warnings
WARNINGS Hypotension Hypotension is the most common adverse effect seen with amiodarone I.V. In clinical trials, treatment-emergent, drug-related hypotension was reported as an adverse effect in 288 (16%) of 1836 patients treated with amiodarone I.V. 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 amiodarone I.V. therapy was reported in 3% of patients, with permanent discontinuation required in less than 2% of patients. Hypotension should be treated initially by slowing the infusion; additional standard therapy may be needed, including the following: vasopressor drugs, positive inotropic agents, and volume expansion. The initial rate of infusion should bemonitored closely and should not exceed that prescribed in DOSAGE AND ADMINISTRATION. In some cases, hypotension may be refractory resulting in fatal outcome (see ADVERSE REACTIONS , Postmarketing Reports ). Bradycardia and AV Block Drug-related bradycardia occurred in 90 (4.9%) of 1836 patients in clinical trials while they were receiving amiodarone I.V. for life-threatening VT/VF; it was not dose-related. Bradycardia should be treated by slowing the infusion rate or discontinuing amiodarone I.V. In some patients, inserting a pacemaker is required. Despite such measures, bradycardia was progressive and terminal in 1 patient during the controlled trials. Patients with a known predisposition to bradycardia or AV block should be treated with amiodarone I.V. in a setting where a temporary pacemaker is available. Liver Enzyme Elevations Elevations of blood hepatic enzyme values - alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) - are seen commonly 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 amiodarone I.V. 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. Acute, centrolobular confluent hepatocellular necrosis leading to hepatic coma, acute renal failure, and death has been associated with the administration of amiodarone I.V. at a much higher loading dose concentration and much faster rate of infusion than recommended in DOSAGE AND ADMINISTRATION . Therefore, the initial concentration and rate of infusion should be monitored closely and should not exceed that prescribed in DOSAGE AND ADMINISTRATION (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 I.V. therapy, but patients receiving amiodarone I.V. should be monitored carefully for evidence of progressive hepatic injury. Consideration should be given to reducing the rate of administration or withdrawing amiodarone I.V. in such cases. Proarrhythmia Like all antiarrhythmic agents, amiodarone I.V. may cause a worsening of existing arrhythmias or precipitate a new arrhythmia. Proarrhythmia, primarily torsades de pointes (TdP), has been associated with prolongation by amiodarone I.V. of the QTc interval to 500 ms or greater. Although QTc prolongation occurred frequently in patients receiving amiodarone I.V., torsades de pointes or new-onset VF occurred infrequently (less than 2%). Patients should be monitored for QTc prolongation during infusion with amiodarone I.V. Combination of amiodarone with other antiarrhythmic therapy that prolongs the QTc should be reserved for patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent. Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTc prolongation. There have been reports of QTc prolongation, with or without TdP, in patients taking amiodarone when fluoroquinolones, macrolide antibiotics, or azoles were administered concomitantly. (See Drug interactions , Other reported interactions with amiodarone: . ) The need to coadminister amiodarone with any other drug known to prolong the QTc interval must be based on a careful assessment of the potential risks and benefits of doing so for each patient. A careful assessment of the potential risks and benefits of administering amiodarone I.V. must be made in patients with yhyroid dysfunction due to the possibility of arrhythmia breakthrough or exacerbation of arrhythmia, which may result in death, in these patients. Pulmonary Disorders Early-onset pulmonary toxicity There have been postmarketing reports of acute-onset (days to weeks) pulmonary injury in patients treated with amiodarone I.V. 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 amiodarone I.V. patients. Amiodarone I.V. 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 I.V. in clinical studies developed pulmonary fibrosis. In that patient, the condition was diagnosed 3 months after treatment with amiodarone I.V., during which time she received oral amiodarone. Pulmonary toxicity is a well-recognized complication of long-term amiodarone use (see labeling for oral amiodarone). 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. In some cases, visual impairment has progressed to permanent blindness. Amiodarone I.V. is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) in patients refractory to other therapy and can also be used to treat patients with VT/VF for whom oral amiodarone is indicated, but who are unable to take oral medication. Optic neuropathy and/or neuritis may occur at any time following initiation of therapy. A causal relationship to the drug has not been clearly established. If symptoms of visual impairment appear, such as changes in visual acuity and decreases in peripheral vision, prompt ophthalmic examination is recommended. Appearance of optic neuropathy and/or neuritis calls for re-evaluation of amiodarone therapy. The risks and complications of antiarrhythmic therapy with amiodarone must be weighed against its benefits in patients whose lives are threatened by cardiac arrhythmias. Regular ophthalmic examination, including fundoscopy and slit-lamp examination is recommended during administrations of amiodarone. (See ADVERSE REACTIONS .) Long-Term Use See labeling for oral amiodarone. There has been limited experience in patients receiving amiodarone I.V. for longer than 3 weeks. Thyrotoxicosis Amiodarone-induced hyperthyroidism may result in thyrotoxicosis and/or the possibility of arrhythmia breakthrough or aggravation. There have been reports of death associated with amiodarone-induced thyrotoxicosis. IF ANY NEW SIGNS F ARRHYTHMIA APPEAR, THE POSSIBILITY OF HYPERTHYROIDISM SHOULD BE CONSIDERED (see PRECAUTIONS , Thyroid Abnormalities ). Neonatal Hypo- or Hyperthyroidism Although amiodarone use during pregnancy is uncommon, there have been a small number of published reports of congenital goiter/hypothyroidism and hyperthyroidism associated with its oral administration. If amiodarone I.V. is administered during pregnancy, the patient should be apprised of the potential hazard to the fetus.