Amiodarone - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Amiodarone should be administered only by physicians who are experienced in the treatment of life-threatening arrhythmias, who are thoroughly familiar with the risks and benefits of amiodarone therapy, and who have access to facilities adequate for monitoring the effectiveness and side effects of treatment.

Because of the long half-life of amiodarone and its metabolite desethylamiodarone, the potential for adverse reactions or interactions, as well as observed adverse effects, can persist following amiodarone withdrawal.

Hypotension: Slow the infusion; as needed, add vasopressor drugs, positive inotropic agents, and volume expansion.

Bradycardia and AV block: Slow the infusion or discontinue.

5.1 Hypotension Hypotension is the most common adverse reaction seen with intravenous amiodarone.

In clinical trials, treatment-emergent, drug-related hypotension was reported as an adverse effect in 288 (16%) of 1836 patients treated with intravenous amiodarone.

Clinically significant hypotension during infusions was seen most often in the first several hours of treatment and was not dose related, but appeared to be related to the rate of infusion.

Hypotension necessitating alterations in intravenous amiodarone therapy was reported in 3% of patients, with permanent discontinuation required in less than 2% of patients.

Treat hypotension initially by slowing the infusion; additional standard therapy may be needed, including the following: vasopressor drugs, positive inotropic agents, and volume expansion.

Monitor the initial rate of infusion closely and do not exceed the recommended rate [see Dosage and Administration ] .

In some cases, hypotension may be refractory and result in a fatal outcome [see Adverse Reactions ] .

5.2 Bradycardia and Atrio-ventricular Block In 90 (4.9%) of 1836 patients in clinical trials, drug-related bradycardia that was not dose-related occurred while they were receiving intravenous amiodarone for life-threatening VT/VF.

Treat bradycardia by slowing the infusion rate or discontinuing amiodarone.

In some patients, a pacemaker is required.

Despite such measures, bradycardia was progressive and terminal in 1 patient during the controlled trials.

Treat patients with a known predisposition to bradycardia or AV block with amiodarone in a setting where a temporary pacemaker is available.

5.3 Hepatic Injury Elevations of blood hepatic enzyme values [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT)] are commonly seen in patients with immediately life-threatening VT/VF.

Interpreting elevated AST activity can be difficult because the values may be elevated in patients who have had recent myocardial infarction, congestive heart failure, or multiple electrical defibrillations.

Approximately 54% of patients receiving intravenous amiodarone in clinical studies had baseline liver enzyme elevations, and 13% had clinically significant elevations.

In 81% of patients with both baseline and on-therapy data available, the liver enzyme elevations either improved during therapy or remained at baseline levels.

Baseline abnormalities in hepatic enzymes are not a contraindication to treatment.

Elevated bilirubin levels have been reported in patients administered intravenous amiodarone.

Acute, centrolobular confluent hepatocellular necrosis leading to hepatic coma, acute renal failure, and death has been associated with the administration of intravenous amiodarone [see Dosage and Administration ] .

In patients with life-threatening arrhythmias, the potential risk of hepatic injury should be weighed against the potential benefit of amiodarone therapy.

Carefully monitor patients receiving amiodarone for evidence of progressive hepatic injury.