Triamterene and Hydrochlorothiazide Capsules, USP

DESCRIPTION

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displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Triamterene is an antikaliuretic agent and hydrochlorothiazide is a diuretic/antihypertensive agent. At 50°C, triamterene is practically insoluble in water (less than 0.1%). It is soluble in formic acid, sparingly soluble in methoxyethanol, and very slightly soluble in alcohol. Triamterene is 2,4,7-triamino-6-phenylpteridine with a chemical formula of C₁₂H₁₁N₇ and a molecular weight of 253.27. The structural formula for triamterene is:

TRIAMTERENE Hydrochlorothiazide is slightly soluble in water. It is soluble in dilute ammonia, dilute aqueous sodium hydroxide, and dimethylformamide. It is sparingly soluble in methanol. Hydrochlorothiazide is 6-chloro-3,4-dihydro-2H-1,2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide with a chemical formula of C₇H₈ClN₃O₄S₂ and a molecular weight of 297.75. The structural formula for hydrochlorothiazide is:

HYDROCHLOROTHIAZIDE Each capsule, for oral administration, contains 37.5 mg triamterene and 25 mg hydrochlorothiazide or 50 mg triamterene and 25 mg hydrochlorothiazide. The 37.5 mg triamterene and 25 mg hydrochlorothiazide capsule inactive ingredients include: citric acid, corn starch, glycine, anhydrous lactose, magnesium stearate, Polysorbate 80, povidone, and sodium starch glycolate. The capsule shells and imprinting inks contain: D & C Yellow #10 Aluminum Lake, FD & C Blue #1 Aluminum Lake, FD & C Blue #2 Aluminum Lake, FD & C Red #40 Aluminum Lake, gelatin, pharmaceutical glaze, propylene glycol, synthetic black iron oxide, and titanium dioxide. The 37.5 mg triamterene and 25 mg hydrochlorothiazide capsule meets USP Dissolution Test 3. The 50 mg triamterene and 25 mg hydrochlorothiazide capsule inactive ingredients include: lactose monohydrate, magnesium stearate, povidone, corn starch. The capsule shells and imprinting inks contain: D&C Red # 40, gelatin, titanium dioxide, pharmaceutical glaze, propylene glycol and simethicone. The 50 mg triamterene and 25 mg hydrochlorothiazide capsule meets USP Dissolution Test 2.

CLINICAL PHARMACOLOGY

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displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

Triamterene and hydrochlorothiazide is a diuretic/antihypertensive drug product that combines natriuretic and antikaliuretic effects. Each component complements the action of the other. The hydrochlorothiazide component blocks the reabsorption of sodium and chloride ions, and thereby increases the quantity of sodium traversing the distal tubule and the volume of water excreted. A portion of the additional sodium presented to the distal tubule is exchanged there for potassium and hydrogen ions. With continued use of hydrochlorothiazide and depletion of sodium, compensatory mechanisms tend to increase this exchange and may produce excessive loss of potassium, hydrogen and chloride ions. Hydrochlorothiazide also decreases the excretion of calcium and uric acid, may increase the excretion of iodide, and may reduce glomerular filtration rate. The exact mechanism of the antihypertensive effect of hydrochlorothiazide is not known. The triamterene component of triamterene and hydrochlorothiazide capsule exerts its diuretic effect on the distal renal tubule to inhibit the reabsorption of sodium in exchange for potassium and hydrogen ions. Its natriuretic activity is limited by the amount of sodium reaching its site of action. Although it blocks the increase in this exchange that is stimulated by mineralocorticoids (chiefly aldosterone), it is not a competitive antagonist of aldosterone and its activity can be demonstrated in adrenalectomized rats and patients with Addison’s disease. As a result, the dose of triamterene required is not proportionally related to the level of mineralocorticoid activity, but is dictated by the response of the individual patients, and the kaliuretic effect of concomitantly administered drugs. By inhibiting the distal tubular exchange mechanism, triamterene maintains or increases the sodium excretion and reduces the excess loss of potassium, hydrogen, and chloride ions induced by hydrochlorothiazide. As with hydrochlorothiazide, 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 excretion. No predictable antihypertensive effect has been demonstrated for triamterene. Duration of diuretic activity and effective dosage range of the hydrochlorothiazide and triamterene components are similar. Onset of diuresis with triamterene and hydrochlorothiazide takes place within one hour, peaks at two to three hours and tapers off during the subsequent seven to nine hours. Triamterene and hydrochlorothiazide capsule are well absorbed. Upon administration of a single oral dose to fasted normal male volunteers, the following mean pharmacokinetic parameters were determined:

INDICATIONS AND USAGE

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displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

This fixed combination drug is not indicated for the initial therapy of edema or hypertension except in individuals in whom the development of hypokalemia cannot be risked. Triamterene and hydrochlorothiazide capsules are indicated for the treatment of hypertension or edema in patients who develop hypokalemia on hydrochlorothiazide alone. Triamterene and hydrochlorothiazide capsules are also indicated for those patients who require a thiazide diuretic and in whom the development of hypokalemia cannot be risked. Triamterene and hydrochlorothiazide may be used alone or as an adjunct to other antihypertensive drugs, such as beta-blockers. Since triamterene and hydrochlorothiazide may enhance the action of these agents, dosage adjustments may be necessary.

ADVERSE REACTIONS

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displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

Adverse effects are listed in decreasing order of severity.

DOSAGE AND ADMINISTRATION

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displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

The usual dose of triamterene and hydrochlorothiazide capsules is one or two capsules given once daily, with appropriate monitoring of serum potassium and of the clinical effect. (See WARNINGS: Hyperkalemia.)

OVERDOSAGE

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displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

Electrolyte imbalance is the major concern (See WARNINGS section). Symptoms reported include: polyuria, nausea, vomiting, weakness, lassitude, fever, flushed face, and hyperactive deep tendon reflexes. If hypotension occurs, it may be treated with pressor agents such as levarterenol to maintain blood pressure. Carefully evaluate the electrolyte pattern and fluid balance. Induce immediate evacuation of the stomach through emesis or gastric lavage. 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. Although triamterene is largely protein-bound (approximately 67%), there may be some benefit to dialysis in cases of overdosage.

HOW SUPPLIED

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displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Capsules containing 37.5 mg triamterene and 25 mg hydrochlorothiazide are available for oral administration as white capsules with single black ink bands imprinted GG 606 in black ink and supplied as: NDC 63187-465-30 bottles of 30 NDC 63187-465-60 bottles of 60 NDC 63187-465-90 bottles of 90

37.5 mg/25 mg Label

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displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

NDC 63187-465-90 Triamterene and Hydrochlorothiazide Capsules, USP 37.5 mg/25 mg Rx only 90 Capsules SANDOZ