HYZAAR® 100-12.5 mg Offers A New Convenient Dosing Option Within The Losartan Family; New Dosage Tablet Combines the Once-Daily Efficacy of COZAAR® 100 mg with a Low-Dose Diuretic

Business Wire, Oct 21, 2005

Cozaar(R) and Hyzaar(R) are registered trademarks of E.I. du Pont de Nemours & Co., Inc., Wilmington, Del., USA

Full prescribing information for HYZAAR is attached.

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HYZAAR(R) 50-12.5 (Losartan Potassium-Hydrochlorothiazide Tablets)

HYZAAR(R) 100-12.5 (Losartan Potassium-Hydrochlorothiazide Tablets)

HYZAAR(R) 100-25 (Losartan Potassium-Hydrochlorothiazide Tablets)

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USE IN PREGNANCY

When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, HYZAAR should be discontinued as soon as possible. See WARNINGS, Fetal/Neonatal Morbidity and Mortality.

DESCRIPTION

HYZAAR* 50-12.5 (losartan potassium-hydrochlorothiazide), HYZAAR* 100-12.5 (losartan potassium-hydrochlorothiazide) and HYZAAR* 100-25 (losartan potassium-hydrochlorothiazide), combine an angiotensin II receptor (type AT1) antagonist and a diuretic, hydrochlorothiazide.

Losartan potassium, a non-peptide molecule, is chemically described as 2-butyl-4-chloro-1-(p-(o-1H-tetrazol-5-ylphenyl)benzyl) imidazole-5-methanol monopotassium salt. Its empirical formula is C22H22ClKN6O, and its structural formula is:

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Losartan potassium is a white to off-white free-flowing crystalline powder with a molecular weight of 461.01. It is freely soluble in water, soluble in alcohols, and slightly soluble in common organic solvents, such as acetonitrile and methyl ethyl ketone.

Oxidation of the 5-hydroxymethyl group on the imidazole ring results in the active metabolite of losartan.

Hydrochlorothiazide is 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C7H8ClN3O4S2 and its structural formula is:

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* Registered trademark of E.I. du Pont de Nemours and Company, Wilmington, Delaware, USA

COPYRIGHT (C) 1995, 2004 MERCK & CO., Inc.

Whitehouse Station, NJ, USA

All rights reserved

Hydrochlorothiazide is a white, or practically white, crystalline powder with a molecular weight of 297.74, which is slightly soluble in water, but freely soluble in sodium hydroxide solution.

HYZAAR is available for oral administration in three tablet combinations of losartan and hydrochlorothiazide. HYZAAR 50-12.5 contains 50 mg of losartan potassium and 12.5 mg of hydrochlorothiazide. HYZAAR 100-12.5 contains 100 mg of losartan potassium and 12.5 mg of hydrochlorothiazide. HYZAAR 100-25 contains 100 mg of losartan potassium and 25 mg of hydrochlorothiazide. Inactive ingredients are microcrystalline cellulose, lactose hydrous, pregelatinized starch, magnesium stearate, hydroxypropyl cellulose, hypromellose, and titanium dioxide. HYZAAR 50-12.5 and HYZAAR 100-25 also contain D&C yellow No. 10 aluminum lake. HYZAAR 100-12.5 may also contain carnauba wax.

HYZAAR 50-12.5 contains 4.24 mg (0.108 mEq) of potassium, HYZAAR 100-12.5 contains 8.48 mg (0.216 mEq) of potassium, and HYZAAR 100-25 contains 8.48 mg (0.216 mEq) of potassium.

CLINICAL PHARMACOLOGY