The multiple toxicities of amiodarone

Amiodarone is an antiarrhythmic agent which is approved for the treatment of "severe tachyarrhythmias unresponsive to other therapy." It is available as a restricted benefit on the PBS. Use has increased rapidly in recent years from 150,000 prescriptions in 1995 to about 430,000 prescriptions/year in 2002-2004.¹

Long term amiodarone has a very long half-life (up to 110 days) and accumulates in adipose tissue and in highly perfused organs (lung, bone marrow, adrenals, liver, pancreas, heart, spleen and kidney), potentially causing serious adverse reactions in these and other body systems as indicated in the Table.² With its long half-life adverse reactions may become manifest after discontinuation.

Table: Adverse reactions reported to ADRAC with amiodarone

Adverse reaction	No. of reports (deaths)
Thyroid disorders	212 (8)
Respiratory disorders	195 (24)
Cardiac arrhythmias	94 (4)
Hepatotoxicity	81 (8)
Hypotension	34 (1)
Muscle disorders	29
Photosensitivity	28
Corneal changes	27
Haematological disorders	18
Total	809 (46)

Because of the frequency of fatal outcome, the most dangerous effect of amiodarone is its pulmonary toxicity, reviewed by ADRAC in 2002.³ Fatal outcomes are typically associated with pneumonitis progressing to pulmonary fibrosis and respiratory failure. Although commonly insidious in onset, amiodarone-induced pulmonary toxicity may also develop rapidly as in a recently reported case. An elderly male taking metoprolol, candesartan, aspirin, atorvastatin and risedronate was prescribed amiodarone 200mg daily for atrial fibrillation and after 6 months developed fatal respiratory failure secondary to pneumonitis. The risk of pulmonary adverse effects increases with increasing cumulative dose, but is also present at low dose over short durations, especially in elderly patients and those with pre-existing lung disease.^4,5 The prognosis is usually good if the drug is stopped early.⁴

Amiodarone has unique properties for the treatment of difficult cardiac arrhythmias. Whereas long-term therapy for life-threatening ventricular arrhythmias may be necessary, not all patients initiated on amiodarone for acute atrial arrhythmias require continuing treatment. If amiodarone is used chronically, the lowest effective dose should be prescribed. Patients should be informed of the warning symptoms of amiodarone toxicity and told to seek medical attention promptly should they occur.

Lung function should be monitored including 6-monthly chest x-ray, and the development of dyspnoea or cough should be investigated immediately.^2,5 Monitoring of ECG, liver function and thyroid function 6-monthly is also recommended.² Hyperthyroidism can present abruptly as weight loss, myopathy and worsening arrhythmia. Annual eye examination is also recommended. Nearly all patients develop corneal deposits, which are usually benign, but other more serious eye effects may occur.

Reference

1. Health Insurance Commission. Pharmaceutical BenefitSchedule Item Statistics. Internet: http://www.medicareaustralia.gov.au/statistics/dyn_pbs/forms/pbs_tab1.shtml (accessed 10May 2005)
2. Cordarone X, Australian Product Information, Sanoffi-Synthelabo Australia Pty Ltd. 22 Oct 2003.
3. ADRAC. Amiodarone and pulmonary toxicity. Aust Adv Drug React Bull 2002; 21: 2.
4. Jessurun GAJ, Crijns HJG. Amiodarone pulmonary toxicity. Brit Med J 1997;314:619-20.
5. Kanji Z, Sunderji R, Gin K. Amiodarone-induced pulmonary toxicity. Pharmacotherapy 1999;19:1463-6.

Reference
Australian Adverse Drug Reactions Bulletin
Volume 24, Number 3, June 2005