Label: TRIAMTERENE- triamterene capsules capsule

Triamterene Capsules are potassium-sparing diuretics.

Triamterene

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.

Each capsule for oral use, with opaque red cap and body, contains Triamterene USP,
50 mg or 100 mg, and is imprinted with AT 50 (for the 50-mg strength) and AT 100 (for the 100-mg strength) in white ink on both the cap and body. Inactive ingredients consist of Lactose monohydrate, Magnesium stearate, Gelatin, D&C Red No.33, FD&C yellow No.6, Titanium dioxide, Sodium lauryl sulfate, Shellac and Potassium hydroxide.

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.

Pharmacokinetics
Onset of action is 2 to 4 hours after ingestion. In normal volunteers the mean peak serum levels were 30 ng/mL at 3 hours. The average percent of drug recovered in the urine (0 to 48 hours) was 21%. Triamterene is primarily metabolized to the sulfate conjugate of hydroxytriamterene. Both the plasma and urine levels of this metabolite greatly exceed triamterene levels. Triamterene is rapidly absorbed, with somewhat less than 50% of the oral dose reaching the urine. Most patients will respond to triamterene during the first day of treatment. Maximum therapeutic effect, however, may not be seen for several days. Duration of diuresis depends on several factors, especially renal function, but it generally tapers off 7 to 9 hours after administration.

Triamterene Capsules USP 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.

Triamterene Capsules USP 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.

Triamterene Capsules USP 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 triamterene.

Triamterene 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 triamterene 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 triamterene and any potassium supplementation, and substitute a thiazide alone. Sodium polystyrene sulfonate (Kayexalate®, Concordia Pharmaceuticals Inc.)  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.

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.

To report SUSPECTED ADVERSE REACTIONS, contact TruPharma, LLC at 1-877-541-5504 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 triamterene capsules are added to other diuretic therapy or when patients are switched to triamterene capsules from other diuretics, all potassium supplementation should be discontinued.

Each capsule for oral use, with opaque red cap and body, contains Triamterene USP, 50 mg or 100 mg, and is imprinted with AT 50 (for the 50-mg strength) and AT 100 (for the 100-mg strength) in white ink on both the cap and body and they are available as follows.

50 mg: NDC 52817-364-10 Bottles of 100 capsules
100 mg: NDC 52817-365-10 Bottles of 100 capsules

STORAGE
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.

Manufactured by:
Agnitio Inc.
N 800 County Road CB,
Appleton, WI 54914 USA

Distributed By:
TruPharma, LLC
Tampa, FL 33609

Revised: April 2019

Trademarks are the property of their respective owners.