Dyazide Information
Dyazide (Triamterine) Description
Each capsule of Dyazide (Triamterine) (hydrochlorothiazide and triamterene) for oral use, with opaque red cap and opaque white body, contains hydrochlorothiazide 25 mg and triamterene 37.5 mg, and is imprinted with the product name Dyazide (Triamterine) and SB. 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-2-1, 2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide, and its structural formula is:
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:
Inactive ingredients consist of benzyl alcohol, cetylpyridinium chloride, D&C Red No. 33, FD&C Yellow No. 6, gelatin, glycine, lactose, magnesium stearate, microcrystalline cellulose, povidone, polysorbate 80, sodium starch glycolate, titanium dioxide, and trace amounts of other inactive ingredients.
Capsules of Dyazide (Triamterine) meet Drug Release Test 3 as published in the current USP monograph for Triamterene and Hydrochlorothiazide Capsules.
Dyazide (Triamterine) Clinical Pharmacology
Dyazide (Triamterine) 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 Dyazide (Triamterine) 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 Dyazide (Triamterine) are similar. Onset of diuresis with Dyazide (Triamterine) takes place within 1 hour, peaks at 2 to 3 hours and tapers off during the subsequent 7 to 9 hours.
Dyazide (Triamterine) is well absorbed.
Upon administration of a single oral dose to fasted normal male volunteers, the following mean pharmacokinetic parameters were determined:
where AUC C, T and Ae represent area under the plasma concentration versus time plot, maximum plasma concentration, time to reach C, and amount excreted in urine over 48 hours.
A capsule of Dyazide (Triamterine) 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 Dyazide (Triamterine) 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.
Dyazide (Triamterine) Clinical Trials
A placebo-controlled, double-blind trial was conducted to evaluate the efficacy of Dyazide (Triamterine) . This trial demonstrated that Dyazide (Triamterine) (25 mg hydrochlorothiazide/37.5 mg triamterene) was effective in controlling blood pressure while reducing the incidence of hydrochlorothiazide-induced hypokalemia. This trial involved 636 patients with mild to moderate hypertension controlled by hydrochlorothiazide 25 mg daily and who had hypokalemia (serum potassium
Blood pressure and serum potassium were monitored at baseline and throughout the trial. All five treatment groups had similar mean blood pressure and serum potassium concentrations at baseline (mean systolic blood pressure range: 137±14 mmHg to 140±16 mmHg; mean diastolic blood pressure range: 86±9 mmHg to 88±8 mmHg; mean serum potassium range: 2.3 to 3.4 mEq/L with the majority of patients having values between 3.1 and 3.4 mEq/L).
While all triamterene regimens reversed hypokalemia, at week 4 the 37.5 mg regimen proved optimal compared with the other tested regimens. On this regimen, 81% of the patients had a significant (p
Dyazide (Triamterine) Indications And Usage
Dyazide (Triamterine) is indicated for the treatment of hypertension or edema in patients who develop hypokalemia on hydrochlorothiazide alone.
Dyazide (Triamterine) is also indicated for those patients who require a thiazide diuretic and in whom the development of hypokalemia cannot be risked.
Dyazide (Triamterine) may be used alone or as an adjunct to other antihypertensive drugs, such as beta-blockers. Since Dyazide (Triamterine) may enhance the action of these agents, dosage adjustments may be necessary.
Dyazide (Triamterine) Contraindications
Dyazide (Triamterine) should not be given to patients receiving other potassium-sparing agents such as spironolactone, amiloride, or other formulations containing triamterene. Concomitant potassium-containing salt substitutes should also not be used.
Potassium supplementation should not be used with Dyazide (Triamterine) except in severe cases of hypokalemia. Such concomitant therapy can be associated with rapid increases in serum potassium levels. If potassium supplementation is used, careful monitoring of the serum potassium level is necessary.
Dyazide (Triamterine) Warnings
Hyperkalemia:
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 hyperkalemia may not be associated with ECG changes.
If hyperkalemia is present, Dyazide (Triamterine) 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 section). 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 administration of Dyazide (Triamterine) to elderly patients and patients with impaired renal function.
Hyperkalemia has been reported in diabetic patients with the use of potassium-sparing agents even in the absence of apparent renal impairment. Accordingly, serum electrolytes must be frequently monitored if Dyazide (Triamterine) is used in diabetic patients.
Dyazide (Triamterine) Adverse Reactions
Adverse effects are listed in decreasing order of severity.
Impotence, sialadenitis.
Thiazides alone have been shown to cause the following additional adverse reactions:
Dyazide (Triamterine) Dosage And Administration
The usual dose of Dyazide (Triamterine) is one or two capsules given once daily, with appropriate monitoring of serum potassium and of the clinical effect (see WARNINGS, Hyperkalemia).
Dyazide (Triamterine) Overdosage
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.
Dyazide (Triamterine) How Supplied
Capsules containing 25 mg hydrochlorothiazide and 37.5 mg triamterene, in bottles of 1,000 capsules; in Patient-Pak™ unit-of-use bottles of 100.
They are supplied as follows:
NDC 0007-3650-22–in Patient-Pak unit-of-use bottles of 100.
NDC 0007-3650-30–bottles of 1,000.
Store at controlled room temperature 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). Protect from light. Dispense in a tight, light-resistant container.
GlaxoSmithKline
Research Triangle Park, NC 27709
Dyazide (Triamterine) is a registered trademark of GlaxoSmithKline.
©2011, GlaxoSmithKline. All rights reserved.
February 2011
DYZ:74PI
Dyazide (Triamterine) Principal Display Panel
Store at controlled room temperature 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).
Protect from light. Dispense in a tight, light-resistant container.
Each capsule contains 25 mg hydrochlorothiazide and 37.5 mg triamterene.
Dyazide (Triamterine) capsules meet Drug Release Test 3 as published in the current USP monograph for Triamterene and Hydrochlorothiazide Capsules.
GlaxoSmithKline
RTP, NC 27709
Made in Canada
Rev. 7/08
A059478
