Triamterene: Dosing, Contraindications, Monitoring, and Alternatives
Adult Dosing
When used as monotherapy, start triamterene 100 mg twice daily after meals, with a maximum total daily dose of 300 mg. 1 However, triamterene is rarely used alone in modern practice—it is almost exclusively prescribed in fixed-dose combination with hydrochlorothiazide. 2, 3
The standard fixed-dose combination is triamterene 37.5–50 mg with hydrochlorothiazide 25–50 mg once daily in the morning. 2, 3 The most commonly prescribed formulation in the United States is triamterene 37.5 mg/hydrochlorothiazide 25 mg (Dyazide) or triamterene 75 mg/hydrochlorothiazide 50 mg (Maxzide). 4, 5 Maxzide offers superior bioavailability compared to Dyazide—one Maxzide tablet delivers approximately twice the hydrochlorothiazide and triamterene to the bloodstream as two Dyazide capsules. 4
When adding triamterene to existing thiazide therapy, discontinue all potassium supplementation immediately. 1 The combination of triamterene with potassium supplements creates a high risk of dangerous hyperkalemia. 1
When combined with other antihypertensives, reduce the initial dose of both agents and titrate to the patient's needs. 1 Triamterene enhances the blood pressure–lowering effect of hydrochlorothiazide by 1–4 mmHg beyond the thiazide alone. 6
Absolute Contraindications
Do not prescribe triamterene when baseline serum potassium exceeds 5.0 mEq/L. 3 Triamterene conserves potassium rather than promoting excretion, and hyperkalemia—though rare—has been associated with cardiac irregularities. 1
Avoid triamterene entirely when eGFR is below 45 mL/min. 2, 3 In moderate-to-severe chronic kidney disease, the risk of hyperkalemia rises dramatically because renal potassium excretion is impaired. 2
Never combine triamterene with potassium supplements or potassium-containing salt substitutes. 3, 1 Most salt substitutes contain substantial amounts of potassium (up to 60 mEq per liter), and concurrent use can result in life-threatening hyperkalemia. 1
Exercise extreme caution when combining triamterene with ACE inhibitors or ARBs. 2, 3, 1 Potassium-sparing agents should be used cautiously with ACE inhibitors due to additive hyperkalemia risk, especially in patients with renal insufficiency. 1 If this combination is necessary, implement intensive potassium monitoring (every 5–7 days initially). 7
Avoid NSAIDs during triamterene therapy. 1, 8 A dangerous interaction between triamterene and indomethacin (and other NSAIDs) has been reported, culminating in acute renal failure. 1, 8 NSAIDs reduce renal clearance of triamterene and promote potassium retention. 8
Triamterene is contraindicated in pregnancy. 3 Discontinue immediately if pregnancy is detected. 3
Critical Monitoring Parameters
Check serum potassium, sodium, creatinine, and magnesium within 5–7 days after initiating triamterene. 2, 7, 3 Continue monitoring every 5–7 days until potassium values stabilize. 2, 7
Once stable, recheck electrolytes and renal function at 1–2 weeks, then at 3 months, and subsequently every 6 months. 2, 7, 3 More frequent monitoring is required in patients with renal impairment, heart failure, diabetes, or those on medications affecting potassium homeostasis. 2, 7
If serum potassium rises above 5.5 mEq/L, halve the triamterene dose and recheck within 1–2 weeks. 7, 3 If potassium exceeds 6.0 mEq/L, discontinue triamterene immediately. 7
The normal adult serum potassium range is 3.5–5.0 mEq/L, with 4.5 mEq/L often used as a reference point. 1 Potassium levels persistently above 6 mEq/L require careful observation and treatment. 1 However, serum potassium levels do not necessarily indicate true body potassium concentration—a rise in plasma pH may cause a decrease in plasma potassium concentration and an increase in intracellular potassium. 1
Monitor for signs of electrolyte imbalance, including cardiac irregularities, muscle weakness, and metabolic acidosis. 1 Triamterene may cause a decreasing alkali reserve with the possibility of metabolic acidosis. 1
In patients with cirrhosis and splenomegaly, perform periodic blood studies because triamterene is a weak folic acid antagonist and may contribute to megaloblastosis when folic acid stores are depleted. 1 Observe these patients for exacerbations of underlying liver disease. 1
Triamterene has elevated uric acid levels, especially in persons predisposed to gouty arthritis. 1 Monitor uric acid periodically in susceptible patients. 1
Triamterene has been reported in renal stones in association with other calculus components. 1 Use with caution in patients with histories of renal stones and monitor for abnormalities in urinary sediment. 1, 8
When lithium and triamterene are used concomitantly, monitor serum lithium levels closely because diuretic-induced sodium loss may reduce renal clearance of lithium and increase serum lithium levels with risk of lithium toxicity. 1
Potassium-Sparing Alternatives When Used with Thiazides
Spironolactone 25–100 mg daily is the preferred potassium-sparing diuretic for most patients requiring combination therapy with a thiazide. 2, 7, 3 Spironolactone offers superior evidence for cardiovascular outcomes, including proven mortality benefit in heart failure with reduced ejection fraction. 7, 3 In resistant hypertension, the European Society of Cardiology recommends a hierarchy: spironolactone first, then eplerenone, then amiloride, then triamterene. 3
Amiloride 5–10 mg daily is an effective alternative to triamterene with a similar mechanism of action (ENaC inhibition). 2, 7, 3, 9 Amiloride has been recognized as a safe and effective potassium-sparing diuretic with potentially fewer adverse renal effects than triamterene. 9 Studies suggest amiloride-hydrochlorothiazide enhances renal prostaglandin E2 production, whereas triamterene-hydrochlorothiazide actually decreases it—an important renal consequence that should be considered when choosing between these combinations. 9
Eplerenone 50–100 mg daily (often requiring twice-daily dosing) is preferred over spironolactone when gynecomastia or sexual dysfunction is a concern. 2 Eplerenone has a lower risk of anti-androgenic side effects compared to spironolactone. 2
For patients with heart failure and reduced ejection fraction, aldosterone receptor antagonists (spironolactone or eplerenone) are strongly preferred over triamterene due to proven mortality benefit. 3 The American Heart Association recommends aldosterone antagonists in this population. 3
Special Considerations and Common Pitfalls
Triamterene is not a first-line antihypertensive agent. 3 The European Society of Cardiology recommends ACE inhibitors, ARBs, calcium channel blockers, and thiazide/thiazide-like diuretics as first-line therapy. 3 Triamterene serves as adjunctive therapy when hypokalemia develops on thiazide monotherapy, when the patient cannot tolerate potassium supplementation, or in resistant hypertension when spironolactone is contraindicated or not tolerated. 3
Avoid using full doses of triamterene when salt intake is restricted, as this can result in low-salt syndrome. 1 Electrolyte imbalance is often encountered in congestive heart failure, renal disease, or cirrhosis and may be aggravated by any effective diuretic including triamterene. 1
Triamterene can cause mild nitrogen retention, which is reversible upon withdrawal and is seldom observed with intermittent (every-other-day) therapy. 1 Monitor blood urea nitrogen and creatinine regularly. 1
In patients who have received intensive therapy or prolonged treatment, withdraw triamterene gradually because a rebound kaliuresis (potassium loss) could occur upon abrupt discontinuation. 1
Triamterene may raise blood glucose levels; for adult-onset diabetes, dosage adjustments of hypoglycemic agents may be necessary during and after therapy. 1 Concurrent use with chlorpropamide may increase the risk of severe hyponatremia. 1
Triamterene interferes with the fluorescent measurement of quinidine due to similar fluorescence spectra. 1 This is an important drug-laboratory test interaction to consider. 1
The effects of antihypertensive medications, other diuretics, preanesthetic and anesthetic agents, and skeletal muscle relaxants (non-depolarizing) may be potentiated when given together with triamterene. 1
Advise patients to take triamterene after meals to help avoid stomach upset. 1 If a single daily dose is prescribed, taking it in the morning minimizes the effect of increased urination on nighttime sleep. 1 If a dose is missed, the patient should not take more than the prescribed dose at the next dosing interval. 1
The postmarketing surveillance study of 70,898 patients showed that adverse reactions occurred more frequently in those taking concomitant medications, and the withdrawal rate due to adverse events was significantly lower with smaller doses (half tablet) compared to larger doses (whole tablet). 5 Older patients tended to achieve goal blood pressure more frequently than younger patients. 5