II. Indications

  1. Hypertension (first-line agent)
  2. Osteoporosis Prevention (investigational)
  3. Severe Congestive Heart Failure
    1. Adjunct to Loop Diuretics
  4. Meniere's Disease

III. Contraindications

  1. Hyponatremia
    1. Do not use Thiazide Diuretics in patients with a history of Hyponatremia

IV. Precautions: Renal Insufficiency (GFR <30 ml/min)

  1. Thiazide Diuretics are minimally effective when GFR falls below 30 ml/min
  2. Switch to Loop Diuretics at this level of Renal Insufficiency

V. Safety

  1. Pregnancy
    1. Thiazides are considered Category D
    2. However most risks have been disproven (neonatal Thrombocytopenia, IUGR, fluid and Electrolyte abnormalities)
    3. Hydrochlorothiazide is likely safe in pregnancy
    4. al Balas (2009) Can Fam Physician 55(1): 44-5 [PubMed]
  2. Lactation
    1. Doses of 50 mg/day or less appear safe (minimal concentration in Breast Milk, no significant Breast Milk suppression)
    2. At doses higher than 50 mg daily do appear to suppress Breast Milk
    3. LactMed
      1. https://www.ncbi.nlm.nih.gov/books/NBK500965/

VI. Adverse effects

  1. Hyperuricemia
    1. Occurs more often with doses of Hydrochlorothiazide over 25 mg
    2. Less of an issue if avoid Hypokalemia
    3. Avoid Thiazide Diuretics in gout!
  2. Hyperglycemia
  3. Hyperlipidemia
  4. Hypokalemia
    1. Hypokalemia is less common when Thiazide Diuretic is combined with ACE Inhibitor or Angiotensin Receptor Blocker
    2. One banana a day is sufficient Potassium Replacement
      1. Each inch of banana supplies 1 meq of Potassium
    3. Cost benefit is lost when Potassium supplement used
  5. Hyponatremia
  6. Hypomagnesemia
  7. Nonmelanoma Skin Cancer (esp. Squamous Cell Skin Cancer) with Hydrochlorothiazide
    1. NNH: 16,000 for one new case of Squamous Cell Skin Cancer per year with Hydrochlorothiazide
    2. Hydrochlorothiazide 25 mg daily for 5.5 years is associated with one new case of SCC per 6700
    3. May be associated with Hydrochlorothiazide associated photosensitivity
    4. (2020) presc lett 27(10):60
    5. https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-label-changes-hydrochlorothiazide-describe-small-risk-non-melanoma-skin-cancer
    6. Pedersen (2018) J Am Acad Dermatol 78(4):673-81 [PubMed]

VII. Preparations: Single Agents

  1. Hydrochlorothiazide (Esidrex, HydroDIURIL)
    1. Hypertension: 12 to 25 mg orally daily (maximum 50 mg/day)
    2. Available as generic scored tablets (25 and 50 mg) and capsules (25 mg)
    3. Renal excretion, unchanged in urine
    4. Less potent than Chlorthalidone
      1. Chlorthalidone reduces systolic Blood Pressure 10 mmHg more than Hydrochlorothiazide
    5. Shorter Half-Life (6-12 hours) than the 24 hour half life of Chlorthalidone and Indapamide
      1. Immediate release Hydrochlorothiazide may only reduce daytime systolic Blood Pressure
      2. Controlled release Hydrochlorothiazide (available outside the U.S.) has 24 hour activity
  2. Chlorothiazide (Diuril)
    1. Hypertension: 125-250 orally daily or divided bid
  3. Indapamide (Lozol)
    1. Hypertension: 1.25 to 5 mg orally daily
    2. Preferred over Hydrochlorothiazide
      1. Longer Half-Life (24 hours)
      2. May have cardiovascular benefit in elderly (CHF, CVA)
  4. Metolazone (Zaroxolyn)
    1. Hypertension: 0.5 mg orally daily (max: 1 mg daily)
    2. CHF with edema: 2.5 mg daily (max: 20 mg/day)
  5. Chlorthalidone (Hygroton)
    1. Hypertension: 12.5 to 25 mg orally daily
    2. 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. Conversion: Use 12.5 mg of Chlorthalidone in place of 25 mg Hydrochlorothiazide
    3. Monitor Serum Potassium at baseline, 2 weeks and every 6-12 months (increased Hypokalemia risk)
      1. Decrease Sodium intake
        1. High Sodium intake is associated with increased Potassium losses
        2. Also associated with worse Blood Pressure control)
      2. 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
      3. 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
    4. References
      1. (2012) Presc Lett 19(2): 8
      2. (2014) Presc Lett 21(9): 52

VIII. Preparations: Combinations

  1. Hydrochlorothiazide and Triamterene
    1. Hctz/Triamterene 25/50 (Dyazide) one daily
    2. Hctz/Triamterene 50/75 (Maxzide) one daily

IX. Drug Interactions

  1. Lithium
    1. Increases Lithium levels via decreased Lithium excretion
  2. NSAIDs
    1. Decrease Thiazide efficacy

Images: Related links to external sites (from Bing)

Related Studies

Cost: Medications

hydrochlorothiazide (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
HYDROCHLOROTHIAZIDE 12.5 MG CP Generic $0.03 each
HYDROCHLOROTHIAZIDE 12.5 MG TB Generic $0.04 each
HYDROCHLOROTHIAZIDE 25 MG TAB Generic $0.01 each
HYDROCHLOROTHIAZIDE 50 MG TAB Generic $0.03 each
chlorthalidone (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
CHLORTHALIDONE 25 MG TABLET Generic $0.11 each
CHLORTHALIDONE 50 MG TABLET Generic $0.14 each
indapamide (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
INDAPAMIDE 1.25 MG TABLET Generic $0.12 each
INDAPAMIDE 2.5 MG TABLET Generic $0.12 each
metolazone (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
METOLAZONE 10 MG TABLET Generic $0.81 each
METOLAZONE 2.5 MG TABLET Generic $0.52 each
METOLAZONE 5 MG TABLET Generic $0.80 each