Dyrenium

Abnormal elevation of serum potassium levels (greater than or equal to 5.5 mEq/liter) can occur with all potassium-sparing agents, including Dyrenium. Hyperkalemia is more likely to occur in patients with renal impairment and diabetes (even without evidence of renal impairment), and in the elderly or severely ill. Since uncorrected hyperkalemia may be fatal, serum potassium levels must be monitored at frequent intervals especially in patients receiving Dyrenium, when dosages are changed or with any illness that may influence renal function.

Each capsule for oral use, with opaque red cap and body, contains Triamterene USP, 50 or 100 mg, and is imprinted with the product name, DYRENIUM, strength (50 mg or 100 mg) and WPC 002 (for the 50-mg strength) and WPC 003 (for the 100-mg strength). Inactive ingredients consist of D&C Red No. 33, FD&C Yellow No. 6, Gelatin NF, Lactose NF, Magnesium Stearate NF, Sodium Lauryl Sulfate NF, Titanium Dioxide USP and Silicon Dioxide NF.

Triamterene is 2,4,7-triamino-6-phenyl-pteridine:

Its molecular weight is 253.27. At 50°C, triamterene is slightly soluble in water. It is soluble in dilute ammonia, dilute aqueous sodium hydroxide and dimethylformamide. It is sparingly soluble in methanol.

Triamterene has a unique mode of action; it inhibits the reabsorption of sodium ions in exchange for potassium and hydrogen ions at that segment of the distal tubule under the control of adrenal mineralocorticoids (especially aldosterone). This activity is not directly related to aldosterone secretion or antagonism; it is a result of a direct effect on the renal tubule.

The fraction of filtered sodium reaching this distal tubular exchange site is relatively small, and the amount which is exchanged depends on the level of mineralocorticoid activity. Thus, the degree of natriuresis and diuresis produced by inhibition of the exchange mechanism is necessarily limited. Increasing the amount of available sodium and the level of mineralocorticoid activity by the use of more proximally acting diuretics will increase the degree of diuresis and potassium conservation.

Triamterene occasionally causes increases in serum potassium which can result in hyperkalemia. It does not produce alkalosis, because it does not cause excessive excretion of titratable acid and ammonium.

Triamterene has been shown to cross the placental barrier and appear in the cord blood of animals.

Dyrenium (triamterene) is indicated in the treatment of edema associated with congestive heart failure, cirrhosis of the liver and the nephrotic syndrome; steroid-induced edema, idiopathic edema and edema due to secondary hyperaldosteronism.

Dyrenium may be used alone or with other diuretics, either for its added diuretic effect or its potassium-sparing potential. It also promotes increased diuresis when patients prove resistant or only partially responsive to thiazides or other diuretics because of secondary hyperaldosteronism.

Usage in Pregnancy. The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy, and there is no satisfactory evidence that they are useful in the treatment of developed toxemia.

Edema during pregnancy may arise from pathological causes or from the physiologic and mechanical consequences of pregnancy. Diuretics are indicated in pregnancy (however, see PRECAUTIONS below) when edema is due to pathologic causes, just as they are in the absence of pregnancy. Dependent edema in pregnancy, resulting from restriction of venous return by the expanded uterus, is properly treated through elevation of the lower extremities and use of support hose; use of diuretics to lower intravascular volume in this case is illogical and unnecessary. There is hypervolemia during normal pregnancy which is harmful to neither the fetus nor the mother (in the absence of cardiovascular disease), but which is associated with edema, including generalized edema, in the majority of pregnant women. If this edema produces discomfort, increased recumbency will often provide relief. In rare instances, this edema may cause extreme discomfort which is not relieved by rest. In these cases, a short course of diuretics may provide relief and may be appropriate.

Anuria. Severe or progressive kidney disease or dysfunction, with the possible exception of nephrosis. Severe hepatic disease. Hypersensitivity to the drug or any of its components.

Dyrenium (triamterene) should not be used in patients with pre-existing elevated serum potassium, as is sometimes seen in patients with impaired renal function or azotemia, or in patients who develop hyperkalemia while on the drug. Patients should not be placed on dietary potassium supplements, potassium salts or potassium-containing salt substitutes in conjunction with Dyrenium.

Dyrenium should not be given to patients receiving other potassium-sparing agents, such as spironolactone, amiloride hydrochloride, or other formulations containing triamterene. Two deaths have been reported in patients receiving concomitant spironolactone and Dyrenium or Dyazide^®. Although dosage recommendations were exceeded in one case and in the other serum electrolytes were not properly monitored, these two drugs should not be given concomitantly.

There have been isolated reports of hypersensitivity reactions; therefore, patients should be observed regularly for the possible occurrence of blood dyscrasias, liver damage or other idiosyncratic reactions.

Periodic BUN and serum potassium determinations should be made to check kidney function, especially in patients with suspected or confirmed renal insufficiency. It is particularly important to make serum potassium determinations in elderly or diabetic patients receiving the drug; these patients should be observed carefully for possible serum potassium increases.

If hyperkalemia is present or suspected, an electrocardiogram should be obtained. If the ECG shows no widening of the QRS or arrhythmia in the presence of hyperkalemia, it is usually sufficient to discontinue Dyrenium (triamterene) and any potassium supplementation, and substitute a thiazide alone. Sodium polystyrene sulfonate (Kayexalate^®, Sanofi Synthelabo) may be administered to enhance the excretion of excess potassium. The presence of a 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 A-V block transvenous pacing is also recommended.

The effect of calcium and sodium bicarbonate is transient and repeated administration may be required. When indicated by the clinical situation, excess K+ may be removed by dialysis or oral or rectal administration of Kayexalate^®. Infusion of glucose and insulin has also been used to treat hyperkalemia.

Dyrenium (triamterene) tends to conserve potassium rather than to promote the excretion as do many diuretics and, occasionally, can cause increases in serum potassium which, in some instances, can result in hyperkalemia. In rare instances, hyperkalemia has been associated with cardiac irregularities.

Electrolyte imbalance often encountered in such diseases as congestive heart failure, renal disease or cirrhosis may be aggravated or caused independently by any effective diuretic agent includingDyrenium. The use of full doses of a diuretic when salt intake is restricted can result in a low-salt syndrome.

Triamterene can cause mild nitrogen retention, which is reversible upon withdrawal of the drug, and is seldom observed with intermittent (every-other-day) therapy.

Triamterene may cause a decreasing alkali reserve, with the possibility of metabolic acidosis.

By the very nature of their illness, cirrhotics with splenomegaly sometimes have marked variations in their blood. Since triamterene is a weak folic acid antagonist, it may contribute to the appearance of megaloblastosis in cases where folic acid stores have been depleted. Therefore, periodic blood studies in these patients are recommended. They should also be observed for exacerbations of underlying liver disease.

Triamterene has elevated uric acid, especially in persons predisposed to gouty arthritis.

Triamterene has been reported in renal stones in association with other calculus components. Dyrenium should be used with caution in patients with histories of renal stones.

Adverse effects are listed in decreasing order of frequency; however, the most serious adverse effects are listed first, regardless of frequency. All adverse effects occur rarely (that is, 1 in 1000, or less).

Hypersensitivity: anaphylaxis, rash, photosensitivity.

Metabolic: hyperkalemia, hypokalemia.

Renal: azotemia, elevated BUN and creatinine, renal stones, acute interstitial nephritis (rare), acute renal failure (one case of irreversible renal failure has been reported).

Gastrointestinal: jaundice and/or liver enzyme abnormalities, nausea and vomiting, diarrhea.

Hematologic: thrombocytopenia, megaloblastic anemia.

Central Nervous System: weakness, fatigue, dizziness, headache, dry mouth.

In the event of overdosage, it can be theorized that electrolyte 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 and weakness. It is conceivable that some hypotension could occur. As with an overdose of any drug, immediate evacuation of the stomach should be induced through emesis and gastric lavage. Careful evaluation of the electrolyte pattern and fluid balance should be made. There is no specific antidote.

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.

The oral LD50 in mice is 380 mg/kg. The amount of drug in a single dose ordinarily associated with symptoms of overdose or likely to be life-threatening is not known.

Although triamterene is 67% protein bound, there may be some benefit to dialysis in cases of overdosage.

Adult Dosage

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 or antihypertensive agent, the total daily dosage of each agent should usually be lowered initially and then adjusted to the patient’s needs. The total daily dosage should not exceed 300 mg. Please refer to PRECAUTIONS−General.

When Dyrenium (triamterene) is added to other diuretic therapy or when patients are switched to Dyrenium from other diuretics, all potassium supplementation should be discontinued.

Product: 68151-1494

NDC: 68151-1494-0 1 CAPSULE in a PACKAGE

Store at 25°C (77°F); excursions permitted to 15° - 30°C (59° - 86°F) [See USP Controlled Room Temperature]. Dispense in a tight, light resistant container.

50 mg 100s: NDC 65197-002-01

100 mg 100s: NDC 65197-003-01

DATE OF ISSUANCE MARCH 2009

©WellSpring, 2009

Manufactured for
WellSpring Pharmaceutical Corporation
Sarasota, FL 34243 USA
By WellSpring Pharmaceutical Canada Corp.
Oakville, Ontario L6H 1M5 Canada 

Rev. 03/09