nction
As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (eg, patients with severe congestive heart failure), treatment with ACE inhibitors has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. Irbesartan would be expected to behave similarly. In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or BUN have been reported. There has been no known use of irbesartan in patients with unilateral or bilateral renal artery stenosis, but a similar effect should be anticipated.
Thiazides should be used with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
Irbesartan-Hydrochlorothiazide
AVALIDE (irbesartan-hydrochlorothiazide) Tablets has been eva luated for safety in 1694 patients treated for essential hypertension in 6 clinical trials. In Studies I through IV with AVALIDE, no adverse events peculiar to this combination drug product have been observed. Adverse events have been limited to those that were reported previously with irbesartan or hydrochlorothiazide (HCTZ). The overall incidence of adverse events was similar with the combination and placebo. In general, treatment with AVALIDE was well tolerated. For the most part, adverse events have been mild and transient in nature and have not required discontinuation of therapy. In controlled clinical trials, discontinuation of AVALIDE therapy due to clinical adverse events was required in only 3.6%. This incidence was significantly less (p=0.023) than the 6.8% of patients treated with placebo who discontinued therapy.
In these double-blind controlled clinical trials, the following adverse events reported with AVALIDE occurred in ≥1% of patients, and more often on the irbesartan-hydrochlorothiazide combination than on placebo, regardless of drug relationship:
Irbesartan/HCTZ
(n=898)
(%) Placebo
(n=236)
(%) Irbesartan
(n=400)
(%) HCTZ
(n=380)
(%)
Body as a Whole
Chest Pain 2 1 2 2
Fatigue 7 3 4 3
Influenza 3 1 2 2
Cardiovascular
Edema 3 3 2 2
Tachycardia 1 0 1 1
Gastrointestinal
Abdominal Pain 2 1 2 2
Dyspepsia/heartburn 2 1 0 2
Nausea/vomiting 3 0 2 0
Immunology
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