What is Triamterene?

Triamterene: A Potassium-Sparing Diuretic

Triamterene is a potassium-sparing diuretic that inhibits the epithelial sodium channel (ENaC) in the cortical collecting duct of the kidney, reducing potassium secretion while promoting sodium excretion. 1

Mechanism and Classification

• Triamterene (2,4,7-triamino-6-phenyl-pteridine) belongs to the class of potassium-sparing diuretics, which are minimally effective as antihypertensive agents when used alone 2
• It works by blocking sodium reabsorption in the distal tubule and collecting duct, thereby reducing potassium and hydrogen ion excretion 1
• Unlike aldosterone antagonists (spironolactone, eplerenone), triamterene directly blocks the epithelial sodium channel rather than antagonizing aldosterone 1

Clinical Uses

• Most commonly used in combination with thiazide diuretics (particularly hydrochlorothiazide) to prevent hypokalemia while maintaining antihypertensive efficacy 2, 3
• Used as add-on therapy in patients being treated with drugs from other antihypertensive classes 2
• Can be considered in patients with hypokalemia on thiazide monotherapy 2
• Used in heart failure management, though not as a first-line agent 2

Dosing

• Initial dose: 50-100 mg daily or twice daily 2
• Usual maintenance dose: 1-2 mg/kg/day up to 300 mg/day 2
• Typically administered twice daily (BID) 2
• In combination products with hydrochlorothiazide (e.g., Maxzide: 75 mg triamterene/50 mg hydrochlorothiazide) 4
• Best taken after meals to minimize stomach upset 1

Efficacy

• Triamterene enhances the blood pressure-lowering effect of hydrochlorothiazide by approximately 1-4 mmHg systolic, depending on concurrent medications 3
• In combination products, the bioavailability of both components is important for optimal efficacy 4

Major Side Effects and Precautions

• Hyperkalemia: The most significant risk, especially when combined with ACE inhibitors, ARBs, or in patients with renal dysfunction 2, 1
• Potassium levels should be monitored regularly, with particular caution if serum potassium exceeds 6 mEq/L 1
• Nitrogen retention (usually reversible upon discontinuation) 1
• May decrease alkali reserve, potentially causing metabolic acidosis 1
• Can elevate uric acid levels, caution in patients predisposed to gout 1
• Associated with kidney stones (triamterene crystals may be components of renal calculi) 1, 5
• Rare cases of acute interstitial nephritis and renal failure have been reported 5, 6

Important Drug Interactions

• ACE inhibitors/ARBs: Increased risk of hyperkalemia; use with caution and monitor potassium levels 2, 1
• NSAIDs: Potential for acute renal failure when combined; avoid concurrent use if possible 1, 5
• Lithium: May reduce renal clearance of lithium, increasing risk of toxicity 1
• Potassium supplements: Avoid concurrent use due to hyperkalemia risk 1
• Other potassium-sparing diuretics: Do not combine with other potassium-sparing agents 2

Monitoring Requirements

• Serum electrolytes (particularly potassium) should be monitored shortly after initiating therapy and periodically thereafter 2, 1
• Renal function should be monitored, especially in elderly patients or those with pre-existing renal impairment 1
• If hyperkalemia develops, triamterene should be withdrawn 1

Contraindications

• Significant renal dysfunction (GFR <45 mL/min) 2
• Pre-existing hyperkalemia 1
• Concurrent use with other potassium-sparing diuretics 2
• Caution in patients with liver disease 1

Special Populations

• In pediatric patients: Initial dose 1-2 mg/kg/day with maximum dose of 3-4 mg/kg/day up to 300 mg/day 2
• Elderly patients may require closer monitoring of electrolytes and renal function 1
• Avoid in pregnancy 2

Triamterene's primary clinical value is in combination with thiazide diuretics, where it helps prevent hypokalemia while contributing modestly to blood pressure reduction. However, the risk of hyperkalemia necessitates careful patient selection and monitoring.