Hydrochlorothiazide

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Hydrochlorothiazide
Hydrochlorothiazide.svg
Hydrochlorothiazide-from-xtal-3D-balls.png
Clinical data
Trade names Hydrodiuril, others
Other namesHCTZ, HCT
AHFS/Drugs.com Monograph
MedlinePlus a682571
License data
Pregnancy
category
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
  • US: WARNING [2] Rx-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability Variable (~70% on average)
Metabolism Not significant [3]
Elimination half-life 5.6–14.8 h
Excretion Primarily kidney (>95% as unchanged drug)
Identifiers
  • 6-chloro-1,1-dioxo-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.367 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C7H8ClN3O4S2
Molar mass 297.73 g·mol−1
3D model (JSmol)
  • O=S(=O)(N)c1c(Cl)cc2c(c1)S(=O)(=O)NCN2
  • InChI=1S/C7H8ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-2,10-11H,3H2,(H2,9,12,13) Yes check.svgY
  • Key:JZUFKLXOESDKRF-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Hydrochlorothiazide, sold under the brand name Hydrodiuril among others, is a diuretic medication used to treat hypertension and swelling due to fluid build-up. [4] Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in those with a high calcium level in the urine. [4] Hydrochlorothiazide is taken by mouth and may be combined with other blood pressure medications as a single pill to increase effectiveness. [4] Hydrochlorothiazide is a thiazide medication which inhibits reabsorption of sodium and chloride ions from the distal convoluted tubules of the kidneys, causing a natriuresis. [4] [5] This initially increases urine volume and lowers blood volume. [6] It is believed to reduce peripheral vascular resistance. [6]

Contents

Potential side effects include poor kidney function, electrolyte imbalances, including low blood potassium, and, less commonly, low blood sodium, gout, high blood sugar, and feeling lightheaded with standing. [4]

Two companies, Merck & Co. and Ciba Specialty Chemicals, state they discovered the medication which became commercially available in 1959. [7] It is on the World Health Organization's List of Essential Medicines. [8] It is available as a generic drug [4] and is relatively affordable. [9] In 2022, it was the twelfth most commonly prescribed medication in the United States, with more than 38 million prescriptions. [10] [11]

Medical uses

Hydrochlorothiazide is used for the treatment of hypertension, congestive heart failure, symptomatic edema, diabetes insipidus, renal tubular acidosis. [4] It is also used for the prevention of kidney stones in those who have high levels of calcium in their urine. [4]

Multiple studies suggest hydrochlorothiazide could be used as initial monotherapy in people with primary hypertension; however, the decision should be weighed against the consequence of long-term adverse metabolic abnormalities. [12] [13] Doses of hydrochlorothiazide of 50 mg or less over four years reduced mortality and development of cardiovascular diseases better than high-dose hydrochlorothiazide (50 mg or more) and beta-blockers. [5] A 2019 review supported equivalence between drug classes for initiating monotherapy in hypertension, although thiazide or thiazide-like diuretics showed better primary effectiveness and safety profiles than angiotensin-converting enzyme inhibitors and non-dihydropyridine calcium channel blockers. [12]

Low doses (50 mg or less) of hydrochlorothiazide as first‐line therapy for hypertension were found to reduce total mortality and cardiovascular disease events over a four-year study. [5] Hydrochlorothiazide appears be more effective than chlorthalidone in preventing heart attacks and strokes. [14] Hydrochlorothiazide is less potent but may be more effective than chlorthalidone in reducing blood pressure. [14] [15] More robust studies are required to confirm which drug is superior in reducing cardiovascular events. [16] Side effect profile for both drugs appear similar and are dose dependent. [14]

Hydrochlorothiazide is also sometimes used to prevent osteopenia and treat hypoparathyroidism, [17] hypercalciuria, Dent's disease, and Ménière's disease.

A low level of evidence, predominantly from observational studies, suggests that thiazide diuretics have a modest beneficial effect on bone mineral density and are associated with a decreased fracture risk when compared with people not taking thiazides. [18] [19] [20] Thiazides decrease mineral bone loss by promoting calcium retention in the kidney, and by directly stimulating osteoblast differentiation and bone mineral formation. [21]

The combination of fixed-dose preparation such as losartan/hydrochlorothiazide has added advantages of a more potent antihypertensive effect with additional antihypertensive efficacy at the dose of 100 mg/25 mg when compared to monotherapy. [22] [23]

Adverse effects

Package inserts contain vague and inconsistent data surrounding the use of thiazide diuretics in patients with allergies to sulfa drugs, with little evidence to support these statements. [26] A retrospective cohort study conducted by Strom et al. concluded that there is an increased risk of an allergic reaction occurring in patients with a predisposition to allergic reactions in general rather than cross reactivity from structural components of the sulfonamide-based drug. [27] Prescribers should examine the evidence carefully and assess each patient individually, paying particular attention to their prior history of sulfonamide hypersensitivity rather than relying on drug monograph information. [28]

There is an increased risk of non-melanoma skin cancer. [29] In August 2020, the Australian Therapeutic Goods Administration required the Product Information (PI) and Consumer Medicine Information (CMI) for medicines containing hydrochlorothiazide to be updated to include details about an increased risk of non-melanoma skin cancer. [30] In August 2020, the U.S. Food and Drug Administration (FDA) updated the drug label about an increased risk of non-melanoma skin cancer (basal cell skin cancer or squamous cell skin cancer). [31]

Society and culture

Co-Diovan (valsartan and hydrochlorothiazide) Two boxes and a blister pack of Co-Diovan (Valsartan and hydrochlorothiazide), Singapore - 20150210.jpg
Co-Diovan (valsartan and hydrochlorothiazide)
Two generic benazepril HCl 20 mg and hydrochlorothiazide 25 mg oral tablets 001850277lg Benazepril hydrochloride 20 MG Hydrochlorothiazide 25 MG Oral Tablet.jpg
Two generic benazepril HCl 20 mg and hydrochlorothiazide 25 mg oral tablets

Brand names

Hydrochlorothiazide is available as a generic drug under a large number of brand names, including Apo-Hydro, Aquazide, BPZide, Dichlotride, Esidrex, Hydrochlorot, Hydrodiuril, HydroSaluric, Hypothiazid, Microzide, Oretic and many others.[ medical citation needed ]

To reduce pill burden and in order to reduce side effects, hydrochlorothiazide is often used in fixed-dose combinations with many other classes of antihypertensive drugs such as:

Sport

Use of hydrochlorothiazide is prohibited by the World Anti-Doping Agency for its ability to mask the use of performance-enhancing drugs. [34]

Related Research Articles

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Although used to treat high blood pressure, it does not seem to improve mortality in those with the condition. Other uses include the prevention of migraines and treatment of certain irregular heart beats. It is taken orally or by intravenous injection. It can also be used with other blood pressure medications.

<span class="mw-page-title-main">Indapamide</span> Thiazide-like diuretic drug

Indapamide is a thiazide-like diuretic drug used in the treatment of hypertension, as well as decompensated heart failure. Combination preparations with perindopril are available. The thiazide-like diuretics reduce risk of major cardiovascular events and heart failure in hypertensive patients compared with hydrochlorothiazide with a comparable incidence of adverse events. Both thiazide diuretics and thiazide-like diuretics are effective in reducing risk of stroke. Both drug classes appear to have comparable rates of adverse effects as other antihypertensives such as angiotensin II receptor blockers and dihydropyridine calcium channel blockers and lesser prevalence of side-effects when compared to ACE-inhibitors and non-dihydropyridine calcium channel blockers.

<span class="mw-page-title-main">Angiotensin II receptor blocker</span> Group of pharmaceuticals that modulate the renin–angiotensin system

Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals that bind to and inhibit the angiotensin II receptor type 1 (AT1) and thereby block the arteriolar contraction and sodium retention effects of renin–angiotensin system.

<span class="mw-page-title-main">Irbesartan</span> Chemical compound

Irbesartan, sold under the brand name Aprovel among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination irbesartan/hydrochlorothiazide.

<span class="mw-page-title-main">Loop diuretic</span> Diuretics that act along the loop of Henle in the kidneys

Loop diuretics are pharmacological agents that primarily inhibit the Na-K-Cl cotransporter located on the luminal membrane of cells along the thick ascending limb of the loop of Henle. They are often used for the treatment of hypertension and edema secondary to congestive heart failure, liver cirrhosis, or chronic kidney disease. While thiazide diuretics are more effective in patients with normal kidney function, loop diuretics are more effective in patients with impaired kidney function.

<span class="mw-page-title-main">Amiloride</span> Medication

Amiloride, sold under the trade name Midamor among others, is a medication typically used with other medications to treat high blood pressure or swelling due to heart failure or cirrhosis of the liver. Amiloride is classified as a potassium-sparing diuretic. Amiloride is often used together with another diuretic, such as a thiazide or loop diuretic. It is taken by mouth. Onset of action is about two hours and it lasts for about a day.

<span class="mw-page-title-main">Chlortalidone</span> Thiazide-like diuretic drug

Chlortalidone, also known as chlorthalidone, is a thiazide-like diuretic drug used to treat high blood pressure, swelling, diabetes insipidus, and renal tubular acidosis. Because chlortalidone is effective in most patients with high blood pressure, it is considered a preferred initial treatment. It is also used to prevent calcium-based kidney stones. It is taken by mouth. Effects generally begin within three hours and last for up to three days. Long-term treatment with chlortalidone is more effective than hydrochlorothiazide for prevention of heart attack or stroke.

<span class="mw-page-title-main">Thiazide</span> Class of chemical compounds

Thiazide refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The first approved drug of this class, chlorothiazide, was marketed under the trade name Diuril beginning in 1958. In most countries, thiazides are the least expensive antihypertensive drugs available.

<span class="mw-page-title-main">Reserpine</span> Drug used to treat high blood pressure

Reserpine is a drug that is used for the treatment of high blood pressure, usually in combination with a thiazide diuretic or vasodilator. Large clinical trials have shown that combined treatment with reserpine plus a thiazide diuretic reduces mortality of people with hypertension. Although the use of reserpine as a solo drug has declined since it was first approved by the FDA in 1955, the combined use of reserpine and a thiazide diuretic or vasodilator is still recommended in patients who do not achieve adequate lowering of blood pressure with first-line drug treatment alone. The reserpine-hydrochlorothiazide combo pill was the 17th most commonly prescribed of the 43 combination antihypertensive pills available in 2012.

<span class="mw-page-title-main">Triamterene</span> Chemical compound

Triamterene is a potassium-sparing diuretic often used in combination with thiazide diuretics for the treatment of high blood pressure or swelling. The combination with hydrochlorothiazide, is known as hydrochlorothiazide/triamterene.

<span class="mw-page-title-main">Losartan</span> Blood pressure medication

Losartan, sold under the brand name Cozaar among others, is a medication used to treat high blood pressure (hypertension). It is in the angiotensin receptor blocker (ARB) family of medication, and is considered protective of the kidneys. Besides hypertension, it is also used in diabetic kidney disease, heart failure, and left ventricular enlargement. It comes as a tablet that is taken by mouth. It may be used alone or in addition to other blood pressure medication. Up to six weeks may be required for the full effects to occur.

<span class="mw-page-title-main">Valsartan</span> Angiotensin II receptor antagonist

Valsartan, sold under the brand name Diovan among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It belongs to a class of medications referred to as angiotensin II receptor blockers (ARBs). It is a reasonable initial treatment for high blood pressure. It is taken by mouth.

<span class="mw-page-title-main">Metolazone</span> Chemical compound

Metolazone is a thiazide-like diuretic marketed under the brand names Zytanix, Metoz, Zaroxolyn, and Mykrox. It is primarily used to treat congestive heart failure and high blood pressure. Metolazone indirectly decreases the amount of water reabsorbed into the bloodstream by the kidney, so that blood volume decreases and urine volume increases. This lowers blood pressure and prevents excess fluid accumulation in heart failure. Metolazone is sometimes used together with loop diuretics such as furosemide or bumetanide, but these highly effective combinations can lead to dehydration and electrolyte abnormalities.

<span class="mw-page-title-main">Perindopril</span> High blood pressure medication

Perindopril is a medication used to treat high blood pressure, heart failure, or stable coronary artery disease.

<span class="mw-page-title-main">Perindopril/indapamide</span> Combination medication

Perindopril/indapamide is a combination medication which contains perindopril and indapamide both of which are used for the treatment of essential hypertension.

<span class="mw-page-title-main">Valsartan/hydrochlorothiazide</span> Chemical compound

Valsartan/hydrochlorothiazide, sold under the brand name Diovan HCT among others, is a medication used to treat high blood pressure when valsartan is not sufficient. It is a combination of valsartan, an angiotensin receptor blocker with hydrochlorothiazide, a diuretic. It is taken by mouth.

<span class="mw-page-title-main">Diuretic</span> Substance that promotes the production of urine

A diuretic is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics increase the excretion of water from the body, through the kidneys. There exist several classes of diuretic, and each works in a distinct way. Alternatively, an antidiuretic, such as vasopressin, is an agent or drug which reduces the excretion of water in urine.

Hypertension is managed using lifestyle modification and antihypertensive medications. Hypertension is usually treated to achieve a blood pressure of below 140/90 mmHg to 160/100 mmHg. According to one 2003 review, reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21% and reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease.

Aliskiren/hydrochlorothiazide, sold under the brand name Tekturna HCT among others, is a fixed-dose combination medication for the treatment of hypertension. It contains aliskiren, a renin inhibitor, and hydrochlorothiazide, a diuretic. It is taken by mouth.

References

  1. ↑ "Hydrochlorothiazide Use During Pregnancy". Drugs.com. 30 July 2019. Retrieved 19 January 2020.
  2. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  3. ↑ Beermann B, Groschinsky-Grind M, Rosén A (May 1976). "Absorption, metabolism, and excretion of hydrochlorothiazide". Clinical Pharmacology and Therapeutics. 19 (5 Pt 1): 531–537. doi:10.1002/cpt1976195part1531. PMID   1277708. S2CID   22159706.
  4. 1 2 3 4 5 6 7 8 "Hydrochlorothiazide". Drugs.com. 15 November 2022. Retrieved 31 May 2023.
  5. 1 2 3 Wright JM, Musini VM, Gill R (April 2018). "First-line drugs for hypertension". The Cochrane Database of Systematic Reviews. 2018 (4): CD001841. doi:10.1002/14651858.CD001841.pub3. PMC   6513559 . PMID   29667175.
  6. 1 2 Duarte JD, Cooper-DeHoff RM (June 2010). "Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics". Expert Review of Cardiovascular Therapy. 8 (6): 793–802. doi:10.1586/erc.10.27. PMC   2904515 . PMID   20528637. NIHMSID: NIHMS215063.
  7. ↑ Ravina E (2011). The evolution of drug discovery: from traditional medicines to modern drugs (1st ed.). Weinheim: Wiley-VCH. p. 74. ISBN   9783527326693. Archived from the original on 10 January 2015.
  8. ↑ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl: 10665/371090 . WHO/MHP/HPS/EML/2023.02.
  9. ↑ "Best drugs to treat high blood pressure The least expensive medications may be the best for many people". November 2014. Archived from the original on 3 January 2015. Retrieved 10 January 2015.
  10. ↑ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  11. ↑ "Hydrochlorothiazide Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  12. 1 2 Suchard MA, Schuemie MJ, Krumholz HM, You SC, Chen R, Pratt N, et al. (November 2019). "Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: a systematic, multinational, large-scale analysis". Lancet. 394 (10211): 1816–1826. doi:10.1016/S0140-6736(19)32317-7. PMC   6924620 . PMID   31668726.{{cite journal}}: CS1 maint: overridden setting (link)
  13. ↑ Musini VM, Gueyffier F, Puil L, Salzwedel DM, Wright JM, et al. (Cochrane Hypertension Group) (August 2017). "Pharmacotherapy for hypertension in adults aged 18 to 59 years". The Cochrane Database of Systematic Reviews. 2017 (8): CD008276. doi:10.1002/14651858.CD008276.pub2. PMC   6483466 . PMID   28813123.
  14. 1 2 3 Hripcsak G, Suchard MA, Shea S, Chen R, You SC, Pratt N, et al. (April 2020). "Comparison of Cardiovascular and Safety Outcomes of Chlorthalidone vs Hydrochlorothiazide to Treat Hypertension". JAMA Internal Medicine. 180 (4): 542–551. doi:10.1001/jamainternmed.2019.7454. PMC   7042845 . PMID   32065600.{{cite journal}}: CS1 maint: overridden setting (link)
  15. ↑ Peterzan MA, Hardy R, Chaturvedi N, Hughes AD (June 2012). "Meta-analysis of dose-response relationships for hydrochlorothiazide, chlorthalidone, and bendroflumethiazide on blood pressure, serum potassium, and urate". Hypertension. 59 (6): 1104–1109. doi:10.1161/HYPERTENSIONAHA.111.190637. PMC   4930655 . PMID   22547443.
  16. ↑ Dorsch MP, Gillespie BW, Erickson SR, Bleske BE, Weder AB (April 2011). "Chlorthalidone reduces cardiovascular events compared with hydrochlorothiazide: a retrospective cohort analysis". Hypertension. 57 (4): 689–694. doi: 10.1161/HYPERTENSIONAHA.110.161505 . PMID   21383313. S2CID   13017777.
  17. ↑ Mitchell DM, Regan S, Cooley MR, Lauter KB, Vrla MC, Becker CB, et al. (December 2012). "Long-term follow-up of patients with hypoparathyroidism". The Journal of Clinical Endocrinology and Metabolism. 97 (12): 4507–4514. doi:10.1210/jc.2012-1808. PMC   3513540 . PMID   23043192.{{cite journal}}: CS1 maint: overridden setting (link)
  18. ↑ Aung K, Htay T, et al. (Cochrane Hypertension Group) (October 2011). "Thiazide diuretics and the risk of hip fracture". The Cochrane Database of Systematic Reviews (10): CD005185. doi:10.1002/14651858.CD005185.pub2. PMID   21975748.
  19. ↑ Xiao X, Xu Y, Wu Q (July 2018). "Thiazide diuretic usage and risk of fracture: a meta-analysis of cohort studies". Osteoporosis International. 29 (7): 1515–1524. doi:10.1007/s00198-018-4486-9. PMID   29574519. S2CID   4322516.
  20. ↑ Solomon DH, Ruppert K, Zhao Z, Lian YJ, Kuo IH, Greendale GA, et al. (March 2016). "Bone mineral density changes among women initiating blood pressure lowering drugs: a SWAN cohort study". Osteoporosis International. 27 (3): 1181–1189. doi:10.1007/s00198-015-3332-6. PMC   4813302 . PMID   26449354.
  21. ↑ Dvorak MM, De Joussineau C, Carter DH, Pisitkun T, Knepper MA, Gamba G, et al. (September 2007). "Thiazide diuretics directly induce osteoblast differentiation and mineralized nodule formation by interacting with a sodium chloride co-transporter in bone". Journal of the American Society of Nephrology. 18 (9): 2509–2516. doi:10.1681/ASN.2007030348. PMC   2216427 . PMID   17656470.{{cite journal}}: CS1 maint: overridden setting (link)
  22. ↑ Lacourcière Y, Poirier L (December 2003). "Antihypertensive effects of two fixed-dose combinations of losartan and hydrochlorothiazide versus hydrochlorothiazide monotherapy in subjects with ambulatory systolic hypertension". American Journal of Hypertension. 16 (12): 1036–1042. doi: 10.1016/j.amjhyper.2003.07.014 . PMID   14643578. S2CID   26447230.
  23. 1 2 Musini VM, Nazer M, Bassett K, Wright JM (May 2014). "Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension". The Cochrane Database of Systematic Reviews. 2014 (5): CD003824. doi:10.1002/14651858.cd003824.pub2. PMC   10612990 . PMID   24869750.
  24. ↑ Hueskes BA, Roovers EA, Mantel-Teeuwisse AK, Janssens HJ, van de Lisdonk EH, Janssen M (June 2012). "Use of diuretics and the risk of gouty arthritis: a systematic review". Seminars in Arthritis and Rheumatism. 41 (6): 879–889. doi:10.1016/j.semarthrit.2011.11.008. PMID   22221907.
  25. ↑ Wilson L, Nair KV, Saseen JJ (December 2014). "Comparison of new-onset gout in adults prescribed chlorthalidone vs. hydrochlorothiazide for hypertension". Journal of Clinical Hypertension. 16 (12): 864–868. doi: 10.1111/jch.12413 . PMC   8031516 . PMID   25258088.
  26. ↑ Johnson KK, Green DL, Rife JP, Limon L (February 2005). "Sulfonamide cross-reactivity: fact or fiction?". The Annals of Pharmacotherapy. 39 (2): 290–301. doi:10.1345/aph.1E350. PMID   15644481. S2CID   10642527.
  27. ↑ Strom BL, Schinnar R, Apter AJ, Margolis DJ, Lautenbach E, Hennessy S, et al. (October 2003). "Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics". The New England Journal of Medicine. 349 (17): 1628–1635. doi: 10.1056/NEJMoa022963 . PMID   14573734.{{cite journal}}: CS1 maint: overridden setting (link)
  28. ↑ Ghimire S, Kyung E, Lee JH, Kim JW, Kang W, Kim E (June 2013). "An evidence-based approach for providing cautionary recommendations to sulfonamide-allergic patients and determining cross-reactivity among sulfonamide-containing medications". Journal of Clinical Pharmacy and Therapeutics. 38 (3): 196–202. doi: 10.1111/jcpt.12048 . PMID   23489131.
  29. ↑ Pedersen SA, Gaist D, Schmidt SA, Hölmich LR, Friis S, Pottegård A (April 2018). "Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark". Journal of the American Academy of Dermatology. 78 (4): 673–681.e9. doi: 10.1016/j.jaad.2017.11.042 . PMID   29217346.
  30. ↑ "Hydrochlorothiazide". Therapeutic Goods Administration (TGA). 24 August 2020. Retrieved 22 September 2020.
  31. ↑ "FDA approves label changes to hydrochlorothiazide". U.S. Food and Drug Administration (FDA). 20 August 2020. Retrieved 28 August 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  32. ↑ "List of nationally authorised medicinal products : Active substance: bisoprolol / hydrochlorothiazide Procedure no.: PSUSA/00000420/202111" (PDF). Ema.europa.eu. Retrieved 16 July 2022.
  33. ↑ "Triamterene and Hydrochlorothiazide". MedlinePlus. 1 January 2020. Archived from the original on 2 January 2020. Retrieved 1 January 2020.
  34. ↑ "Prohibited List" (PDF). World Anti-Doping Agency. January 2018.
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