Hydrochlorothiazide (HCTZ) is a thiazide diuretic, a “water pill” that makes the kidneys excrete more sodium, chloride and water. Merck’s HydroDIURIL was approved in the US in 1959, and HCTZ is now sold as many generics and in fixed-dose combinations with other blood pressure drugs. Its approved uses are high blood pressure and edema (fluid retention) from heart, liver or kidney disease and from corticosteroid or estrogen therapy.
In physique sports, HCTZ is one of the diuretics some competitors take before a show to shed water. It is not an anabolic agent, and no controlled study has tested whether it improves stage appearance. The World Anti-Doping Agency (WADA) bans it at all times, both as a diuretic and as a masking agent. Since 2020, US labels have also warned of a higher risk of non-melanoma skin cancer with long-term use.
This page summarizes what the FDA labels, clinical trials and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Thiazide diuretic (a sulfonamide-derived benzothiadiazine) |
| Brands / approval | HydroDIURIL (Merck), NDA 011835, approved 1959, now discontinued; Microzide capsules, NDA 020504 (1996); many generics and combination products |
| Route | Oral tablet or capsule |
| Strengths | 12.5 mg capsules; 12.5, 25 and 50 mg tablets |
| Labeled adult dose | Hypertension: 25 mg/day, up to 50 mg/day; edema: 25–100 mg/day |
| Half-life (label) | 5.6–14.8 h (tablet label); 6–15 h (capsule label) |
| Timing of effect | Diuresis starts within 2 h, peaks at about 4 h, lasts about 6–12 h |
| Metabolism | Not metabolized; excreted unchanged in urine |
| US status | Prescription only; not a controlled substance |
| WADA status | Prohibited at all times (class S5, diuretics and masking agents) |
What it is
Hydrochlorothiazide is 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, formula C₇H₈ClN₃O₄S₂, molecular weight 297.7 g/mol (FDA label; PubChem). It is the 3,4-dihydro derivative of an older thiazide, chlorothiazide. Because it contains a sulfonamide group, the labels contraindicate it in people allergic to other sulfonamide-derived drugs.
Merck’s HydroDIURIL tablets received FDA approval on February 24, 1959 (Drugs@FDA, NDA 011835). A low-dose 12.5 mg capsule, Microzide, was approved in December 1996 (Drugs@FDA, NDA 020504). Today HCTZ also appears in fixed-dose combinations, including:
- with ACE inhibitors (lisinopril, enalapril) and angiotensin receptor blockers (losartan, valsartan, olmesartan, irbesartan, telmisartan);
- with beta-blockers (bisoprolol, metoprolol);
- with potassium-sparing diuretics (triamterene, spironolactone).
Mechanism
Thiazides act mainly by blocking the sodium-chloride cotransporter (NCC) in the distal convoluted tubule of the kidney (Ellison and Loffing, Hypertension 2009). They are quite specific for this protein and do not block the loop-diuretic target that furosemide acts on. With less sodium reabsorbed, more sodium, chloride and water leave in the urine.
The extra sodium reaching later parts of the tubule is partly swapped for potassium and hydrogen ions. That is why HCTZ tends to lower blood potassium and can cause a metabolic alkalosis (capsule label). HCTZ also reduces urinary calcium and uric acid excretion and increases magnesium loss.
How HCTZ lowers blood pressure is not fully known. The label describes an early fall in blood volume and cardiac output. With continued use, plasma volume drifts back toward normal while resistance in the blood vessels falls. The labels note that thiazides do not usually lower normal blood pressure.
The library covers two other diuretics that are often compared with HCTZ (Ellison and Loffing, Hypertension 2009; Escalante et al., BMC Sports Sci Med Rehabil 2021):
| Diuretic | Type | Effect on potassium |
|---|---|---|
| Hydrochlorothiazide | Thiazide; blocks the Na-Cl cotransporter | Lowers |
| Furosemide (Lasix) | Loop diuretic; blocks the Na-K-2Cl cotransporter | Lowers |
| Spironolactone | Potassium-sparing diuretic | Spares (can raise) |
Pharmacokinetics
From the hydrochlorothiazide capsule label (DailyMed):
| Parameter | Value |
|---|---|
| Oral absorption | 65–75% |
| Time to peak | 1–5 h |
| Peak plasma level | 70–490 ng/mL after 12.5–100 mg; rises in line with dose |
| Protein binding | ≈40–68% |
| Elimination half-life | 6–15 h (tablet label: 5.6–14.8 h) |
| Elimination | 55–77% of the dose appears in urine; over 95% of the absorbed drug is excreted unchanged |
| Effect of food | Bioavailability −10%, peak level −20%, time to peak 1.6 → 2.9 h |
The diuretic effect begins within 2 hours, peaks at about 4 hours and lasts about 6–12 hours (tablet label). The blood pressure effect lasts up to 24 hours. In kidney disease, levels are higher and the half-life is longer. Absorption is reduced in heart failure.
Approved medical use
The tablet label lists these indications (FDA label):
- add-on treatment of edema from congestive heart failure, liver cirrhosis, and corticosteroid or estrogen therapy;
- edema from kidney disorders such as nephrotic syndrome, acute glomerulonephritis and chronic renal failure;
- hypertension, alone or together with other blood pressure drugs.
The 12.5 mg capsule is labeled for hypertension only.
| Use | Labeled adult dose |
|---|---|
| Hypertension | 25 mg once daily to start; may be raised to 50 mg/day as one or two doses |
| Edema | 25–100 mg/day as one or divided doses; many patients respond to alternate-day or 3–5 days/week dosing |
| Children (diuresis or hypertension) | 1–2 mg/kg/day; maximum 37.5 mg/day up to age 2 and 100 mg/day from 2–12 years |
The label warns that doses above 50 mg/day are “often associated with marked reductions in serum potassium.” It also states that routine diuretic use in a healthy pregnancy is inappropriate.
What the research shows
Blood pressure lowering by dose
A 2014 Cochrane review pooled 60 double-blind randomized trials of thiazide monotherapy versus placebo (11,282 participants, mean 8 weeks). For HCTZ, 33 trials showed a clear dose-response (Musini et al., Cochrane 2014):
| HCTZ dose | Systolic drop vs placebo (95% CI) | Diastolic drop vs placebo (95% CI) | Evidence quality |
|---|---|---|---|
| 6.25 mg/day | 4 mmHg (2–6) | 2 mmHg (1–4) | Moderate |
| 12.5 mg/day | 6 mmHg (5–7) | 3 mmHg (3–4) | High |
| 25 mg/day | 8 mmHg (7–9) | 3 mmHg (3–4) | High |
| 50 mg/day | 11 mmHg (6–15) | 5 mmHg (3–7) | Low |
The same review found that thiazides lowered potassium and raised uric acid, total cholesterol and triglycerides. These effects rose with dose and were smallest for HCTZ.
Compared with other drugs
A 2011 meta-analysis looked at trials that measured blood pressure over 24 hours with an ambulatory monitor (Messerli et al., JACC 2011). It included 14 studies of HCTZ 12.5–25 mg (1,234 patients) and 5 studies of 50 mg (229 patients):
| Treatment | Mean 24-hour BP reduction (systolic/diastolic) |
|---|---|
| HCTZ 12.5–25 mg | 6.5/4.5 mmHg |
| HCTZ 50 mg | 12.0/5.4 mmHg |
| ACE inhibitors | 12.9/7.7 mmHg |
| Angiotensin receptor blockers | 13.3/7.8 mmHg |
| Beta-blockers | 11.2/8.5 mmHg |
| Calcium antagonists | 11.0/8.1 mmHg |
At the commonly prescribed 12.5–25 mg doses, HCTZ lowered 24-hour pressure less than every other drug class. A separate meta-analysis of 14 head-to-head trials (883 patients) found that indapamide and chlorthalidone lowered systolic pressure more than HCTZ, by 5.1 and 3.6 mmHg; the chlorthalidone difference was borderline (p = 0.052) (Roush et al., Hypertension 2015).
Cardiovascular outcomes: HCTZ vs chlorthalidone
The Diuretic Comparison Project was a pragmatic trial in 13,523 US veterans aged 65 or older who were already taking HCTZ 25 or 50 mg/day (Ishani et al., NEJM 2022). They either stayed on HCTZ or switched to chlorthalidone, and were followed for a median of 2.4 years.
| Outcome | Chlorthalidone | HCTZ |
|---|---|---|
| Primary composite (heart attack, stroke, heart failure admission, urgent revascularization, non-cancer death) | 10.4% | 10.0% |
| Hypokalemia | 6.0% | 4.4% |
The hazard ratio for the primary outcome was 1.04 (95% CI 0.94–1.16), so switching drugs made no measurable difference. Hypokalemia was more common on chlorthalidone (p under 0.001).
Use for “drying out” before competition
Bodybuilders use diuretics to raise urine output and shed water, aiming to look leaner on stage or to make a weight class. A 2021 review of peak-week practices found a “dearth of evidence” for the common peaking methods, and noted that self-prescribed diuretic use has been linked to dangerous outcomes (Escalante et al., BMC Sports Sci Med Rehabil 2021). We found no controlled study of HCTZ’s effect on muscle definition or stage appearance.
“Diuretics only remove water under the skin.” This is a common claim, but HCTZ does not target any one fluid compartment. It makes the kidneys excrete sodium and water, which first lowers blood volume, and it also drains potassium and magnesium (capsule label). No study has shown that it selectively removes subcutaneous water.
Side effects and risks
HCTZ has no boxed warning. Its main risks follow from the fluid and electrolyte losses it causes.
Fluid and electrolyte disturbances
The labels warn of these imbalances:
- hypokalemia (low potassium), especially with brisk diuresis, cirrhosis, long-term use, or use with corticosteroids or ACTH;
- hyponatremia (low sodium) and hypochloremic alkalosis;
- hypomagnesemia (low magnesium);
- mild rises in blood calcium.
Low potassium and low magnesium can provoke ventricular arrhythmias, and they make the heart more sensitive to digitalis toxicity. Warning signs listed on the label include dry mouth, thirst, weakness, muscle cramps, low blood pressure, low urine output and a fast heart rate. Clinically important hypokalemia is less common at 12.5 mg than at higher doses.
Low sodium is common in routine care. In a Boston cohort of 2,613 adults newly treated for hypertension, 30% of patients who stayed on a thiazide developed a sodium of 130 mmol/L or lower (Leung et al., Am J Med 2011). The adjusted rate was 140 vs 87 cases per 1,000 person-years without a thiazide (rate ratio 1.61, 95% CI 1.15–2.25).
Diuretic misuse with fluid restriction
Case reports show what can happen when diuretics are combined with fluid restriction outside medical care. A 22-year-old bodybuilder who took triamterene/HCTZ while restricting fluids developed the following (Pfisterer et al., Clin J Sport Med 2020):
- a potassium level of 1.8 mmol/L (normal range 3.4–4.5);
- weakness of all four limbs, sensory loss and urinary retention;
- a corrected QT interval of 625 ms on the ECG, a level linked to dangerous heart rhythms.
He recovered within 2 days with IV fluids and potassium. A report from Vienna describes hypokalemic paralysis in a professional bodybuilder and notes that the extent of diuretic misuse in professional bodybuilding is unknown (Mayr et al., Am J Emerg Med 2012).
Non-melanoma skin cancer
HCTZ makes skin more sensitive to sunlight. A Danish nationwide case-control study linked high cumulative use to skin cancer (Pedersen et al., JAAD 2018):
| Cumulative HCTZ dose | Basal cell carcinoma, OR (95% CI) | Squamous cell carcinoma, OR (95% CI) |
|---|---|---|
| ≥50,000 mg | 1.29 (1.23–1.35) | 3.98 (3.68–4.31) |
| ≥200,000 mg | 1.54 (1.38–1.71) | 7.38 (6.32–8.60) |
For scale, 50,000 mg equals about 5.5 years at 25 mg/day. The study had no data on sun exposure. Other diuretics and blood pressure drugs were not linked to these cancers.
An FDA Sentinel study compared 5.2 million matched users of HCTZ or ACE inhibitors in the US (Eworuke et al., JNCI Cancer Spectr 2021). It found a small increase in squamous cell carcinoma overall (HR 1.04, 95% CI 1.02–1.06). The risk was higher in white patients: HR 1.15 for squamous cell carcinoma and 1.09 for basal cell carcinoma.
FDA issued a Drug Safety Communication and label update on August 20, 2020 (Chen et al., Pharmacoepidemiol Drug Saf 2024). The current label estimates about 1 extra squamous cell carcinoma per 16,000 patients per year overall. For white patients with a cumulative dose of 50,000 mg or more, the estimate is about 1 extra case per 6,700 patients per year.
Metabolic effects
The labels list these metabolic effects:
- higher blood sugar, which can unmask latent diabetes;
- higher uric acid, which can trigger gout;
- higher cholesterol and triglycerides.
In the Cochrane review, these changes rose with dose (Musini et al., Cochrane 2014).
Eye emergencies and other reactions
As a sulfonamide, HCTZ can cause sudden short-sightedness (acute myopia) and acute angle-closure glaucoma. Symptoms are blurred vision or eye pain, usually within hours to weeks of starting the drug. Untreated angle-closure glaucoma can cause permanent vision loss.
Other listed reactions include the following:
- photosensitivity and rash;
- pancreatitis;
- blood disorders such as aplastic anemia and agranulocytosis;
- severe skin reactions such as Stevens-Johnson syndrome;
- impotence;
- flares of systemic lupus erythematosus.
Interactions
From the tablet label (FDA label):
| Drug | Effect with HCTZ |
|---|---|
| Lithium | Reduced lithium clearance and high risk of lithium toxicity; generally should not be combined |
| Corticosteroids, ACTH | More electrolyte loss, especially potassium |
| Digitalis (digoxin) | Low potassium increases the risk of arrhythmia |
| NSAIDs | Can blunt the diuretic and blood pressure effects |
| Cholestyramine, colestipol | Reduce HCTZ absorption by up to 85% and 43% |
| Insulin, oral diabetes drugs | Dose adjustment may be needed |
| Alcohol, barbiturates, narcotics | More orthostatic hypotension (dizziness on standing) |
| Other blood pressure drugs | Additive effect |
Who should not use it
The labels contraindicate HCTZ in people with:
- anuria (no urine production);
- allergy to HCTZ or other sulfonamide-derived drugs.
The label advises caution in severe kidney disease, where HCTZ can raise blood urea, and in liver disease, where small fluid and electrolyte shifts can trigger hepatic coma. HCTZ crosses the placenta and passes into breast milk.
Monitoring
The labels call for periodic checks of serum electrolytes, particularly in patients at risk of low potassium. Other label points:
- blood sugar in people with diabetes, whose medication may need adjusting;
- uric acid, if gout symptoms appear;
- stopping HCTZ before parathyroid function tests;
- sun protection and regular skin cancer screening.
Legal status and anti-doping
In the US, HCTZ is a prescription-only drug and is not a controlled substance. The WADA 2026 Prohibited List names hydrochlorothiazide under S5, diuretics and masking agents. Substances in this class are:
- prohibited at all times, in and out of competition;
- classed as Specified Substances.
Diuretics are banned because athletes use them to lose weight quickly and to mask the presence of other banned substances (Cadwallader et al., Br J Pharmacol 2010). Under the WADA list, finding a diuretic together with certain threshold substances (such as ephedrine or salbutamol) counts as a violation unless the athlete has an approved exemption for both.
Key takeaways
- A blood pressure and edema drug, not an anabolic. HCTZ blocks sodium-chloride reabsorption in the kidney. It has been FDA-approved since 1959 and is one of the most widely used diuretics.
- Modest effect at usual doses. 12.5–25 mg/day lowers blood pressure by about 6–8/3 mmHg versus placebo, less than other major drug classes at their usual doses.
- Electrolytes are the main short-term risk. Low potassium, sodium and magnesium can cause cramps, weakness and arrhythmias, and risk rises with dose, other diuretics, corticosteroids and fluid restriction.
- Long-term skin cancer signal. High cumulative doses are linked to more squamous cell carcinoma, and US labels have advised sun protection and skin screening since 2020.
- No evidence for “drying out.” No controlled study shows HCTZ improves stage appearance, and case reports describe severe hypokalemia in bodybuilders who used diuretics.
- Banned in sport at all times. WADA lists it under S5 as a diuretic and masking agent.
Sources
- Teva Pharmaceuticals. Hydrochlorothiazide tablets, USP, prescribing information (Rev. 9/2025). DailyMed.
- Actavis Pharma. Hydrochlorothiazide capsules, USP, 12.5 mg, prescribing information. DailyMed.
- Food and Drug Administration. HydroDIURIL (hydrochlorothiazide), NDA 011835, Merck; Microzide (hydrochlorothiazide) capsules, NDA 020504. Drugs@FDA, NDA 011835; Drugs@FDA, NDA 020504.
- National Center for Biotechnology Information. Hydrochlorothiazide, PubChem CID 3639. PubChem.
- Ellison DH, Loffing J. Thiazide effects and adverse effects: insights from molecular genetics. Hypertension. 2009;54(2):196–202. PubMed.
- Musini VM, Nazer M, Bassett K, Wright JM. Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension. Cochrane Database Syst Rev. 2014;(5):CD003824. PubMed.
- Messerli FH, Makani H, Benjo A, et al. Antihypertensive efficacy of hydrochlorothiazide as evaluated by ambulatory blood pressure monitoring: a meta-analysis of randomized trials. J Am Coll Cardiol. 2011;57(5):590–600. PubMed.
- Roush GC, Ernst ME, Kostis JB, et al. Head-to-head comparisons of hydrochlorothiazide with indapamide and chlorthalidone: antihypertensive and metabolic effects. Hypertension. 2015;65(5):1041–1046. PubMed.
- Ishani A, Cushman WC, Leatherman SM, et al. Chlorthalidone vs. hydrochlorothiazide for hypertension-cardiovascular events. N Engl J Med. 2022;387(26):2401–2410. PubMed.
- Escalante G, Stevenson SW, Barakat C, et al. Peak week recommendations for bodybuilders: an evidence based approach. BMC Sports Sci Med Rehabil. 2021;13(1):68. PubMed.
- Leung AA, Wright A, Pazo V, et al. Risk of thiazide-induced hyponatremia in patients with hypertension. Am J Med. 2011;124(11):1064–1072. PubMed.
- Pfisterer N, Stöllberger C, Finsterer J. Severe acquired hypokalemic paralysis in a bodybuilder after self-medication with triamterene/hydrochlorothiazide. Clin J Sport Med. 2020;30(5):e172–e174. PubMed.
- Mayr FB, Domanovits H, Laggner AN. Hypokalemic paralysis in a professional bodybuilder. Am J Emerg Med. 2012;30(7):1324.e5–1324.e8. PubMed.
- Pedersen SA, Gaist D, Schmidt SAJ, et al. Hydrochlorothiazide use and risk of nonmelanoma skin cancer: a nationwide case-control study from Denmark. J Am Acad Dermatol. 2018;78(4):673–681.e9. PubMed.
- Eworuke E, Haug N, Bradley M, et al. Risk of nonmelanoma skin cancer in association with use of hydrochlorothiazide-containing products in the United States. JNCI Cancer Spectr. 2021;5(2):pkab009. PubMed.
- Chen C, Eworuke E, Rai A, et al. Use of hydrochlorothiazide in the United States following label update about skin cancer risk. Pharmacoepidemiol Drug Saf. 2024;33(10):e70040. PubMed.
- Cadwallader AB, de la Torre X, Tieri A, Botrè F. The abuse of diuretics as performance-enhancing drugs and masking agents in sport doping: pharmacology, toxicology and analysis. Br J Pharmacol. 2010;161(1):1–16. PubMed.
- World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. WADA 2026 Prohibited List.