hydrochlorothiazide

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Hydrochlorothiazide is a thiazide diuretic.

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

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.{{cite journal | vauthors = Suchard MA, Schuemie MJ, Krumholz HM, You SC, Chen R, Pratt N, Reich CG, Duke J, Madigan D, Hripcsak G, Ryan PB | display-authors = 6 | title = Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: a systematic, multinational, large-scale analysis | journal = Lancet | volume = 394 | issue = 10211 | pages = 1816–1826 | date = November 2019 | pmid = 31668726 | pmc = 6924620 | doi = 10.1016/S0140-6736(19)32317-7 }}{{cite journal | vauthors = Musini VM, Gueyffier F, Puil L, Salzwedel DM, Wright JM | title = Pharmacotherapy for hypertension in adults aged 18 to 59 years | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 8 | pages = CD008276 | date = August 2017 | pmid = 28813123 | pmc = 6483466 | doi = 10.1002/14651858.CD008276.pub2 | collaboration = Cochrane Hypertension Group }} 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. 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.

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.{{cite journal |vauthors=Wright JM, Musini VM, Gill R |title=First-line drugs for hypertension |journal=The Cochrane Database of Systematic Reviews |volume=2018 |issue=4 |pages=CD001841 |date=April 2018 |pmid=29667175 |pmc=6513559 |doi=10.1002/14651858.CD001841.pub3}} Hydrochlorothiazide appears be more effective than chlorthalidone in preventing heart attacks and strokes.{{cite journal | vauthors = Hripcsak G, Suchard MA, Shea S, Chen R, You SC, Pratt N, Madigan D, Krumholz HM, Ryan PB, Schuemie MJ | display-authors = 6 | title = Comparison of Cardiovascular and Safety Outcomes of Chlorthalidone vs Hydrochlorothiazide to Treat Hypertension | journal = JAMA Internal Medicine | volume = 180 | issue = 4 | pages = 542–551 | date = April 2020 | pmid = 32065600 | pmc = 7042845 | doi = 10.1001/jamainternmed.2019.7454 }} Hydrochlorothiazide is less potent but may be more effective than chlorthalidone in reducing blood pressure.{{cite journal | vauthors = Peterzan MA, Hardy R, Chaturvedi N, Hughes AD | title = Meta-analysis of dose-response relationships for hydrochlorothiazide, chlorthalidone, and bendroflumethiazide on blood pressure, serum potassium, and urate | journal = Hypertension | volume = 59 | issue = 6 | pages = 1104–1109 | date = June 2012 | pmid = 22547443 | pmc = 4930655 | doi = 10.1161/HYPERTENSIONAHA.111.190637 }} More robust studies are required to confirm which drug is superior in reducing cardiovascular events.{{cite journal | vauthors = Dorsch MP, Gillespie BW, Erickson SR, Bleske BE, Weder AB | title = Chlorthalidone reduces cardiovascular events compared with hydrochlorothiazide: a retrospective cohort analysis | journal = Hypertension | volume = 57 | issue = 4 | pages = 689–694 | date = April 2011 | pmid = 21383313 | doi = 10.1161/HYPERTENSIONAHA.110.161505 | s2cid = 13017777 | doi-access = free }} Side effect profile for both drugs appear similar and are dose dependent.

Hydrochlorothiazide is also sometimes used to prevent osteopenia and treat hypoparathyroidism,{{cite journal | vauthors = Mitchell DM, Regan S, Cooley MR, Lauter KB, Vrla MC, Becker CB, Burnett-Bowie SA, Mannstadt M | display-authors = 6 | title = Long-term follow-up of patients with hypoparathyroidism | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 97 | issue = 12 | pages = 4507–4514 | date = December 2012 | pmid = 23043192 | pmc = 3513540 | doi = 10.1210/jc.2012-1808 }} 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.{{cite journal | vauthors = Aung K, Htay T | title = Thiazide diuretics and the risk of hip fracture | journal = The Cochrane Database of Systematic Reviews | issue = 10 | pages = CD005185 | date = October 2011 | pmid = 21975748 | doi = 10.1002/14651858.CD005185.pub2 | collaboration = Cochrane Hypertension Group}}{{cite journal | vauthors = Xiao X, Xu Y, Wu Q | title = Thiazide diuretic usage and risk of fracture: a meta-analysis of cohort studies | journal = Osteoporosis International | volume = 29 | issue = 7 | pages = 1515–1524 | date = July 2018 | pmid = 29574519 | doi = 10.1007/s00198-018-4486-9 | s2cid = 4322516}}{{cite journal | vauthors = Solomon DH, Ruppert K, Zhao Z, Lian YJ, Kuo IH, Greendale GA, Finkelstein JS | title = Bone mineral density changes among women initiating blood pressure lowering drugs: a SWAN cohort study | journal = Osteoporosis International | volume = 27 | issue = 3 | pages = 1181–1189 | date = March 2016 | pmid = 26449354 | pmc = 4813302 | doi = 10.1007/s00198-015-3332-6 }} Thiazides decrease mineral bone loss by promoting calcium retention in the kidney, and by directly stimulating osteoblast differentiation and bone mineral formation.{{cite journal | vauthors = Dvorak MM, De Joussineau C, Carter DH, Pisitkun T, Knepper MA, Gamba G, Kemp PJ, Riccardi D | display-authors = 6 | title = Thiazide diuretics directly induce osteoblast differentiation and mineralized nodule formation by interacting with a sodium chloride co-transporter in bone | journal = Journal of the American Society of Nephrology | volume = 18 | issue = 9 | pages = 2509–2516 | date = September 2007 | pmid = 17656470 | pmc = 2216427 | doi = 10.1681/ASN.2007030348}}

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.{{cite journal | vauthors = Lacourcière Y, Poirier L | title = Antihypertensive effects of two fixed-dose combinations of losartan and hydrochlorothiazide versus hydrochlorothiazide monotherapy in subjects with ambulatory systolic hypertension | journal = American Journal of Hypertension | volume = 16 | issue = 12 | pages = 1036–1042 | date = December 2003 | pmid = 14643578 | doi = 10.1016/j.amjhyper.2003.07.014 | s2cid = 26447230 | doi-access = free }}{{cite journal | vauthors = Musini VM, Nazer M, Bassett K, Wright JM | title = Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD003824 | date = May 2014 | volume = 2014 | pmid = 24869750 | doi = 10.1002/14651858.cd003824.pub2| pmc = 10612990 }}

• Hypokalemia, or low blood levels of potassium are an occasional side effect. It can be usually prevented by potassium supplements or by combining hydrochlorothiazide with a potassium-sparing diuretic
• Other disturbances in the levels of serum electrolytes, including hypomagnesemia (low magnesium), hyponatremia (low sodium), and hypercalcemia (high calcium)
• Hyperuricemia (high levels of uric acid in the blood). All thiazide diuretics including hydrochlorothiazide can inhibit excretion of uric acid by the kidneys, thereby increasing serum concentrations of uric acid. This may increase the incidence of gout in doses of ≥ 25 mg per day and in more susceptible patients such as male gender of <60 years old.{{cite journal | vauthors = Hueskes BA, Roovers EA, Mantel-Teeuwisse AK, Janssens HJ, van de Lisdonk EH, Janssen M | title = Use of diuretics and the risk of gouty arthritis: a systematic review | journal = Seminars in Arthritis and Rheumatism | volume = 41 | issue = 6 | pages = 879–889 | date = June 2012 | pmid = 22221907 | doi = 10.1016/j.semarthrit.2011.11.008 }}{{cite journal | vauthors = Wilson L, Nair KV, Saseen JJ | title = Comparison of new-onset gout in adults prescribed chlorthalidone vs. hydrochlorothiazide for hypertension | journal = Journal of Clinical Hypertension | volume = 16 | issue = 12 | pages = 864–868 | date = December 2014 | pmid = 25258088 | pmc = 8031516 | doi = 10.1111/jch.12413 | doi-access = free}}
• Hyperglycemia, high blood sugar
• Hyperlipidemia, high cholesterol and triglycerides
• Headache
• Nausea/vomiting
• Photosensitivity
• Weight gain
• Pancreatitis

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.{{cite journal | vauthors = Johnson KK, Green DL, Rife JP, Limon L | title = Sulfonamide cross-reactivity: fact or fiction? | journal = The Annals of Pharmacotherapy | volume = 39 | issue = 2 | pages = 290–301 | date = February 2005 | pmid = 15644481 | doi = 10.1345/aph.1E350 | s2cid = 10642527}} 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.{{cite journal | vauthors = Strom BL, Schinnar R, Apter AJ, Margolis DJ, Lautenbach E, Hennessy S, Bilker WB, Pettitt D | display-authors = 6 | title = Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics | journal = The New England Journal of Medicine | volume = 349 | issue = 17 | pages = 1628–1635 | date = October 2003 | pmid = 14573734 | doi = 10.1056/NEJMoa022963| doi-access = free }} 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.{{cite journal | vauthors = Ghimire S, Kyung E, Lee JH, Kim JW, Kang W, Kim E | title = An evidence-based approach for providing cautionary recommendations to sulfonamide-allergic patients and determining cross-reactivity among sulfonamide-containing medications | journal = Journal of Clinical Pharmacy and Therapeutics | volume = 38 | issue = 3 | pages = 196–202 | date = June 2013 | pmid = 23489131 | doi = 10.1111/jcpt.12048 | doi-access = free}}

There is an increased risk of non-melanoma skin cancer.{{cite journal | vauthors = Pedersen SA, Gaist D, Schmidt SA, Hölmich LR, Friis S, Pottegård A | title = Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark | journal = Journal of the American Academy of Dermatology | volume = 78 | issue = 4 | pages = 673–681.e9 | date = April 2018 | pmid = 29217346 | doi = 10.1016/j.jaad.2017.11.042 | doi-access = free }} 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.{{cite web | title=Hydrochlorothiazide | website=Therapeutic Goods Administration (TGA) | date=24 August 2020 | url=https://www.tga.gov.au/alert/hydrochlorothiazide | access-date=22 September 2020}} 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).{{cite web | title=FDA approves label changes to hydrochlorothiazide | website=U.S. Food and Drug Administration (FDA) | date=20 August 2020 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-label-changes-hydrochlorothiazide-describe-small-risk-non-melanoma-skin-cancer | access-date=28 August 2020}} {{PD-notice}}

In November 2024, International Agency for Research on Cancer (IARC) classified hydrochlorothiazide, voriconazole and tacrolimus as group 1 carcinogens.{{cite journal |url=https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00685-5/fulltext |title=Carcinogenicity of hydrochlorothiazide, voriconazole, and tacrolimus |journal=The Lancet Oncology|date=2024-11-29 |volume=26 |issue=1 |pages=15–16 |doi=10.1016/S1470-2045(24)00685-5 |author=Cogliano VJ, Corsini E, Fournier A, Nelson HH, Sergi CM, Antunes AMM|display-authors=etal|url-access=subscription }}{{cite web |url=https://monographs.iarc.who.int/list-of-classifications |title=List of Classifications|work=IARC|access-date=2025-04-12}}

File:Two boxes and a blister pack of Co-Diovan (Valsartan and hydrochlorothiazide), Singapore - 20150210.jpg)]]

File:001850277lg Benazepril hydrochloride 20 MG Hydrochlorothiazide 25 MG Oral Tablet.jpg 20 mg and hydrochlorothiazide 25 mg oral tablets]]

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|date=January 2020}}

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:

• ACE inhibitors – e.g. Prinzide or Zestoretic (with lisinopril), Co-Renitec (with enalapril), Capozide (with captopril), Accuretic (with quinapril), Monopril HCT (with fosinopril), Lotensin HCT (with benazepril), etc.
• Angiotensin receptor blockers – e.g. Hyzaar (with losartan), Co-Diovan or Diovan HCT (with valsartan), Teveten Plus (with eprosartan), Avalide or CoAprovel (with irbesartan), Atacand HCT or Atacand Plus (with candesartan), etc.
• Beta blockers – e.g. Ziac or Lodoz (with bisoprolol),{{cite web|url=https://www.ema.europa.eu/documents/psusa/bisoprolol/hydrochlorothiazide-list-nationally-authorised-medicinal-products-psusa/00000420/202111_en.pdf|title=List of nationally authorised medicinal products : Active substance: bisoprolol / hydrochlorothiazide Procedure no.: PSUSA/00000420/202111|website=Ema.europa.eu|access-date=16 July 2022}} Nebilet Plus or Nebilet HCT (with nebivolol), Dutoprol or Lopressor HCT (with metoprolol), etc.
• Direct renin inhibitors – e.g. Co-Rasilez or Tekturna HCT (with aliskiren)
• Potassium sparing diuretics – Dyazide and Maxzide triamterene{{cite web | title=Triamterene and Hydrochlorothiazide | website=MedlinePlus | date=1 January 2020 | url=https://medlineplus.gov/druginfo/meds/a601125.html | archive-url=https://web.archive.org/web/20200102052553/https://medlineplus.gov/druginfo/meds/a601125.html | archive-date=2 January 2020 | url-status=live | access-date=1 January 2020}}

Use of hydrochlorothiazide is prohibited by the World Anti-Doping Agency for its ability to mask the use of performance-enhancing drugs.{{cite web | url = https://www.wada-ama.org/sites/default/files/prohibited_list_2018_en.pdf | title = Prohibited List | date = January 2018 | publisher = World Anti-Doping Agency}}

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