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DYRENIUM® (triamterene USP) Capsules
INDICATIONS AND USAGE
potassium supplementation, and substitute a thiazide alone. 50 mg and 100 mg potassium-sparing diuretic
Dyrenium (triamterene) is indicated in the treatment of edema Sodium polystyrene sulfonate (Kayexalate®, Sanofi associated with congestive heart failure, cirrhosis of the liver Synthelabo) may be administered to enhance the excretion of and the nephrotic syndrome; steroid-induced edema, idiopathic excess potassium. The presence of a widened QRS complex
WARNINGS
edema and edema due to secondary hyperaldosteronism. or arrhythmia in association with hyperkalemia requires
Abnormal elevation of serum potassium levels (greater than prompt additional therapy. For tachyarrhythmia, infuse 44
or equal to 5.5 mEq/liter) can occur with all Dyrenium may be used alone or with other diuretics, either for mEq of sodium bicarbonate or 10 mL of 10% calcium potassium-sparing agents, including Dyrenium. its added diuretic effect or its potassium-sparing potential. It gluconate or calcium chloride over several minutes. For Hyperkalemia is more likely to occur in patients with renal also promotes increased diuresis when patients prove resistant asystole, bradycardia or A-V block transvenous pacing is also impairment and diabetes (even without evidence of renal or only partially responsive to thiazides or other diuretics impairment), and in the elderly or severely ill. Since because of secondary hyperaldosteronism. uncorrected hyperkalemia may be fatal, serum potassium The effect of calcium and sodium bicarbonate is transient and levels must be monitored at frequent intervals especially in Usage in Pregnancy. The routine use of diuretics in an repeated administration may be required. When indicated by patients receiving Dyrenium, when dosages are changed or otherwise healthy woman is inappropriate and exposes mother the clinical situation, excess K+ may be removed by dialysis with any illness that may influence renal function. and fetus to unnecessary hazard. Diuretics do not prevent or oral or rectal administration of Kayexalate®. Infusion of development of toxemia of pregnancy, and there is no glucose and insulin has also been used to treat hyperkalemia. DESCRIPTION
satisfactory evidence that they are useful in the treatment of developed toxemia. Each capsule for oral use, with opaque red cap and body, PRECAUTIONS
contains Triamterene USP, 50 or 100 mg, and is imprinted Edema during pregnancy may arise from pathological causes with the product name, DYRENIUM, strength (50 mg or 100 or from the physiologic and mechanical consequences of Dyrenium (triamterene) tends to conserve potassium rather mg) and WPC 002 (for the 50-mg strength) and WPC 003 (for pregnancy. Diuretics are indicated in pregnancy (however, see than to promote the excretion as do many diuretics and, the 100-mg strength). Inactive ingredients consist of D&C Red low) when edema is due to pathologic occasionally, can cause increases in serum potassium which, in No. 33, FD&C Yellow No. 6, Gelatin NF, Lactose NF, causes, just as they are in the absence of pregnancy. some instances, can result in hyperkalemia. In rare instances, Magnesium Stearate NF, Sodium Lauryl Sulfate NF, Titanium Dependent edema in pregnancy, resulting from restriction of hyperkalemia has been associated with cardiac irregularities. venous return by the expanded uterus, is properly treated Electrolyte imbalance often encountered in such diseases as through elevation of the lower extremities and use of support Triamterene is 2,4,7-triamino-6-phenyl-pteridine: hose; use of diuretics to lower intravascular volume in this congestive heart failure, renal disease or cirrhosis may be aggravated or caused independently by any effective diuretic case is illogical and unnecessary. There is hypervolemia during normal pregnancy which is harmful to neither the fetus agent including Dyrenium. The use of full doses of a diuretic nor the mother (in the absence of cardiovascular disease), but when salt intake is restricted can result in a low-salt syndrome. which is associated with edema, including generalized edema, Triamterene can cause mild nitrogen retention, which is in the majority of pregnant women. If this edema produces reversible upon withdrawal of the drug, and is seldom discomfort, increased recumbency will often provide relief. In observed with intermittent (every-other-day) therapy. rare instances, this edema may cause extreme discomfort which is not relieved by rest. In these cases, a short course of Triamterene may cause a decreasing alkali reserve, with the diuretics may provide relief and may be appropriate. CONTRAINDICATIONS
By the very nature of their illness, cirrhotics with Its molecular weight is 253.27. At 50°C, triamterene is slightly Anuria. Severe or progressive kidney disease or dysfunction, splenomegaly sometimes have marked variations in their soluble in water. It is soluble in dilute ammonia, dilute with the possible exception of nephrosis. Severe hepatic blood. Since triamterene is a weak folic acid antagonist, it may aqueous sodium hydroxide and dimethylformamide. It is disease. Hypersensitivity to the drug or any of its components. contribute to the appearance of megaloblastosis in cases where folic acid stores have been depleted. Therefore, periodic blood Dyrenium (triamterene) should not be used in patients with studies in these patients are recommended. They should also CLINICAL PHARMACOLOGY
pre-existing elevated serum potassium, as is sometimes seen in be observed for exacerbations of underlying liver disease. patients with impaired renal function or azotemia, or in Triamterene has a unique mode of action; it inhibits the patients who develop hyperkalemia while on the drug. Patients Triamterene has elevated uric acid, especially in persons reabsorption of sodium ions in exchange for potassium and should not be placed on dietary potassium supplements, hydrogen ions at that segment of the distal tubule under the potassium salts or potassium-containing salt substitutes in control of adrenal mineralocorticoids (especially aldosterone). conjunction with Dyrenium. Triamterene has been reported in renal stones in association This activity is not directly related to aldosterone secretion or with other calculus components. Dyrenium should be used antagonism; it is a result of a direct effect on the renal tubule. Dyrenium should not be given to patients receiving other with caution in patients with histories of renal stones. potassium-sparing agents, such as spironolactone, amiloride The fraction of filtered sodium reaching this distal tubular hydrochloride, or other formulations containing triamterene. exchange site is relatively small, and the amount which is Information for Patients
Two deaths have been reported in patients receiving exchanged depends on the level of mineralocorticoid activity. To help avoid stomach upset, it is recommended that the drug concomitant spironolactone and Dyrenium or Dyazide®. Thus, the degree of natriuresis and diuresis produced by Although dosage recommendations were exceeded in one case inhibition of the exchange mechanism is necessarily limited. and in the other serum electrolytes were not properly Increasing the amount of available sodium and the level of If a single daily dose is prescribed, it may be preferable to take monitored, these two drugs should not be given concomitantly. mineralocorticoid activity by the use of more proximally it in the morning to minimize the effect of increased frequency acting diuretics will increase the degree of diuresis and WARNINGS
If a dose is missed, the patient should not take more than the Abnormal elevation of serum potassium levels (greater than Triamterene occasionally causes increases in serum potassium prescribed dose at the next dosing interval. or equal to 5.5 mEq/liter) can occur with all which can result in hyperkalemia. It does not produce potassium-sparing agents, including Dyrenium. alkalosis, because it does not cause excessive excretion of Hyperkalemia is more likely to occur in patients with renal Laboratory Tests
impairment and diabetes (even without evidence of renal Hyperkalemia will rarely occur in patients with adequate impairment), and in the elderly or severely ill. Since urinary output, but it is a possibility if large doses are used for Triamterene has been shown to cross the placental barrier and uncorrected hyperkalemia may be fatal, serum potassium considerable periods of time. If hyperkalemia is observed, levels must be monitored at frequent intervals especially in Dyrenium (triamterene) should be withdrawn. The normal patients receiving Dyrenium, when dosages are changed or adult range of serum potassium is 3.5 to 5.0 mEq per liter, Pharmacokinetics
with any illness that may influence renal function. with 4.5 mEq often being used for a reference point. Potassium Onset of action is 2 to 4 hours after ingestion. In normal levels persistently above 6 mEq per liter require careful volunteers the mean peak serum levels were 30 ng/mL at 3 There have been isolated reports of hypersensitivity reactions; observation and treatment. Normal potassium levels tend to be hours. The average percent of drug recovered in the urine (0 to therefore, patients should be observed regularly for the higher in neonates (7.7 mEq per liter) than in adults. Serum 48 hours) was 21%. Triamterene is primarily metabolized to possible occurrence of blood dyscrasias, liver damage or other potassium levels do not necessarily indicate true body the sulfate conjugate of hydroxytriamterene. Both the plasma potassium concentration. A rise in plasma pH may cause a and urine levels of this metabolite greatly exceed triamterene decrease in plasma potassium concentration and an increase in levels. Triamterene is rapidly absorbed, with somewhat less Periodic BUN and serum potassium determinations should be the intracellular potassium concentration. Because Dyrenium than 50% of the oral dose reaching the urine. Most patients made to check kidney function, especially in patients with conserves potassium, it has been theorized that in patients who will respond to Dyrenium (triamterene) during the first day of suspected or confirmed renal insufficiency. It is particularly have received intensive therapy or been given the drug for important to make serum potassium determinations in elderly prolonged periods, a rebound kaliuresis could occur upon or diabetic patients receiving the drug; these patients should be abrupt withdrawal. In such patients, withdrawal of Dyrenium Maximum therapeutic effect, however, may not be seen for observed carefully for possible serum potassium increases. several days. Duration of diuresis depends on several factors, especially renal function, but it generally tapers off 7 to 9 If hyperkalemia is present or suspected, an electrocardiogram Drug Interactions
should be obtained. If the ECG shows no widening of the QRS or arrhythmia in the presence of hyperkalemia, it is usually Caution should be used when lithium and diuretics are used sufficient to discontinue Dyrenium (triamterene) and any concomitantly because diuretic-induced sodium loss may reduce the renal clearance of lithium and increase serum (MRHD) on the basis of body weight, and 6 times the MRHD HOW SUPPLIED
lithium levels with risk of lithium toxicity. Patients receiving on the basis of body-surface area, without evidence of harm to Capsules: 50 mg in bottles of 100, and 100 mg in bottles of such combined therapy should have serum lithium levels the fetus due to triamterene. Because animal reproduction monitored closely and the lithium dosage adjusted if studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. A possible interaction resulting in acute renal failure has been Store at 25°C (77°F); excursions permitted to 15° - 30°C (59° Nonteratogenic Effects:
reported in a few subjects when indomethacin, a nonsteroidal - 86°F) [See USP Controlled Room Temperature]. Dispense in anti-inflammatory agent, was given with triamterene. Caution Triamterene has been shown to cross the placental barrier and is advised in administering nonsteroidal anti-inflammatory appear in cord blood. The use of triamterene in pregnant women requires that the anticipated benefits be weighed against possible hazards to the fetus. These possible hazards The effects of the following drugs may be potentiated when include adverse reactions which have occurred in the adult. given together with triamterene: antihypertensive medication, other diuretics, preanesthetic and anesthetic agents, skeletal Nursing Mothers:
Triamterene has not been studied in nursing mothers. Triamterene appears in animal milk and is likely present in Potassium-sparing agents should be used with caution in human milk. If use of the drug product is deemed essential, the conjunction with angiotensin-converting enzyme (ACE) inhibitors due to an increased risk of hyperkalemia. WellSpring Pharmaceutical Corporation
The following agents, given together with triamterene, may Pediatric Use:
promote serum potassium accumulation and possibly result in Safety and effectiveness in pediatric patients have not been By WellSpring Pharmaceutical Canada Corp. hyperkalemia because of the potassium-sparing nature of triamterene, especially in patients with renal insufficiency: blood from blood bank (may contain up to 30 mEq of ADVERSE REACTIONS
potassium per liter of plasma or up to 65 mEq per liter of Adverse effects are listed in decreasing order of frequency; whole blood when stored for more than 10 days); low-salt milk however, the most serious adverse effects are listed first, (may contain up to 60 mEq of potassium per liter); regardless of frequency. All adverse effects occur rarely (that potassium-containing medications (such as parenteral penicillin G potassium); salt substitutes (most contain substantial amounts of potassium). Hypersensitivity: anaphylaxis, rash, photosensitivity. Dyrenium (triamterene) may raise blood glucose levels; for adult-onset diabetes, dosage adjustments of hypoglycemic agents may be necessary during and/or after therapy; Renal: azotemia, elevated BUN and creatinine, renal stones, concurrent use with chlorpropamide may increase the risk of acute interstitial nephritis (rare), acute renal failure (one case of irreversible renal failure has been reported). Drug/Laboratory Test Interactions
Gastrointestinal: jaundice and/or liver enzyme abnormalities, Triamterene and quinidine have similar fluorescence spectra; thus, triamterene will interfere with the fluorescent Hematologic: thrombocytopenia, megaloblastic anemia. Central Nervous System: weakness, fatigue, dizziness, Carcinogenesis, Mutagenesis, Impairment of
Fertility
Carcinogenesis: In studies conducted under the auspices of
the National Toxicology Program, groups of rats were fed
To report SUSPECTED ADVERSE REACTIONS, contact diets containing 0, 150, 300 or 600 ppm of triamterene, and WellSpring Pharmaceutical Corporation at 1-866-337-4500 groups of mice were fed diets containing 0, 100, 200 or 400 ppm triamterene. Male and female rats exposed to the highest tested concentration received triamterene at about 25 and 30 OVERDOSAGE
mg/kg/day, respectively. Male and female mice exposed to the In the event of overdosage, it can be theorized that electrolyte highest tested concentration received triamterene at about 45 imbalance would be the major concern, with particular attention to possible hyperkalemia. Other symptoms that might be seen would be nausea and vomiting, other G.I. disturbances There was an increased incidence of hepatocellular neoplasia and weakness. It is conceivable that some hypotension could (primarily adenomas) in male and female mice at the highest occur. As with an overdose of any drug, immediate evacuation dosage level. These doses represent 7.5X and 10X the of the stomach should be induced through emesis and gastric Maximum Recommended Human Dose (MRHD) of 300 lavage. Careful evaluation of the electrolyte pattern and fluid mg/kg/day (or 6 mg/kg/day based on a 50 kg patient) for male balance should be made. There is no specific antidote. and female mice, respectively, when based on body weight and 0.7X and 0.9X the MRHD when based on body-surface Reversible acute renal failure following ingestion of 50 tablets of a product containing a combination of 50 mg triamterene and 25 mg hydrochlorothiazide has been reported. Although hepatocellular neoplasia (exclusively adenomas) in the rat study was limited to triamterene-exposed males, The oral LD50 in mice is 380 mg/kg. The amount of drug in a incidence was not dose dependent and there was no single dose ordinarily associated with symptoms of overdose statistically significant difference from control incidence at or likely to be life-threatening is not known. Although triamterene is 67% protein bound, there may be Mutagenesis: Triamterene was not mutagenic in bacteria
some benefit to dialysis in cases of overdosage. (Salmonella typhimurium strains TA98, TA100, TA1535 or TA1537) with or without metabolic activation. It did not DOSAGE AND ADMINISTRATION
induce chromosomal aberrations in Chinese hamster ovary (CHO) cells in vitro with or without metabolic activation, but Adult Dosage
it did induce sister chromatid exchanges in CHO cells in vitro Dosage should be titrated to the needs of the individual patient. When used alone, the usual starting dose is 100 mg twice daily after meals. When combined with another diuretic Impairment of Fertility: Studies of the effects of
or antihypertensive agent, the total daily dosage of each agent should usually be lowered initially and then adjusted to the triamterene on animal reproductive function have not been patient’s needs. The total daily dosage should not exceed 300 Pregnancy: Category C
When Dyrenium (triamterene) is added to other diuretic Teratogenic Effects:
therapy or when patients are switched to Dyrenium from other Reproduction studies have been performed in rats at doses as diuretics, all potassium supplementation should be high as 20 times the Maximum Recommended Human Dose

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