Hydrochlorothiazide; Triamterene

What it is

This is a fixed-dose combination of two diuretics in one capsule or tablet: hydrochlorothiazide, a thiazide diuretic, and triamterene, a potassium-sparing diuretic. The label describes it as a diuretic and antihypertensive product that combines natriuretic and antikaliuretic effects, with each component complementing the other. Common US strengths pair 25 mg or 50 mg of hydrochlorothiazide with 37.5 mg or 75 mg of triamterene. It is prescription-only.

What the research says

Thiazide diuretics have high-quality randomised evidence that they lower blood pressure and reduce death, stroke and coronary heart disease when used first-line for hypertension. The triamterene in this combination is not there for blood pressure (the label says no predictable antihypertensive effect has been shown for it) but to stop hydrochlorothiazide from driving potassium down, which its registration trial showed it does. The trade-off is the opposite problem: the product carries a boxed warning for dangerously high potassium. Hydrochlorothiazide also carries a strong dose-dependent association with non-melanoma skin cancer, and raises the risk of low sodium, gout, high calcium, new diabetes and acute angle-closure glaucoma.

Evidence grade: Well established.

How it works

Drug class: Fixed-dose combination of a thiazide diuretic (hydrochlorothiazide) and a potassium-sparing distal tubule diuretic (triamterene)

Hydrochlorothiazide works on a short stretch of the kidney tubule, blocking the reabsorption of sodium and chloride so that more salt and water are passed out as urine; that lowers blood volume and, by a mechanism the label says is not fully known, blood pressure. A side effect of flushing extra sodium past the next stretch of tubule is that the kidney swaps it for potassium and acid, which is how thiazides drain potassium. Triamterene blocks that swap, so potassium stays in the body. Hydrochlorothiazide also holds calcium back and reduces uric acid clearance, which is where the high-calcium and gout problems come from. (Source 1)

Boxed warning

Abnormal elevation of serum potassium levels (≥5.5 mEq/liter) can occur with all potassium-sparing diuretic combinations, including triamterene and hydrochlorothiazide. Hyperkalemia is more likely to occur in patients with renal impairment and diabetes (even without evidence of renal impairment) and in the elderly or severely ill. Since uncorrected hyperkalemia may be fatal, serum potassium levels must be monitored at frequent intervals especially in patients first receiving triamterene and hydrochlorothiazide, when dosages are changed, or with any illness that may influence renal function.

(Source 2)

What it is used for

• Thiazides as a class have high-quality randomised evidence of reducing death and cardiovascular events. The combination's own trial tested potassium over four weeks, not events, and showed triamterene 37.5 mg reversed hypokalaemia in 81% versus 59% on hydrochlorothiazide plus placebo while blood pressure control was maintained. The label is explicit that the fixed combination is not for initial therapy. Evidence: established. (Source 3)
• The label approves the combination for oedema on the same reasoning as hypertension, but we found no outcome trial of the combination in oedema. The label also warns that routine diuretic use in otherwise healthy pregnancy is inappropriate and that diuretics do not prevent or treat toxaemia of pregnancy. Evidence: limited. (Source 4)
• Thiazides were used for decades to prevent stones on the basis that they reduce urinary calcium. The randomised NOSTONE trial found no reduction in stone recurrence at 12.5, 25 or 50 mg daily versus placebo over a median 2.9 years, with no dose-response, while hypokalaemia, gout, new-onset diabetes and rising creatinine were all more common on the drug. Triamterene itself has been found inside kidney stones. Evidence: not-supported. (Source 5)
• The label itself rules this out: the fixed combination is not indicated for initial therapy except in individuals in whom the development of hypokalaemia cannot be risked. A 28-week randomised comparison also found it reached goal blood pressure less often than diltiazem as a first choice, with twice the adverse event rate, although that study had only 61 completers. Evidence: not-supported. (Source 4)

Interactions

• Potassium supplements, potassium-containing salt substitutes and low-salt milk (label): Triamterene already blocks potassium loss, so adding potassium from any source can push levels into the dangerous range. The label lists salt substitutes (most of which contain substantial potassium), low-salt milk at up to 60 mEq/L of potassium, potassium-containing medicines and banked blood as agents that can cause hyperkalaemia with triamterene, and makes concomitant potassium-containing salt substitutes a contraindication. (Source 6)
• Other potassium-sparing diuretics (spironolactone, amiloride) and potassium supplementation (label): The label makes this an outright contraindication rather than a caution, because the hyperkalaemia risk compounds. (Source 7)
• NSAIDs such as ibuprofen and indomethacin (case reports): Case reports describe acute kidney failure when an NSAID was added to triamterene and hydrochlorothiazide. The label advises caution. NSAIDs also blunt the blood-pressure-lowering effect of diuretics generally. (Source 8)
• Lithium (label): Diuretics reduce lithium's clearance by the kidney, which raises lithium levels and the risk of lithium toxicity. The label says lithium generally should not be given with diuretics. (Source 9)
• ACE inhibitors and other renin-angiotensin blockers (label): These also raise potassium, so combining them with a potassium-sparing diuretic increases the hyperkalaemia risk. The label from the same product warns that potassium-sparing agents should be used with caution alongside ACE inhibitors. (Source 2)
• Vitamin D and calcium supplements (case reports): Thiazides reduce calcium excretion in the urine, so calcium can build up. A Japanese pharmacovigilance analysis found a reporting signal for high calcium when thiazides were taken with topical vitamin D3 analogues, with thiazide use among the factors associated with increased hypercalcaemia reporting. A population study separately found thiazide-associated hypercalcaemia at 12 to 20 cases per 100,000 a year. (Source 10)
• Laxatives, including herbal and over-the-counter stimulant laxatives (label): Chronic or heavy laxative use drains potassium through the gut and can defeat the potassium-retaining point of triamterene. The label says laxatives may interfere with the potassium-retaining effects of triamterene. (Source 6)
• Corticosteroids and corticotropin (ACTH) (label): These worsen the electrolyte disturbance, particularly potassium loss, although the label notes the triamterene component offsets some of that. (Source 11)
• Warfarin and other oral anticoagulants (label): The label states the effect of oral anticoagulants may be decreased when used with hydrochlorothiazide and that dose adjustment may be needed. (Source 11)
• Gout medicines (and anything affecting uric acid) (label): The combination raises blood uric acid, so doses of gout medication may need changing. A case-control study of 91,530 gout cases put the adjusted odds ratio for current thiazide use at 1.70 (95% CI 1.62-1.79), while potassium-sparing diuretics showed no increase. (Source 11)
• A high-fat meal (pharmacokinetic study): In a 12-subject study, taking the capsule with a high-fat meal raised triamterene bioavailability by about 67% and hydrochlorothiazide by about 17%, and delayed absorption by up to two hours. Taking it the same way each day is what keeps exposure steady. Limit: The label's own numbers do not support the size of the food effect it states. It reports mean triamterene bioavailability rising about 67% with a 90% confidence interval of 0.99 to 1.90 - an interval that includes 1.00, which is no change at all, so at the label's own confidence level the increase is not established. The hydrochlorothiazide figure has the same problem (about 17%, interval 0.90 to 1.34), and the interval is not centred on the stated increase either. The study had 12 people. What to take from it: food can change how much triamterene is absorbed, so taking the capsule the same way each day keeps exposure steady - not that a meal reliably raises the dose by two thirds. (Source 12)
• Salt-restricted diet, vomiting and hot weather (label): The drug's electrolyte effects get worse when salt and fluid intake drop or losses rise. The label flags salt-restricted diets and excessive vomiting as situations needing electrolyte measurement, and notes dilutional low sodium can occur in oedematous patients in hot weather. (Source 13)

Stopping it

• The label's stopping instruction is condition-driven rather than a taper: if potassium rises abnormally, stop the combination and substitute a thiazide diuretic alone until potassium normalises. (Source 14)
• If hyperkalaemia is already present the label says to stop immediately rather than reduce, and that potassium above 6.5 mEq/L needs active treatment. (Source 2)
• For hydrochlorothiazide-induced acute angle-closure glaucoma, the label says the primary treatment is to stop the drug as rapidly as possible, because untreated the condition can cost vision permanently. (Source 15)
• Stopping does not always undo the harm. In a population-based cohort of 221 people with thiazide-associated high calcium, 71% of those who stopped the thiazide still had raised calcium afterwards, and a quarter turned out to have primary hyperparathyroidism. (Source 16)
• The label also treats rising kidney blood tests as a stopping trigger: if azotaemia increases, discontinue the combination, and levels usually return to normal once it is stopped. (Source 17)

What goes wrong

The combination carries a boxed warning for dangerously high potassium, which the label says may be fatal if uncorrected. (Source 2)

• Official position, Certainty not rated.
• Size: not applicable (boxed warning; label version published 2026)
• Who: everyone taking the combination, with higher risk in kidney impairment, diabetes, the elderly and the severely ill.
• How long: throughout treatment; the label asks for frequent monitoring especially at the start and after dose changes.
• Result: the threshold given is serum potassium of 5.5 mEq/L or above; no incidence figure is given in the warning.
• Funding: not applicable (FDA-approved labelling)

Abnormal elevation of serum potassium levels (≥5.5 mEq/liter) can occur with all potassium-sparing diuretic combinations, including triamterene and hydrochlorothiazide.

A post-marketing surveillance study of more than 21,000 patients taking triamterene-hydrochlorothiazide measured how often high potassium actually happened: under 1% of non-diabetics and about 1% of diabetics, concentrated in the over-60s. (Source 18)

• Cohort study, Low certainty.
• Size: 20,809 non-diabetics and 922 diabetics who were normokalaemic at baseline.
• Who: patients prescribed a triamterene-hydrochlorothiazide combination (Maxzide) in a post-marketing surveillance trial.
• How long: not stated in the abstract.
• Result: hyperkalaemia in 0.59% of 20,809 non-diabetics and 1.08% of 922 diabetics; three- to fivefold more likely in those over 60; hypokalaemia occurred in about 5% and was not influenced by age or diabetes.
• Funding: post-marketing surveillance following the product's introduction (manufacturer-linked data source); funding not stated.

In patients normokalemic at baseline, hyperkalemia developed with a frequency of 0.59% in 20,809 nondiabetics and in 1.08% of 922 diabetics. Hyperkalemia was threefold to fivefold more likely in those more than 60 years of age, and all of the excess hyperkalemia in diabetics occurred in the elderly.

A nationwide Danish case-control study found a strong dose-dependent association between cumulative hydrochlorothiazide use and non-melanoma skin cancer, especially squamous cell carcinoma. (Source 19)

• Case-control study, Low certainty.
• Size: patients with non-melanoma skin cancer in 2004-2012 from the Danish Cancer Registry, matched 1:20 by age and sex to controls.
• Who: the Danish population; cumulative hydrochlorothiazide use assessed from the national prescription registry for 1995-2012.
• How long: exposure window 1995-2012, cancers 2004-2012.
• Result: high use (50,000 mg or more): odds ratio 1.29 (95% CI 1.23-1.35) for basal cell carcinoma and 3.98 (3.68-4.31) for squamous cell carcinoma; at 200,000 mg or more, 1.54 (1.38-1.71) and 7.38 (6.32-8.60); other diuretics and antihypertensives showed no association.
• Funding: not stated in the abstract; the authors note no data on sun exposure were available, which is the obvious confounder.

High use of hydrochlorothiazide (≥50,000 mg) was associated with ORs of 1.29 (95% confidence interval [CI], 1.23-1.35) for BCC and 3.98 (95% CI, 3.68-4.31) for SCC. We found clear dose-response relationships between hydrochlorothiazide use and both BCC and SCC; the highest cumulative dose category (≥200,000 mg of HCTZ) had ORs of 1.54 (95% CI, 1.38-1.71) and 7.38 (95% CI, 6.32-8.60) for BCC and SCC, respectively.

A propensity-matched cohort of 44,104 people found that developing low sodium soon after starting a thiazide was associated with nearly double the one-year death rate. (Source 20)

• Cohort study, Low certainty.
• Size: 22,052 in each matched cohort after propensity score matching (from 22,057 with hyponatraemia and 234,466 controls)
• Who: adults aged 40-90 with essential hypertension in a US federated electronic health record network who started a thiazide diuretic between 2010 and 2021.
• How long: hyponatraemia within 6 months of starting; mortality at one year.
• Result: one-year mortality hazard ratio 1.96 (95% CI 1.72-2.28); higher hazards also for sepsis, pneumonia, urinary tract infection, cellulitis, myocardial infarction, stroke, heart failure, ataxia and hip fracture.
• Funding: not stated in the abstract; the authors list the retrospective design as a limitation.

Patients in the hyponatremia cohort had a higher hazard of mortality than patients in control, HR 1.96 (95% CI, 1.72-2.28; P < 0.001).

A case-control study of 91,530 incident gout cases found thiazide diuretics raised gout risk, whereas potassium-sparing diuretics such as triamterene did not. (Source 21)

• Case-control study, Low certainty.
• Size: 91,530 incident gout cases and the same number of matched controls.
• Who: UK General Practice Research Database patients diagnosed with incident gout between 1990 and 2010, matched for age, sex, practice and calendar time.
• How long: 1990 to 2010.
• Result: current use versus past use within the same class: thiazide diuretics adjusted OR 1.70 (95% CI 1.62-1.79), thiazide-like 2.30 (1.95-2.70), loop 2.64 (2.47-2.83), potassium-sparing 1.06 (0.91-1.23); loop plus thiazide together 4.65 (3.51-6.16)
• Funding: not stated in the abstract.

adjusted ORs for current use of loop diuretics, thiazide diuretics, thiazide-like diuretics, and potassium-sparing diuretics were 2.64 (95% CI 2.47-2.83), 1.70 (95% CI 1.62-1.79), 2.30 (95% CI 1.95-2.70), and 1.06 (95% CI 0.91-1.23), respectively.

In the Cochrane first-line hypertension review, more people stopped low-dose thiazides because of side effects than stopped placebo, roughly doubling the withdrawal rate. (Source 22)

• Systematic review, Low certainty.
• Size: withdrawal data pooled from the trials in the review (24 trials, 58,040 patients across all classes)
• Who: adults with moderate to severe primary hypertension.
• How long: three to five years.
• Result: withdrawals due to adverse effects 5.0% with control vs 11.3% with low-dose thiazides, RR 2.38, 95% CI 2.06 to 2.75; with high-dose thiazides 2.2% vs 9.8%, RR 4.48, 3.83 to 5.24.
• Funding: not stated in the abstract (Cochrane review); the review rates this evidence low quality.

There was low-quality evidence that withdrawals due to adverse effects were increased with first-line low-dose thiazides (5.0% with control versus 11.3% with treatment; RR 2.38, 95% CI 2.06 to 2.75)

The kidney-stone trial measured the metabolic harms directly: hypokalaemia, gout, new-onset diabetes, skin allergy and rising creatinine were all more common on hydrochlorothiazide than placebo. (Source 5)

• Randomized trial, High certainty.
• Size: 416 patients randomised.
• Who: patients with recurrent calcium-containing kidney stones given hydrochlorothiazide 12.5, 25 or 50 mg daily or placebo.
• How long: median 2.9 years.
• Result: the trial reports these events as more common on hydrochlorothiazide without giving per-arm rates in the abstract.
• Funding: Swiss National Science Foundation and Inselspital per the funding statement.

Hypokalemia, gout, new-onset diabetes mellitus, skin allergy, and a plasma creatinine level exceeding 150% of the baseline level were more common among patients who received hydrochlorothiazide than among those who received placebo.

Hydrochlorothiazide can trigger sudden short-sightedness and acute angle-closure glaucoma within hours to weeks of starting, which can cause permanent vision loss if untreated. (Source 15)

• Official position, Certainty not rated.
• Size: not applicable (idiosyncratic reaction described in the label; no rate given)
• Who: people taking hydrochlorothiazide; risk factors may include a history of sulfonamide or penicillin allergy.
• How long: typically within hours to weeks of starting the drug.
• Result: no rate given; the label states untreated acute angle-closure glaucoma can lead to permanent vision loss.
• Funding: not applicable (FDA-approved labelling)

Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss.

A population-based study found thiazide-associated high calcium occurring at around 12 to 20 cases per 100,000 people a year, and in most cases the raised calcium did not resolve when the thiazide was stopped. (Source 16)

• Cohort study, Low certainty.
• Size: 221 residents identified with thiazide-associated hypercalcaemia.
• Who: residents of Olmsted County, Minnesota, identified through the Rochester Epidemiology Project from 1992 to 2010.
• How long: hypercalcaemia appeared an average of 5.2 years after starting treatment.
• Result: annual incidence peaked at 20 per 100,000 in 2006, against an overall rate of 12 per 100,000 in 1992-2010; of those who stopped the thiazide, 71% still had hypercalcaemia; primary hyperparathyroidism was diagnosed in 53 (24%)
• Funding: not stated in the abstract.

Overall, 221 Olmsted County residents were identified with thiazide-associated hypercalcemia an average of 5.2 years after initiation of treatment. Subjects were older (mean age, 67 years) and primarily women (86.4%). The incidence of thiazide-associated hypercalcemia increased after 1997 and peaked in 2006 with an annual incidence of 20 per 100,000, compared to an overall rate of 12 per 100,000 in 1992-2010.

Triamterene itself has been recovered from kidney stones, and the label advises caution in anyone with a stone history. (Source 23)

• Official position, Certainty not rated.
• Size: not applicable (label statement based on reported stone analyses)
• Who: people taking triamterene-containing products, particularly those with a history of renal stones.
• How long: not specified.
• Result: no rate given.
• Funding: not applicable (FDA-approved labelling)

Triamterene has been found in renal stones in association with the other usual calculus components. Triamterene and hydrochlorothiazide should be used with caution in patients with a history of renal stones.

Thiazides can raise blood sugar and unmask diabetes, so insulin or tablet doses may need changing. (Source 24)

• Official position, Certainty not rated.
• Size: not applicable (regulatory label position)
• Who: people with diabetes or at risk of it who take the combination.
• How long: not specified.
• Result: no rate given.
• Funding: not applicable (FDA-approved labelling)

Caution should be exercised when administering triamterene and hydrochlorothiazide to patients with diabetes, since thiazides may cause hyperglycemia, glycosuria, and alter insulin requirements in diabetes. Also, diabetes mellitus may become manifest during thiazide administration.

The label instructs prescribers to tell anyone taking hydrochlorothiazide to protect their skin from the sun and to have regular skin cancer screening. (Source 25)

• Official position, Certainty not rated.
• Size: not applicable - regulatory labelling.
• Who: anyone prescribed hydrochlorothiazide.
• How long: not stated.
• Result: no rate given; the label states the counselling requirement without quantifying risk, which is quantified separately in the Danish case-control data.
• Funding: not stated.

Instruct patients taking hydrochlorothiazide to protect skin from the sun and undergo regular skin cancer screening.

What the evidence supports

A Cochrane review found high-quality evidence that low-dose thiazide diuretics, used as first-line treatment for raised blood pressure, reduce death, stroke, coronary heart disease and total cardiovascular events; this is evidence for thiazides alone, not for the triamterene combination. (Source 3)

• Systematic review, High certainty.
• Size: 24 trials with 28 active treatment arms, 58,040 patients in total (all first-line drug classes combined)
• Who: adults with blood pressure over 140/90 mmHg at baseline, mostly moderate to severe primary hypertension, mean age 56.
• How long: three to five years of follow-up.
• Result: mortality 11.0% control vs 9.8% treated (RR 0.89, 95% CI 0.82 to 0.97); total cardiovascular events 12.9% vs 9.0% (RR 0.70, 0.64 to 0.76); stroke 6.2% vs 4.2% (RR 0.68, 0.60 to 0.77); coronary heart disease 3.9% vs 2.8% (RR 0.72, 0.61 to 0.84)
• Funding: not stated in the abstract (Cochrane review)

High-quality evidence showed that first-line low-dose thiazides reduced mortality (11.0% with control versus 9.8% with treatment; RR 0.89, 95% CI 0.82 to 0.97)

The combination's own registration trial was a four-week study with potassium, not cardiovascular events, as its endpoint: adding triamterene 37.5 mg reversed hydrochlorothiazide-induced low potassium in 81% of patients versus 59% on hydrochlorothiazide plus placebo. (Source 26)

• Randomized trial, Certainty not rated.
• Size: 636 patients randomised across five arms.
• Who: patients with mild to moderate hypertension already controlled on hydrochlorothiazide 25 mg daily who had developed serum potassium below 3.5 mEq/L.
• How long: 4 weeks.
• Result: reversal of hypokalaemia in 81% on triamterene 37.5 mg vs 59% on placebo/hydrochlorothiazide (P<0.05, an absolute difference of 22 percentage points from the two reported figures); mean potassium rose 3.2 to 3.7 mEq/L vs 3.2 to 3.5; a rise of at least 0.5 mEq/L in 51% vs 33%.
• Funding: not stated (trial reported in the manufacturer's FDA label)

On this regimen, 81% of the patients had a significant (P<0.05) reversal of hypokalemia vs. 59% of patients on the placebo/hydrochlorothiazide regimen.

In a 13,523-patient pragmatic randomised trial, hydrochlorothiazide performed as well as chlorthalidone for major cardiovascular events, and caused less low potassium. (Source 27)

• Randomized trial, High certainty.
• Size: 13,523 patients randomised.
• Who: US Veterans Affairs patients aged 65 or older with hypertension already taking hydrochlorothiazide 25 or 50 mg daily; mean age 72.
• How long: median follow-up 2.4 years.
• Result: primary outcome 702 (10.4%) with chlorthalidone vs 675 (10.0%) with hydrochlorothiazide, hazard ratio 1.04, 95% CI 0.94 to 1.16, P=0.45; hypokalaemia 6.0% vs 4.4%, P<0.001.
• Funding: Veterans Affairs Cooperative Studies Program (public funder) per the funding statement.

there was little difference in the occurrence of primary-outcome events between the chlorthalidone group (702 patients [10.4%]) and the hydrochlorothiazide group (675 patients [10.0%]) (hazard ratio, 1.04; 95% confidence interval, 0.94 to 1.16; P = 0.45)

What the evidence does not support

A dose-ranging randomised trial found hydrochlorothiazide did not reduce recurrence of calcium kidney stones at any dose, overturning a long-standing off-label practice. (Source 5)

• Randomized trial, High certainty.
• Size: 416 patients randomised to placebo or hydrochlorothiazide 12.5, 25 or 50 mg daily.
• Who: patients with recurrent calcium-containing kidney stones.
• How long: median follow-up 2.9 years.
• Result: primary endpoint in 60/102 (59%) placebo, 62/105 (59%) on 12.5 mg (rate ratio 1.33, 95% CI 0.92-1.93), 61/108 (56%) on 25 mg (1.24, 0.86-1.79), 49/101 (49%) on 50 mg (0.92, 0.63-1.36); no dose-response (P=0.66)
• Funding: Swiss National Science Foundation and Inselspital (public and hospital funders) per the funding statement.

Limit of this finding: One pairing in this trial looks self-contradictory and is not. The 12.5 mg group had exactly the same proportion of patients with an event as placebo (59% in both) yet a rate ratio of 1.33. The trial counted the rate of stone recurrences over time, not the proportion of people who had one, so a group can match placebo on the headcount and still differ on the number of events. None of the three rate ratios excluded 1, so the trial found no benefit at any of the three doses.

A primary end-point event occurred in 60 of 102 patients (59%) in the placebo group, in 62 of 105 patients (59%) in the 12.5-mg hydrochlorothiazide group (rate ratio vs. placebo, 1.33; 95% confidence interval [CI], 0.92 to 1.93), in 61 of 108 patients (56%) in the 25-mg group (rate ratio, 1.24; 95% CI, 0.86 to 1.79), and in 49 of 101 patients (49%) in the 50-mg group (rate ratio, 0.92; 95% CI, 0.63 to 1.36).

An early controlled study of exchangeable body potassium found triamterene at the dose tested did not meaningfully protect against diuretic-induced potassium loss, while spironolactone and potassium chloride did. (Source 28)

• Randomized trial, Very low certainty.
• Size: not stated beyond 'hypertensive subjects' tested serially; a small early study.
• Who: hypertensive subjects on oral diuretic therapy.
• How long: 4 to 12 weeks.
• Result: triamterene 50 mg twice daily was reported ineffective at the dose used; spironolactone 25 mg twice daily reduced potassium loss considerably; Slow-K 32 mEq daily fully reversed deficits.
• Funding: not stated.

Limit of this finding: This 1971 paper groups Slow-K with triamterene and spironolactone as 'three pharmacological agents in use as "potassium-sparing" drugs'. Slow-K is a potassium chloride supplement: it replaces potassium rather than stopping the kidney from losing it, so the fact that it worked best says nothing about potassium-sparing diuretics. The paper's own quotation marks around "potassium-sparing" are as close as it comes to acknowledging that. The study is also very small and old, and it tested triamterene at 50 mg twice daily, which is not the 37.5 mg in the modern fixed combination, so do not read it as showing that today's triamterene dose fails.

Triamterene seemed ineffective in the dosage used (50 mg twice daily). Spironolactone (25 mg twice daily) reduced K loss to a considerable extent, while Slow-K (32 mEq daily) completely reversed previous K(E) deficits. Plasma K levels were a poor indication of degree of K(E) restoration.

In a 28-week randomised multicentre comparison, hydrochlorothiazide/triamterene controlled blood pressure less often than diltiazem and caused about twice as many adverse events. (Source 29)

• Randomized trial, Very low certainty.
• Size: 61 patients completed 28 weeks of treatment.
• Who: patients aged 18-70 with mild-to-moderate hypertension (diastolic 95-114 mmHg)
• How long: 28 weeks.
• Result: goal blood pressure reached by 90% on diltiazem alone vs 73.7% on hydrochlorothiazide/triamterene alone; one or more possibly drug-related adverse events in 46% on hydrochlorothiazide/triamterene vs 24% on diltiazem; endpoint blood pressures did not differ significantly between groups.
• Funding: not stated.

Limit of this finding: Two things in this 1991 abstract are broken and are reproduced here as printed. The entry criterion appears as 'diastolic blood pressure (DBP) 95/114'. That is a range of 95 to 114 mmHg flattened by old indexing into something that looks like a blood pressure reading; it is not one, and 95/114 should not be read as a blood pressure. And the percentages cannot be reconciled with each other: 90%, 73.7%, 71.4% and 57.1% imply groups of roughly 20, 19, 7 and 7 of the 61 people who finished, while the later '81.5% vs. 69.7%' needs groups of about 27 and 33. The abstract never states the group sizes, so the exact figures cannot be checked. The direction the authors report - fewer people reaching target blood pressure, and about twice as many adverse events, on the combination than on diltiazem - is what this entry rests on; the precise percentages are not reliable, and 61 people is a very small trial.

Forty-six percent on hydrochlorothiazide/triamterene alone and 24% on diltiazem alone reported one or more adverse events, possibly related to study medication. Patients with diltiazem as the first choice had better BP control than those on hydrochlorothiazide/triamterene alone (81.5% vs. 69.7%). Furthermore, among non-goal achievers at week 12, there was a greater response in the group when hydrochlorothiazide/triamterene was added to diltiazem than when diltiazem was added to hydrochlorothiazide/triamterene. This study suggests that in mild-to-moderate hypertension, diltiazem is better than hydrochlorothiazide/triamterene as first line therapy.

Where the evidence is mixed

A prespecified secondary analysis of the same trial found that in people with a prior heart attack or stroke, hydrochlorothiazide did worse than chlorthalidone, while in everyone else it did slightly better. (Source 30)

• Randomized trial, Moderate certainty.
• Size: 13,523 randomised; subgroups of 1,455 with and 12,068 without prior myocardial infarction or stroke.
• Who: US Veterans Affairs patients aged 65 or older with hypertension, median age 72, 96.8% male.
• How long: mean study duration 2.4 years.
• Result: with prior MI or stroke: 105/733 (14.3%) on chlorthalidone vs 140/722 (19.4%) on hydrochlorothiazide, HR 0.73, 95% CI 0.57-0.94, P=.01; without prior MI or stroke: 597/6023 (9.9%) vs 535/6045 (8.9%), HR 1.12, 95% CI 1.00-1.26, P=.054; P=.01 for interaction.
• Funding: Veterans Affairs Cooperative Studies Program (secondary analysis of a publicly funded trial)

Participants with prior MI or stroke randomized to CTD had a lower risk of the primary outcome than those receiving HCTZ (105 of 733 [14.3%] vs 140 of 722 [19.4%]; hazard ratio [HR], 0.73; 95% CI, 0.57-0.94; P = .01) compared with participants without prior MI or stroke, among whom incidence of the primary outcome was slightly higher in the CTD arm compared with the HCTZ arm (597 of 6023 [9.9%] vs 535 of 6045 [8.9%]; HR, 1.12; 95% CI, 1.00-1.26; P = .054) (P = .01 for interaction).

Where the research disagrees

Whether hydrochlorothiazide or chlorthalidone is the better thiazide-type diuretic

• Diuretic Comparison Project main result (2022), pragmatic randomised trial in 13,523 patients: "patients who received chlorthalidone did not have a lower occurrence of major cardiovascular outcome events or non-cancer-related deaths than patients who received hydrochlorothiazide" (Source 31)
• Prespecified secondary analysis of the same trial (2024), prespecified subgroup analysis of the same randomised trial, 1,455 with prior MI or stroke: "Results of this secondary analysis of the DCP trial suggest that CTD may be associated with reduced major adverse CV events and noncancer deaths in patients with prior MI or stroke compared with HCTZ" (Source 32)

Whether hydrochlorothiazide prevents kidney stones

• NOSTONE randomised trial (2023), double-blind dose-ranging randomised trial, 416 patients, median 2.9 years: "Among patients with recurrent kidney stones, the incidence of recurrence did not appear to differ substantially among patients receiving hydrochlorothiazide once daily at a dose of 12.5 mg, 25 mg, or 50 mg or placebo once daily" (Source 33)
• Long-standing practice reflected in the trial's own rationale, the practice rested on urinary calcium as a surrogate rather than on placebo-controlled recurrence data: "Thiazide diuretic agents are widely used for prevention of the recurrence of kidney stones, but data regarding the efficacy of such agents as compared with placebo are limited" (Source 34)

How much

• Reference intake: There is no reference intake for a prescription diuretic; the dose is set by the prescriber. As a position, the FDA label (triamterene and hydrochlorothiazide capsules, label version published 2026) gives the usual dose as one or two capsules once daily with monitoring of serum potassium and clinical effect. (Source 35)
• Upper limit: No upper limit in the nutritional sense exists. As a position, the label's stated usual maximum is two capsules once daily. The label separately records that reversible acute kidney failure has been reported after an overdose of 50 tablets of a 50 mg triamterene / 25 mg hydrochlorothiazide product. (Source 36)
• Studied: The combination's registration trial gave hydrochlorothiazide 25 mg daily with triamterene 25, 37.5, 50 or 75 mg daily for four weeks in 636 patients. (Source 37)
• Studied: The Diuretic Comparison Project randomised 13,523 veterans already on hydrochlorothiazide 25 or 50 mg daily to continue it or switch to chlorthalidone 12.5 or 25 mg daily. (Source 27)
• Studied: NOSTONE tested hydrochlorothiazide at 12.5 mg, 25 mg and 50 mg once daily against placebo in 416 recurrent stone formers. (Source 5)
• Studied: An early controlled study tested triamterene 50 mg twice daily against spironolactone 25 mg twice daily and potassium chloride 32 mEq daily for exchangeable potassium. (Source 28)

A common belief, and what the research shows

The belief: Adding triamterene makes a thiazide safe for potassium, so potassium no longer needs watching.

What the research shows: It swaps one risk for another. The product's boxed warning says "Abnormal elevation of serum potassium levels (≥5.5 mEq/liter) can occur with all potassium-sparing diuretic combinations, including triamterene and hydrochlorothiazide." and that "Since uncorrected hyperkalemia may be fatal, serum potassium levels must be monitored at frequent intervals". Surveillance data put hyperkalaemia at "0.59% in 20,809 nondiabetics and in 1.08% of 922 diabetics", and the label also notes low potassium still occurs: "Hypokalemia is uncommon with triamterene and hydrochlorothiazide" is its wording, while the same surveillance found hypokalaemia in about 5%.

Questions and answers

What is it?

This is one capsule or tablet holding two different diuretics. Hydrochlorothiazide is a thiazide diuretic that makes the kidneys excrete more sodium, chloride and water; triamterene is a potassium-sparing diuretic that stops the kidney from dumping potassium at the same time. The label describes the pair as a diuretic/antihypertensive product combining natriuretic and antikaliuretic effects, each component complementing the other. It is sold as Dyazide and Maxzide among other names and is prescription-only. (Source 1)

What does it do in the body?

Hydrochlorothiazide blocks sodium and chloride reabsorption in the distal tubule of the kidney, so more sodium and water leave in the urine; it also reduces calcium and uric acid excretion. Triamterene works on the same part of the kidney to block the sodium-for-potassium swap, so potassium is retained. Diuresis starts within an hour, peaks at two to three hours and tapers off over the next seven to nine. The label states that no predictable blood-pressure-lowering effect has been shown for triamterene on its own. (Source 38)

Is it good or bad for you?

Good in the right person, and the combination exists to fix one specific problem. Thiazides as a class have high-quality evidence of reducing death, stroke and heart disease in people with raised blood pressure. The triamterene part is there to stop potassium falling, and its own trial showed it did that in 81% of patients versus 59% on hydrochlorothiazide alone. The flip side is that it can push potassium too high, which the boxed warning says may be fatal if uncorrected, and hydrochlorothiazide carries a dose-dependent association with skin cancer. (Source 3)

How do you get more of it?

It is not something to get more of. The label's position is one or two capsules once daily with monitoring of serum potassium and clinical effect, and it explicitly says the fixed combination is not for initial therapy of hypertension or oedema except where hypokalaemia cannot be risked. Taking a high-fat meal with it raises triamterene absorption by about 67%, which is a reason for consistency rather than a way to increase the dose. Only a prescriber sets the dose. (Source 35)

If it is harmful, what reduces it?

Where the harm is high potassium, the label's instruction is to stop this product immediately and substitute a thiazide alone until potassium returns to normal; above 6.5 mEq/L, more active treatment such as calcium chloride, bicarbonate, insulin with glucose, exchange resins or dialysis is used. Where the harm is acute angle-closure glaucoma, the label's primary treatment is to stop hydrochlorothiazide as rapidly as possible. (Source 14)

Why might someone be low in it or missing it?

Most people are not on it because they do not need it. Among people who do take a thiazide, this particular combination is reserved for those who became low in potassium on hydrochlorothiazide alone, or who cannot risk becoming low. The label states the combination is not indicated as initial therapy for oedema or hypertension except in those individuals. It is also contraindicated alongside other potassium-sparing drugs or potassium-containing salt substitutes, and in pre-existing high potassium. (Source 4)

Which whole foods contain it or feed it?

No food contains these drugs, but several foods matter while taking them. The label names salt substitutes (most of which contain substantial potassium), low-salt milk (up to 60 mEq/L of potassium) and potassium-containing medicines as things that can push potassium dangerously high alongside triamterene. A high-fat meal increases triamterene absorption. Potassium-rich foods are, conversely, what the label suggests if potassium falls too low. (Source 6)

What happens if you do not have it?

For someone with untreated raised blood pressure, going without a thiazide-type diuretic means losing a measurable reduction in events: in the Cochrane review, mortality was 11.0% on control versus 9.8% on low-dose thiazide and stroke 6.2% versus 4.2% over three to five years. Going without the triamterene half specifically means the potassium-lowering effect of hydrochlorothiazide is unopposed; in the registration trial 59% of those on hydrochlorothiazide plus placebo still corrected their low potassium, so it is not inevitable. (Source 3)

How can you test for it?

The monitoring tests are blood tests, and they are central rather than optional. Serum potassium is the main one: the label gives 3.5 to 5.0 mEq/L as the normal adult range, says levels persistently above 6 mEq/L need careful observation and treatment, and warns that serum potassium does not necessarily reflect true body potassium. Blood urea nitrogen and creatinine are also checked periodically, especially in older people and suspected kidney impairment. Thiazides should be stopped before parathyroid function testing. (Source 14)

References

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