Triamterene

Usage

Triamterene is primarily prescribed for the treatment of edema (fluid retention) associated with congestive heart failure, cirrhosis of the liver, and nephrotic syndrome. It is also used to treat edema caused by excess aldosterone (a hormone that regulates salt and water balance) and sometimes for hypertension (high blood pressure), although this is considered an off-label use. Its pharmacological classification is potassium-sparing diuretic. Triamterene works by blocking the sodium channels in the distal tubules of the kidneys, increasing sodium and water excretion while minimizing potassium loss.

Alternate Names

Triamterene is the generic name. A common brand name is Dyrenium. There are also combination products containing triamterene and hydrochlorothiazide, marketed under brand names such as Dyazide and Maxzide.

How It Works

Pharmacodynamics: Triamterene exerts its diuretic effect by directly inhibiting the epithelial sodium channel (ENaC) in the distal tubule of the nephron, preventing sodium reabsorption. This leads to increased excretion of sodium and water, thereby reducing edema. Unlike thiazide diuretics, triamterene spares potassium, preventing its excessive loss in the urine.

Pharmacokinetics: Triamterene is well-absorbed orally. Peak plasma concentrations are reached within 1 to 2 hours. It is metabolized in the liver, and metabolites are primarily excreted in the urine. Elimination half-life is approximately 2 to 4 hours.

Mode of Action: Triamterene acts directly on the ENaC, blocking sodium entry into the principal cells of the distal tubule and collecting duct. This inhibition occurs independently of aldosterone. Consequently, sodium reabsorption is reduced, and potassium secretion is minimized.

Elimination Pathways: Primarily renal excretion, with some hepatic metabolism.

Dosage

Standard Dosage

Adults:

For edema: The initial dose is typically 100 mg twice daily after meals. The dose may be adjusted as needed up to a maximum of 300 mg/day. When used in combination with other diuretics, lower initial doses of each agent are recommended, with subsequent adjustments as needed.

Children:

Safety and efficacy in children have not been fully established. However, a suggested dose for hypertension, based on limited clinical experience, is 1-2 mg/kg/day orally, divided every 12 hours. The maximum dose is 3-4 mg/kg/day, divided every 12 hours, up to 300 mg/day.

Special Cases:

• Elderly Patients: Lower starting doses are recommended due to potential age-related decrease in renal function and an increased risk of hyperkalemia. Close monitoring of potassium levels is essential.

• Patients with Renal Impairment: Triamterene is contraindicated in patients with severe renal impairment (creatinine clearance < 10 mL/min). Dose reductions may be necessary for moderate renal impairment.

• Patients with Hepatic Dysfunction: Dose reduction is recommended for patients with cirrhosis. Use with caution in other forms of hepatic impairment.

• Patients with Comorbid Conditions: Close monitoring of potassium levels is crucial in patients with conditions that may predispose to hyperkalemia (e.g., diabetes, heart failure). Dosage adjustments may be necessary.

Clinical Use Cases

Triamterene does not have specific dosage recommendations for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its main clinical use is managing edema and hypertension.

Dosage Adjustments

Dose modifications might be necessary based on patient-specific factors like renal/hepatic dysfunction, electrolyte imbalances, or other comorbid conditions. Close monitoring of serum potassium levels is essential, especially when initiating or adjusting the dose.

Side Effects

Common Side Effects:

Nausea, vomiting, diarrhea, dizziness, headache, dry mouth, weakness, fatigue, rash.

Rare but Serious Side Effects:

Hyperkalemia (high potassium levels), kidney stones, acute interstitial nephritis, acute renal failure, liver enzyme abnormalities, megaloblastic anemia, thrombocytopenia, severe allergic reactions (anaphylaxis), hypotension.

Long-Term Effects:

Chronic kidney disease, electrolyte imbalances.

Adverse Drug Reactions (ADR):

Hyperkalemia, acute renal failure, severe allergic reactions (anaphylaxis), significant hypotension.

Contraindications

Absolute contraindications include hyperkalemia, severe renal impairment (anuria, creatinine clearance < 10 mL/min), severe liver disease, and hypersensitivity to triamterene. Concurrent use with potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes is also contraindicated.

Drug Interactions

Triamterene can interact with several drugs, including:

• Other potassium-sparing diuretics (e.g., amiloride, spironolactone): Increased risk of hyperkalemia.
• ACE inhibitors (e.g., lisinopril, enalapril), angiotensin receptor blockers (ARBs) (e.g., valsartan, losartan), and renin inhibitors (e.g., aliskiren): Increased risk of hyperkalemia.
• NSAIDs (e.g., ibuprofen, naproxen): Reduced diuretic effect and increased risk of renal impairment.
• Lithium: Increased lithium levels.
• Digoxin: Increased risk of digoxin toxicity.

Pregnancy and Breastfeeding

Triamterene is classified as Pregnancy Category C. Its use during pregnancy should be avoided unless the potential benefits outweigh the risks to the fetus. It is unknown if triamterene passes into breast milk. It is generally recommended to avoid breastfeeding while taking this medication.

Drug Profile Summary

• Mechanism of Action: Blocks epithelial sodium channels in the distal tubules of the kidneys, increasing sodium and water excretion while sparing potassium.
• Side Effects: Nausea, vomiting, dizziness, headache, dry mouth, hyperkalemia, kidney stones.
• Contraindications: Hyperkalemia, severe renal or hepatic impairment, concurrent use of potassium-sparing diuretics.
• Drug Interactions: ACE inhibitors, ARBs, NSAIDs, lithium.
• Pregnancy & Breastfeeding: Category C; not recommended.
• Dosage: 100 mg twice daily, adjustable up to 300 mg/day.
• Monitoring Parameters: Serum potassium, renal function, blood pressure.

Popular Combinations

Triamterene is frequently combined with hydrochlorothiazide (a thiazide diuretic). This combination provides synergistic diuretic effects while mitigating potassium loss caused by hydrochlorothiazide.

Precautions

• Baseline assessment of renal and hepatic function, electrolyte levels, and blood pressure are necessary.
• Monitor serum potassium levels closely, especially in patients with renal impairment, diabetes, or heart failure.
• Caution is advised in elderly patients and those with gout or a history of kidney stones.
• Advise patients to avoid excessive sun exposure.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Triamterene?

A: The initial recommended dose is 100 mg twice daily after meals for adults, adjustable up to 300 mg/day. Pediatric dosages are 1-2 mg/kg/day divided every 12 hours, up to a maximum of 3-4 mg/kg/day or 300 mg/day. Lower dosages should be considered for elderly patients and those with renal or hepatic impairment.

Q2: What are the major contraindications for Triamterene use?

A: Hyperkalemia, severe renal failure, severe liver disease, and concomitant use of other potassium-sparing diuretics or potassium supplements.

Q3: How does Triamterene differ from other diuretics like hydrochlorothiazide?

A: Triamterene is a potassium-sparing diuretic, meaning it promotes sodium and water excretion without causing significant potassium loss. Hydrochlorothiazide, a thiazide diuretic, can cause potassium loss.

Q4: What are the most important drug interactions to be aware of with Triamterene?

A: Interactions with ACE inhibitors, ARBs, NSAIDs, lithium, and other potassium-sparing diuretics can lead to adverse effects, most notably hyperkalemia.

Q5: Can Triamterene be used during pregnancy or breastfeeding?

A: It’s generally not recommended due to potential fetal risks and the unknown effects on breastfed infants. Consult with a specialist to evaluate risks versus benefits.

Q6: What are the signs and symptoms of hyperkalemia, a potentially serious side effect of Triamterene?

A: Muscle weakness, fatigue, numbness or tingling, slow heart rate, difficulty breathing, and chest pain.

Q7: What monitoring parameters are essential for patients on Triamterene?

A: Serum potassium levels should be closely monitored. Regular assessment of renal function and blood pressure is also necessary.

Q8: What should patients be advised regarding lifestyle modifications while taking Triamterene?

A: Patients should avoid excessive sun exposure due to the risk of photosensitivity. Discuss dietary potassium intake and limit potassium-rich foods if necessary.

Q9: When is the optimal time to administer Triamterene?

A: Administering triamterene after meals can help reduce gastrointestinal upset. If nocturia is a concern, adjust the timing to minimize nighttime urination.

Q10: What should be done if a patient misses a dose of Triamterene?

A: Take the missed dose as soon as possible. However, if it is almost time for the next dose, skip the missed dose and continue with the regular dosing schedule. Do not double the dose.