Triamterene

Overview

Triamterene is a potassium-sparing diuretic that may be considered as an alternative to spironolactone for the adjunctive treatment of congestive heart failure in dogs. However, it is rarely used in veterinary medicine, and there is limited clinical experience with its use in dogs and cats.

Mechanism of Action (MOA): Triamterene acts directly on the distal renal tubules, where it inhibits the reabsorption of sodium in exchange for hydrogen and potassium ions. It promotes renal excretion of sodium, calcium, magnesium, and bicarbonate while reducing potassium loss; urine pH may increase slightly, and serum potassium and chloride concentrations may rise. Unlike spironolactone, it does not competitively inhibit aldosterone – although some references still describe it as an aldosterone antagonist – and it is a relatively weak diuretic because only 2% to 3% of filtered sodium is reabsorbed at its site of action.

Indications

Triamterene is used as a potassium-sparing diuretic for the adjunctive management of congestive heart failure in dogs. Because of the limited clinical experience in dogs and cats, it is rarely recommended in veterinary medicine.

• Congestive heart failure (dogs): Adjunctive treatment; may be considered as an alternative to spironolactone, although spironolactone remains the recommended agent and no controlled studies compare the two.

Dosage (Reference)

Dog

Published dosage information for triamterene in dogs is limited.  

Cat

Clinical experience with triamterene in cats is minimal and dosing information is limited; the regimen below is published for dogs and cats.

Warnings & Precautions

Triamterene is contraindicated in patients with conditions that increase the risk of hyperkalemia or impaired drug elimination. Serum potassium, renal function, hydration status, body weight and signs of edema should be monitored at baseline and periodically during therapy, and blood pressure should be checked if indicated.

• Contraindications: Do not use in patients with anuria, severe or progressive renal disease, severe hepatic disease, hypersensitivity to triamterene, pre-existing hyperkalemia, or a history of triamterene-induced hyperkalemia.
• Concurrent potassium-sparing therapy: Do not administer with other potassium-sparing diuretics (e.g., spironolactone or amiloride) or potassium supplements.
• Renal impairment and diabetes: In humans, hyperkalemia is more likely in patients with renal impairment or diabetes and in elderly or severely ill patients.
• Dehydration: Do not use in dehydrated patients.
• Pregnancy and lactation: Safety has not been established in animals. Use only when the maternal benefits outweigh the potential risks to the offspring.
• Placental transfer and nursing: Triamterene crosses the placenta and is distributed into milk; although the risk to nursing animals is thought to be low, safety during nursing cannot be assured.

Drug Interactions

The following drug interactions have been reported or are considered theoretical in humans or animals; no interaction specific to dogs or cats has been documented. Concurrent use is not necessarily contraindicated unless otherwise stated, but additional monitoring may be required.

• ACE inhibitors (e.g., enalapril, benazepril): Increased risk of hyperkalemia.
• Antidiabetic agents (e.g., insulin, oral hypoglycemic agents): Triamterene may increase blood glucose concentrations.
• Antihypertensive agents: May potentiate hypotensive effects.
• Potassium-sparing diuretics (e.g., spironolactone, amiloride): Increased risk of hyperkalemia; concurrent use is contraindicated.
• Lithium: Triamterene may reduce lithium clearance.
• NSAIDs (especially indomethacin): May increase the risk of nephrotoxicity, and may also interfere with the diuretic effect.
• Potassium supplements or high-potassium foods: Increased risk of hyperkalemia.
• Trimethoprim: May cause potassium retention; use cautiously and monitor serum potassium.
• Metformin: May reduce the urinary excretion of metformin.

Side Effects & Overdose

Side Effects

Because triamterene has been infrequently used in veterinary medicine, its adverse effect profile in dogs and cats has not been well established.

• Hyperkalemia: The most important potential adverse effect; monitoring of serum electrolytes and renal function is recommended. In humans it rarely occurs when urine output and potassium intake are normal.
• Gastrointestinal effects: Nausea, vomiting, and diarrhea have been reported in humans.
• Neurologic effects: Headache and dizziness have been reported in humans.
• Renal and electrolyte abnormalities: Azotemia and hyponatremia have been reported in humans.
• Photosensitivity: Increased sensitivity to sunlight has been reported in humans.
• Hypersensitivity reactions: Rarely reported in humans.
• Rare adverse effects: Nephrolithiasis, liver enzyme abnormalities, agranulocytosis, nephrotoxicity, thrombocytopenia, and megaloblastosis have been reported in humans.

Overdose

Fluid and electrolyte imbalance is the most likely consequence of triamterene overdose.

• Clinical signs: Gastrointestinal effects and hypotension may occur; reported signs of oral diuretic toxicosis in dogs and cats also include vomiting, depression, transient polyuria and polydipsia, and electrolyte changes such as hyperkalemia or hypokalemia.
• Management: Consider gastrointestinal decontamination after very large or unknown ingestions.
• Supportive care: Treat with observation, fluid diuresis, and monitoring of serum electrolytes (especially potassium) and acid-base status.
• Poison consultation: Consultation with a veterinary poison center is recommended for suspected overdose.
• Toxic dose and margin of safety: The reported oral LD50 in mice is 380 mg/kg. Oral diuretics as a group have a wide margin of safety in dogs and cats.

Key Notes

Practical clinical points for the use of triamterene in dogs and cats:

• Administration with food: Giving triamterene with food may help reduce stomach upset.
• Urine discoloration: The urine may develop a bluish hue during treatment. This is a normal, reversible effect that resolves after the medication is discontinued.
• Pharmacokinetics (human data): No pharmacokinetic data have been reported in dogs or cats; in humans, oral bioavailability is 85%, triamterene is metabolized in the liver, and the elimination half-life is 2 hours.
• Onset and duration of diuresis: In humans, diuresis begins 2 to 4 hours after dosing; sources differ on how long it lasts, one reporting a peak at 6 hours with diuresis persisting 12 to 16 hours and another that it tapers off 7 to 9 hours after administration.
• Availability and dispensing: There is no veterinary-labeled product, so use in dogs and cats is extra-label, using human 50 mg and 100 mg capsules; in humans triamterene is often supplied as a fixed-dose combination with hydrochlorothiazide.
• Effect on blood pressure and glomerular filtration: Used alone, triamterene has little effect on blood pressure; it can reduce glomerular filtration rate slightly by affecting renal blood flow, and that effect is reversible when the drug is stopped.
• Laboratory interference: Triamterene may interfere with the fluorescent assay of quinidine.