TRIAMTERENE, and, HYDROCHLOROTHIAZIDE, CAPSULES, USP, 37.5 mg/25 mg

/TRIAMTERENE, and, HYDROCHLOROTHIAZIDE, CAPSULES, USP, 37.5 mg/25 mg
TRIAMTERENE, and, HYDROCHLOROTHIAZIDE, CAPSULES, USP, 37.5 mg/25 mg2018-09-06T09:12:40+00:00

Prescription Drug Name:

TRIAMTERENE, and, HYDROCHLOROTHIAZIDE, CAPSULES, USP, 37.5 mg/25 mg

ID:

bd9a0909-1e4c-4ef3-a37b-bf4226d9e400

Code:

45129-4

DESCRIPTION


id: 11424709-b9b5-4cf6-b1ab-d417b65c46a9
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Each triamterene and hydrochlorothiazide capsule for oral administration contains hydrochlorothiazide 25 mg and triamterene 37.5 mg. Hydrochlorothiazide is a diuretic/antihypertensive agent and triamterene is an antikaliuretic agent. 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 and its structural formula is: Molecular Formula: C7H8ClN3O4S2 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 and its structural formula is: Molecular Formula: C12H11N7 Inactive ingredients consist of colloidal silicon dioxide, croscarmellose sodium, gelatin, magnesium stearate, microcrystalline cellulose, pharmaceutical glaze, polyethylene glycol, polysorbate 80, propylene glycol, silicon dioxide, sodium bicarbonate, sodium lauryl sulfate, synthetic black iron oxide, titanium dioxide, yellow iron oxide, D&C Yellow #10 Aluminum Lake, FD&C Blue #1, FD&C Blue #1 Aluminum Lake, FD&C Blue #2 Aluminum Lake, and FD&C Red #40 Aluminum Lake. Triamterene and Hydrochlorothiazide Capsules, USP 37.5 mg/25 mg meet USP Dissolution Test 3.

CLINICAL PHARMACOLOGY


id: 6ca0e9eb-a3e3-4989-9d3b-d6d410411b41
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

The triamterene and hydrochlorothiazide capsule 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 capsules 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 of triamterene and hydrochlorothiazide capsules are similar. Onset of diuresis with triamterene and hydrochlorothiazide takes place within 1 hour, peaks at 2 to 3 hours and tapers off during the subsequent 7 to 9 hours. Triamterene and hydrochlorothiazide capsules are well absorbed. Upon administration of a single oral dose to fasted normal male volunteers, the following mean pharmacokinetic parameters were determined:

AUC(0–48)
ng*hrs/mL
(±SD)
Cmax
ng/mL
(±SD)
Median
Tmax
hrs
Ae
mg
(±SD)
triamterene 148.7 (87.9) 46.4 (29.4) 1.1 2.7 (1.4)
hydroxytriamterene sulfate 1865 (471) 720 (364) 1.3 19.7 (6.1)
hydrochlorothiazide 834 (177) 135.1 (35.7) 2.0 14.3 (3.8)
where AUC(0–48), Cmax, Tmax and Ae represent area under the plasma concentration versus time plot, maximum plasma concentration, time to reach Cmax and amount excreted in urine over 48 hours. One triamterene and hydrochlorothiazide capsule is bioequivalent to a single-entity 25 mg hydrochlorothiazide tablet and 37.5 mg triamterene capsule used in the double-blind clinical trial below. (See Clinical Trials.) In a limited study involving 12 subjects, coadministration of triamterene and hydrochlorothiazide capsules with a high-fat meal resulted in: (1) an increase in the mean bioavailability of triamterene by about 67% (90% confidence interval = 0.99, 1.90), p-hydroxytriamterene sulfate by about 50% (90% confidence interval = 1.06, 1.77), hydrochlorothiazide by about 17% (90% confidence interval = 0.90, 1.34); (2) increases in the peak concentrations of triamterene and p-hydroxytriamterene; and (3) a delay of up to 2 hours in the absorption of the active constituents.

INDICATIONS AND USAGE


id: 2998e170-77ee-466d-a4cc-313e272a277e
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 capsules may be used alone or as an adjunct to other antihypertensive drugs, such as beta-blockers. Since triamterene and hydrochlorothiazide capsules may enhance the action of these agents, dosage adjustments may be necessary.

ADVERSE REACTIONS


id: fbeca8b3-df4a-4cd0-9e0b-77415fa7a257
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

Adverse effects are listed in decreasing order of frequency; however, the most serious adverse effects are listed first regardless of frequency. The serious adverse effects associated with triamterene and hydrochlorothiazide capsules have commonly occurred in less than 0.1% of patients treated with this product. Hypersensitivity: anaphylaxis, rash, urticaria, photosensitivity. Cardiovascular: arrhythmia, postural hypotension. Metabolic: diabetes mellitus, hyperkalemia, hyperglycemia, glycosuria, hyperuricemia, hypokalemia, hyponatremia, acidosis, hypochloremia. Gastrointestinal: jaundice and/or liver enzyme abnormalities, pancreatitis, nausea and vomiting, diarrhea, constipation, abdominal pain. Renal: acute renal failure (one case of irreversible renal failure has been reported), interstitial nephritis, renal stones composed primarily of triamterene, elevated BUN and serum creatinine, abnormal urinary sediment. Hematologic: leukopenia, thrombocytopenia and purpura, megaloblastic anemia. Musculoskeletal: muscle cramps. Central Nervous System: weakness, fatigue, dizziness, headache, dry mouth. Miscellaneous: impotence, sialadenitis. Thiazides alone have been shown to cause the following additional adverse reactions: Central Nervous System: paresthesias, vertigo. Ophthalmic: xanthopsia, transient blurred vision. Respiratory: allergic pneumonitis, pulmonary edema, respiratory distress. Other: necrotizing vasculitis, exacerbation of lupus. Hematologic: aplastic anemia, agranulocytosis, hemolytic anemia. Neonate and Infancy: thrombocytopenia and pancreatitis – rarely, in newborns whose mothers have received thiazides during pregnancy.

OVERDOSAGE


id: 5d14e03f-ebbc-478c-8196-44677328bc7c
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

Electrolyte imbalance is the major concern (see WARNINGS). 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 norepinephrine 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.

DOSAGE AND ADMINISTRATION


id: ab74ed67-3a39-41bd-8812-ae142d13882e
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.)

HOW SUPPLIED


id: f24d8a1a-ffd4-4656-aced-b240bdc44119
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Triamterene and Hydrochlorothiazide Capsules, USP are available containing 37.5 mg triamterene and 25 mg hydrochlorothiazide in opaque olive and opaque rich yellow capsules imprinted in black ink with MYLAN over 2537 on both body and cap. They are supplied by State of Florida DOH Central Pharmacy as follows:

NDC Strength Quantity/Form Color Source Prod. Code
53808-0802-1 25 mg / 37.5 mg 30 Capsules in a Blister Pack Rich yellow Opaque 0378-2537

37.5/25 mg Triamterene and Hydrochlorothiazide


id: 24c8413d-9290-4808-ae0f-f1f545f82cdb
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4