II. Indications

  1. Ventricular Arrhythmias
    1. Stable Wide Complex Tachycardia
    2. Stable Ventricular Tachycardia
    3. Pulseless Ventricular Tachycardia
    4. Pulseless Ventricular Fibrillation
  2. Supraventricular Arrhythmias
    1. Supraventricular Tachycardia
    2. Ventricular rate control
      1. Rapid atrial Arrhythmias (Atrial Fibrillation)
      2. Accessory pathway (Wolff-Parkinson-White Syndrome)
    3. Atrial Fibrillation Cardioversion
      1. Time to Cardioversion: 8-24 hours
      2. Conversion Rate: 43-68%
      3. Chronic Efficacy: 55-65%

III. Precautions

  1. Hepatocellular necrosis risk (FDA black box warning)
  2. Amiodarone Pulmonary Toxicity risk (FDA black box warning)
  3. Drug Interactions and adverse effects persist for weeks after stopping Amiodarone (60 day Half-Life)

IV. Mechanism

  1. Class IA Antiarrhythmic
    1. High affinity for inactive Sodium channels
    2. Most effective in tissue with long Action Potentials
  2. Class II Antiarrhythmic
    1. Non-competitive Beta-Blocker
  3. Class III Antiarrhythmic
    1. Prolongs refractory period via Action Potential
  4. Class IV Antiarrhythmic
    1. Weak Calcium Channel Blocker

V. Pharmacokinetics

  1. Half life: 60 days (range 13 to 103 days)
  2. Effective plasma concentration: 1-2 ug/ml

VI. Effects

  1. General cardiac effects
    1. Inhibits abnormal automaticity
    2. Increases refractory period in all conduction system
    3. Anti-Anginal effects
  2. Atrial effects
    1. Slows sinus node rate
    2. Slows Atrioventricular Node conduction
  3. Ventricular effects
    1. Prolongs QT Interval
    2. Prolongs QRS Duration slightly
  4. Non-cardiac effects
    1. Peripheral vascular dilatation

VII. Adverse Effects

  1. Precautions
    1. More than half of patients experience adverse effects
    2. Mnemonic for toxicity
      1. PFTs (Pulmonary Function Tests)
      2. TFTs (Thyroid Function Tests)
      3. LFTs (Liver Function Tests)
  2. Cardiac
    1. Symptomatic Bradycardia
    2. Heart Block
    3. Hypotension (Pressure support often required)
    4. Congestive Heart Failure exacerbation
    5. Proarrhthmia effect (2-5%)
  3. Eye
    1. Optic Neuritis
    2. Corneal deposits (90%)
      1. Yellow-brown microcrystal deposits in Cornea
      2. Deposits appear within weeks of treatment
      3. May interfere with Vision in 10% of cases
        1. Halos in peripheral Visual Fields (night-time)
        2. Visual Acuity rarely decreased
  4. Skin Deposits
    1. Photodermatitis (25%)
    2. Grayish-blue Skin Discoloration (5-9%)
  5. Neurologic
    1. Paresthesias
    2. Tremor
    3. Ataxia
    4. Headache
  6. Endocrine
    1. Amiodarone resembles T4 and T3 Hormone and may cause either Hypothyroidism or Hyperthyroidism
    2. Hypothyroidism (6%)
      1. Amiodarone may cause Myxedema Coma with elevated TSH (but normal or high T4 and T3)
    3. Hyperthyroidism (2%)
    4. Fatigue
  7. Gastrointestinal
    1. Constipation (20%)
    2. Hepatocellular necrosis
  8. Pulmonary
    1. Amiodarone Pulmonary Toxicity (diffuse pneumonitis)
    2. Pulmonary fibrosis (in up to 17%)

VIII. Drug Interactions

  1. Decreased Heart Rate and AV Node Conduction
    1. Beta Blockers
    2. Calcium Channel Blockers
  2. QT Prolongation with proarrhythmia risk
    1. Fluoroquinolones (e.g. Ciprofloxacin)
    2. Macrolides (e.g. Azithromycin)
  3. Reduces clearance of other drugs
    1. Warfarin (Coumadin)
      1. Decrease Warfarin dose 20% at start of Amiodarone
      2. Expect INR stabilization to take as long as 6-8 weeks
      3. Direct Oral Anticoagulants (e.g. Rivaroxaban) likely also interact, but effect is not measurable
    2. Theophylline
    3. Quinidine
    4. Procainamide
    5. Flecainide
    6. Digoxin (Levels may be increased by 70%)
      1. Decrease Digoxin dose by 50% on starting Amiodarone
    7. Statins
      1. Simvastatin (risk of Myopathy if dose >20 mg/day)
      2. Atorvastatin likely also interacts
      3. Pravastatin and Rosuvastatin are less likely to interact
    8. Sildenafil (Viagra)
    9. Cyclosporine
  4. Severe Bradycardia when combined with Sofosbuvir (Sovaldi)
    1. See Hepatitis C Antiviral Regimen
    2. Has resulted in Cardiac Arrest and pacer placement
    3. Avoid combining Amiodarone with Sofosbuvir (Sovaldi)
    4. If unable to avoid combination
      1. Admit for cardiac monitoring for 48 hours when initiating combination
      2. Patient should monitor Heart Rate at home for 2 weeks after initiating dose
      3. Patients should return for light headed, dizzy, Near Syncope, Heart Rate <60 bpm
    5. References
      1. FDA Alert
        1. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm439662.htm

IX. Dosing: Adult

  1. Life-threatening Arrhythmia (Wide Complex Tachycardia)
    1. Intravenous Dosing
      1. Load: 150 mg over 10 minutes
        1. May be repeated in 10 to 30 minutes
      2. Maintenance
        1. First: 1 mg/min for 6 hours
        2. Next: 0.5 mg/min for 18 hours
        3. Last: Reduce IV dose and convert to oral dosing
    2. Oral Dosing
      1. Load: 800 to 1600 mg PO per day in divided dosing
        1. Continue daily until total of 10 grams given
      2. Maintenance: 200-400 mg orally daily
    3. Maximum: 2 grams per day total
  2. Pulseless Arrhythmia (e.g. Ventricular Fibrillation)
    1. Load: 300 mg in 20-30 ml Saline rapid IV infusion
    2. Maintenance and maximum dose as above
  3. Atrial Fibrillation
    1. Load: 400 to 800 mg orally per day in divided dosing
      1. Continue daily until total of 10 grams given
    2. Maintenance: 100-200 mg orally daily

X. Dosing: Child (Life-threatening Arrhythmia)

  1. Dose: 5 mg/kg IV or IO
  2. Administer over 20 to 60 minutes (unless pulseless)

XI. Monitoring

  1. Baseline labs
    1. Chest XRay
    2. Thyroid Stimulating Hormone (TSH)
    3. Aspartate Aminotransferase (AST)
    4. Alanine Aminotransferase (ALT)
    5. Pulmonary Function Tests (including DLCO)
    6. Consider ophthalmologic baseline exam
  2. Other Monitoring
    1. Closely monitor heart rhythm in first week of therapy
    2. Prothrombin Time with INR if on Warfarin
    3. Serum Digoxin level (as needed)
  3. Repeat Lab testing at 3 months and then every 6 months
    1. Thyroid Stimulating Hormone (TSH)
    2. Aspartate Aminotransferase (AST)
    3. Alanine Aminotransferase (ALT)
  4. Additional testing
    1. Chest XRay and Pulmonary Function Tests (with DLCO)
      1. Indicated for suspected pneumonitis
  5. Other anticipatory guidance
    1. Use Sunscreen
      1. May prevent Skin Discoloration (as well as photosensitivity)

XII. References

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Related Studies

Cost: Medications

amiodarone (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
AMIODARONE HCL 100 MG TABLET Generic $2.37 each
AMIODARONE HCL 200 MG TABLET Generic $0.13 each
AMIODARONE HCL 400 MG TABLET Generic $3.18 each

Ontology: Amiodarone (C0002598)

Definition (CHV) a drug used to treat angina and arrythmia
Definition (NCI) An iodine-rich benzofuran derivative with antiarrhythmic and vasodilatory activities. As a class III antiarrhythmic agent, amiodarone blocks the myocardial calcium, potassium and sodium channels in cardiac tissue, resulting in prolongation of the cardiac action potential and refractory period. In addition, this agent inhibits alpha- and beta-adrenergic receptors, resulting in a reduction in sympathetic stimulation of the heart, a negative chronotropic effect, and a decrease in myocardial oxygen demands. Amiodarone may cause vasodilation by stimulation of the release of nitric oxide and cyclooxygenase-dependent relaxing endothelial factors.
Definition (MSH) An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.
Definition (CSP) 2-butyl-3-(3,5-diiodo-4-beta diethylaminoethoxybenzoyl) benzofuran; coronary vasodilator used as an antiarrhythmic; severe risk of pulmonary and hepatic toxicity via disruption of lysosomal function; also has amphiphilic phototoxin properties.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D000638
SnomedCT 372821002, 69236009
LNC LP16028-0, MTHU004841
English Amiodarone, Methanone, (2-butyl-3-benzofuranyl)(4-(2-(diethylamino)ethoxy)-3,5-diiodophenyl)-, Amiodarone [Chemical/Ingredient], AMIODARONE, amiodarone, Amiodarone (product), Amiodarone (substance)
Swedish Amiodaron
Czech amiodaron
Finnish Amiodaroni
Japanese アミオダロン
Polish Amiodaron
Spanish amiodarona (producto), amiodarona (sustancia), amiodarona, Amiodarona
French Amiodarone
German Amiodaron
Italian Amiodarone
Portuguese Amiodarona

Ontology: Cordarone (C0701076)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D000638
English Kordaron, cordarone, Cordarone, Cordarex, Sanofi Winthrop Brand of Amiodarone Hydrochloride, Trangorex, Wyeth Brand of Amiodarone Hydrochloride, Amiodarex
German Kordaron, Trangorex, Amiodarex, Cordarex, Cordarone