Generic Name: triamterene

Brand Names: Dyrenium

Uses

Edema

Management of edema associated with CHF, cirrhosis of the liver, or nephrotic syndrome.

Management of steroid-induced edema, idiopathic edema, and edema caused by secondary hyperaldosteronism.

May be used alone but most valuable when used in combination with other diuretics to promote diuresis and/or decrease potassium excretion caused by kaliuretic diuretics.

May be particularly useful in patients excreting excessive amounts of potassium (especially those who cannot tolerate potassium supplements) and for those in whom potassium loss could be detrimental, such as patients receiving digitalis glycosides or those with myasthenia gravis.

Promotes increased diuresis in patients resistant or only partially responsive to thiazides or other diuretics because of secondary hyperaldosteronism.

May be effective in some patients unresponsive to spironolactone; unlike spironolactone, diuretic effect of triamterene is independent of aldosterone concentrations.

Used in fixed combination with hydrochlorothiazide for treatment of edema in patients who require a thiazide diuretic and in whom the development of hypokalemia cannot be risked.

Used in fixed combination with hydrochlorothiazide for treatment of edema in patients who develop hypokalemia during hydrochlorothiazide monotherapy.

Do not use for routine therapy in pregnant women with mild edema who are otherwise healthy.

CHF

In the management of edema associated with CHF, generally used in conjunction with other more effective, rapidly acting diuretics (e.g., thiazides, chlorthalidone, loop diuretics). Some patients resistant to triamterene monotherapy may respond to such combined therapy.

Most experts state that all patients with symptomatic CHF who have evidence or a prior history of fluid retention generally should receive diuretic therapy in conjunction with moderate sodium restriction (≤3 g of sodium daily), an ACE inhibitor, and usually a β-adrenergic blocking agent, with or without a cardiac glycoside.

Most experts state that the diuretics of choice for most patients with CHF are loop diuretics (e.g., bumetanide, ethacrynic acid, furosemide, torsemide).

Do not use diuretics as monotherapy in CHF even if symptoms (e.g., peripheral edema, pulmonary congestion) are well controlled; diuretics alone do not prevent progression of heart failure.

Once fluid retention in CHF has resolved, diuretic therapy should be maintained to prevent its recurrence. Ideally, diuretic therapy should be adjusted according to changes in body weight (as an indicator of fluid retention) rather than maintained at a fixed dosage.

Diuretics should be continued in CHF and comorbid conditions (e.g., hypertension) where ongoing therapy with the drugs is indicated.

Hypertension

Triamterene alone has little if any hypotensive effect; however, it may be used with another diuretic (e.g., hydrochlorothiazide) or a hypotensive agent in the management of mild to moderate hypertension. However, JNC 7 recommends that thiazides be used as initial therapy for the treatment of uncomplicated hypertension in most patients, either alone or combined with other classes of antihypertensive drugs that have demonstrated benefit (e.g., ACE inhibitors, angiotensin II receptor antagonists, β-blockers, calcium-channel blockers).

Used principally in patients with diuretic-induced hypokalemia or to prevent hypokalemia in patients receiving diuretics who are at risk of this adverse effect.

Used in fixed combination with hydrochlorothiazide for treatment of hypertension in patients who require a thiazide diuretic and in whom the development of hypokalemia cannot be risked.

Used in fixed combination with hydrochlorothiazide for treatment of hypertension in patients who develop hypokalemia during hydrochlorothiazide monotherapy.

Used in fixed combination with hydrochlorothiazide for treatment of hypertension as an adjunct to other antihypertensive drugs (e.g., β-blockers).

Dosage and Administration

General

• Monitor serum potassium concentrations following changes in dosage or with concurrent illness or drug therapy. (See Hyperkalemia under Cautions and also see Interactions.)
• Avoid use of potassium-sparing diuretics, including triamterene, in patients with renal insufficiency, in those with hyperkalemia who have serum potassium concentrations >5 mEq/L while not receiving drug therapy, and in those who develop hyperkalemia during therapy.
• Do not use concurrent potassium supplementation or potassium-containing salt substitutes. Discontinue potassium supplementation when triamterene is added to other diuretic therapy or when patients are switched to triamterene from other diuretics.
• Do not use fixed-combination triamterene/hydrochlorothiazide tablets or capsules for initial therapy of edema or hypertension, except in patients in whom the clinical consequences of hypokalemia represent an important risk (e.g., patients receiving cardiac glycosides or patients with cardiac arrhythmias).
• Do not use as initial monotherapy in severe CHF since bowel edema or intestinal hypoperfusion may delay absorption and subsequent therapeutic effect.
• Careful etiologic diagnosis should precede the use of any diuretic.

Administration

Oral Administration

Capsules: Administer orally twice daily after meals.

Fixed-combination triamterene/hydrochlorothiazide tablets or capsules: Administer orally once daily.

Twice-daily administration of the fixed combination of triamterene and hydrochlorothiazide may increase risk of electrolyte imbalance and renal dysfunction.

Dosage

Individualize dosage according to patient’s requirements and response.

If added to an existing antihypertensive regimen, initially reduce dosage of each antihypertensive agent and then individualize dosage according to patient’s requirements and response.

Abrupt discontinuance may result in rebound kaliuresis; taper dosage gradually.

Different commercially available fixed-combination triamterene/hydrochlorothiazide preparations may not be therapeutic equivalents. The oral bioavailabilities of the individual drugs and the amounts and ratios of these drugs in various commercially available fixed-combination preparations may differ.

Pediatric Patients

Usual Dosage

Oral

Initially, 2–4 mg/kg daily or 115 mg/m² daily, given in a single dose or 2 divided doses after meals.†

If necessary, increase dosage to 6 mg/kg daily. Do not exceed 300 mg daily.†

Hypertension

Oral

Initially, 1–2 mg/kg daily given in 2 divided doses after meals. Increase dosage as necessary up to 3–4 mg/kg daily given in 2 divided doses. Do not exceed 300 mg daily.†

Adults

Edema

Monotherapy

Oral

Initially, 100 mg twice daily after meals. After edema is controlled, usual maintenance dosage is 100 mg daily or every other day. Do not exceed 300 mg daily.

Combination Therapy

Oral

When Dyazide^®, Maxzide^® or Maxzide^®-25 mg, or therapeutically equivalent formulations of these combinations are used, the usual dosage in terms of triamterene is 37.5–75 mg once daily.

Patients receiving 25 mg of hydrochlorothiazide who become hypokalemic may be switched to Maxzide^®-25 mg (37.5 mg triamterene/25 mg hydrochlorothiazide).

Patients receiving 50 mg of hydrochlorothiazide who become hypokalemic may be switched to Maxzide^® (75 mg triamterene/50 mg hydrochlorothiazide).

Hypertension

Monotherapy

Oral

Usual dosage recommended by JNC 7 as monotherapy: 50–100 mg daily. Some patients may benefit from dividing the daily dosage into 2 doses.

Combination Therapy

Oral

Usually combined with a kaliuretic diuretic.

In conjunction with a kaliuretic diuretic, an initial triamterene dosage of 25 mg once daily has been recommended. Titrate dosage upward as needed and tolerated to a suggested maximum triamterene dosage of 100 mg daily.

Initially, administer each drug separately to adjust dosage.

May use in fixed combination with hydrochlorothiazide if optimum maintenance dosage corresponds to drug ratio in combination preparation.

Administer each drug separately whenever dosage adjustment is necessary.

When Dyazide^®, Maxzide^® or Maxzide^®-25 mg, or therapeutically equivalent formulations of these combinations are used, the usual dosage in terms of triamterene is 37.5–75 mg once daily.

Patients receiving 25 mg of hydrochlorothiazide who become hypokalemic may be switched to Maxzide^®-25 mg (37.5 mg triamterene/25 mg hydrochlorothiazide).

Patients receiving 50 mg of hydrochlorothiazide who become hypokalemic may be switched to Maxzide^® (75 mg triamterene/50 mg hydrochlorothiazide).

If BP is not adequately controlled by use of 75 mg once daily (of triamterene in the fixed combination of triamterene/hydrochlorothiazide), another antihypertensive agent may be added.

Prescribing Limits

Pediatric Patients

Oral

Maximum 300 mg daily.

Adults

Oral

Maximum 300 mg daily.

The manufacturer states there is no clinical experience to date with dosages of fixed-combination Maxzide^® or Maxzide^®-25 mg exceeding 75 mg of triamterene and 50 mg of hydrochlorothiazide daily.

Special Populations

Hepatic Impairment

No specific dosage recommendations for hepatic impairment; caution if using fixed combination with hydrochlorothiazide because of risk of precipitating hepatic coma. (See Contraindications under Cautions.)

Renal Impairment

No specific dosage recommendations for renal impairment; do not use in patients with renal impairment and elevated serum potassium; discontinue in patients who develop hyperkalemia while on the drug. (See Contraindications under Cautions and also see Hyperkalemia under Cautions.)

Cautions

Contraindications

• Anuria, severe or progressive renal disease or dysfunction (except possibly nephrosis), acute or chronic renal insufficiency, substantial renal impairment.
• Preexisting hyperkalemia (≥5.5 mEq/L).
• History of triamterene-induced hyperkalemia.
• Concurrent potassium supplementation, including potassium salts or potassium-containing salt substitutes. (See Interactions.)
• Concurrent therapy with potassium-sparing agents (e.g., spironolactone, amiloride hydrochloride, or fixed-combination formulations containing triamterene). (See Interactions.)
• Severe hepatic disease.
• Known hypersensitivity to triamterene or any ingredient in the formulation.

Warnings/Precautions

Warnings

Hyperkalemia

Hyperkalemia (i.e., serum potassium concentrations ≥5.5 mEq/L) may occur with all potassium-sparing agents, including triamterene. (See Boxed Warning.) Serum potassium concentrations persistently >6 mEq/L require careful observation and treatment.

If hyperkalemia occurs, discontinue triamterene; if using a triamterene/hydrochlorothiazide fixed combination, switch to a thiazide alone.

Evaluate BUN and serum potassium concentrations regularly, especially in patients with suspected or confirmed renal insufficiency. Monitor serum potassium concentrations closely in geriatric and diabetic patients.

Warning signs of hyperkalemia include paresthesias, muscular weakness, fatigue, flaccid paralysis of the extremities, bradycardia, and shock.

Hyperkalemia has been associated with cardiac irregularities. Obtain ECG if hyperkalemia present or suspected. If ECG does not show widening of QRS or arrhythmia in the presence of hyperkalemia, usually sufficient to discontinue triamterene and any potassium supplementation and switch to a thiazide alone. May administer sodium polystyrene sulfonate to enhance excretion of excess potassium.

Presence of widened QRS complex or arrhythmia in association with hyperkalemia requires prompt additional therapy. For tachyarrhythmia, infuse 44 mEq of sodium bicarbonate or 10 mL of 10% calcium gluconate or calcium chloride over several minutes. For asystole, bradycardia, or AV block, transvenous pacing also is recommended. The effect of calcium and sodium bicarbonate is transient and repeated administration may be required. When indicated by the clinical situation, excess potassium may be removed by dialysis or oral or rectal administration of sodium polystyrene sulfonate. Infusion of glucose and insulin has also been used to treat hyperkalemia.

Potassium Supplementation

Do not use potassium supplementation (e.g., potassium salts, high potassium diet, salt substitutes) in patients receiving triamterene alone. Discontinue potassium supplements when triamterene is added to existing diuretic therapy or when patients are switched to triamterene from other diuretics.

Do not use potassium supplementation with fixed-combination triamterene/hydrochlorothiazide except in severe cases of hypokalemia or if dietary intake of potassium is markedly impaired. Such concomitant therapy may be associated with rapid increases in serum potassium concentrations. Monitor serum potassium concentrations frequently if potassium supplementation is used, especially in patients receiving digitalis or with a history of cardiac arrhythmias. (See Interactions.)

If serious hypokalemia (serum potassium <3.0 mEq/L demonstrated by repeat serum potassium determinations) occurs in a patient receiving fixed-combination triamterene/hydrochlorothiazide, discontinue fixed combination and initiate potassium supplementation.

If hyperkalemia occurs in a patient receiving fixed-combination triamterene/hydrochlorothiazide and supplemental potassium therapy, discontinue supplementation and substitute a thiazide diuretic alone for fixed-combination triamterene/hydrochlorothiazide until potassium concentrations return to normal.

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., anaphylaxis, rash, photosensitivity) reported; monitor for blood dyscrasias, liver damage or other idiosyncratic reactions.

General Precautions

Use of Fixed Combinations

When triamterene is used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.

Use during Pregnancy

Routine use of diuretics, including triamterene, in otherwise healthy women exposes mother and fetus to unnecessary risk and is not generally indicated. Diuretics do not prevent development of toxemia of pregnancy and do not appear to be beneficial in the treatment of toxemia.

Edema may develop during pregnancy due to comorbid pathology or the physiologic and mechanical consequences of pregnancy. Diuretic therapy may be appropiate in the management of edema due to a pathologic cause manifesting during pregnancy. However, dependent edema in pregnancy resulting from restriction of venous return by the gravid uterus may be treated by elevating the lower extremities and using support hose; diuretic therapy to lower intravascular volume is not appropriate in such cases.

Hypervolemia and associated edema, including generalized edema, occurs in the majority of pregnant women and is not harmful to fetus or mother. Increased recumbency will generally provide relief; however, edema may cause extreme discomfort which is not relieved by rest. Rarely, in such cases, a short course of diuretic therapy may be appropriate to provide relief.

Electrolyte Imbalance

Electrolyte imbalance may worsen or develop during diuretic therapy, including triamterene. Risk of electrolyte imbalance is increased in patients with CHF, renal disease, or cirrhosis. Full-dose diuretic therapy in patients on restricted salt intake may cause a low-salt syndrome.

Monitor serum electrolytes regularly.

Renal Effects

Elevations in BUN and/or S_cr may occur, possibly secondary to a reversible reduction of GFR or a depletion of the intravascular fluid volume. May occur more frequently in patients receiving twice-daily dosing with fixed combination of triamterene and hydrochlorothiazide.

Monitor BUN and S_cr, especially in geriatric patients and those with suspected or confirmed hepatic or renal disease. If azotemia increases, discontinue fixed-combination triamterene/hydrochlorothiazide preparation.

Nitrogen Retention

May cause mild nitrogen retention, which is reversible upon drug discontinuance; seldom observed with intermittent (every-other-day) therapy.

Metabolic Acidosis

May cause a decreasing alkali reserve with the possibility of metabolic acidosis.

Avoid use of potassium-sparing diuretics in severely ill patients in whom respiratory or metabolic acidosis may occur; acidosis may result in rapid increases in serum potassium concentrations. Perform frequent assessments of acid-base balance and serum electrolytes.

Megaloblastosis

Triamterene is a weak folic acid antagonist and may contribute to the appearance of megaloblastosis, especially in patients with depleted folic acid stores (e.g., pregnant women, alcoholics). Patients with cirrhosis and splenomegaly may have marked hematologic abnormalities; these patients should have periodic blood studies and be observed for exacerbations of underlying liver disease.

Hyperuricemia

May cause elevations in serum uric acid concentrations, especially in patients predisposed to gouty arthritis.

Renal Calculi

Has been reported in renal calcluli associated with usual calculus components. Manufacturers state that triamterene may be used with caution in patients with histories of renal calcluli; however, some clinicians recommend that the drug not be used in these patients because of the risk of triamterene nephrolithiasis.

If a patient passes a urinary calculus during triamterene therapy, the drug should be discontinued and the calculus analyzed for the presence of triamterene and/or its metabolites.

Rebound Kaliuresis

Because triamterene conserves potassium, it has been suggested that patients who have received intensive therapy or have been given the drug for prolonged periods may develop a rebound kaliuresis if such therapy is discontinued abruptly. Discontinue drug gradually in such patients.

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk in animals and is likely to distribute into human milk. Discontinue nursing or the drug.

Pediatric Use

Safety and efficacy in pediatric patients remain to be fully established for triamterene or triamterene in fixed combination with hydrochlorothiazide; however, some experts have suggested a triamterene dosage for hypertension based on limited clinical experience.

Geriatric Use

Reduced clearance and increased risk of hyperkalemia; monitor serum potassium concentrations frequently. (See Hyperkalemia under Cautions.)

Hepatic Impairment

Use with caution in patients with impaired hepatic function. Do not use in patients with severe hepatic disease. Diuretic therapy in such patients should be initiated while the patient is hospitalized, because rapid alterations in fluid and electrolyte balance may precipitate hepatic coma. Monitor serum potassium concentrations closely in patients with hepatic cirrhosis and administer potassium supplementation if required. (See Contraindications under Cautions.)

Potassium loss has been reported during triamterene therapy in some patients with hepatic cirrhosis and may result in signs and symptoms of hepatic coma or precoma.

Patients with cirrhosis and splenomegaly may have marked hematologic abnormalities; these patients should have periodic blood studies and be observed for exacerbations of underlying liver disease. (See Megablastosis under Cautions.)

Renal Impairment

Use with caution; increased risk of hyperkalemia. Monitor serum potassium concentrations closely. Do not use in patients with renal impairment and elevated serum potassium; discontinue in patients who develop hyperkalemia while on the drug. (See Contraindications under Cautions and also see Hyperkalemia under Cautions.)

Common Adverse Effects

Hyperkalemia, azotemia, increased BUN and creatinine, renal calculi, jaundice and/or liver enzyme abnormalities, nausea and vomiting, diarrhea, thrombocytopenia, megaloblastic anemia, weakness, fatigue, dizziness, headache, dry mouth.

Interactions

Specific Drugs, Foods, and Laboratory Tests

Pharmacokinetics

Absorption

Bioavailability

Triamterene and fixed combinations with hydrochlorothiazide are rapidly absorbed following oral administration; peak plasma concentrations achieved within 1–4 hours. Interindividual variation in degree of absorption reported.

Oral bioavailabilities of triamterene and hydrochlorothiazide from Dyazide^® capsules are comparable to those of aqueous suspensions of the individual drugs, averaging 85 and 82%, respectively, for the fixed-dose formulation and 100 and 100%, respectively, for the suspensions. Dyazide^® capsules also are bioequivalent to single-entity 25-mg hydrochlorothiazide tablets and 37.5-mg triamterene capsules.

Oral bioavailabilities of triamterene and hydrochlorothiazide from Maxzide^® tablets are comparable to those of aqueous suspensions of the individual drugs. The hydrochlorothiazide component of Maxzide^® tablets is bioequivalent to single-entity hydrochlorothiazide tablet formulations.

Onset

Onset of diuresis following oral administration of triamterene usually occurs within 2–4 hours; maximum therapeutic effect may not occur until after several days of therapy.

Onset of diuresis after oral administration of Dyazide^® usually occurs within 1 hour and peaks at 2–3 hours.

Duration

After oral administration of triamterene, diuresis diminishes in approximately 7–9 hours, although the total duration of action may be ≥24 hours.

After oral administration of Dyazide^®, diuresis diminishes in approximately 7–9 hours.

Food

Administration of Dyazide^® with a high-fat meal in healthy adults increased the average bioavailabilities of triamterene, 6-p-hydroxytriamterene, and hydrochlorothiazide by about 67, 50, and 17%, respectively; increased the peak concentrations of triamterene and its p-hydroxy metabolite; and delayed absorption of the active drugs by up to 2 hours.

Administration with food does not affect absorption of triamterene or hydrochlorothiazide from Maxzide^® tablets.

Distribution

Extent

Distributed into bile.

Crosses the placenta and distributes into milk in animals.

Plasma Protein Binding

Approximately 67%.

Elimination

Metabolism

Primarily metabolized to 6-p-hydroxytriamterene and its sulfate conjugate.

Elimination Route

Excreted in urine, primarily as 6-p-hydroxytriamterene.

Half-life

100–150 minutes.

Special Populations

Renal clearances of triamterene, hydroxytriamterene sulfate, and hydrochlorothiazide may be reduced in geriatric patients receiving combined triamterene and hydrochlorothiazide therapy, principally as a result of age-related reductions in renal function.

Stability

Storage

Oral

Capsules

Tight, light resistant containers at 15–30°C.

Fixed-dose Combination Formulations

Dyazide^® capsules: Tight, light resistant containers at 20–25°C.

Maxzide^® tablets: Tight, light resistant containers at 15–30°C.

Actions

• A pteridine derivative, potassium-sparing diuretic that is structurally related to folic acid.
• Does not competitively inhibit aldosterone; activity is independent of aldosterone concentrations.
• Does not inhibit carbonic anhydrase.
• Acts directly on the distal renal tubule of the nephron to depress aldosterone-stimulated reabsorption of sodium and excretion of potassium and hydrogen at that site.
• Increases excretion of sodium, calcium, magnesium, and bicarbonate.
• Potassium excretion usually reduced; serum concentrations of potassium and chloride are usually increased.
• Serum bicarbonate concentrations consistently decreased; urinary pH increased slightly.
• Reductions in glomerular filtration observed during daily, but not intermittent, administration; suggests a reversible effect on renal blood flow.
• Although effective alone, often used in combination with other diuretics that act at different sites in the nephron.
• Little if any hypotensive effect when used alone.

Advice to Patients

• Importance of taking drug after meals to help avoid stomach upset.
• Importance of informing patients that if a single daily dose is prescribed, it may be preferable to take it in the morning to minimize the effect of increased frequency of urination on nighttime sleep.
• Importance of informing patients that if a dose is missed, the patient should take only the prescribed dose at the next dosing interval.
• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions July 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.