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]
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
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.[23][24][25]
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]
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:
^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.
^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. PMID21975748.
^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. PMID29574519. S2CID4322516.
^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. PMID22221907.
^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. PMID15644481. S2CID10642527.
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