Dyrenium (Triamterene): 50 mg, 100 mg Capsules

By | March 15, 2016

TRIAMTERENE (Dyrenium)

POTASSIUM-SPARING DIURETIC

Highlights of Prescribing Information

  • Potassium-sparing diuretic that may be considered as an alternative to spironolactone for treating CHF in dogs; limited clinical experience with this drug in dogs/cats
  • Contraindications: Anuria, severe or progressive renal disease, severe hepatic disease, hypersensitivity to triamterene, preexisting hyperkalemia, concurrent therapy with another potassium-sparing agent (spironolactone, amiloride) or potassium supplementation
  • Hyperkalemia possible; must monitor serum K+

What Is Drug Used For?

Triamterene is a potassium-sparing diuretic that potentially could be used as an alternative to spironolactone for the adjunctive treatment of congestive heart failure in dogs, however, there is little experience associated with its use in dogs or cats.

Pharmacology / Actions

By exerting a direct effect on the distal renal tubule, triamterene inhibits the reabsorption of sodium in exchange for hydrogen and potassium ions. Unlike spironolactone, it does not competitively inhibit aldosterone. Triamterene increases excretion of sodium, calcium, magnesium and bicarbonate; urinary pH may be slightly increased. Serum concentrations of potassium and chloride maybe increased. When used alone, triamterene has little effect on blood pressure. Triamterene can reduce GFR slightly, probably by affecting renal blood flow. This effect is reversible when the medication is discontinued.

Pharmacokinetics

Pharmacokinetic data for dogs or cats was not located. In humans, triamterene is rapidly absorbed after oral administration and oral bioavailability is about 85%. Onset of diuresis occurs in 2-4 hours and diminishes after about 8 hours. Triamterene is metabolized in the liver to 6-p-hydroxytriamterine and its sulfate conjugate. These metabolites are eliminated in the bile/feces and urine; elimination half-life is about 2 hours.

Before you take Drug

Contraindications / Precautions / Warnings

Triamterene is contraindicated for human patients (and presumably dogs and cats) with anuria, severe or progressive renal disease, severe hepatic disease, hypersensitivity to triamterene, preexisting hyperkalemia, history of triamterene-induced hyperkalemia, concurrent therapy with another potassium-sparing agent (spironolactone, amiloride) or potassium supplementation.

Adverse Effects

Because triamterene has been infrequently used in veterinary medicine, an accurate adverse effect profile for small animals is not known, however, hyperkalemia is a definite possibility and monitoring of electrolytes and renal function are necessary. In humans, hyperkalemia rarely occurs in patients with normal urine output and potassium intake.

Less common adverse effects reported in humans include headache/dizziness, GI effects, hyponatremia, and an increased sensitivity to sunlight. Rarely, hypersensitivity reactions have occurred in human patients taking triamterene. Other rare adverse effects include triamterene-nephrolithiasis, agranulocytosis, thrombocytopenia, or megaloblastosis.

Reproductive / Nursing Safety

Studies to determine triamterene’s effects on fertility have not been performed.

Studies in pregnant rats given triamterene at 6-20X (human dose) did not show adverse effects to the fetuses. Triamterene crosses the placental barrier. For humans, triamterene is either in FDA category B or category C, depending on the reference. Category C for use during pregnancy states: Animal studies have shown an adverse effect on the fetus, hut there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. If considering use of this product in a pregnant animal, weigh the potential benefits of treatment versus the risks.

Triamterene is distributed into milk. Although unlikely to pose much risk to nursing animals, safety during nursing cannot be assured.

Overdosage / Acute Toxicity

The oral LD50 for triamterene in mice is 380 mg/kg. Fluid and electrolyte imbalance is the most likely risk associated with an overdose. GI effects or hypotension are also possible. Consider gut emptying protocols for very large or quantity unknown ingestions. Acute overdoses should generally be managed by observation, with fluid, electrolyte (especially serum potassium) and acid-base monitoring. Supportive treatment should be initiated if required.

Drug Interactions

The following drug interactions have either been reported or are theoretical in humans or animals receiving triamterene and may be of significance in veterinary patients:

■ ACE INHIBITORS (e.g., enalapril, benazepril): Increased risks for hyperkalemia

■ ANTIDIABETIC AGENTS (insulin, oral hypoglycemic agents): Triamterene may increase blood glucose

■ Antihypertensive agents: Possible potentiation of hypotensive effects

■ DIURETICS, POTASSIUM-SPARING (spironolactone, amiloride): Increase risk of hyperkalemia; use of these drugs with triamterene in humans is contraindicated

■ LITHIUM: Triamterene may reduce lithium clearance

■ NSAIDs: Triamterene with NSAIDs (esp. indomethacin) may increase the risks of nephrotoxicity

■ potassium supplements or high potassium foods: Increased risk for hyperkalemia

Laboratory Considerations

■ Quinidine: Triamterene may interfere with fluorescent assay of quinidine

How to use Drug

Drug dosage for dogs:

a) For adjunctive treatment of recurrent heart failure associated with chronic mitral valve insufficiency: 1-2 mg/kg PO q12h. Documentation of use is limited; spironolactone is drug of choice. ()

b) As a diuretic for adjunctive treatment of CHF: 2 – (4) mg/kg/ day PO ()

Monitoring

■ Serum electrolytes (especially potassium), BUN, creatinine

■ Hydration status

■ Blood pressure, if indicated

■ Signs of edema; patient weight, if indicated

Client Information

■ Give this medication with food to help prevent stomach upset

■ Urine may develop a bluish hue, this is normal

■ Because this medication has not been used very much in dogs or cats; report any unusual effects to the veterinarian

Chemistry / Synonyms

Triamterene is structurally related to folic acid and occurs as a yellow, odorless, crystalline powder. It is practically insoluble in water and very slightly soluble in alcohol. At 50°C, it is slightly soluble in water. In acidified solutions, triamterene gives off a blue fluorescence.

Triamterene may also be known as NSC-77625, KF-8542, FI-6143, triamteren, trimaterenum or triamtereen, Dyrenium, . International trade names include Dytac, Dyazide, Maxzide-25 and Triteren. There are many international trade names for combination products with hydrochlorothiazide.

Storage / Stability

Triamterene capsules should be stored between 15-30°C (59-86°F) in tight, light-resistant containers.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance.

Human-Labeled Products:

Triamterene Capsules: 50 mg, 100 mg; Dyrenium (Wellspring); (Rx)

In humans, triamterene is often prescribed as a fixed-dose combination with hydrochlorothiazide. Products include: Triamterene 37.5 mg/Hydrochlorothiazide 25 mg Tablets and Capsules; generic, Dyazide, Maxzide-25; (Rx) Triamterene 50 mg/Hydrochlorothiazide 25 mg Capsules; generic; (Rx)

Triamterene 75 mg/Hydrochlorothiazide 50 mg Tablets; generic, Maxzide; (Rx)

 

Selections from the book: “Plumb’s Veterinary Drug Handbook. Sixth Edition”. 2008