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(HCTZ) (on 6/18/2017 at Walmart.com)
Hydrochlorothiazide(HCTZ)12.5mg #30 capsules for $4.00 $0.13 each
Hydrochlorothiazide(HCTZ)12.5mg #90 capsules for $10.00 $0.11 each
Hydrochlorothiazide (HCTZ) (on 6/18/2017 at Walmart.com)
Hydrochlorothiazide (HCTZ) 25mg #30 tablets for $4.00 $0.13 each
Hydrochlorothiazide (HCTZ) 25mg #90 tablets for $10.00 $0.11 each
Hydrochlorothiazide (HCTZ) 50mg #30 tablets for $4.00 $0.13 each
Hydrochlorothiazide (HCTZ) 50mg #90 tablets for $10.00 $0.11 each
Indapamide (on 6/18/2017 at Walmart.com)
Indapamide 1.25mg #30 tablets for $4.00 $0.13 each
Indapamide 1.25mg #90 tablets for $10.00 $0.11 each
Indapamide 2.5mg #30 tablets for $4.00 $0.13 each
Indapamide 2.5mg #90 tablets for $10.00 $0.11 each
hydrochlorothiazide (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
HYDROCHLOROTHIAZIDE 12.5 MG CP Generic $0.04 each
HYDROCHLOROTHIAZIDE 12.5 MG TB Generic $0.10 each
chlorothiazide (on 11/23/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
CHLOROTHIAZIDE 250 MG TABLET Generic $0.52 each
CHLOROTHIAZIDE 500 MG TABLET Generic $0.95 each
chlorthalidone (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
CHLORTHALIDONE 25 MG TABLET Generic $0.78 each
CHLORTHALIDONE 50 MG TABLET Generic $1.00 each
indapamide (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
INDAPAMIDE 1.25 MG TABLET Generic $0.25 each
INDAPAMIDE 2.5 MG TABLET Generic $0.25 each
metolazone (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
METOLAZONE 10 MG TABLET Generic $1.60 each
METOLAZONE 2.5 MG TABLET Generic $1.07 each
METOLAZONE 5 MG TABLET Generic $1.35 each

Ontology: Chlorothiazide (C0008273)

Definition (NCI) A short-acting, benzothiadiazinesulfonamide derivative and prototypical thiazide diuretic. Chlorothiazide is excreted unchanged by the kidneys.
Definition (MSH) A thiazide diuretic with actions and uses similar to those of HYDROCHLOROTHIAZIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p812)
Definition (CSP) thiazide diuretic used to treat hypertension.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D002740
SnomedCT 372782002, 5786005
LNC LP16071-0, MTHU008128
English Chlorothiazide, 2H-1,2,4-Benzothiadiazine-7-sulfonamide, 6-chloro-, 1,1-dioxide, chlorothiazide, chlorothiazide (medication), CHLOROTHIAZIDE, Chlorothiazide [Chemical/Ingredient], chlorothiazides, Chlorothiazide (product), Chlorothiazide (substance)
Swedish Klortiazid
Czech chlorthiazid
Finnish Klooritiatsidi
Croatian Not Translated[Chlorothiazide]
Spanish Clorotiazida, Clorotiacida, clorotiazida (producto), clorotiazida (sustancia), clorotiazida
Polish Chlorotiazyd, Diuryl
French Chlorothiazide
German Chlorothiazid
Italian Clorotiazide
Portuguese Clorotiazida

Ontology: Chlorthalidone (C0008294)

Definition (NCI) A long acting thiazide-like diuretic of the sulfamoylbenzamide class and is devoid of the benzothiadiazine structure. Chlorthalidone directly inhibits sodium and chloride reabsorption on the luminal membrane of the early segment in the distal convoluted tubule (DCT) in the kidney. This leads to an increase in sodium, chloride, bicarbonate, and potassium secretion resulting in the excretion of water. In addition, this agent, like other thiazide diuretics, decreases calcium and uric acid secretion. In addition, this agent inhibits many carbonic anhydrase (CA) isoenzymes. Chlorthalidone is used in the treatment of high blood pressure, edema and congestive heart failure. The elimination half-life is about 40 to 50 hours.
Definition (MSH) A benzenesulfonamide-phthalimidine that tautomerizes to a BENZOPHENONES form. It is considered a thiazide-like diuretic.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D002752
SnomedCT 387324004, 57893000
LNC LP16077-7, MTHU006890
English Chlorphthalidolone, Chlorthalidone, Oxodoline, Phthalamudine, Benzenesulfonamide, 2-chloro-5-(2,3-dihydro-1-hydroxy-3-oxo-1H-isoindol-1-yl)-, Chlortalidone, Benzenesulfonamide, 2-Chloro-5-(2,3-dihydro-1-hydroxy-3-oxo-1H-isoindol-1-yl)-, Benzenesulfonamide, 2-chloro-5-(1-hydroxy-3-oxo-1-isoindolinyl)-, chlorthalidone, chlorthalidone (medication), CHLORTHALIDONE, Chlorthalidone [Chemical/Ingredient], chlortalidone, Chlorthalidone (product), Chlorthalidone (substance)
Swedish Klortalidon
Czech chlorthalidon
Finnish Klooritalidoni
French Phthalamudine, Chlorthalidone, Chlortalidone
Japanese クロルサリドン, クロルフタリドロン, フタルアムジン, クロルタリドン
Polish Chlortalidon
Spanish clortalidona (producto), clortalidona (sustancia), clortalidona, Clorftalidolona, Clortalidona, Ftalamudina
German Chlorphthalidolon, Chlortalidon, Chlorthalidon, Phthalamudin
Italian Clortalidone
Portuguese Clorftalidolona, Clortalidona, Ftalamudina

Ontology: Thiazide Diuretics (C0012802)

Definition (NCI) Any benzothiadiazide derivative or other thiazide-like agent with diuretic and anti-hypertensive activity. Thiazide diuretics inhibit the sodium-chloride transporter in the distal tubule in the kidneys, thereby suppressing sodium and chloride reabsorption from the distal convoluted tubules (DCT) and increasing the excretion of sodium, chloride, potassium and water. In addition, thiazide diuretics decrease excretion of calcium and uric acid. These agents cause vasodilation possibly by activating calcium-activated potassium channels in vascular smooth muscle and inhibiting various carbonic anhydrases in vascular tissue.
Definition (MSH) Diuretics characterized as analogs of 1,2,4-benzothiadiazine-1,1-dioxide. All have a common mechanism of action and differ primarily in the dose required to produce a given effect. They act directly on the kidney to increase the excretion of sodium chloride and water and also increase excretion of potassium ions.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D049993
SnomedCT 371342005, 350616005, 371343000, 372747003, 45518007
English Thiazide Diuretic, THIAZIDES/RELATED DIURETICS, thiazides, thiazide diuretics, thiazide diuretics (medication), [CV701] THIAZIDES/RELATED DIURETICS, thiazide diuretic, diuretic thiazide, diuretics thiazide, diuretic thiazides, Thiazide-related diuretic product (product), Thiazide-related diuretic (product), Thiazide diuretic product (product), Thiazide-related diuretic product, Thiazide diuretic, Thiazide diuretic (substance), Thiazide diuretic (product), Thiazide diuretic product, Thiazide Diuretics, Thiazide diuretic, NOS, Thiazide-related diuretic (substance), Thiazide-related diuretic, Thizaide-related diuretic, Benzothiadiazine Diuretics, Diuretics, Benzothiadiazine, Diuretics, Thiazide
French Diurétiques thiazides, Diurétiques thiazidiques, Benzothiadiazides, Diurétiques thiaziques
Czech diuretika thiazidová
German Diuretika, Thiazid-, Benzothiadiazindiuretika, Thiaziddiuretika
Italian Diuretici tiazidici
Spanish diurético tipo tiazida, producto con diurético tiazídico (producto), diurético relacionado con las tiazidas, producto con diurético tiazídico, diurético relacionado con las tiazidas (producto), diurético tiazídico (sustancia), diurético tiazídico, producto (producto), diurético tiazídico, producto, diurético tiazídico, diurético tipo tiazida (producto), diurético tipo tiazida (sustancia), diurético tiazídico (producto), tiazida

Ontology: Hydrochlorothiazide (C0020261)

Definition (MSH) A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism.
Definition (CHV) drug that increases voiding
Definition (CHV) drug that increases voiding
Definition (NCI) A short acting thiazide diuretic. Hydrochlorothiazide (HCTZ) is widely used to treat hypertension and edema. This agent's metabolite appears to preferentially bind to and accumulate in red blood cells. This agent is primarily excreted by the kidneys.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D006852
SnomedCT 387525002, 91667005
LNC LP16160-1, MTHU016732
English Dichlothiazide, Dihydrochlorothiazide, HCTZ, Hydrochlorothiazide, 2H-1,2,4-Benzothiadiazine-7-sulfonamide, 6-chloro-3,4-dihydro-, 1,1-dioxide, 6-Chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, hydrochlorothiazide, hydrochlorothiazide (medication), HYDROCHLOROTHIAZIDE, Hydrochlorothiazide [Chemical/Ingredient], hctz, Hydrochlorothiazide (product), Hydrochlorothiazide (substance)
Spanish Hidroclorotiazida, hidroclorotiazida (producto), hidroclorotiazida (sustancia), hidroclorotiazida
Swedish Hydroklortiazid
Czech hydrochlorthiazid
Finnish Hydroklooritiatsidi
Japanese ヒドロクロロチアジド
Italian HCTZ, Diidroclorotiazide, Idroclorotiazide
Polish Hydrochlorotiazyd
French Hydrochlorothiazide
German Hydrochlorothiazid
Portuguese Hidroclorotiazida

Ontology: Indapamide (C0021186)

Definition (MSH) A benzamide-sulfonamide-indole derived DIURETIC that functions by inhibiting SODIUM CHLORIDE SYMPORTERS.
Definition (NCI) An indole derivative of chlorosulphonamide and a sulfamyl diuretic with antihypertensive activity. Indapamide may interact directly with the subunits of delayed rectifier potassium channels, thereby blocking both slow and rapid K+ (IKs and IKr) currents through the channels. Through the homeostasis mechanism in balancing total ion concentration (Ca++, Na+), it reduces vascular hyperreactivity and peripheral and arterial vascular resistance, possibly by inhibiting transmembrane ionic influx, probably calcium ions, and stimulating prostaglandin E2 synthesis, thereby causing vasodilatation. Indapamide exerts its diuretic effect by inhibiting reabsorption of sodium and chloride, primarily as a result of action on the cortical diluting segment of the renal distal tubule, thereby promoting urinary excretion of water and electrolytes.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D007190
SnomedCT 387419003, 74213004
English Indapamide, Metindamide, Benzamide, 3-(aminosulfonyl)-4-chloro-N-(2,3-dihydro-2-methyl-1H-indol-1-yl)-, indapamide, indapamide (medication), INDAPAMIDE, Indapamide [Chemical/Ingredient], Indapamide (product), Indapamide (substance)
Swedish Indapamid
Czech indapamid
Finnish Indapamidi
Japanese インダパミド, メチンダミド
Polish Indapamid
Spanish indapamida (producto), indapamida (sustancia), indapamida, Indapamida, Metindamida
French Indapamide
German Indapamid, Metindamid
Italian Indapamide
Portuguese Indapamida, Metindamida

Ontology: Metolazone (C0025854)

Definition (MSH) A quinazoline-sulfonamide derived DIURETIC that functions by inhibiting SODIUM CHLORIDE SYMPORTERS.
Definition (NCI) A long acting, quinazoline-based sulfonamide thiazide-like, diuretic. Similar to the thiazides, metolazone acts on the distal convoluted tubule (DCT) and inhibits the sodium-chloride symporter, thereby preventing sodium and chloride reabsorption and excretion of water.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D008788
SnomedCT 22198003, 387123003
LNC LP17954-6, MTHU003340
English Metolazone, 6-Quinazolinesulfonamide, 7-chloro-1,2,3,4-tetrahydro-2-methyl-3-(2-methylphenyl)-4-oxo-, 2-Methyl-3-o-tolyl-6-sulfamyl-7-chloro-1,2,3,4-tetrahydro-4-quinazolinone, 7-Chloro-1,2,3,4-tetrahydro-2-methyl-3-(2-methylphenyl)-4-oxo-6-quinazolinesulfonamide, 7-Chloro-1,2,3,4-tetrahydro-2-methyl-4-oxo-3-o-tolyl-6-quinazolinesulfonamide, metolazone, metolazone (medication), METOLAZONE, Metolazone [Chemical/Ingredient], Metolazone (product), Metolazone (substance)
Swedish Metolazon
Czech metolazon
Finnish Metolatsoni
Japanese メトラゾン
Polish Metolazon
Spanish metolazona (producto), metolazona (sustancia), metolazona, Metolazona
French Métolazone
German Metolazon
Italian Metolazone
Portuguese Metolazona

Ontology: Thiazides (C0541746)

Definition (CSP) family of bicyclic compounds in which one ring has a sulfony l and 2 nitrogen heteroatoms; they inhibit renal sodium resorption, and so are used as diuretics and antihypertensives.
Definition (MSH) Heterocyclic compounds with SULFUR and NITROGEN in the ring. This term commonly refers to the BENZOTHIADIAZINES that inhibit SODIUM-POTASSIUM-CHLORIDE SYMPORTERS and are used as DIURETICS.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D049971
LNC LP18072-6, MTHU003336
Italian Tiazidi
Swedish Tiazider
Czech thiazidy
Finnish Tiatsididiureetit
English Thiazides, Thiazides [Chemical/Ingredient], thiazides, thiazide
Croatian Not Translated[Thiazides]
Polish Tiazydu pochodne
Spanish Tiacidas, Tiazidas
Portuguese Tiazidas
German Thiazide
French Thiazides

Ontology: Zaroxolyn (C0701383)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D008788
English zaroxolyn, UCB Pharma Brand of Metolazone, Zaroxolyn