The Heart Rhythm Drug Amiodarone and Its Adverse Effects

Amiodarone (PACERONE) was approved by the Food and Drug Administration (FDA) in 1985 to treat and prevent life-threatening abnormal heart rhythms — specifically ventricular fibrillation and ventricular tachycardia.[1]

Public Citizen’s Health Research Group has designated amiodarone as Limited Use because long-term use of this drug can cause many types of adverse effects that can range from mild to life-threatening.[2] It should be used only when other therapies are ineffective or cannot be tolerated. It is best for patients to start amiodarone in the hospital.

The FDA requires that patients filling a prescription for amiodarone be given a Medication Guide advising them of the risks of using this drug and the precautions that can be taken to mitigate these risks.

Amiodarone’s numerous adverse effects[3]

Importantly, amiodarone accumulates in the body over time, leading to a substantial number of potential adverse events that persist even after stopping the drug. The FDA required a black-box warning — the strongest warning that the agency can require — to be added to the labeling for amiodarone about the potentially fatal toxic reactions it can cause in the heart, lungs and liver.

Amiodarone can cause a very slow heart rate, which can lead to lightheadedness, loss of consciousness and, very rarely, death. In about 2% to 5% of patients, use of the drug worsens the abnormal heart rhythms for which it is prescribed. It also can cause new abnormal heart rhythms.

As many as 17% of patients using amiodarone experience lung toxicity, which is fatal in about 10% of cases. The lung toxicity typically involves hypersensitivity (allergic-like) reactions that cause widespread inflammation in the lungs. Therefore, patients need to have a chest X-ray and lung function tests before starting the drug and every three to six months during treatment to monitor for lung toxicity.

Abnormal liver blood tests are common with use of amiodarone. In some patients, the drug causes severe liver injury, which can be fatal. Patients taking amiodarone need to undergo periodic liver blood tests, and if these tests show significant abnormalities, the drug should be stopped or the dose reduced.

Importantly, amiodarone can have dangerous interactions with numerous other medications, including certain heart drugs (such as digoxin [LANOXIN]) and cholesterol-lowering drugs (such as simvastatin [FLOLIPID, ZOCOR]), potentially leading to significantly elevated blood levels of these interacting drugs and an increased risk of toxicity.

Amiodarone also can affect developing fetuses and infants. It crosses the placenta, resulting in low heart rate and low thyroid activity in the fetus, as well as premature birth. Measurable amounts of the drug have been detected in breast milk, which also can cause low heart rate and low thyroid hormone levels in nursing infants. Therefore, pregnant women should be advised of the risks amiodarone poses to the fetus, and nursing mothers should avoid using the drug.

Finally, amiodarone can cause a wide array of adverse effects on the thyroid.

Amiodarone’s effects on the thyroid

The thyroid is a small butterfly-shaped gland found in the front of the neck and is responsible for the production and secretion of two important hormones, called thyroxine (T4) and triiodothyronine (T3). These hormones are critical for regulating the body’s metabolic rate, body temperature, and the function of multiple organs — including the brain, heart, muscles and digestive tract — as well as growth and development.[4]

The thyroid uses an element known as iodine to make these hormones. The body does not make iodine, so it must be obtained from foods. Thyroid hormone regulation is highly sensitive to small changes in iodine levels. Therefore, iodine deficiency or iodine overexposure can greatly affect thyroid function.

Because amiodarone contains high amounts of iodine, the drug should not be used in patients with a known allergy to this substance.[5] The iodine from the drug also can accumulate in the thyroid. Iodine levels may remain elevated for up to nine months after discontinuation of the drug.[6]

Amiodarone can induce thyroid dysfunction through direct damage to the thyroid.[7] It also can indirectly affect the thyroid by inhibiting thyroid hormone uptake by other organs, as well as inhibiting hormone activation, both of which lead to changes in hormone blood levels. It also can induce immune responses that indirectly affect thyroid function.[8],[9]

Amiodarone-induced thyroid dysfunction includes either an overactive thyroid (hyperthyroidism) or decreased thyroid function (hypothyroidism).[10] Hyperthyroidism is associated with weight loss, rapid heart rate, insomnia, nervousness and increased appetite. Hypothyroidism is characterized by slow heart rate, fatigue, hair loss and cold intolerance.

Not everyone who takes amiodarone develops thyroid dysfunction. It is estimated that as many as 30% of patients who take amiodarone will develop some form of thyroid dysfunction.[11] Of note, amiodarone is most likely to induce hypothyroidism in patients with adequate iodine intake and hyperthyroidism in patients with deficient iodine intake.

Amiodarone-induced thyroid dysfunction also is most likely to occur in patients with a history of thyroid disease. Older adults are more susceptible to amiodarone-induced hypothyroidism, potentially due to preexisting underlying thyroid abnormalities.[12] Women also are more likely to develop amiodarone-induced hypothyroidism, whereas men are more likely to have amiodarone-induced hyperthyroidism.

What You Can Do

If you or a family member is taking amiodarone, carefully read the Medication Guide for the drug. Tell your doctor about your medical history, including whether you have had liver, lung or thyroid disorders or are sensitive to iodine. Talk to your doctor if you experience fatigue; difficulty breathing or cough; nausea, vomiting or jaundice (yellow eyes or skin); nervousness or anxiety; changes in weight, heart rate or appetite; or any other signs or symptoms of thyroid dysfunction. You should undergo regular monitoring with blood tests for liver and thyroid function, chest X-rays, and lung function tests while taking amiodarone. Do not stop taking amiodarone without consulting your doctor.
 

References

[1] Upsher-Smith Laboratories, LLC. Label: amiodarone (PACERONE). January 2019. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=4c4ec9b0-13a5-49a8-b57b-b3f64e4316a7&type=display. Accessed November 25, 2019.

[2] Drug profile: amiodarone (PACERONE). /monographs/view/209. Accessed November 25, 2019.

[3] Upsher-Smith Laboratories, LLC. Label: amiodarone (PACERONE). January 2019. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=4c4ec9b0-13a5-49a8-b57b-b3f64e4316a7&type=display. Accessed November 25, 2019.

[4] American Thyroid Association. Thyroid function tests. https://www.thyroid.org/thyroid-function-tests/. Accessed November 25, 2019.

[5] Upsher-Smith Laboratories, LLC. Label: amiodarone (PACERONE). January 2019. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=4c4ec9b0-13a5-49a8-b57b-b3f64e4316a7&type=display. Accessed November 25, 2019.

[6] Gopalan M. Thyroid dysfunction induced by amiodarone therapy. October 8, 2018. Medscape. https://emedicine.medscape.com/article/129033-overview. Accessed November 25, 2019.

[7] Ross DS. Amiodarone and thyroid dysfunction. Up to Date. February 22, 2018.

[8] Danzi S, Klein I. Amiodarone-induced thyroid dysfunction. J Intensive Care Med. 2015;30(4):179-185.

[9] Burch HB. Drug effects on the thyroid. N Engl J Med. 2019;381:749-761.

[10] Ibid.

[11] Ross DS. Amiodarone and thyroid dysfunction. Up to Date. February 22, 2018.

[12] Gopalan M. Thyroid dysfunction induced by amiodarone therapy. Medscape. October 8, 2018. https://emedicine.medscape.com/article/129033-overview. Accessed November 25, 2019.