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

WHITEHOUSE STATION, N.J. -- Merck & Co., Inc., today announced the availability of HYZAAR(R) 100-12.5 mg (losartan potassium/hydrochlorothiazide tablets), a new tablet that combines the once-daily efficacy of 100 mg COZAAR(R) (losartan potassium tablets) with a low-dose diuretic to provide greater convenience and enhance titration options within the losartan family. HYZAAR 100-12.5 mg contains 100 mg of losartan and 12.5 mg of hydrochlorothiazide (HCTZ).

The addition of HYZAAR 100-12.5 mg to the losartan family of medicines offers a new, convenient titration step for doctors treating hypertension in patients whose blood pressure is not adequately controlled by COZAAR 100 mg. HYZAAR 100-12.5 mg, now available at pharmacies, is available by prescription only and is priced the same as COZAAR 100 mg.

HYZAAR is also indicated to reduce the risk of stroke in patients with hypertension and LVH (Left Ventricular Hypertrophy)

In April 2005, the FDA approved HYZAAR to reduce the risk of stroke based on the landmark LIFE (Losartan Intervention for Endpoint Reduction in Hypertension) study. HYZAAR and COZAAR are the only angiotensin II receptor blockers (ARBs) indicated to reduce the risk of stroke in patients with hypertension and LVH. There is evidence that this benefit does not apply to black patients.

In the LIFE trial, 4,605 patients were randomized to receive once daily losartan 50 mg and 4,588 patients to receive once daily atenolol 50 mg. If goal blood pressure (<140/90 mmHg) was not reached, hydrochlorothiazide (12.5 mg) was added first and, if needed, the dose of losartan or atenolol was then increased to 100 mg once daily. If necessary, other antihypertensive treatments (e.g., increase in dose of hydrochlorothiazide therapy to 25 mg or addition of other diuretic therapy, calcium channel blockers, alpha-blockers or centrally acting agents, but not ACE inhibitors, angiotensin II antagonists or beta-blockers) were added to the treatment regimen to reach the goal blood pressure. Patients in the LIFE trial were followed for an average of 4.8 years.

The results showed that in patients treated with losartan, the risk of first occurrence of cardiovascular death, nonfatal stroke or nonfatal myocardial infarction (primary endpoint) was reduced by a statistically significant 13 percent (p= 0.021) compared to patients treated with atenolol, despite similar blood pressure reductions in both treatment arms. This difference was primarily the result of an effect on fatal and nonfatal stroke, where the treatment with a regimen based on losartan (COZAAR) significantly reduced the risk of stroke (fatal and nonfatal) by 25 percent in patients with hypertension and LVH versus treatment with a regimen based on the beta-blocker atenolol (p=0.001). There were 232 fatal and nonfatal strokes in the group treated with losartan, and 309 in the atenolol group. Other findings from the LIFE study showed no significant difference between the treatment groups in the risk of heart attack or cardiovascular death.

Blood pressure reduction measured at trough was similar for both treatment groups. At the end of the study or at the last visit before a primary endpoint, the mean blood pressures were 144.1/81.3 mmHg for the losartan-based group and 145.4/80.9 mmHg for the atenolol-based group. The difference in systolic blood pressure of 1.3 mmHg was significant (p<0.001), while the difference of 0.4 mmHg in diastolic blood pressure was not significant (p=0.098).

The label for HYZAAR also states that, in the LIFE trial, black patients with hypertension and LVH taking atenolol had a lower risk of stroke than those taking COZAAR. Given the difficulty in interpreting subset differences in large trials, it cannot be known whether the observed difference is the result of chance. However, the LIFE study does not provide evidence that the benefits of COZAAR on reducing the risk of cardiovascular events in hypertensive patients with left ventricular hypertrophy apply to black patients.

Dosing information

In patients with hypertension, the usual starting dose is COZAAR 50 mg once daily. The maximum daily dose is 100 mg. If the antihypertensive effect measured at trough using once-a-day dosing is inadequate, a twice-a-day regimen at the same total daily dose or an increase in dose may give a more satisfactory response. In patients who are volume-depleted, symptomatic hypotension may occur after initiation of therapy with COZAAR. This condition should be corrected prior to administration of COZAAR, or a dosage of COZAAR 25 mg should be used. In patients with a history of hepatic impairment, a starting dose of COZAAR 25 mg should be used.

A patient whose blood pressure is not adequately controlled with COZAAR 100 mg may be switched to HYZAAR 100-12.5 mg once daily. If blood pressure remains uncontrolled after about three weeks of therapy, the dose may be increased to HYZAAR 100-25 mg (losartan 100 mg/hydrochlorothiazide 25 mg) once daily. The maximum dose is one tablet of HYZAAR 100-25 mg once daily.

In hypertensive patients with left ventricular hypertrophy, treatment should be initiated with COZAAR 50 mg once daily. Hydrochlorothiazide 12.5 mg should be added or HYZAAR 50-12.5 mg substituted if the blood pressure reduction is inadequate. If additional blood pressure reduction is needed, COZAAR 100 mg and hydrochlorothiazide 12.5 mg or HYZAAR 100-12.5 mg may be substituted followed by COZAAR 100 mg and hydrochlorothiazide 25 mg or HYZAAR 100-25 mg.

Additional indication for HYZAAR

HYZAAR is the only combination antihypertensive product that is indicated for initial use in appropriate patients with severe hypertension. HYZAAR is not indicated for initial therapy of hypertension, except when the hypertension is severe enough that the value of achieving prompt blood pressure control exceeds the risk of initiating combination therapy in these patients. This unique indication is based on a six week double-blind, randomized study to determine the efficacy and safety of HYZAAR versus. losartan monotherapy in 585 patients as initial therapy for severe hypertension (defined as a mean SiDBP =>110mmHg confirmed on two separate occasions off all antihypertensive therapy).