II. Indications
- Hypertension (first-line agent)
- Osteoporosis Prevention (investigational)
- Severe Congestive Heart Failure
- Adjunct to Loop Diuretics
- Meniere's Disease
III. Contraindications
-
Hyponatremia
- Do not use Thiazide Diuretics in patients with a history of Hyponatremia
IV. Precautions: Renal Insufficiency (GFR <30 ml/min)
- Thiazide Diuretics are minimally effective when GFR falls below 30 ml/min
- Switch to Loop Diuretics at this level of Renal Insufficiency
V. Adverse effects
-
Hyperuricemia
- Occurs more often with doses of Hydrochlorothiazide over 25 mg
- Less of an issue if avoid Hypokalemia
- Avoid Thiazide Diuretics in gout!
- Hyperglycemia
- Hyperlipidemia
-
Hypokalemia
- Hypokalemia is less common when Thiazide Diuretic is combined with ACE Inhibitor, ARB or Potassium sparing Diuretic
- One banana a day is sufficient Potassium Replacement (each inch of banana supplies 1 meq of Potassium)
- Cost benefit is lost when Potassium supplement used
- Hyponatremia
- Hypomagnesemia
-
Nonmelanoma Skin Cancer (esp. Squamous Cell Skin Cancer) with Hydrochlorothiazide
- NNH: 16,000 for one new case of Squamous Cell Skin Cancer per year with Hydrochlorothiazide
- Hydrochlorothiazide 25 mg daily for 5.5 years is associated with one new case of SCC per 6700
- May be associated with Hydrochlorothiazide associated photosensitivity
- (2020) presc lett 27(10):60
- https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-label-changes-hydrochlorothiazide-describe-small-risk-non-melanoma-skin-cancer
- Pedersen (2018) J Am Acad Dermatol 78(4):673-81 [PubMed]
VI. Medications: Hydrochlorothiazide (Esidrex, HydroDIURIL)
-
Hypertension: 12 to 25 mg orally daily
- Typical maintenance dose 25 mg orally daily
- Maximum 50 mg/day (higher doses worsen Hypokalemia without additional antihypertensive benefit)
- Available as generic scored tablets (25 and 50 mg) and capsules (25 mg)
- Renal excretion, unchanged in urine
- Less potent than Chlorthalidone
- Chlorthalidone reduces systolic Blood Pressure 10 mmHg more than Hydrochlorothiazide
- Shorter Half-Life (6-12 hours) than the 24 hour half life of Chlorthalidone and Indapamide
- Immediate release Hydrochlorothiazide may only reduce daytime systolic Blood Pressure
- Controlled release Hydrochlorothiazide (available outside the U.S.) has 24 hour activity
- Resources: Hydrochlorothiazide (DailyMed)
VII. Medications: Chlorthalidone (Hygroton)
-
Hypertension: 12.5 to 25 mg orally daily
- Maximum: 50 mg/day (higher doses worsen Hypokalemia without additional antihypertensive benefit)
- May be preferred over Hydrochlorothiazide
- Longer half life than immediate release Hydrochlorothiazide
- Two to three times as potent as Hydrochlorothiazide
- Chlorthalidone lowers systolic Blood Pressure 10 mmHg more than Hydrochlorothiazide
- Conversion: Use 12.5 mg of Chlorthalidone in place of 25 mg Hydrochlorothiazide
- Monitor Serum Potassium at baseline, 2 weeks and every 6-12 months (increased Hypokalemia risk)
- Decrease Sodium intake
- High Sodium intake is associated with increased Potassium losses
- Also associated with worse Blood Pressure control)
- Consider Potassium Supplementation
- Avoid if on Potassium sparing agents or significant Chronic Kidney Disease
- Potassium chloride 20 meq orally daily for Hypokalemia or prevention of Hypokalemia or
- Dietary Potassium for prevention of Hypokalemia
- Consider using Chlorthalidone in combination with agents balance Potassium losses
- Additional Blood Pressure lowering required
- No additional Blood Pressure lowering required
- Decrease Sodium intake
- Resources: Chlorthalidone (DailyMed)
- References
- (2012) Presc Lett 19(2): 8
- (2014) Presc Lett 21(9): 52
VIII. Medications: Metolazone (Zaroxolyn)
- Hypertension: 0.5 mg orally daily (max: 1 mg daily)
- CHF with edema: 2.5 mg daily (max: 20 mg/day)
- Resources: Metolazone (DailyMed)
IX. Medications: Indapamide (Lozol)
- Hypertension: 1.25 to 5 mg orally daily
- Preferred over Hydrochlorothiazide
- Longer Half-Life (24 hours)
- May have cardiovascular benefit in elderly (CHF, CVA)
- Resources: Indapamide (DailyMed)
X. Medications: Chlorothiazide (Diuril)
-
Hypertension: 125-250 orally daily or divided twice daily
- Maximum: 500 mg orally twice daily
- Resources: Chlorothiazide (DailyMed)
XI. Medications: Combinations
- Hydrochlorothiazide and Triamterene
- Hctz/Triamterene 25/50 (Dyazide) one daily
- Hctz/Triamterene 50/75 (Maxzide) one daily
XII. Safety
- Pregnancy
- Thiazides are considered Category D when used for Pregnancy Induced Hypertension
- However most risks have been disproven (neonatal Thrombocytopenia, IUGR, fluid and Electrolyte abnormalities)
- Other than chlorthiazide which is Pregnancy Category C, all other Thiazides are considered pregnancy category B
- Hydrochlorothiazide is likely safe in pregnancy
- al Balas (2009) Can Fam Physician 55(1): 44-5 [PubMed]
-
Lactation
- Doses of 50 mg/day or less appear safe (minimal concentration in Breast Milk, no significant Breast Milk suppression)
- At doses higher than 50 mg daily do appear to suppress Breast Milk
- LactMed
XIII. Drug Interactions
XIV. References
- (2021) Presc Lett, Resource #370507, Commonly Used Diuretics
- (2020) Med Lett Drugs Ther 62(1598): 73-80
- Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 62-3
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
- (2011) J Clin Hypertens 13:639-43 [PubMed]
Images: Related links to external sites (from Bing)
Related Studies
| 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 |