What are the symptoms of Amiodarone (antiarrhythmic medication) toxicity?

From the Guidelines

Amiodarone toxicity can manifest with a range of symptoms affecting multiple organ systems, including thyroid dysfunction, pulmonary toxicity, liver abnormalities, neurological effects, and skin changes, among others, as reported in studies such as 1 and 1. The most common signs of amiodarone toxicity include:

• Thyroid dysfunction (both hyperthyroidism and hypothyroidism)
• Pulmonary toxicity (presenting as shortness of breath, cough, and sometimes pulmonary fibrosis)
• Liver abnormalities (elevated liver enzymes)
• Neurological effects (tremors, ataxia, peripheral neuropathy)
• Corneal deposits causing visual disturbances
• Skin changes including photosensitivity and blue-gray discoloration These toxicities occur because amiodarone is highly lipophilic with a very long half-life (up to 100 days), causing it to accumulate in tissues throughout the body, as noted in 1. The drug also contains iodine which affects thyroid function, and patients on amiodarone should undergo regular monitoring of thyroid, liver, and pulmonary function, along with eye examinations and ECGs to detect toxicity early, as outlined in 1. Regular monitoring is crucial to detect toxicity early, and symptoms may develop even after discontinuation of the medication due to its prolonged elimination time, highlighting the importance of long-term follow-up, as emphasized in 1 and 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. Pulmonary Fibrosis Only 1 of more than 1000 patients treated with amiodarone HCl injection in clinical studies developed pulmonary fibrosis. Loss of Vision Cases of optic neuropathy and/or optic neuritis, usually resulting in visual impairment, have been reported in patients treated with oral amiodarone. Thyrotoxicosis Amiodarone-induced hyperthyroidism may result in thyrotoxicosis and/or the possibility of arrhythmia breakthrough or aggravation. Proarrhythmia Like all antiarrhythmic agents, amiodarone HCl injection may cause a worsening of existing arrhythmias or precipitate a new arrhythmia

The symptoms of Amiodarone toxicity include:

• Pulmonary toxicity: pulmonary infiltrates, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, hypoxia, and respiratory failure
• ARDS: bilateral, diffuse pulmonary infiltrates with pulmonary edema and varying degrees of respiratory insufficiency
• Pulmonary fibrosis: scarring of the lungs
• Optic neuropathy and/or neuritis: visual impairment, changes in visual acuity, and decreases in peripheral vision
• Thyrotoxicosis: arrhythmia breakthrough or aggravation
• Proarrhythmia: worsening of existing arrhythmias or precipitation of a new arrhythmia, including torsade de pointes (TdP) 2 2

From the Research

Symptoms of Amiodarone Toxicity

The symptoms of Amiodarone toxicity can be diverse and affect multiple organ systems. Some of the common symptoms include:

• Thyroid dysfunction, which can manifest as hypothyroidism or hyperthyroidism 3
• Pulmonary toxicity, which can range from mild to severe and may present as pneumonitis, pleural disease, or nodules 4, 5, 6
• Hepatotoxicity, which can be indicated by elevated liver enzyme levels 5
• Cardiac system effects, although less commonly discussed in the context of toxicity, are an important consideration given the drug's use in treating arrhythmias 7
• Respiratory distress, including acute respiratory distress syndrome (ARDS) and diffuse alveolar hemorrhage (DAH) 5
• Changes in thyroid function tests, such as elevated free T4 and suppressed thyroid stimulating hormone (TSH) 5

Organ-Specific Toxicity

Pulmonary Toxicity

Pulmonary toxicity is a significant concern with Amiodarone use, occurring in about 1% to 5% of cases 6. It can manifest in various forms, including:

• Acute or subacute pneumonitis
• Pleural disease
• Migratory infiltrates
• Single or multiple nodules
• Diffuse ground glass opacities and interstitial thickening

Thyroid Toxicity

Thyroid dysfunction is another common side effect, with both hypothyroidism and hyperthyroidism being possible 3, 5. The diagnosis and management of these conditions can be challenging, especially in the case of amiodarone-induced thyrotoxicosis (AIT).

Hepatic Toxicity

Elevated liver enzyme levels can indicate hepatotoxicity, highlighting the need for monitoring liver function in patients on Amiodarone 5.

Management and Prognosis

The management of Amiodarone toxicity often involves discontinuation of the drug and, in some cases, the administration of corticosteroids 4, 6. The prognosis can vary, with some cases being reversible and others irreversible or even fatal 5, 6. Regular monitoring of patients on Amiodarone, including pulmonary function tests, laboratory tests, and imaging studies, is crucial for early detection and management of toxicity 5, 7.