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Carvedilol

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Carvedilol, Coreg

  • See Also
  1. Beta Blocker
  2. Beta Blocker Overdose
  3. Labetalol
  4. Alpha Adrenergic Antagonist
  • Indications
  1. Stable Congestive Heart Failure (Compensated)
  2. Hypertension
  • Contraindications
  1. Asthma
  2. Bradycardia
  3. Severe Hepatic Impairment
  • Mechanism
  1. Not Cardioselective
  2. Combination of classes ("Third generation Beta Blocker", similar to Labetalol)
    1. Lowers Blood Pressure without reflex Tachycardia
    2. Nonselective Beta Blocker
      1. Binds vascular (and Bronchial) Smooth Muscle beta receptors
      2. Decreases Heart Rate, Cardiac Output and Blood Pressure
      3. Blunts sympathetic drive while still preserving cardiac contractility
    3. Selective Alpha-1 Adrenergic Antagonist (weak compared with beta activity)
      1. Competitively binds vascular Smooth Muscle alpha-1 Adrenergic Receptors
      2. Blocks peripheral blood vessel Vasoconstriction
  3. Other effects
    1. Does not affect Blood Glucose
  • Dosing
  • Carvedilol Regular Release or Immediate Release (Coreg)
  1. Stable Congestive Heart Failure
    1. Start: 3.125 mg orally twice daily with food
    2. Titrate up by doubling dose every 2 weeks
    3. Maximum dose
      1. Weight <85 kg: 25 mg twice daily
      2. Weight >85 kg: 50 mg twice daily
  2. LV Dysfunction following Myocardial Infarction
    1. Start: 6.25 mg orally twice daily with food
      1. Start 3.125 mg twice daily if lower Heart Rate or Blood Pressure
    2. Titrate up by doubling dose every 2 weeks
    3. Target: 25 mg orally twice daily
    4. Continue for up to 3 years after Myocardial Infarction
  3. Hypertension
    1. Start: 6.25 orally twice daily with food
    2. Double dose as needed every 7-14 days to maximum of 25 mg orally twice daily
  4. Conversion from prior Beta Blocker
    1. No overlap from Metoprolol 50 mg or Atenolol 50 mg
      1. Start Carvedilol 6.25 mg bid and increase as above
    2. Overlap from Atenolol 50-150 or Metoprolol 100-200
      1. Add Carvedilol 3.125 mg bid for 2 weeks
      2. Raise Carvedilol and lower other Beta Blocker
        1. Double Carvedilol every two weeks
        2. Reduce Atenolol or Metoprolol by 50 mg every 2 weeks
        3. When to stop other Beta Blocker
          1. After 2 weeks on Metoprolol 50 mg or
          2. After 2 weeks on Atenolol 25 mg
      3. Reference
        1. Abraham (2003) Congest Heart Fail 9:251-8 [PubMed]
  • Dosing
  • Carvedilol Phosphate Sustained Release or Extended Release (Coreg CR)
  1. Stable Congestive Heart Failure
    1. Start: 10 mg orally daily
    2. Titrate up by doubling dose every 2 weeks as needed
    3. Maximum dose: 80 mg/day
  2. LV Dysfunction following Myocardial Infarction
    1. Start: 20 mg mg orally once daily
      1. Start 10 mg orally daily if lower Heart Rate or Blood Pressure
    2. Titrate up by doubling dose every 2 weeks as needed
    3. Target dose: 80 mg/day
    4. Continue for up to 3 years after Myocardial Infarction
  3. Hypertension
    1. Start: 20 mg orally daily
    2. Titrate up by doubling dose every 2 weeks as needed
    3. Maximum dose: 80 mg/day
  4. Conversion from regular release Carvedilol
    1. Start with Coreg CR 20 mg daily when patient takes Immediate Release 12.5 mg twice daily
    2. Start with Coreg CR 40 mg daily when patient takes Immediate Release 25 mg twice daily
  • Efficacy
  1. Carvedilol reduces mortality in severe Congestive Heart Failure (including COPERNICUS Trial)
    1. Packer (1996) N Engl J Med 334:1349-55 [PubMed]
    2. Eichhorn EJ, Bristow MR. (2001) Curr Control Trials Cardiovasc Med 2(1):20-3 +PMID: 11806769 [PubMed]
  2. Reduces Mortality in CHF compared with Metoprolol (COMET Trial)
    1. Poole (2003) Lancet 362:7-13 [PubMed]
  3. Carvedilol improves Ejection Fraction in CHF
    1. Olsen (1995) J Am Coll Cardiol 25(6):1225-31 +PMID: 7722114 [PubMed]
  4. LV Dysfunction following Myocardial Infarction (CAPRICORN Trial)
    1. Decreases mortality in patients who are also on ACE Inhibitor or ARB
    2. Dargie (2001) Lancet 357(9266):1385-90 +PMID: 11356434 [PubMed]
  • Adverse Effects
  1. May worsen acute exacerbations of Congestive Heart Failure
  2. Fatigue
  3. Erectile Dysfunction
  4. Orthostatic Hypotension
  • Drug Interactions
  1. CYP2D6 and CYP2C9 Substrate
  2. Systemic Beta Agonists
    1. Carvedilol blocks bronchodilation
  • Pharmacokinetics
  1. Highly lipophilic
  2. Bioavailability: 25 to 35% (due to first pass hepatic metabolism)
  3. Hepatic Elimination
  • Resources
  1. Carvedilol Tablet (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=68c275e8-992a-4520-8065-ab6d615d89cc
  • References
  1. (2019) Presc Lett, Resource #350503, Comparison of Oral Beta Blockers
  2. Olson (2020) Clinical Pharmacology, MedMaster, Miami, p. 66
  3. Hamilton (2020) Tarascon Pocket Pharmacopeia, Jones and Bartlett, accessed on IOS, 4/9/2021