80-86, 2000.

Pleskot M, Parizek P, Hodac M, Haman L, Stastek J, Cervinka P, Tauchman M: Revascularisation of the myocardium and electrical instability of the ventricles (In Czech). Vn Lek 45:75-80.

Polak BC, Tutein NPA, Rietveld E: Visual impairment due to optic neuropathy in 2 patients on amiodarone or ethambutol and isoniazide therapy. Nederland tiejdschrift voor geneeskunde (In Dutch). 145:922-926, 2001.

Poll LW, May P, Koch JA, Hetzel G, Heering P, Modder U: HRCT findings of amiodarone pulmonary toxicity: clinical and radiology regression, J Cardiovasc Pharmacol Ther 6:307-311, 2001.

Reddy Prahashni, Dunn Alisha B, White CM, Tsikouris JP, Satyendra G, Kluger J: An economic analysis of amiodarone versus placebo for the prevention of atrial fibrillation after open heart surgery. Pharmacotherapy 22:75-80, 2002.

Reithmann C, Dorwarth U, Gerth A, Remp T, Steinbeck G, Hoffmann E: Early reinitiation of atrial fibrillation following an external electrical cardioversion in amiodarone- treated patients. J Intervent Card Electrophysiol 5:285-292, 2001.

Routitie F, Boissel JP, Conolly SJ, Camm AJ, Cairns JA, Julian DG, Gent M, Janse MJ, Dorian P, Frangin G: Amiodarone interaction with beta-blockers: analysis of the merged EMIAT (European Myocardial Infarction Amiodarone Trial) and CAMIAT (Canadian Amiodarone Myocardial Infarction Amiodarone Trial) database, The EMIAT and CAMIAT Investigators, Circulation 99:2268-2275, 1999.

Sangha S, Uber P, Mehra M: Difficult cases in heart failure: amiodarone lung injury: another heart failure mimic? Congest Heart Fail 8:93-96, 2002.

Sanoski CA, Bauman JL: Clinical observations with the amiodarone/warfarin interaction: dosing relationship with long-term therapy. Chest 121:19-23, 2002.

Sheikzadeh A, Schafer U, Schnabel A: Drug-induced lupus erythematosus by amiodarone, Arch Intern Med 162:834-836, 2002.

Scharf C, Oechslin EN, Salomon F, Kiowski W: Clinical picture: Amiodarone-induced pulmonary mass and cutaneous vasculitis. Lancet 358:2045, 2001.

Schlant RC, Collins JJ Jr., Engle MA, Frye RL, Kaplan NM, Orourke RA: Yearbook of Cardiology, Mosby-Year Book Inc., 1992, pp. 441.

Schlapfer J, Rapp F, Kappenberger L, Fromer M: Electro physiologically guided amiodarone therapy versus the implantable cardioverter-defibrillator for sustained ventricular tachy-arrhythmias after myocardial infarction: results of long-term follow-up. J Amer Coll Cardiol 39:1813-1819, 2002.

Starmer CF: The cardiac vulnerable period and re-entrant arrhythmias: targets of anti- and pro-arrhythmic processes. Pac Clin Electrophysiol 20:4456-4454, 1997.

Stewart CE: Amiodarone for ACLS: a critical evaluation. Emerg Med Serv 30:61-67, 2001.

Suchopar J, ed. Remedia: Compendium Panax Publ. (In Czech). Prague 1997.

Skop B (ed.): AISLP, Automated Information System of Medical Preparations (In Czech). Computer Programme, Praha 2003.

Spinar J, Vitovec J, Kubecova L, Parenica J: Clinical Trials in Cardiology (In Czech). Avicenum/Grada Publ., Praha 2001, pp. 487.

Tardos L, Szekeres L, Papp JG: Pharmacological Control of Heart and Circulation Ed., Advances in Pharmacological Research and Practice, Gen Ed J Knoll Pergamon Press, Budapest 1979, pp. 439.

Tokmakoglu H, Kandemir O, Gunyadin S, Catav Z, Yorgancioglu C, Zorlutuna Y: Amiodarone versus digoxin and metoprolol combination for the prevention of postcoronary Bypass atrial fibrillation, Eur J Thor Cardiovasc Surg 21:401-405, 2002.

Tsikouris JP, Cox CD: A review of class III anti-arrhythmic agents for atrial fibrillation: maintenance of normal sinus rhythm. Pharmacotherapy 12:1514-1529, 2001.

Vanbesien J, Casteels A, Bougatef A, De Catte L, W. Foulon, S. De Bock, J. Smitz, J. De Schepper: Transient fetal hypothyreoidism due to direct fetal administration of amiodarone for drug resistant fetal tachycardia, Amer. J. Perinat. 18: 113-116, 2001.

Veloso HH: Is amiodarone the first or the last choice for the maintenance of sinus rhythm after successful conversion of atrial fibrillation? Medical science monitor: international medical J Exp Clin Res 7:526-530, 2001.

Weirich J, Wenzel W: Aktuelle Einteilung antiarrhytmisch wirksamer Substanzen. Freiburg Z Kardiol 89:62-67, 2000.

What is What 1997: a guide to acronyms for cardiovascular trials. 4th edition, Astra-Hassle, Molndal 1997.

Wichterle D: The rationale for amiodarone treatment after acute myocardial infarction- will we be given a unequivocal definition of target patients' population? (In Czech) JACC-CZ 2:321-322, 2000.

Widimsky J: Amiodarone treatment safety. VI. Congress of Internal Medicine with an International Participation for Doctors in Practice (In Czech), Symposium fy Sanofi-Synthelabo, Zlin 1999.

Widimsky J: The side effects of amiodarone (In Czech). Cor Vasa 2000: pp. 235-242.

Wurderman RL, Moos AN, Mohiuddin Seyed M, Lenz TL: Amiodarone vs. Sotalol as prophylaxis against atrial fibrillation/flutter after heart surgery: a meta-analysis. Chest 121:1203-1210, 2002.

Ybarra J, Fuster D, Martin F, Lomena F, Torregrossa JV: Clinical picture: amiodarone-induced thyreoiditis. Lancet 359:69, 2002.

Yung A, Agnew K, Snow J, Oliver F: Two unusual cases of toxic epidermal necrolysis. Austr J Dermatol 43:35-38, 2002.

The search for novel anti-arrhythmic strategies. Sicilian Gambit Jap Circ J 62:633-648, 1998.

Reingardiene DJ: Effect of treatment with amiodarone on sinus node function. Kardiologiya 47:59-61, 2007.

Reingardene DI, Pilvinis VK: Amiodaron effects on atrioventricular conduction. Terapevticheskii Arkhiv 78:49-52, 2006.