A new antihypertensive agent: Maxzide (75 mg triamterene/50 mg hydrochlorothiazide)

Abstract

The combination of potassium-sparing diuretics with hydrochlorothiazide is extensively used by hypertensive patients. In the United States, a capsule formulation containing 50 mg triamterene and 25 mg hydrochlorothiazide (Dyazide) is the most popular fixed-combination product. However, several investigators have confirmed that absorption of both the triamterene and hydrochlorothiazide components of Dyazide is markedly reduced. This reduced bioavailability may reduce its effectiveness in hypertensive patients who change from optimally bioavailable hydrochlorothiazide tablets to Dyazide capsules in an effort to correct hypokalemia. Scored tablets containing 75 mg triamterene/50 mg hydrochlorothiazide (Maxzide) have been developed using a patented parallel granulation manufacturing process and evaluated in a series of bioavailability-bioequivalence studies. The triamterene and hydrochlorothiazide components of Maxzide tablets were found to be as bioavailable as liquid preparations of the active ingredients given singly or in combination. Unlike Dyazide capsules, the hydrochlorothiazide component of Maxzide tablets was found to be absorbed to the same extent as single-entity hydrochlorothiazide tablets. These studies demonstrated that two Dyazide capsules (total of 100 mg triamterene/50 mg hydrochlorothiazide) deliver to the bloodstream approximately one-half the quantity of hydrochlorothiazide as one Maxzide (75 mg triamterene/50 mg hydrochlorothiazide) tablet or one 50 mg hydrochlorothiazide tablet. Similarly, two Dyazide capsules deliver approximately one-half the quantity of triamterene as one Maxzide tablet. The safety of Maxzide tablets (dose of one tablet a day) was then evaluated in three groups of hypertensive patients: those who previously had been given two Dyazide capsules a day, those who had received four Dyazide capsules a day, and newly diagnosed patients who had received no medication. The clinical condition of the patients who changed from two or four Dyazide capsules to one Maxzide tablet was not compromised. Indeed, significant reductions in blood pressures were observed, especially in some patients who had remained hypertensive while receiving Dyazide. As expected, the blood pressures of the previously untreated group also decreased significantly with Maxzide tablets. Clinically significant hyperkalemia or hypokalemia did not develop. There were no clinically significant changes in blood urea nitrogen, creatinine, or uric acid levels. In addition to enhanced bioavailability, Maxzide tablets offer the advantages of once-a-day dosing.