What is the risk of Amiodarone (antiarrhythmic medication) inducing pneumonitis?

From the Guidelines

Amiodarone-induced pneumonitis is a serious pulmonary complication that requires immediate discontinuation of the medication and supportive care, as it can be reversible in most instances. The condition typically develops gradually over weeks to months, though acute presentations can occur. Risk factors include higher daily doses (>400 mg/day), longer duration of therapy (especially beyond 2 months), pre-existing lung disease, and recent pulmonary insults such as surgery [ 1 ]. Patients present with progressive dyspnea, nonproductive cough, fatigue, weight loss, and occasionally low-grade fever. Diagnosis requires a high index of suspicion in any patient on amiodarone with new respiratory symptoms, and is supported by findings on chest imaging (bilateral interstitial or alveolar infiltrates), pulmonary function tests (restrictive pattern with decreased diffusion capacity), and exclusion of other causes.

Some key points to consider in the management of amiodarone-induced pneumonitis include:

• Discontinuation of amiodarone is essential, but complicated by the drug's long half-life (up to 60 days) [ 1 ]
• Corticosteroids (prednisone 40-60 mg daily with gradual taper over 2-6 months) are often used in moderate to severe cases to accelerate recovery
• Oxygen therapy and supportive care should be provided as needed
• The condition may initially worsen after drug discontinuation due to amiodarone's prolonged tissue retention, and complete resolution can take months [ 1 ]
• Some patients develop permanent pulmonary fibrosis despite appropriate management

It's also important to note that regular monitoring of lung, liver, and thyroid function is needed when administering amiodarone, as the longer the therapy and the higher the dose of amiodarone, the greater the likelihood that adverse side effects will require discontinuation of the drug [ 1 ].

From the FDA Drug Label

Pulmonary Disorders Early-onset Pulmonary Toxicity There have been postmarketing reports of acute-onset (days to weeks) pulmonary injury in patients treated with intravenous amiodarone. Findings have included pulmonary infiltrates and/or mass on X-ray, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and hypoxia. Some cases have progressed to respiratory failure and/or death ARDS Two percent (2%) of patients were reported to have adult respiratory distress syndrome (ARDS) during clinical studies involving 48 hours of therapy. ARDS is a disorder characterized by bilateral, diffuse pulmonary infiltrates with pulmonary edema and varying degrees of respiratory insufficiency The clinical and radiographic picture can arise after a variety of lung injuries, such as those resulting from trauma, shock, prolonged cardiopulmonary resuscitation, and aspiration pneumonia, conditions present in many of the patients enrolled in the clinical studies. There have been postmarketing reports of ARDS in intravenous amiodarone patients Intravenous amiodarone may play a role in causing or exacerbating pulmonary disorders in those patients. Postoperatively, occurrences of ARDS have been reported in patients receiving oral amiodarone therapy who have undergone either cardiac or noncardiac surgery. Although patients usually respond well to vigorous respiratory therapy, in rare instances the outcome has been fatal Until further studies have been performed, it is recommended that FiO 2 and the determinants of oxygen delivery to the tissues (e.g., SaO 2, PaO 2) be closely monitored in patients on amiodarone. Pulmonary Fibrosis Only 1 of more than 1000 patients treated with amiodarone HCl injection in clinical studies developed pulmonary fibrosis. In that patient, the condition was diagnosed 3 months after treatment with amiodarone HCl injection, during which time she received oral amiodarone Pulmonary toxicity is a well-recognized complication of long-term amiodarone use (see labeling for oral amiodarone).

Amiodarone-induced pneumonitis is a possible adverse effect of amiodarone therapy, as reported in the drug label 2 and 2. The findings of pneumonitis include pulmonary infiltrates and/or mass on X-ray, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and hypoxia. Some cases have progressed to respiratory failure and/or death.

• Key points:
  • Amiodarone may cause pulmonary toxicity, including pneumonitis and pulmonary fibrosis.
  • The risk of pulmonary toxicity is higher with long-term use of amiodarone.
  • Patients receiving amiodarone should be closely monitored for signs of pulmonary toxicity, including respiratory symptoms and changes in lung function.
  • The use of amiodarone should be carefully weighed against the potential risks and benefits in patients with pre-existing pulmonary disease. It is essential to monitor patients on amiodarone closely for signs of pneumonitis, and to adjust the treatment plan accordingly 2.

From the Research

Amiodarone-Induced Pneumonitis

• Amiodarone-induced pneumonitis is a rare but serious complication of amiodarone therapy, often presenting as progressive respiratory failure 3.
• The incidence of pulmonary toxicity due to amiodarone is estimated to be around 1% to 5% 3, 4.
• Recognized risk factors for amiodarone-induced pneumonitis include old age, high daily doses, and long-lasting therapy 3.

Clinical Presentation

• Patients with amiodarone-induced pneumonitis typically present with nonspecific respiratory symptoms, including dyspnea, cough, and occasionally fever 3.
• The initial presentation can be challenging due to the nonspecific nature of the symptoms 3.
• Chest radiographs and computed tomography (CT) scans often reveal ground-glass opacities and interstitial thickening 3, 5.

Diagnosis and Management

• Diagnosing amiodarone-induced pneumonitis requires a combination of clinical, radiological, and histological data 3.
• Management of amiodarone-induced pneumonitis focuses on discontinuing amiodarone and initiating corticosteroid therapy 3, 4, 5, 6.
• Early withdrawal of amiodarone is crucial for symptom resolution and preventing progression to severe lung injury or irreversible fibrosis 3.

Prognosis

• The prognosis of amiodarone-induced pneumonitis is generally favorable with prompt treatment and discontinuation of amiodarone 4.
• However, pulmonary toxicity may initially progress despite drug discontinuation and may recur after steroid withdrawal due to amiodarone's accumulation in fatty tissues and long elimination half-life 4.