Candesartan Cilexetil and Hydrochlorothiazide: Package Insert and Label Information
By Bryant Ranch Prepack | Last revised: 15 May 2014
CANDESARTAN CILEXETIL AND HYDROCHLOROTHIAZIDE- candesartan cilexetil and hydrochlorothiazide tablet
Bryant Ranch Prepack
WARNING: FETAL TOXICITY
When pregnancy is detected, discontinue candesartan cilexetil and hydrochlorothiazide tablets as soon as possible.
Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. See Warnings: Fetal Toxicity
DESCRIPTION
Candesartan cilexetil and hydrochlorothiazide tablets combines an angiotensin II receptor (type AT1 ) antagonist and a diuretic, hydrochlorothiazide.
Candesartan cilexetil, a nonpeptide, is chemically described as (�)-1-Hydroxyethyl 2-ethoxy-1-[p -(o -1H -tetrazol-5-ylphenyl)benzyl]-7-benzimidazolecarboxylate, cyclohexyl carbonate (ester).
Its empirical formula is C33 H34 N6 O6 , and its structural formula is
Chemical Structure for Candesartan cilexetil
(click image for full-size original)
Candesartan cilexetil is a white to off-white powder with a molecular weight of 610.67. It is practically insoluble in water and sparingly soluble in methanol. Candesartan cilexetil is a racemic mixture containing one chiral center at the cyclohexyloxycarbonyloxy ethyl ester group. Following oral administration, candesartan cilexetil undergoes hydrolysis at the ester link to form the active drug, candesartan, which is achiral.
Hydrochlorothiazide is 6-chloro-3,4-dihydro-2H -1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C7 H8 ClN3 O4 S2 and its structural formula is
Chemical Structure for Hydrochlorothiazide
Hydrochlorothiazide is a white, or practically white, odourless, crystalline powder with a molecular weight of 297.72, which is slightly soluble in water, but freely soluble in sodium hydroxide solution.
Candesartan cilexetil and hydrochlorothiazide tablets are available for oral administration in three tablet strengths of candesartan cilexetil and hydrochlorothiazide.
Candesartan cilexetil and hydrochlorothiazide tablets, 16 mg/12.5 mg contain 16 mg of candesartan cilexetil and 12.5 mg of hydrochlorothiazide.
Candesartan cilexetil and hydrochlorothiazide tablets, 32 mg/12.5 mg contain 32 mg of candesartan cilexetil and 12.5 mg of hydrochlorothiazide. Candesartan cilexetil and hydrochlorothiazide tablets, 32 mg/25 mg contain 32 mg of candesartan cilexetil and 25 mg of hydrochlorothiazide. The inactive ingredients of the tablets are lactose monohydrate, corn starch, hydroxypropyl cellulose, carboxymethyl cellulose calcium, triacetin, magnesium stearate, and ferric oxide yellow. Ferric oxide red is added only to the 16/12.5 mg and 32/25 mg tablets as colorant.
CLINICAL PHARMACOLOGY
Mechanism of Action
Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Candesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is, therefore, independent of the pathways for angiotensin II synthesis.
