r 4weeks. In long-term follow-up studies (without placebo control) the effect of valsartan appeared to be maintained for up to two years. The antihypertensive effect is independent of age, gender or race. The latter finding regarding race is based on pooled data and should be viewed with caution, because antihypertensive drugs that affect the renin-angiotensin system (that is, ACE inhibitors and angiotensinII blockers) have generally been found to be less effective in low-renin hypertensives (frequently Blacks) than in high-renin hypertensives (frequently Whites). In pooled, randomized, controlled trials of Diovan that included a total of 140 Blacks and 830 Whites, valsartan and an ACE-inhibitor control were generally at least as effective in Blacks as Whites. The explanation for this difference from previous findings is unclear.
Abrupt withdrawal of valsartan has not been associated with a rapid increase in blood pressure.
The 7 studies of valsartan monotherapy included over 2000 patients randomized to various doses of valsartan and about 800 patients randomized to placebo. Doses below 80mg were not consistently distinguished from those of placebo at trough, but doses of 80, 160 and 320mg produced dose-related decreases in systolic and diastolic blood pressure, with the difference from placebo of approximately 6-9/3-5mmHg at 80-160mg and 9/6mmHg at 320mg.
Patients with an inadequate response to 80mg once daily were titrated to either 160mg once daily or 80mg twice daily, which resulted in a comparable response in both groups.
In another 4-week study, 1876 patients randomized to valsartan 320mg once daily had an incremental blood pressure reduction 3/1mmHg lower than did 1900 patients randomized to valsartan 160mg once daily.
In controlled trials, the antihypertensive effect of once daily valsartan 80mg was similar to that of once daily enalapril 20mg or once daily lisinopril 10mg.
There was essentially no change in heart rate in valsartan-treated patients in controlled trials.
14.2 Initial Therapy-Hypertension
The safety and efficacy of DiovanHCT as initial therapy for patients with severe hypertension (defined as a sitting diastolic blood pressure ≥110mmHg and systolic blood pressure ≥140mmHg off all antihypertensive therapy) was studied in a 6-week multicenter, randomized, double-blind study. Patients were randomized to either DiovanHCT (valsartan and hydrochlorothiazide 160/12.5mg once daily) or to valsartan (160mg once daily) and followed for blood pressure response. Patients were force-titrated at 2-week intervals. Patients on combination therapy were subsequently titrated to 160/25mg followed by 320/25mg valsartan/hydrochlorothiazide. Patients on monotherapy were subsequently titrated to 320mg valsartan followed by a titration to 320mg valsartan to maintain the blind.
The study randomized 608 patients, including 261 (43%) females, 147 (24%) Blacks, and 75 (12%) ≥65 years of age. The mean blood pressure at baseline for the total population was 168/112mmHg. The mean age was 52 years. After 4 weeks of therapy, reductions in systolic and diastolic blood pressure were 9/5mmHg greater in the group treated with DiovanHCT compared to valsartan. Similar trends were seen when the patients were grouped according to gender, race or age.
16HOW SUPPLIED/STORAGE AND HANDLING
DiovanHCT (valsartan and hydrochlorothiazide, USP) is available as non-scored tablets containing valsartan/hydrochlorothiazide 80/1 |
