Action And Clinical Pharmacology: Triamterene exerts its diuretic effect on the distal renal tubule to inhibit the reabsorption of sodium in exchange for potassium and hydrogen ions. This natriuretic activity is limited by the amount of sodium reaching its site of action.
Although triamterene blocks the increase in this exchange, which is stimulated by mineralocorticoids (chiefly aldosterone), its action takes place through a direct effect on the renal tubule and not by competitive antagonism of aldosterone activity. This action of triamterene is not directly related to the level of aldosterone secretion, since it can be demonstrated in adrenalectomized rats and in patients with Addison’s disease.
By inhibiting the distal tubular exchange mechanism, triamterene maintains or increases the sodium excretion and reduces the loss of potassium, hydrogen, and chloride ions. Triamterene may reduce glomerular filtration and renal plasma flow. Via this mechanism it may reduce uric acid excretion although it has no tubular effect on uric acid reabsorption or secretion. Triamterene does not affect calcium secretion.
Diuretic activity following a single dose is evident within the first hour, reaches a peak at 2 to 3 hours, and tapers off during the subsequent 7 to 9 hours.
Indications And Clinical Uses: The treatment of edema associated with congestive heart failure, hepatic cirrhosis, nephrotic syndrome; also in idiopathic edema, steroid- and estrogen-induced edema and edema due to secondary hyperaldosteronism. May be useful when patients prove resistant or only partially responsive to other diuretics and may be given concurrently with other diuretics either for its added diuretic effect or for its potassium conserving potential. The use of triamterene for potassium conservation is indicated in patients who have developed hypokalemia while on diuretic therapy, or in those patients in whom potassium depletion is considered especially dangerous (e.g., digitalized patients). Triamterene has been used most frequently with thiazides. Triamterene itself has little or no antihypertensive effect.
Contra-Indications: Severe or progressive renal dysfunction including oliguria and progressively increasing azotemia, with the possible exception of nephrosis. Severe or progressive hepatic dysfunction. Hypersensitivity to triamterene. Nursing mothers.
Triamterene should not be used in patients who develop hyperkalemia while on the drug; or in patients receiving other potassium-sparing agents such as spironolactone, amiloride or angiotensin converting enzyme inhibitors; nor should it be used in patients with preexisting elevated serum potassium, as is sometimes seen in patients with impaired renal function or azotemia.
Manufacturers’ Warnings In Clinical States: Hyperkalemia: Abnormal elevation of serum potassium, though uncommon is potentially the most severe electrolyte disturbance with Dyrenium therapy. When used in combination with a thiazide diuretic, hyperkalemia (>5.4 mEq/L) has been reported ranging from 4% in patients less than 60 years of age to 12% in patients 60 years and older, with an overall incidence of less than 8%. Hyperkalemia has been reported to be associated with cardiac irregularities. Accordingly, serum potassium determinations should be performed regularly during the course of therapy. This is particularly important in the treatment of patients with suspected or confirmed renal insufficiency such as elderly or diabetic patients. In those patients who develop hyperkalemia, triamterene should be withdrawn.
Potassium supplementation, either in the form of medication or as a potassium-rich diet, should not be used in conjunction with triamterene since hyperkalemia may result.
Hyperkalemia rarely occurs in patients with adequate urinary output, but it is a possibility if large doses of triamterene are administered for prolonged periods or in patients on a salt-restricted diet. The use of full doses of a diuretic when salt intake is restricted can result in a low-salt syndrome. If hyperkalemia is observed, triamterene should be withdrawn.
Because triamterene conserves potassium, it has been theorized that in patients who have received intensive therapy or been given the drug for prolonged periods, a rebound kaliuresis could occur upon abrupt withdrawal. In such patients, withdrawal of triamterene should be gradual.
Hypokalemia: Because of the potassium-conserving effect of triamterene, hypokalemia is a less common occurrence with the use of triamterene than with non-potassium sparing diuretics.
The myocardial effects of digitalis may be exaggerated in patients with hypokalemia. In these patients, signs of digitalis intoxication may be produced by previously tolerated doses of digitalis.
Renal Stones: Triamterene has been found in renal stones in association with the other usual calculus components. This should be taken into consideration especially in those patients with histories of renal stones.
Precautions: Pertinent laboratory data such as serum potassium, BUN and electrocardiograms should be checked periodically when using triamterene, especially in elderly patients, in persons with suspected or confirmed renal insufficiency, in diabetics, and in those patients who have developed hyperkalemia during a previous course of therapy with the drug. (Blood samples require careful handling to prevent hemolysis on standing, and resulting false serum potassium readings).
Patients should be observed regularly for the possible occurrence of electrolyte imbalance, blood dyscrasias, liver damage or other idiosyncratic reactions. Appropriate laboratory studies should be done as required.
Electrolyte imbalance: Often encountered in such diseases as heart failure, renal disease or cirrhosis of the liver, electrolyte imbalance may be aggravated or caused independently by any diuretic agent, including triamterene. Signs and symptoms include dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscular fatigue, hypotension, oliguria, tachycardia and gastrointestinal symptoms.
Triamterene may cause a decrease in alkali reserve, with the possibilty of metabolic acidosis.
Blood Dyscrasias: Rare cases of blood dyscrasias (agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia) have been reported with triamterene. Cirrhotics with splenomegaly, by the nature of their illness, may have marked variations in their blood pictures – including thrombocyte and leukocyte levels – which are not related to drug therapy; therefore, periodic blood studies are recommended in these patients.
Triamterene is a weak folic acid antagonist; it may contribute to the appearance of megaloblastosis in cases where folic acid stores are depleted.
Liver: Hepatic coma may result from electrolyte imbalance in acutely ill cirrhotic patients. As with the use of any diuretic, the physician should proceed cautiously in such patients and be alert for early signs of impending coma such as confusion, drowsiness and tremor.
Blood Chemistry: Triamterene may produce an elevated blood urea nitrogen level, creatinine level, or both. This apparently is secondary to a reversible reduction of glomerular filtration rate or a depletion of intravascular fluid volume (prerenal azotemia) rather than renal toxicity; levels return to normal when Triamterene is discontinued. Elevated levels are seldom seen with every-other-day therapy. If azotemia increases, discontinue triamterene.
Slight elevations in serum transaminase (AST, ALT) levels sometimes accompany the administration of triamterene.
Endocrine: Triamterene appears to have little or no effect on serum uric acid levels or carbohydrate metabolism although some elevation of uric acid was seen in persons predisposed to gouty arthritis. Present experience suggests it is unlikely that triamterene therapy will precipitate either gout or diabetes, but caution is required in susceptible patients.
Other Conditions: Sensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma.
Drug Interactions: Although triamterene has not proved to be a consistent antihypertensive agent, the physician should be aware of a possible lowering of blood pressure. Concomitant use with antihypertensive drugs may result in an additive effect.
Lithium generally should not be given with diuretics because they reduce its renal clearance and increase the risk of lithium toxicity. Read circulars for lithium preparations before use of such concomitant therapy with triamterene.
Caution is advised in administering nonsteroidal anti-inflammatory agents with triamterene. A possible interaction resulting in acute renal failure has been reported in a few subjects when indomethacin, a nonsteroidal anti-inflammatory agent, was given with triamterene.
Triamterene and quinidine have similar fluorescence spectra; thus, triamterene will interfere with the fluorescent measurement of quinidine.
Pregnancy: Reproduction studies in animals have produced no evidence of drug-induced fetal abnormalities. However, as with any drug, care should be observed when prescribing Triamterene for pregnant patients or women of childbearing age. Its safety in pregnancy has not yet been fully established, and therefore it should be used only when, in the judgment of the physician, its use is deemed necessary for the welfare of the patient.
Lactation: Triamterene may appear in breast milk. If its use is deemed essential, the patient should stop nursing (see Contraindications).
Children: Adequate information on the use of triamterene in children is not available.
Adverse Reactions: The following adverse reactions have been associated with the use of triamterene:
Gastrointestinal: dry mouth, anorexia, gastric irritation, nausea, vomiting, diarrhea, constipation, jaundice (intrahepatic cholestatic), pancreatitis, sialadenitis. Nausea can usually be prevented by giving the drug after meals. It should be noted that symptoms of nausea and vomiting can also be indicative of electrolyte imbalance (see Precautions).
CNS: dizziness, vertigo, paresthesias, headache, xanthopsia.
Dermatologic-Hypersensitivity: fever, purpura, anaphylaxis, photosensitivity, rash, urticaria, necrotizing angiitis (vasculitis).
Hematologic: agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia.
Cardiovascular: orthostatic hypotension (which may be potentiated by alcohol, barbiturates, or narcotics).
Renal: Triamterene has been found in renal stones in association with the other usual components.
Electrolyte imbalance: (see Precautions).
Miscellaneous: glycosuria, hyperglycemia, hyperuricemia; muscle cramps, weakness, restlessness, transient blurred vision; allergic pneumonitis; rare cases of impotence (causal relationship not established).
Symptoms And Treatment Of Overdose: Electrolyte imbalance is the major concern, with particular attention to possible hyperkalemia.Symptoms: Symptoms reported include polyuria, nausea, vomiting, weakness, lassitude, hypotension, fever, flushed face and hyperactive deep tendon reflexes.
Treatment: There is no specific antidote. Treatment should be symptomatic and supportive. Immediate evacuation of the stomach should be induced through emesis or gastric lavage. Careful evaluation of the electrolyte pattern and fluid balance should be made. If profound hypotension occurs, pressor agents such as norepinephrine may be used along with the usual measures to maintain blood pressure levels.
Although triamterene is largely protein-bound (approximately 67%), dialysis may be of some benefit in cases of overdosage.
Dosage And Administration: It is recommended that triamterene be taken after an adequate meal.
Adults: Adult dosage should be adjusted according to the needs of the individual patient and his response to the drug. When used alone as mild diuretic, the usual starting dosage is 100 mg twice daily after meals. When adequate control of edema has been achieved, the dosage may be reduced, e.g., 100 mg daily; in some patients 100 mg every other day may suffice. Maximum daily dosage should not exceed 300 mg; at this dosage the incidence of side effects may increase.
Most patients will respond to triamterene during the first day of treatment. Maximum therapeutic effect, however, may not be seen for several days. (Triamterene-100 tablets are suitable for use as a mild diuretic.)
When changing from other diuretics to triamterene simply stop the previous therapy and start triamterene at the recommended dosage.
When triamterene is given concomitantly with another diuretic, total dosage of each agent should be lowered initially and then adjusted to the patient’s needs. Triamterene has been used most frequently with thiazides. (Triamterene-50 tablets are particularly suitable for this use.)
When triamterene is added to existing diuretic therapy, or when patients are switched to triamterene from other diuretics, all potassium supplementation should be discontinued, and serum potassium determinations should be made periodically.
Children: Adequate information on the use of triamterene in children is not available.
Availability And Storage: Dyrenium-50: Each round, flat, beveled-edged, yellow, compressed tablet, debossed SKF H11, contains: triamterene 50 mg. Nonmedicinal ingredients: magnesium stearate, povidone, silica, sodium lauryl sulfate and wheat starch. Bottles of 100.
Dyrenium-100: Each round, flat, beveled-edged, yellow, compressed tablet, debossed SKF H10, contains: triamterene 100 mg. Nonmedicinal ingredients: magnesium stearate, povidone, silica, sodium lauryl sulfate and wheat starch. Bottles of 100. (Shown in Product Recognition Section)
DYRENIUM® SmithKline Beecham Triamterene Diuretic