ZIAC- bisoprolol fumarate and hydrochlorothiazide tablet, film coated
Teva Women’s Health, Inc.
ZIAC® (bisoprolol fumarate and hydrochlorothiazide) is indicated for the treatment of hypertension. It combines two antihypertensive agents in a once-daily dosage: a synthetic beta1 -selective (cardioselective) adrenoceptor blocking agent (bisoprolol fumarate) and a benzothiadiazine diuretic (hydrochlorothiazide).
Bisoprolol fumarate is chemically described as (±)-1-[4-[[2-(1-methylethoxy)ethoxy]methyl]phenoxy]-3-[(1-methylethyl)amino]-2-propanol(E)-2-butenedioate (2:1) (salt). It possesses an asymmetric carbon atom in its structure and is provided as a racemic mixture. The S(-) enantiomer is responsible for most of the beta-blocking activity. Its empirical formula is (C18 H31 NO4 )2•C4 H4 O4 and it has a molecular weight of 766.97
Hydrochlorothiazide (HCTZ) is 6-Chloro-3,4-dihydro-2H -1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. It is a white, or practically white, practically odorless crystalline powder. It is slightly soluble in water, sparingly soluble in dilute sodium hydroxide solution, freely soluble in n-butylamine and dimethylformamide, sparingly soluble in methanol, and insoluble in ether, chloroform, and dilute mineral acids. Its empirical formula is C7 H8 ClN3 O4 S2 and it has a molecular weight of 297.73.
Bisoprolol fumarate and HCTZ have been used individually and in combination for the treatment of hypertension. The antihypertensive effects of these agents are additive; HCTZ 6.25 mg significantly increases the antihypertensive effect of bisoprolol fumarate. The incidence of hypokalemia with the bisoprolol fumarate and HCTZ 6.25 mg combination (B/H) is significantly lower than with HCTZ 25 mg. In clinical trials of ZIAC, mean changes in serum potassium for patients treated with ZIAC 2.5/6.25 mg, 5/6.25 mg or 10/6.25 mg or placebo were less than ± 0.1 mEq/L. Mean changes in serum potassium for patients treated with any dose of bisoprolol in combination with HCTZ 25 mg ranged from -0.1 to -0.3 mEq/L.
Bisoprolol fumarate is a beta1 -selective (cardioselective) adrenoceptor blocking agent without significant membrane stabilizing or intrinsic sympathomimetic activities in its therapeutic dose range. At higher doses (? 20 mg) bisoprolol fumarate also inhibits beta2 -adrenoreceptors located in bronchial and vascular musculature. To retain relative selectivity, it is important to use the lowest effective dose.
Hydrochlorothiazide is a benzothiadiazine diuretic. Thiazides affect renal tubular mechanisms of electrolyte reabsorption and increase excretion of sodium and chloride in approximately equivalent amounts. Natriuresis causes a secondary loss of potassium.
INDICATIONS AND USAGE
ZIAC (bisoprolol fumarate and hydrochlorothiazide) is indicated in the management of hypertension.
ZIAC is contraindicated in patients in cardiogenic shock, overt cardiac failure (see WARNINGS), second or third degree AV block, marked sinus bradycardia, anuria, and hypersensitivity to either component of this product or to other sulfonamide-derived drugs.
DOSAGE AND ADMINISTRATION
Bisoprolol is an effective treatment of hypertension in once-daily doses of 2.5 to 40 mg, while hydrochlorothiazide is effective in doses of 12.5 to 50 mg. In clinical trials of bisoprolol/hydrochlorothiazide combination therapy using bisoprolol doses of 2.5 to 20 mg and hydrochlorothiazide doses of 6.25 to 25 mg, the antihypertensive effects increased with increasing doses of either component.