HCTZ is approved by the US Food and Drug Administration (FDA) to treat hypertension either alone or in combination with other antihypertensives.1
Hydrochlorothiazide (HCTZ) is FDA approved as an adjunctive therapy for edema associated with congestive heart failure, hepatic cirrhosis, corticosteroid therapy, and estrogen therapy.1
HCTZ is listed in national and international guidelines as one of several classes of antihypertensive medications for the first-line management of hypertension.2-5 In the 2017 high blood pressure guideline from the report of the American College of Cardiology and American Heart Association Task Force, thiazide-type diuretics are listed along with calcium channel blockers (CCBs), angiotensin-converting-enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) as initial antihypertensive treatment in the general non-black population [Strong recommendation (Grade A)].5 Additional recommendations are that a thiazide-type diuretic or CCB should be included in the initial antihypertensive treatment of people in the general black population (without heart failure or chronic kidney disease), including those with diabetes [Strong recommendation (Grade B)].
The 2013 American College of Cardiology Foundation (ACCF)/AHA guidelines include thiazide diuretics in the pharmacological management of patients with heart failure.6 These guidelines state that while loop diuretics are preferred in most patients with heart failure, thiazide diuretics may be considered in hypertensive patients with heart failure and mild fluid retention because of their antihypertensive effects. The 2017 Focused Update of the 2013 guidelines confirmed this recommendation.7
Non-FDA approved uses of HCTZ include the treatment of diabetes insipidus, nephrolithiasis, Meniere’s disease, and hypoparathyroidism.8-14 It has also been used in the prevention of bone loss and osteoporosis.15-18
The 2014 American Urological Association guidelines recommend that clinicians offer thiazide diuretics to patients with high or relatively high urine calcium levels and recurrent calcium stones.10 They should also be offered to patients with recurrent calcium stones in whom other metabolic abnormalities are absent or have been addressed.
Thiazide diuretics help improve renal calcium reabsorption and raise serum calcium in long term therapy of hypoparathyroidism when used in conjunction with standard therapy of 1,25(OH)2 D-3 (such as calcitriol) and calcium.14,19
Thiazide diuretics are also sometimes used to treat Meniere’s disease.11,12 However, high quality data is still lacking.11 Systematic reviews of their use for this indication did not identify any randomized controlled trials of sufficient quality to include in their review.11,12 One review concluded that low evidence-level studies suggest thiazides may help manage Meniere’s disease.12 However, while the frequency of vertigo episodes was improved with thiazides, the evidence was less convincing for hearing improvement.
A few randomized controlled trials of HCTZ and its effects on bone mineral density showed HCTZ slows cortical bone loss.15-17 A 2011 Cochrane systematic review of thiazide diuretics and the risk of hip fracture found that thiazides appear to reduce the risk in observational studies.18 Randomized control trials related to risk of hip fracture have not been performed.18
References
- Hydrochlorothiazide [package insert]. Morgantown, WV: Mylan Pharmaceuticals, Inc.; 2011.
- James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults. JAMA 2014; 311 (5): 507-520.
- Qaseem A, Wilt TJ, Rich R, Humphrey LL, Frost J, Forciea MA. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med 2017; 166 (6): 430-430.
- Rosendorff C, Lackland DT, Allison M, et al. Treatment of hypertension in patients with coronary artery disease: a scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. Circulation 2015; 131 (19): e435-470.
- Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2017.
- Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 62 (16): e147-239.
- Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a reportof the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation 2017; 136 (6): e137-e161.
- Knoers N. Nephrogenic Diabetes Insipidus. Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; 2012.
- Sinke AP, Kortenoeven ML, de Groot T, et al. Hydrochlorothiazide attenuates lithium-induced nephrogenic diabetes insipidus independently of the sodium-chloride cotransporter. Am J Physiol Renal Physiol 2014; 306 (5): F525-533.
- Pearle MS, Goldfarb DS, Assimos DG, et al. Medical management of kidney stones: AUA guideline. J Urol 2014; 192 (2): 316-324.
- Crowson MG, Patki A, Tucci DL. A Systematic Review of Diuretics in the Medical Management of Meniere's Disease. Otolaryngol Head Neck Surg 2016; 154 (5): 824-834.
- Thirlwall AS, Kundu S. Diuretics for Meniere's disease or syndrome. Cochrane Database Syst Rev 2006; (3): Cd003599.
- Makaryus AN, McFarlane SI. Diabetes insipidus: diagnosis and treatment of a complex disease. Cleve Clin J Med 2006; 73 (1): 65-71.
- Al-Azem H, Khan AA. Hypoparathyroidism. Best Pract Res Clin Endocrinol Metab 2012; 26 (4): 517-522.
- Bolland MJ, Ames RW, Horne AM, Orr-Walker BJ, Gamble GD, Reid IR. The effect of treatment with a thiazide diuretic for 4 years on bone density in normal postmenopausal women. Osteoporos Int 2007; 18 (4): 479-486.
- Dalbeth N, Gamble GD, Horne A, Reid IR. Relationship Between Changes in Serum Urate and Bone Mineral Density During Treatment with Thiazide Diuretics: Secondary Analysis from a Randomized Controlled Trial. Calcif Tissue Int 2016; 98 (5): 474-478.
- Reid IR, Ames RW, Orr-Walker BJ, et al. Hydrochlorothiazide reduces loss of cortical bone in normal postmenopausal women: a randomized controlled trial. Am J Med 2000; 109 (5): 362-370.
- Aung K, Htay T. Thiazide diuretics and the risk of hip fracture. Cochrane Database Syst Rev 2011; (10): Cd005185.
- Brickman AS, Massry SG, Coburn JW. changes in serum and urinary calcium during treatment with hydrochlorothiazide: studies on mechanisms. J Clin Invest 1972; 51 (4): 945-954.
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