Triamterene and Hydrochlorothiazide 37.5 mg; 25 mg Tablet, 500-count — NDC 60505-2656-5 (Billing 60505-2656-05)

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

If hyperkalemia is suspected, (warning signs include paresthesias, muscular weakness, fatigue, flaccid paralysis of the extremities, bradycardia and shock) an electrocardiogram (ECG) should be obtained. However, it is important to monitor serum potassium levels because mild hyperkalemia may not be associated with ECG changes. If hyperkalemia is present, triamterene and hydrochlorothiazide should be discontinued immediately, and a thiazide alone should be substituted.

If the serum potassium exceeds 6.5 mEq/liter, more vigorous therapy is required. The clinical situation dictates the procedures to be employed. These include the intravenous administration of calcium chloride solution, sodium bicarbonate solution and/or the oral or parenteral administration of glucose with a rapid-acting insulin preparation.

Cationic exchange resins such as sodium polystyrene sulfonate may be orally or rectally administered. Persistent hyperkalemia may require dialysis. The development of hyperkalemia associated with potassium-sparing diuretics is accentuated in the presence of renal impairment (see CONTRAINDICATIONS ).

Patients with mild renal functional impairment should not receive this drug without frequent and continuing monitoring of serum electrolytes. Cumulative drug effects may be observed in patients with impaired renal function. The renal clearances of hydrochlorothiazide and the pharmacologically active metabolite of triamterene, the sulfate ester of hydroxytriamterene, have been shown to be reduced and the plasma levels increased following triamterene and hydrochlorothiazide administration to elderly patients and patients with impaired renal function.

Hyperkalemia has been reported in diabetic patients with the use of potassium-conserving agents even in the absence of apparent renal impairment. Accordingly, triamterene and hydrochlorothiazide should be avoided in diabetic patients. If it is employed, serum electrolytes must be frequently monitored.

Because of the potassium-sparing properties of angiotensin-converting enzyme (ACE) inhibitors, triamterene and hydrochlorothiazide should be used cautiously, if at all, with these agents (see PRECAUTIONS, Drug Interactions ). Metabolic or Respiratory Acidosis Potassium-conserving therapy should also be avoided in severely ill patients in whom respiratory or metabolic acidosis may occur. Acidosis may be associated with rapid elevations in serum potassium levels.

If triamterene and hydrochlorothiazide is employed, frequent evaluations of acid/base balance and serum electrolytes are necessary. Acute Myopia and Secondary Angle-Closure Glaucoma Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation.

Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled.

Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

ADVERSE REACTIONS Side effects observed in association with the use of triamterene and hydrochlorothiazide tablets, other combination products containing triamterene/hydrochlorothiazide, and products containing triamterene or hydrochlorothiazide include the following: Gastrointestinal: jaundice (intrahepatic cholestatic jaundice), pancreatitis, nausea, appetite disturbance, taste alteration, vomiting, diarrhea, constipation, anorexia, gastric irritation, cramping. Central Nervous System: drowsiness and fatigue, insomnia, headache, dizziness, dry mouth, depression, anxiety, vertigo, restlessness, paresthesias.

Cardiovascular: tachycardia, shortness of breath and chest pain, orthostatic hypotension (may be aggravated by alcohol, barbiturates or narcotics). Renal: acute renal failure, acute interstitial nephritis, renal stones composed of triamterene in association with other calculus materials, urine discoloration. Hematologic: leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia and megaloblastosis.

Ophthalmic: xanthopsia, transient blurred vision. Hypersensitivity: anaphylaxis, photosensitivity, rash, urticaria, purpura, necrotizing angiitis (vasculitis, cutaneous vasculitis), fever, respiratory distress including pneumonitis. Other: muscle cramps and weakness, decreased sexual performance and sialadenitis.

Whenever adverse reactions are moderate to severe, therapy should be reduced or withdrawn. Altered Laboratory Findings Serum Electrolytes: hyperkalemia, hypokalemia, hyponatremia, hypomagnesemia, hypochloremia (see WARNINGS and PRECAUTIONS ). Creatinine, Blood Urea Nitrogen: Reversible elevations in BUN and serum creatinine have been observed in hypertensive patients treated with triamterene and hydrochlorothiazide.

Glucose: hyperglycemia, glycosuria and diabetes mellitus (see PRECAUTIONS ). Serum Uric Acid, PBI and Calcium: (see PRECAUTIONS ). Other: Elevated liver enzymes have been reported in patients receiving triamterene and hydrochlorothiazide.

Postmarketing Experience Non-melanoma Skin Cancer Hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer. In a study conducted in the Sentinel System, increased risk was predominantly for squamous cell carcinoma (SCC) and in white patients taking large cumulative doses. The increased risk for SCC in the overall population was approximately 1 additional case per 16,000 patients per year, and for white patients taking a cumulative dose of ≥ 50,000 mg the risk increase was approximately 1 additional SCC case for every 6,700 patients per year.

Drug Interactions Thiazides may add to or potentiate the action of other antihypertensive drugs. The thiazides may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use.

Thiazides have also been shown to increase the responsiveness to tubocurarine. Lithium generally should not be given with diuretics because they reduce its renal clearance and add a high risk of lithium toxicity. Refer to the package insert on lithium before use of such concomitant therapy.

Acute renal failure has been reported in a few patients receiving indomethacin and formulations containing triamterene and hydrochlorothiazide. Caution is therefore advised when administering non-steroidal anti-inflammatory agents with triamterene and hydrochlorothiazide. Potassium-sparing agents should be used very cautiously, if at all, in conjunction with angiotensin-converting enzyme (ACE) inhibitors due to a greatly increased risk of hyperkalemia.

Serum potassium should be monitored frequently.

Drug/Laboratory Test Interactions Triamterene and quinidine have similar fluorescence spectra; thus, triamterene and hydrochlorothiazide may interfere with the measurement of quinidine.

PRECAUTIONS General Electrolyte Imbalance and BUN Increases Patients receiving triamterene and hydrochlorothiazide should be carefully monitored for fluid or electrolyte imbalances, i.e., hyponatremia, hypochloremic alkalosis, hypokalemia and hypomagnesemia. Determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals. Serum and urine electrolyte determinations are especially important and should be frequently performed when the patient is vomiting or receiving parenteral fluids.

Warning signs or symptoms of fluid and electrolyte imbalance include: dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia and gastrointestinal disturbances such as nausea and vomiting. Any chloride deficit during thiazide therapy is generally mild and usually does not require any specific treatment except under extraordinary circumstances (as in liver disease or renal disease). Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction, rather than administration of salt, except in rare instances when the hyponatremia is life threatening.

In actual salt depletion, appropriate replacement is the therapy of choice. Hypokalemia may develop with thiazide therapy, especially with brisk diuresis, when severe cirrhosis is present, or during concomitant use of corticosteroids, ACTH, amphotericin B or after prolonged thiazide therapy. However, hypokalemia of this type is usually prevented by the triamterene component of triamterene and hydrochlorothiazide.

Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia can sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability). Triamterene and hydrochlorothiazide may produce an elevated blood urea nitrogen level (BUN), creatinine level or both.

This is probably not the result of renal toxicity but is secondary to a reversible reduction of the glomerular filtration rate or a depletion of the intravascular fluid volume. Elevations in BUN and creatinine levels may be more frequent in patients receiving divided dose diuretic therapy. Periodic BUN and creatinine determinations should be made especially in elderly patients, patients with suspected or confirmed hepatic disease or renal insufficiencies.

If azotemia increases, triamterene and hydrochlorothiazide should be discontinued. Hepatic Coma Triamterene and hydrochlorothiazide should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. Renal Stones Triamterene has been reported in renal stones in association with other calculus components.

Triamterene and hydrochlorothiazide should be used with caution in patients with histories of renal lithiasis. Folic Acid Deficiency Triamterene is a weak folic acid antagonist and may contribute to the appearance of megaloblastosis in instances where folic acid stores are decreased. In such patients, periodic blood elevations are recommended.

Hyperuricemia Hyperuricemia may occur or acute gout may be precipitated in certain patients receiving thiazide therapy. Metabolic and Endocrine Effects The thiazides may decrease serum PBI levels without signs of thyroid disturbance. Calcium excretion is decreased by thiazides.

Pathological changes in the parathyroid gland with hypercalcemia and hypophosphatemia have been observed in a few patients on prolonged thiazide therapy. The common complications of hyperparathyroidism such as renal lithiasis, bone resorption, and peptic ulceration have not been seen. Thiazides should be discontinued before carrying out tests for parathyroid function.

Insulin requirements in diabetic patients may be increased, decreased or unchanged. Diabetes mellitus which… [Excerpted — this section continues on DailyMed.]