Introduction
Amiodarone is an antiarrhythmic agent used to treat atrial fibrillation (irregular heartbeat) and ventricular arrhythmia (irregular heartbeats originating in the ventricles). The drug prevents ventricular arrhythmia recurrence and reduces the chance of death in high-risk individuals. In cases where long-term treatment with amiodarone is required, the potential adverse effects and drug interactions should be considered. The dosage should be reduced to the lowest effective value. In the case of patients under warfarin or digoxin therapy, the drug interaction should be considered.
What Is the Pharmacology of Amiodarone?
Amiodarone is structurally similar to thyroxine. The drug is an iodine-containing compound and thus affects the thyroid gland. The bioavailability of the drug varies from 22 to 95 percent. The drug absorption is increased when taken along with food. As it is a lipid-soluble drug, it is mainly stored in the muscles and fat, but storage also occurs in the lungs, liver, and spleen. The drug crosses the placenta and enters measurable levels in breast milk.
The main metabolite is DEA (desethylamiodarone), which has antiarrhythmic properties.
The electrophysiological effects of amiodarone are:
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Prolongs the QT interval.
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Slows heart rate.
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Slows intracardiac conduction.
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Slows atrioventricular nodal conduction.
What Are the Indications of Amiodarone?
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For secondary prevention of ventricular arrhythmia that are life-threatening.
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Treatment of atrial fibrillation.
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As a primary prevention measure to prevent sudden death in high-risk individuals. However, studies suggest that ICDs (implantable cardioverter-defibrillators) are a better option than amiodarone for reducing mortality risk in the high-risk groups.
What Are the Adverse Effects?
Amiodarone has been linked with adverse effects that involve the thyroid glands, lungs, skin, eyes, liver, and nerves. The frequency of these adverse effects depends on the drug exposure, that is, the drug dosage and duration of exposure. Therefore, only the lowest possible effective dosage should be administered, and in case of adverse effects, the drug should be discontinued.
1. Pulmonary Toxicity:
Amiodarone-induced pulmonary toxicity (APT) is the most potentially serious adverse effect. The incidence rate is 5 percent for a dose of 400 milligrams or more daily. Lung toxicity can occur indirectly due to immune-mediated hypersensitivity or by releasing free radicals. The risk factors that can increase the toxicity are suggested to be advanced age, pre-existing lung disease, daily dose above 400 milligrams, and cumulative doses.
The most common clinical presentation is interstitial/alveolar pneumonitis with a subacute onset. The patient presents with symptoms like:
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Fever.
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Non-productive cough.
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Malaise.
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Pleuritic chest pain.
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Shortness of breath.
Chest X-rays show patchy interstitial infiltrates, and pulmonary function test shows reduced diffusing capacity. In cases where the patient complains of progressive dyspnea (breathing difficult) or cough, a prompt assessment for lung toxicity should be done.
The primary treatment option for lung toxicity is drug withdrawal and corticosteroid administration. These should be carried out longer due to the longer half-life of amiodarone that can result in new exacerbation of symptoms.
2. Liver Toxicity:
Liver toxicity is common in those who are under long-term amiodarone therapy. The toxicity is manifested as an elevation in the liver transaminase enzyme. Most of the patients with liver toxicity do not show any symptoms. Amiodarone therapy should be discontinued in cases where the enzyme levels are three-fold the normal range except in high-risk patients.
3. Thyroid Toxicity:
Thyroid toxicities have been reported in about 10 percent of individuals under long-term amiodarone therapy. Hypothyroidism is more commonly reported than hyperthyroidism. Amiodarone-induced hyperthyroidism is treated by drug withdrawal (in cases where withdrawal is safe), antithyroid medications, and thyroidectomy (surgical removal of a part or whole of the thyroid gland). In the case of hypothyroid patients where amiodarone is strongly required, the medication is continued along with thyroid supplementation.
4. Gastrointestinal Effects:
The gastrointestinal adverse effects are mainly dose-dependent and improve by reducing the dosage.
These include:
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Nausea.
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Constipation.
5. Dermatologic Effects:
The dermatological adverse effect associated with amiodarone is photosensitivity. So, individuals with the problem are advised to use sunblocks and ensure that the exposed areas on their bodies are covered before going outdoors. A bluish skin discoloration may develop in those with recurrent and prolonged sun exposure.
6. Ocular Effects:
Optic neuritis and optic neuropathy that may progress to complete blindness are seen in some cases. Anyone under amiodarone therapy who notices changes in peripheral vision or visual acuity should undergo an ophthalmologic examination.
7. Cardiovascular Effects:
Heart block and bradycardia are reported in 1 to 3 percent of cases. Amiodarone-induced proarrhythmia is reported in less than 1 percent of cases. Intravenously administered amiodarone is reported to cause hypotension in 16 percent of cases. Intravenously administered amiodarone is reported to cause heart block in 4.9 percent of cases. The drug is discontinued, or the infusion rate is reduced in such cases.
8. Neurologic Toxicity:
The neurologic toxicity associated with the drug are tremors, ataxia (impaired coordination in muscle movement), and paresthesia (abnormal skin sensation like tingling or numbness). These adverse neurologic effects are dose-dependent and improve when the dose of the drug is reduced. In 0.3 percent of cases, peripheral neuropathy ( a condition in which nerves in the extremities get damaged) is reported.
What Are the Drug Interactions?
Amiodarone inhibits the renal and hepatic metabolism of different drugs. The metabolism is inhibited through cytochrome P450 pathways. Drug interaction with digoxin and warfarin are clinically the most important ones. Drug interaction with digoxin, cyclosporine, and sildenafil can increase the respective drugs' plasma concentration. Drug interaction with warfarin increases the prothrombin time.
What Are the Preventive Measures?
Regular assessment is needed for patients undergoing amiodarone therapy to analyze drug efficacy, adverse effects, potential drug interactions, and dosage appropriateness.
The patient follow-up includes baseline assessment like
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Complete physical examination and history, especially regarding arrhythmia symptoms and concomitant medications.
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Chest X-rays.
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Thyroid function tests.
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Pulmonary function tests.
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Checking liver transaminase levels.
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Ophthalmologic examination in case of pre-existing visual problems.
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Close monitoring of prothrombin time in case of warfarin therapy.
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Analyze digoxin level in case of digoxin therapy.
Conclusion
Amiodarone, an antiarrhythmic agent, is prescribed in the lowest possible effective dosage to reduce the chance of associated toxicities. Most toxicities, like pulmonary toxicity, can be managed by drug withdrawal and corticosteroid
