Hydrochlorothiazide

Hydrochlorothiazide

Clinical data
Trade names	Hydrodiuril, others
Other names	HCTZ, HCT
AHFS/Drugs.com	Monograph
MedlinePlus	a682571
License data	US DailyMed: Hydrochlorothiazide
Pregnancy category	AU: C[1]
By mouth
ATC code	C03AA03 (WHO) C03AB03 (WHO) C03AX01 (WHO) C03EA01 (WHO) C09BX03 (WHO) C09DX01 (WHO) C09DX03 (WHO) C09DX06 (WHO) C09DX07 (WHO) C09XA52 (WHO) C09XA54 (WHO)
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
IUPAC name 6-chloro-1,1-dioxo-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide
JSmol)	Interactive image
SMILES O=S(=O)(N)c1c(Cl)cc2c(c1)S(=O)(=O)NCN2
InChI 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) Y Key:JZUFKLXOESDKRF-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Hydrochlorothiazide, sold under the brand name Hydrodiuril among others, is a

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 2021, it was the twelfth most commonly prescribed medication in the United States, with more than 39 million prescriptions.^[10][11]

Medical uses

Hydrochlorothiazide is used for the treatment of

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.

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

• 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
  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]
• 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.^[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

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:

• 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),^[32] 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^[33]

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

References