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Amiodarone Pulmonary Toxicity - Early Recognition is Vital

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Prescriber Update 34(4):
December 2013

Key Messages

All patients receiving amiodarone should be monitored for the development of adverse effects including pulmonary toxicity.
Pulmonary toxicity should be suspected in all patients who develop new or worsening pulmonary symptoms whilst taking amiodarone.
Amiodarone should be stopped in all suspected cases of pulmonary toxicity.
Corticosteroids may be considered as a treatment option. Slow withdrawal of the corticosteroids (over at least two to six months) is recommended to prevent rebound pulmonary toxicity¹.

Pulmonary toxicity is estimated to occur in approximately 5% of patients taking amiodarone and is considered to be the most serious adverse effect associated with its use1. Early recognition of toxicity and withdrawal of amiodarone is associated with a good prognosis in the majority of patients.

Amiodarone is a class III anti-arrhythmic agent that is an effective treatment for ventricular and supraventricular tachyarrhythmias². However, its use can be limited by the development of serious adverse effects including pulmonary, thyroid and liver toxicity.

Monitoring

All patients taking amiodarone require ongoing clinical review and monitoring for adverse effects (Table 1).

Table 1: Recommended minimum screening measures³

Type of test	Time when test is performed
Liver function tests	Baseline and every six months
Thyroid function tests	Baseline and every six months
Chest X-ray	Baseline and every 12 months
Ophthalmological evaluation	Baseline if visual impairment is present or for investigation of symptoms
Pulmonary function tests (including DLCO)	Baseline and for investigation of: unexplained cough or dyspnoea, especially in patients with underlying lung disease suggestive X-ray abnormalities clinical suspicion of pulmonary toxicity.
High resolution CT scan	If clinical suspicion of pulmonary toxicity
Electrocardiogram	Baseline and when clinically relevant

New Zealand Information

PHARMAC data indicate that approximately 7000 patients a year are receiving amiodarone. The majority of these patients (85%) were aged 60 years or over.

The Centre for Adverse Reactions Monitoring (CARM) has received a total of 65 reports of adverse reactions to amiodarone from January 2008 to September 2013. Of these reports, 16 were for pulmonary adverse reactions. These reports include interstitial pneumonia or pneumonitis (8 reports), pulmonary fibrosis (5), respiratory distress or cardio-respiratory failure (2) and unspecified pulmonary disorder (1).

The majority of reports were in men (10 compared with six) and in those aged over 60 (14 reports). The duration of use of amiodarone in these reports ranged from four days to over five years.

Presentation

Amiodarone-induced pulmonary toxicity can present acutely (hours to days after surgery or angiography) or chronically (months to years after starting amiodarone treatment). Acute toxicity (eg, acute respiratory distress syndrome) is rare but is associated with high mortality (up to 50%).

Chronic toxicity (eg, chronic interstitial pneumonitis, organising pneumonia) is more common and presents gradually with symptoms including non-productive cough, dyspnoea, fever, pleuritic chest pain, fatigue and/or weight loss. Mortality has been reported as up to 10% in some studies1.

Risk Factors

Potential risk factors for amiodarone-induced pulmonary toxicity include high daily doses (greater than 400 mg/day), high cumulative doses (treatment duration greater than two months), male gender, increasing age (over 60 years) and pre-existing lung disease.

Recent surgery or pulmonary angiography is associated with acute amiodarone-induced pulmonary toxicity. Cases have occurred with low doses and short treatment durations.

Diagnosis

The diagnosis of amiodarone-induced pulmonary toxicity requires exclusion of other causes (eg, heart failure, infectious pneumonia, pulmonary embolism and malignancy). A reduction of more than 20 percent in the diffusing capacity of the lung for carbon monoxide (DLCO), and demonstration of infiltrates on a chest X-ray or other imaging is highly suggestive but not diagnostic of amiodarone-induced pulmonary toxicity.

Treatment

Treatment consists primarily of stopping amiodarone. Corticosteroids may also be beneficial (although no clinical trials have been performed).

Healthcare professionals should be aware that due to amiodarone's long half-life (estimated to be between 14 and 59 days) symptoms may initially worsen or be slow to resolve⁴.

References

Chan ED, King TE. 2013. Amiodarone pulmonary toxicity. In UpToDate, Flaherty, KR. (ed). Waltham: UpToDate. URL: www.uptodate.com (accessed 19 November 2013).
Goldschlager N, Epstein AE, Naccarelli GV, et al. 2007. A practical guide for clinicians who treat patients with amiodarone: 2007. Heart Rhythm 4(9): 1250–1259.
Van Cott TE. Yehle KS, DeCrane SK, et al. 2013. Amiodarone-induced pulmonary toxicity: Case study with syndrome analysis. Heart and Lung 42: 262–266.
Sanofi-Aventis New Zealand Limited. 2012. Cordarone X Data Sheet. 12 December 2012. URL: www.medsafe.govt.nz/profs/datasheet/c/CordaroneXtabinj.pdf (accessed 19 November 2013).

MEDSAFE

New Zealand Medicines and Medical Devices Safety Authority