pharmacopeia
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Boxed warning

PULMONARY, HEPATIC and CARDIAC TOXICITY Pacerone is intended for use only in patients with the indicated life-threatening arrhythmias because its use is accompanied by substantial toxicity [see Indications and Usage (1) ] . Pacerone can cause pulmonary toxicity (hypersensitivity pneumonitis or interstitial/alveolar pneumonitis) that has resulted in clinically manifest disease at rates as high as 17% in some series of patients. Pulmonary toxicity has been fatal about 10% of the time . Obtain a baseline chest X-ray and pulmonary-function tests, including diffusion capacity, when Pacerone therapy is initiated. Repeat history, physical exam, and chest X-ray every 3 to 6 months [see Warnings and Precautions 5.2) ] . Pacerone can cause hepatoxicity, which can be fatal. Obtain baseline and periodic liver transaminases and discontinue or reduce dose if the increase exceeds three times normal, or doubles in a patient with an elevated baseline. Discontinue Pacerone if the patient experiences signs or symptoms of clinical liver injury [see Warnings and Precautions (5.3) ] . Pacerone can exacerbate arrhythmias. Initiate amiodarone hydrochloride in a clinical setting where continuous electrocardiograms and cardiac resuscitation are available [see Warnings and Precautions (5.4) ] . WARNING: PULMONARY, HEPATIC, and CARDIAC TOXICITY See full prescribing information for complete boxed warning.

2D structure
(2-butyl-1-benzofuran-3-yl)-[4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl]methanone
SMILES CCCCC1=C(C2=CC=CC=C2O1)C(=O)C3=CC(=C(C(=C3)I)OCCN(CC)CC)I
InChIKey IYIKLHRQXLHMJQ-UHFFFAOYSA-N

Mechanism of action

Sourced from openFDA

Amiodarone is considered a class III antiarrhythmic drug, but it possesses electrophysiologic characteristics of all four Vaughan Williams classes. Like class I drugs, amiodarone blocks sodium channels at rapid pacing frequencies, and like class II drugs, amiodarone exerts a noncompetitive antisympathetic action.

Calcium ChannelCytochrome P450 1A2Cytochrome P450 2C9Cytochrome P450 2D6Cytochrome P450 3AP-GlycoproteinSodium Channel

Indications

Sourced from openFDA
  • Pacerone is indicated for the treatment of documented, life-threatening recurrent ventricular fibrillation and life-threatening recurrent hemodynamically unstable tachycardia in adults who have not responded to adequate doses of other available antiarrhythmics or when alternative agents cannot be tolerated. Pacerone is an antiarrhythmic indicated for: Recurrent ventricular fibrillation.

Contraindications

Sourced from openFDA
  • Cardiogenic shock. Sick sinus syndrome, second- or third-degree atrioventricular block, bradycardia leading to syncope without a functioning pacemaker.contraindicated

Dosage & administration

Sourced from openFDA

Dosage must be individualized based on severity of arrhythmia and response. Use the lowest effective dose. Obtain baseline chest x-ray, pulmonary function tests, thyroid function tests, and liver aminotransferases. Correct hypokalemia, hypomagnesemia, and hypocalcemia before initiating treatment. Initiate treatment with a loading dose of 800 to 1600 mg/day until initial therapeutic response occurs (usually 1 to 3 weeks). Once adequate arrhythmia control is achieved, or if side effects become prominent, reduce Pacerone tablets dose to 600 to 800 mg/day for one month and then to the maintenance dose, usually 400 mg/day. ( 2 ) Recommended Dosage: Initiate treatment with a loading dose of 800 to 1600 mg/day until initial therapeutic response occurs (usually 1 to 3 weeks). Once adequate arrhythmia control is achieved, or if side effects become prominent, reduce Pacerone tablet dose to 600 to 800 mg/day for one month and then to the maintenance dose, usually 400 mg/day. Administration: Administer Pacerone tablets consistently with regard to meals [see Clinical Pharmacology (12.3) ] . Administration of Pacerone tablets in divided doses with meals is suggested for total daily doses of 1000 mg or higher, or when gastrointestinal intolerance occurs.

Warnings & precautions

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Persistence of Adverse Effects: Adverse reactions and drug interaction can persist for several weeks following discontinuation. ( 5.1 ) Impaired Vision: Corneal microdeposits (common; reversible), optic neuropathy/neuritis (rare; may lead to blindness). ( 5.5 ) Thyroid Abnormalities: Hyperthyroidism or hypothyroidism. ( 5.6 ) 5.1 Persistence of Adverse Effects Because of the long half-life of amiodarone (15 to 142 days) and its active metabolite desethylamiodarone (14 to 75 days), adverse reactions and drug interactions can persist for several weeks following amiodarone discontinuation [see Clinical Pharmacology (12.3) ] . 5.2 Pulmonary Toxicity Pacerone may cause a clinical syndrome of cough and progressive dyspnea accompanied by functional, radiographic, gallium-scan, and pathological data consistent with pulmonary toxicity. Pulmonary toxicity secondary to Pacerone may result from either indirect or direct toxicity as represented by hypersensitivity pneumonitis (including eosinophilic pneumonia) or interstitial/alveolar pneumonitis, respectively. Rates of pulmonary toxicity have been reported to be as high as 17% and is fatal in about 10% of cases. Obtain a baseline chest X-ray and pulmonary-function tests, including diffusion capacity, when Pacerone therapy is initiated. Repeat history, physical exam, and chest X-ray every 3 to 6 months or if symptoms occur. Consider alternative antiarrhythmic therapy if the patient experiences signs or symptoms of pulmonary toxicity. Prednisone 40 to 60 mg/day tapered over several weeks may be helpful in treating pulmonary toxicity.

Adverse reactions

Sourced from openFDA

The following serious adverse reactions are described in more detail in other sections of the prescribing information: Pulmonary Toxicity [see Warnings and Precautions (5.2) ] Hepatic Injury [see Warnings and Precautions (5.3) ] Worsened Arrhythmia [see Warnings and Precautions (5.4) ] Visual Impairment and Loss of Vision [see Warnings and Precautions (5.5) ] Thyroid Abnormalities [see Warnings and Precautions (5.6) ] Bradycardia [see Warnings and Precautions (5.7) ] Peripheral Neuropathy [see Warnings and Precautions (5.10) ] Photosensitivity and Skin Discoloration [see Warnings and Precautions (5.11) ] The most common reactions (>1%) leading to discontinuation of amiodarone include pulmonary toxicity, paroxysmal ventricular tachycardia, congestive heart failure, and elevation of liver enzymes. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Upsher-Smith Laboratories, LLC at 1-855-899-9180 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. At the usual maintenance dose (400 mg/day) and above, amiodarone hydrochloride causes adverse reactions in about three-fourths of all patients, resulting in discontinuation in 7% to 18%. In surveys of almost 5,000 patients treated in open U.S.

Use in specific populations

Sourced from openFDA

Pregnancy: May cause fetal harm. ( 8.1 ) Lactation: Breastfeeding not recommended. ( 8.2 ) 8.1 Pregnancy Risk Summary Available data from post-marketing reports and published case series indicate that amiodarone use in pregnant women may increase the risk for fetal adverse effects including neonatal hypo- and hyperthyroidism, neonatal bradycardia, neurodevelopmental abnormalities, preterm birth and fetal growth restriction. Amiodarone and its metabolite, desethylamiodarone (DEA), cross the placenta. Untreated underlying arrhythmias, including ventricular arrhythmias, during pregnancy pose a risk to the mother and fetus (see Clinical Considerations ) . In animal studies, administration of amiodarone to rabbits, rats, and mice during organogenesis resulted in embryo-fetal toxicity at doses less than the maximum recommended human maintenance dose (see Data ) . Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Pharmacokinetics

Sourced from openFDA
Metabolism
Absorption Following oral administration in humans, amiodarone hydrochloride is slowly and variably absorbed. The bioavailability of amiodarone hydrochloride is approximately 50%.

Overdosage

Sourced from openFDA

There have been cases, some fatal, of amiodarone hydrochloride overdose. Monitor the patient's cardiac rhythm and blood pressure, and, if bradycardia ensues, a β-adrenergic agonist or a pacemaker may be used. Treat hypotension with inadequate tissue perfusion with positive inotropic and vasopressor agents. Neither Pacerone nor its metabolite is dialyzable.

Approval history

Sourced from openFDA
  • Apr 30, 1998ANDAANDA075135Upsher Smith Labs
  • Jan 25, 2001ANDAANDA075389Dr Reddys Labs Sa
  • Mar 30, 2001ANDAANDA075424Taro
  • Oct 15, 2002ANDAANDA076217Mylan Institutional
  • Oct 15, 2002ANDAANDA075761Fresenius Kabi Usa
  • Nov 29, 2002ANDAANDA076362Taro
  • Apr 8, 2005ANDAANDA077069Chartwell Rx
  • Dec 24, 2008NDANDA022325Baxter Hlthcare

FAERS reports

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Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
10,887 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Dyspnoea1,17411%
  2. 2Asthenia9909.1%
  3. 3Fatigue9118.4%
  4. 4Off Label Use8688.0%
  5. 5Drug Ineffective7336.7%
  6. 6Product Use In Unapproved Indication6726.2%
  7. 7Nausea6195.7%
  8. 8Atrial Fibrillation6115.6%
  9. 9Cough6075.6%
  10. 10Dizziness5835.4%
  11. 11Pneumonia5515.1%
  12. 12Hypotension4874.5%
  13. 13Vomiting4734.3%
  14. 14Drug Interaction4584.2%
  15. 15Pulmonary Toxicity4073.7%

Literature

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Recent PubMed references pinned to Amiodarone as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 234 ClinicalTrials.gov registrations naming Amiodarone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Frequently asked questions

How does Amiodarone work?
Amiodarone is considered a class III antiarrhythmic drug, but it possesses electrophysiologic characteristics of all four Vaughan Williams classes. Like class I drugs, amiodarone blocks sodium channels at rapid pacing frequencies, and like class II drugs, amiodarone exerts a noncompetitive antisympathetic action.
What is Amiodarone used for?
According to FDA labeling, Amiodarone carries indications including: Pacerone is indicated for the treatment of documented, life-threatening recurrent ventricular fibrillation and life-threatening recurrent hemodynamically unstable tachycardia in adults who have not responded to adequate doses of other available antiarrhythmics or when alternative agents cannot be tolerated. Pacerone is an antiarrhythmic indicated for: Recurrent ventricular fibrillation.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Amiodarone?
Amiodarone is classified as Antiarrhythmics, class III, Antiarrhythmic, Adrenergic beta-Antagonists, Calcium Channel Antagonists, Cytochrome P450 1A2 Inhibitors, Cytochrome P450 2C9 Inhibitors, Cytochrome P450 2D6 Inhibitors, Cytochrome P450 3A Inhibitors, P-Glycoprotein Inhibitors, Potassium Channel Interactions, Sodium Channel Antagonists, Atrial Repolarization, Cardiac Rhythm Alteration, Negative Chronotropy, Ventricular Repolarization.
What are the brand names for Amiodarone?
Amiodarone is marketed under brand names including Nexterone, Pacerone.
What are the contraindications for Amiodarone?
Amiodarone labeling lists contraindications including: Cardiogenic shock. Sick sinus syndrome, second- or third-degree atrioventricular block, bradycardia leading to syncope without a functioning pacemaker.. Always consult the full prescribing information and a clinician.
Note. Data for amiodarone is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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