Hydrochlorothiazide

The degree to which hydrochlorothiazide is removed by hemodialysis has not been established. The most common signs and symptoms observed in patients are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.

The oral LDof hydrochlorothiazide is greater than 10 g/kg in both mice and rats, 2000 and 4000 times, respectively, the maximum recommended human dose on a mg/mbasis. (Calculations assume an oral dose of 25 mg/day and a 60-kg patient.)

Valsartan and Hydrochlorothiazide

In rats and marmosets, single oral doses of valsartan up to 1524 and 762 mg/kg in combination with hydrochlorothiazide at doses up to 476 and 238 mg/kg, respectively, were very well tolerated without any treatment-related effects. These no adverse effect doses in rats and marmosets, respectively, represent 46.5 and 23 times the maximum recommended human dose (MRHD) of valsartan and 188 and 113 times the MRHD of hydrochlorothiazide on a mg/mbasis. (Calculations assume an oral dose of 320 mg/day valsartan in combination with 25 mg/day hydrochlorothiazide and a 60-kg patient.)

Exforge HCT is a fixed combination of amlodipine, valsartan and hydrochlorothiazide.

Exforge HCT contains the besylate salt of amlodipine, a dihydropyridine calcium channel blocker (CCB). Amlodipine besylate, USP is a white to pale yellow crystalline powder, slightly soluble in water and sparingly soluble in ethanol. Amlodipine besylate’s chemical name is 3-Ethyl 5-methyl (±)-2-[(2-aminoethoxy)methyl]-4-(o-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate, monobenzenesulfonate ; its structural formula is

Its empirical formula is CHClNO•CHOS and its molecular weight is 567.1.

Valsartan, USP is a nonpeptide, orally active, and specific angiotensin II antagonist acting on the AT receptor subtype. Valsartan is a white to practically white fine powder, soluble in ethanol and methanol and slightly soluble in water. Valsartan’s chemical name is N-(1-oxopentyl)-N-[[2′-(1H-tetrazol-5-yl) [1,1′-biphenyl]-4-yl]methyl]-L-valine; its structural formula is

Its empirical formula is CHNO and its molecular weight is 435.5.

Hydrochlorothiazide, USP is a white, or practically white, practically odorless, crystalline powder. It is slightly soluble in water; freely soluble in sodium hydroxide solution, in n-butylamine, and in dimethylformamide; sparingly soluble in methanol; and insoluble in ether, in chloroform, and in dilute mineral acids. Hydrochlorothiazide is chemically described as 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7- sulfonamide 1,1-dioxide.

Hydrochlorothiazide is a thiazide diuretic. Its empirical formula is CHClNOS, its molecular weight is 297.73, and its structural formula is

Exforge HCT film-coated tablets are formulated in five strengths for oral administration with a combination of amlodipine besylate, valsartan and hydrochlorothiazide, provid