Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
WARNINGS AND PRECAUTIONS
- NEXTERONE 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.
- added...Elevated bilirubin levels have been reported in patients administered intravenous amiodarone.
- added... sometimes leading to fatal outcomes [see Adverse Reactions (6.2)].
- added... with NEXTERONE, as these disorders can exaggerate the degree of QTc prolongation and increase the potential for TdP. Give special attention to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or in patients receiving concomitant diuretics and laxatives.
- added...There have been reports of early development of pulmonary fibrosis (within 1 to 3 months) following initiation of amiodarone treatment.
Loss of Vision
- added...or intravenous amiodarone
- Hyperthyroidism and Thyrotoxicosis section edited
- Hypothyroidism section edited
- Amiodarone can cause fetal harm when administered to a pregnant woman. Fetal exposure may increase the potential for adverse experiences including cardiac, thyroid, neurodevelopmental, neurological and growth effects in neonate. Inform the patient of the potential hazard to the fetus if NEXTERONE is administered during pregnancy or if the patient becomes pregnant while taking NEXTERONE [See Pregnancy (8.1)].
- Anaphylactic/anaphylactoid reactions have been reported with intravenous amiodarone including shock (sometimes fatal), cardiac arrest, and the following manifestations: hypotension, tachycardia, hypoxia, cyanosis, rash, flushing, hyperhidrosis and cold sweat. Since NEXTERONE contains dextrose, patients with allergy to corn or corn products are at risk for allergic reaction.
Clinical Trials Experience
- added...atrioventricular block
The following adverse reactions are described in Warnings and Precautions: hypotension, rhythm disturbances, hepatic injury, pulmonary injury, thyroid injury, hypersensitivity.
- Post-Marketing Experience section ...significant edits
- Drugs prolonging the QT interval: Co-administration of drugs prolonging the QT interval (such as class I and III antiarrhythmics, lithium, certain phenothiazines, tricyclic antidepressants, certain fluoroquinolone and macrolide antibiotics, azole antifungals, halogenated inhalation anesthetic agents) increases the risk ofTorsade de Pointes. In general, avoid concomitant use of drugs that prolong the QT interval [see Warnings and Precautions (5.4)].
- Drugs that slow heart rate: Concomitant use of drugs with depressant effects on the sinus and AV node (e.g., digoxin, beta blockers, verapamil, diltiazem, clonidine) can potentiate the electrophysiologic and hemodynamic effects of amiodarone, resulting in bradycardia, sinus arrest, and AV block. Monitor heart rate in patients on amiodarone and concomitant drugs that slow heart rate.
- Effect of other drugs on amiodarone section edited
- Effect of amiodarone on other drugs section edited
USE IN SPECIFIC POPULATIONS
HMG-CoA Reductase Inhibitors (revised)
- The use of HMG-CoA reductase inhibitors that are CYP3A4 substrates in combination with amiodarone has been associated with reports of myopathy/rhabdomyolysis.
- Limit the dose of simvastatin in patients on amiodarone to 20 mg daily. Limit the daily dose of lovastatin to 40 mg. Lower starting and maintenance doses of other CYP3A4 substrates (e.g., atorvastatin) may be required as amiodarone may increase the plasma concentration of these drugs.