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Amiodarone

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Amiodarone, Cordarone, Pacerone

  • See Also
  1. Amiodarone Pulmonary Toxicity
  2. Ventricular Tachycardia
  3. Cardiac Arrest
  • 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%
  • Contraindications
  1. Pregnancy or Lactation
  2. Cardiogenic Shock
  3. Severe Bradycardia
  4. Sinus Node Dysfunction (unless Pacemaker present)
  • 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)
  4. Consider inpatient telemetry monitoring when starting Amiodarone
  • Mechanism
  1. Class Effects
    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
  2. Activity
    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
  • Pharmacokinetics
  1. Half life: 60 days (range 13 to 103 days)
  2. Effective plasma concentration: 1-2 ug/ml
  • Dosing
  • Adult
  1. Administration
    1. IV : Deliver via nonevacuated glass bottle with inline IV filter
    2. Oral: May be divided twice daily to decrease gastrointestinal adverse effects
  2. Life-threatening Arrhythmia (Wide Complex Tachycardia)
    1. Intravenous Dosing (mixed in D5W)
      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 for 1 to 2 weeks until total of 10 grams given
        2. Next continue at 400 to 800 mg orally daily for 1 month or until limited by adverse effects
      2. Maintenance: 200-400 mg orally daily
        1. Use lowest effective dose
    3. Maximum: 2 grams per day total
  3. Pulseless Arrhythmia (e.g. Ventricular Fibrillation)
    1. Load: 300 mg in 20-30 ml saline rapid IV infusion
    2. IV Maintenance and maximum dose as above
  4. Atrial Fibrillation
    1. Load: 400 to 800 mg orally per day daily or in divided dosing for 7 to 14 days (or until 10 grams given)
    2. Maintenance: 100-200 mg orally daily (up to 400 mg daily)
  • Dosing
  • Child (Life-threatening, ventricular Arrhythmia)
  1. Avoid in infants <30 days old
  2. Exercise caution in children (risk of severe Bradycardia and cardiovascular collapse)
  3. Load 5 mg/kg IV or IO over 30 minutes
    1. Administer over 20 to 60 minutes (unless pulseless)
    2. Administer each 1 mg/kg over 5-10 minutes
    3. Do not give faster than 30 mg/min
  4. Maintenance: 5 mcg/kg/min
    1. May increase as needed up to 10 mcg/kg/min
  5. Maximum: 20 mg/kg/day
  • 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 with IV dosing (Vasopressor support may be needed)
    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%)
  • Safety
  1. Unsafe in Lactation
  2. Pregnancy Category X
    1. Risk of Congenital Hypothyroidism (or Hyperthyroidism)
    2. Other adverse neonatal effects include cardiac, growth and neurodevelopment
  • 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. Electrocardiogram
    5. Pulmonary Function Test (with DLCO)
    6. Ophthalmology exam
    7. Skin exam
  4. Other anticipatory guidance
    1. Use Sunscreen
      1. May prevent Skin Discoloration (as well as photosensitivity)
  • Drug Interactions
  1. Decreased Heart Rate and AV Node Conduction (risk of Bradycardia, AV Block, Sinus Arrest)
    1. Beta Blocker
    2. Non-Dihydropyridine Calcium Channel Blocker (e.g. Diltiazem, Verapamil)
    3. Digoxin
    4. Clonidine
    5. Ivabradine
  2. QT Prolongation with proarrhythmia risk
    1. Fluoroquinolones (e.g. Ciprofloxacin)
    2. Macrolides (e.g. Azithromycin)
    3. Loratadine
    4. Trazodone
    5. Imidazole Antifungal
    6. Concurrent Class IA Antiarrhythmic or Class III Antiarrhythmic
  3. Reduces clearance of other drugs
    1. Warfarin (Coumadin)
      1. Decrease Warfarin dose 20% at start of Amiodarone (and ultimately decrease by 33 to 50%)
      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 (Myopathy and Rhabdomyolysis risk)
      1. Simvastatin (limit dose to 20 mg/day)
      2. Lovastatin (limit dose to 40 mg/day)
      3. Atorvastatin likely also interacts
      4. Pravastatin and Rosuvastatin are less likely to interact
    8. Sildenafil (Viagra)
    9. Cyclosporine
    10. Phenytoin (may triple serum levels)
  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
  5. Decreases activity of other drugs
    1. Clopidogrel (Plavix)
  6. Increased Amiodarone Levels
    1. Protease Inhibitors
    2. Cimetidine
  • Resources
  1. Amiodarone Tablet (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ccd3733-c3af-4a11-8500-0f99194c1472
  2. Amiodarone Injection (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d8d04647-8e25-4127-8ecf-360ce1991c2f
  • References
  1. Katzung (1989) Pharmacology, Lange, p. 176
  2. (2019) Presc Lett 26(1): 5
  3. (2000) Circulation 102(suppl I): 86-89 [PubMed]
  4. Siddoway (2003) Am Fam Physician 68:2189-96 [PubMed]