Pharm

Amiodarone

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Amiodarone, Cordarone

  • 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%
  • 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)
  • 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
  • Pharmacokinetics
  1. Half life: 60 days (range 13 to 103 days)
  2. Effective plasma concentration: 1-2 ug/ml
  • 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
  • Adverse Effects
  1. Precautions
    1. More than half of patients experience adverse effects
  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. Hypothyroidism (6%)
    2. Hyperthyroidism (2%)
    3. Fatigue
  7. Gastrointestinal
    1. Constipation (20%)
    2. Hepatocellular necrosis
  8. Pulmonary
    1. Amiodarone Pulmonary Toxicity (diffuse pneumonitis)
    2. Pulmonary fibrosis (in up to 17%)
  • 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
  • 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
  • Dosing
  • Child (Life-threatening arrhythmia)
  1. Dose: 5 mg/kg IV or IO
  2. Administer over 20 to 60 minutes (unless pulseless)
  • 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)
  • 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]