Introduction
Triamterene is a potassium-sparing diuretic medication used primarily in the management of edema and hypertension. First approved by the FDA in 1964, it belongs to the pteridine class of compounds and is often used in combination with thiazide diuretics to enhance efficacy while mitigating potassium loss. Unlike loop or thiazide diuretics, triamterene acts specifically on the distal tubules of the kidney to reduce potassium excretion.
Mechanism of Action
Triamterene exerts its diuretic effect by directly inhibiting sodium reabsorption in the distal convoluted tubules and collecting ducts of the nephron. It specifically blocks epithelial sodium channels (ENaC) in the apical membrane of renal tubular cells. This action reduces the lumen-negative transepithelial potential difference that normally drives potassium secretion through renal outer medullary potassium (ROMK) channels. By decreasing sodium reabsorption and reducing the electrochemical gradient for potassium secretion, triamterene promotes natriuresis while conserving potassium.
Indications
- Hypertension: Used as adjunctive therapy, typically in combination with thiazide diuretics
- Edema: Management of edema associated with congestive heart failure, cirrhosis, and nephrotic syndrome
- Prevention of hypokalemia: Particularly in patients requiring diuretic therapy who are at risk of potassium depletion
Dosage and Administration
Standard adult dosing:- Hypertension: 25-100 mg daily in divided doses
- Edema: 100 mg twice daily after meals (maximum 300 mg daily)
- Geriatric patients: Initiate with lower doses due to potential decreased renal function
- Renal impairment: Contraindicated in patients with severe renal impairment (CrCl <30 mL/min)
- Hepatic impairment: Use with caution; monitor for electrolyte imbalances
- Pediatric use: Safety and effectiveness not established
- Administer with or after meals to reduce gastrointestinal upset
- Divided doses typically recommended for doses exceeding 100 mg daily
Pharmacokinetics
Absorption: Approximately 30-70% bioavailability; food may enhance absorption Distribution: Volume of distribution: 2.5-3.5 L/kg; 67% protein-bound Metabolism: Extensively metabolized in liver to active metabolite hydroxytriamterene sulfate Elimination: Primarily hepatic metabolism with renal excretion; elimination half-life: 1.5-2.5 hours Onset of action: 2-4 hours after oral administration Duration of effect: 7-9 hoursContraindications
- Hypersensitivity to triamterene or any component of the formulation
- Anuria, acute or chronic renal insufficiency (CrCl <30 mL/min)
- Hyperkalemia (serum potassium >5.5 mEq/L)
- Concomitant use with potassium supplements or other potassium-sparing agents
- Severe hepatic impairment
- Addison's disease
Warnings and Precautions
Hyperkalemia: Serious and potentially fatal hyperkalemia can occur, particularly in patients with renal impairment, diabetes, elderly patients, or those with severe illness Renal function: Regular monitoring of renal function required; discontinue if renal impairment develops Electrolyte imbalances: Monitor for hyponatremia, hypochloremia, and metabolic acidosis Hepatic function: Use with caution in patients with hepatic impairment; may precipitate hepatic encephalopathy in cirrhotic patients Acute kidney injury: Risk increased in volume-depleted patients or those receiving NSAIDs Pregnancy: Category C - Use only if potential benefit justifies potential risk to fetus Lactation: Excreted in breast milk; use with cautionDrug Interactions
Major interactions:- ACE inhibitors/ARBs: Increased risk of hyperkalemia
- Potassium supplements: Contraindicated due to hyperkalemia risk
- Other potassium-sparing diuretics: Contraindicated combination
- NSAIDs: Increased risk of renal impairment and hyperkalemia
- Lithium: Reduced lithium clearance, increased toxicity risk
- Cyclosporine: Increased risk of hyperkalemia and nephrotoxicity
- Digoxin: Triamterene may decrease digoxin clearance
- Antihypertensive agents: Additive hypotensive effects
- Corticosteroids: Enhanced potassium-wasting effects
Adverse Effects
Common (≥1%):- Dizziness, headache
- Hyperkalemia (8-10%)
- Elevated BUN (5-10%)
- Nausea, vomiting, diarrhea
- Muscle cramps, weakness
- Severe hyperkalemia (potentially fatal)
- Acute kidney injury
- Megaloblastic anemia (rare, related to folate antagonism)
- Hypersensitivity reactions including photosensitivity
- Nephrolithiasis (triamterene-containing stones)
- Hepatic encephalopathy in predisposed patients
Monitoring Parameters
Baseline assessment:- Complete metabolic panel (sodium, potassium, chloride, bicarbonate, BUN, creatinine)
- Renal function (eGFR/CrCl)
- Liver function tests
- Complete blood count
- Serum potassium: Within first week, then periodically (more frequently in high-risk patients)
- Renal function: Every 3-6 months or with dosage changes
- Electrolytes: Regular monitoring, especially during illness or dehydration
- Blood pressure: Regular assessment for efficacy
- Signs/symptoms of hyperkalemia: Muscle weakness, cardiac arrhythmias
Patient Education
- Take medication exactly as prescribed; do not exceed recommended dose
- Take with food if gastrointestinal upset occurs
- Avoid potassium supplements and salt substitutes containing potassium
- Report signs of hyperkalemia: muscle weakness, irregular heartbeat, unusual fatigue
- Maintain regular follow-up appointments for blood tests
- Avoid excessive alcohol consumption
- Use sun protection due to potential photosensitivity
- Inform all healthcare providers about triamterene use, especially before surgery
- Do not stop medication abruptly without medical supervision
- Report any unusual bruising, bleeding, or signs of infection
References
1. FDA Prescribing Information: Dyrenium (triamterene) capsules 2. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 13th ed. 2017 3. Lexicomp Online. Triamterene monograph. Wolters Kluwer Clinical Drug Information 4. Micromedex Solutions. Triamterene drug information. IBM Watson Health 5. Ellison DH, Lofting J. Thiazide effects and adverse effects: insights from molecular genetics. Hypertension. 2009;54(2):196-202 6. Sica DA, Carter B, Cushman W, et al. Thiazide and loop diuretics. J Clin Hypertens. 2011;13(9):639-643 7. Palmer BF, Clegg DJ. Diagnosis and treatment of hyperkalemia. Cleve Clin J Med. 2017;84(12):934-942 8. KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int Suppl. 2012;2:337-414
This monograph is for educational purposes only and does not replace professional medical advice. Always consult with a healthcare provider for personalized medical guidance.