Pharm

Chlorthalidone

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Chlorthalidone, Hygroton

  1. Start: 12.5 to 25 mg orally daily
  2. Maximum: 50 mg/day
    1. Higher doses worsen Hypokalemia without additional Antihypertensive benefit
  • Efficacy
  1. May be preferred over Hydrochlorothiazide
    1. Longer half life than immediate release Hydrochlorothiazide
    2. Two to three times as potent as Hydrochlorothiazide
      1. Chlorthalidone lowers systolic Blood Pressure 10 mmHg more than Hydrochlorothiazide
    3. However, 2022 study shows similar cardiovascular outcomes with Hydrochlorothiazide
      1. Ishani (2022) N Engl J Med 387(26):2401-10 +PMID: 36516076 [PubMed]
  2. Chlorthalidone is more likely to result in Hypokalemia (see below)
  3. Conversion: Use 12.5 mg of Chlorthalidone in place of 25 mg Hydrochlorothiazide
  • Precautions
  1. Monitor Serum Potassium at baseline, 2 weeks and every 6-12 months (increased Hypokalemia risk)
  2. Decrease Sodium intake
    1. High Sodium intake is associated with increased Potassium losses
    2. Also associated with worse Blood Pressure control)
  3. Consider Potassium Supplementation
    1. Avoid if on Potassium sparing agents or significant Chronic Kidney Disease
    2. Potassium chloride 20 meq orally daily for Hypokalemia or prevention of Hypokalemia or
    3. Dietary Potassium for prevention of Hypokalemia
  4. Consider using Chlorthalidone in combination with agents balance Potassium losses
    1. Additional Blood Pressure lowering required
      1. ACE Inhibitor or Angiotensin Receptor Blocker
      2. Spironolactone or Eplerenone
    2. No additional Blood Pressure lowering required
      1. Triamterene or Amiloride
  • Pharmacokinetics
  1. Onset of activity: 2 hours
  2. Duration >24 hours
  • Mechanism
  • Adverse Effects
  • Safety
  1. Pregnancy Category B
    1. Pregnancy Category D if used for Pregnancy Induced Hypertension
  2. Unknown Safety in Lactation
  • References
  1. (2012) Presc Lett 19(2): 8
  2. (2014) Presc Lett 21(9): 52
  3. (2021) Presc Lett, Resource #370507, Commonly Used Diuretics
  4. (2020) Med Lett Drugs Ther 62(1598): 73-80
  5. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 62-3
  6. Hamilton (2020) Tarascon Pocket Pharmacopoeia