ATACAND HCT- candesartan cilexetil and hydrochlorothiazide tablet
AstraZeneca Pharmaceuticals LP
WARNING: FETAL TOXICITY
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When pregnancy is detected, discontinue ATACAND HCT as soon as possible.
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Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus
DESCRIPTION
ATACAND HCT (candesartan cilexetil-hydrochlorothiazide) combines an angiotensin II receptor (type AT1 antagonist and diuretic, hydrochlorothiazide.
Candesartan cilexetil, 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
Candesartan cilexetil is white to off-white powder with molecular weight of 610.67. It is practically insoluble in water and sparingly soluble in methanol. Candesartan cilexetil is 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
Hydrochlorothiazide is white, or practically white, crystalline powder with molecular weight of 297.72, which is slightly soluble in water, but freely soluble in sodium hydroxide solution.
ATACAND HCT 16-12.5 contains 16 mg of candesartan cilexetil and 12.5 mg of hydrochlorothiazide. ATACAND HCT 32-12.5 contains 32 mg of candesartan cilexetil and 12.5 mg of hydrochlorothiazide. ATACAND HCT 32?25 contains 32 mg of candesartan cilexetil and 25 mg of hydrochlorothiazide. The inactive ingredients of the tablets are carboxymethylcellulose calcium, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, cornstarch, polyethylene glycol 8000, and ferric oxide (yellow). Ferric oxide (reddish brown) is also added to the 16-12.5 mg and 32?25 mg tablets as colorant.
Mechanism of Action
Angiotensin II is formed from angiotensin in 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.
There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis. Candesartan has much greater affinity (>10,000-fold) for the AT1 receptor than for the AT2 receptor.
Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, reaction also catalyzed by ACE. Because candesartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known. Candesartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.
Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of candesartan on blood pressure.
Hydrochlorothiazide is thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so co?administration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics.
The mechanism of the antihypertensive effect of thiazides is unknown.
INDICATIONS AND USAGE
ATACAND HCT is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from wide variety of pharmacologic classes including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with ATACAND HCT
CONTRAINDICATIONS
ATACAND HCT is contraindicated in patients who are hypersensitive to candesartan, to hydrochlorothiazide or to other sulfonamide-derived drugs.
Do not co-administer aliskiren with ATACAND HCT in patients with diabetes (see PRECAUTIONS, Drug Interactions).
ATACAND HCT is contraindicated in patients with anuria.
Pregnancy Category D
DOSAGE AND ADMINISTRATION
The usual recommended starting dose of candesartan cilexetil is 16 mg once daily when it is used as monotherapy in patients who are not volume depleted. ATACAND can be administered once or twice daily with total daily doses ranging from mg to 32 mg. Patients requiring further reduction in blood pressure should be titrated to 32 mg. Doses larger than 32 mg do not appear to have greater blood pressure lowering effect.
Hydrochlorothiazide is effective in doses of 12.5 to 50 mg once daily.
HOW SUPPLIED
No. 3825 Tablets ATACAND HCT 16-12.5, are peach, oval, biconvex, non-film-coated tablets, scored on both sides and coded with ACS on one side. They are supplied as follows:
NDC 0186-0162-54 unit of use bottles of 90.
No. 3826 Tablets ATACAND HCT 32-12.5, are yellow, oval, biconvex, non-film-coated tablets, scored on both sides and coded with ACJ on one side. They are supplied as follows:
NDC 0186-0322-54 unit of use bottles of 90.
No. 3899 Tablets ATACAND HCT 32?25, are pink, oval, biconvex, non-film-coated tablets, scored on both sides and coded with ACD on one side. They are supplied as follows:
NDC 0186-0324-54 unit of use bottles of 90.
Storage:
Store at 25?C (77?F); excursions permitted to 15-30?C (59-86?F) [see USP Controlled Room Temperature]. Keep container tightly closed.
ATACAND HCT is registered trademark of the AstraZeneca group of companies.
