Because clinical studies are conducted under widely varying conditions, adverse reactions rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies 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.

Hypertension

Diovan HCT (valsartan and hydrochlorothiazide, USP) has been eva luated for safety in more than 5,700 patients, including over 990 treated for over 6 months, and over 370 for over 1 year. Adverse experiences have generally been mild and transient in nature and have only infrequently required discontinuation of therapy. The overall incidence of adverse reactions with Diovan HCT was comparable to placebo.

The overall frequency of adverse reactions was neither dose-related nor related to gender, age, or race. In controlled clinical trials, discontinuation of therapy due to side effects was required in 2.3% of valsartan-hydrochlorothiazide patients and 3.1% of placebo patients. The most common reasons for discontinuation of therapy with Diovan HCT were headache and dizziness.

The only adverse reaction that occurred in controlled clinical trials in at least 2% of patients treated with Diovan HCT and at a higher incidence in valsartan-hydrochlorothiazide (n=4372) than placebo (n=262) patients was nasopharyngitis (2.4% vs. 1.9%).

Dose-related orthostatic effects were seen in fewer than 1% of patients. In individual trials, a dose-related increase in the incidence of dizziness was observed in patients treated with Diovan HCT.

Other adverse reactions that have been reported with valsartan-hydrochlorothiazide (>0.2% of valsartan-hydrochlorothiazide patients in controlled clinical trials) without regard to causality, are listed below:

Cardiovascular : Palpitations and tachycardia

Ear and L abyrinth : Tinnitus and vertigo

Gastrointestinal : Dyspepsia, diarrhea, flatulence, dry mouth, nausea, abdominal pain, abdominal pain upper, and vomiting

General and A dministration S ite C onditions : Asthenia, chest pain, fatigue, peripheral edema and pyrexia

Infections and I nfestations : Bronchitis, bronchitis acute, influenza, gastroenteritis, sinusitis, upper respiratory tract infection and urinary tract infection

Investigations : Blood urea increased

Musculoskeletal : Arthralgia, back pain, muscle cramps, myalgia, and pain in extremity

Nervous S ystem : Dizziness postural, paresthesia, and somnolence

Psychiatric : Anxiety and insomnia

Renal and U rinary : Pollakiuria

Reproductive S ystem : Erectile dysfunction

Respiratory, T horacic and M ediastinal : Dyspnea, cough, nasal congestion, pharyngolaryngeal pain and sinus congestion

Skin and S ubcutaneous T issue : Hyperhidrosis and rash

Vascular : Hypotension

Other reported reactions seen less frequently in clinical trials included abnormal vision, anaphylaxis, bronchospasm, constipation, depression, dehydration, decreased libido, dysuria, epistaxis, flushing, gout, increased appetite, muscle weakness, pharyngitis, pruritus, sunburn, syncope, and viral infection.

Valsartan : In trials in which val