In the placebo-controlled trials involving 2316 patients with hypertension who have been treated with Tareg, the study drug showed an overall incidence of adverse experiences (AEs) comparable with that of placebo.
The following table of AEs is based on 10 placebo-controlled trials in patients treated with various doses of valsartan (10-320 mg) for up to 12 weeks. Of the 2316 patients, 1281 and 660 received 80 or 160 mg, respectively. With none of the AEs did their incidence appear to be related to dose or duration of treatment; therefore, AEs occurring on all doses of valsartan were pooled. The incidence of AEs also showed no association with gender, age or race. All adverse experiences showing an incidence of ≥1% in the Tareg treatment group are included in the following table, irrespective of their causal association with the study drug. (See table.)
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Other adverse experiences with a frequency <1% included oedema, asthenia, insomnia, rash, decreased libido and vertigo. It is unknown whether these effects were causally related to valsartan therapy.
Post-marketing data revealed very rare cases of angioedema, rash, pruritus and other hypersensitivity/allergic reactions including serum sickness and vasculitis. Very rare cases of impaired renal function have also been reported.
In double-blind, short-term heart failure trials, including the first 4 months of the Val-HeFT, the following drug-related adverse events were observed with an incidence >1% and more frequent in valsartan-treated patients than placebo-treated patients: Dizziness (excluding vertigo), hypotension, postural dizziness, postural hypotension, fatigue, diarrhoea, headache, nausea, renal impairment, hyperkalemia and vertigo. All patients received standard drug therapy for heart failure, frequently as multiple medications which could include diuretics, digitalis, β-blockers or ACE inhibitors.
From the long-term data in Val-HeFT, there did not appear to be any significant adverse events not already identified during short-term exposure.
Laboratory Findings: In rare cases, valsartan may be associated with decreases in haemoglobin and haematocrit. In controlled clinical trials, 0.8% and 0.4% of patients receiving Tareg showed significant decreases (>20%) in haematocrit and haemoglobin, respectively.
In comparison, 0.1% of patients receiving placebo showed decreases in both haematocrit and haemoglobin.
Neutropenia was observed in 1.9% of patients treated with valsartan vs 1.6% of patients treated with an ACE inhibitor.
In controlled clinical trials in hypertensive patients, significant increases in serum creatinine, potassium and total bilirubin were observed, respectively, in 0.8%, 4.4% and 6% of patients treated with valsartan vs 1.6%, 6.4% and 12.9% of those treated with an ACE inhibitor. Occasional elevations of liver function values were reported in patients treated with valsartan.
No special monitoring of laboratory parameters is necessary for patients with essential hypertension receiving valsartan therapy.
In heart failure patients, >50% increases in serum creatinine were observed in 3.9% of Tareg-treated patients compared to 0.9% of placebo-treated patients. In these patients, >20% increases in serum potassium were observed in 10% of Tareg-treated patients compared to 5.1% of placebo-treated patients.
In heart failure trials, >50% increases in blood urea nitrogen (BUN) were observed in 16.6% of patients treated with valsartan as compared to 6.3% of patients treated with placebo.