Nebivolol and Valsartan Tablets

The following serious adverse reactions are included in more detail in the WARNINGS AND PRECAUTIONS section of the label:

• Hypotension [see WARNINGS AND PRECAUTIONS]
• Hyperkalemia [see WARNINGS AND PRECAUTIONS]

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.

BYVALSON has been evaluated for safety in patients with hypertension. A total of 1,664 patients received at least 1 dose of a fixed-dose combination of nebivolol/valsartan in an 8-week trial. A total of 807 patients received at least 1 dose of nebivolol and valsartan in an open-label safety study; of these, 621 patients completed 180 days and 476 patients completed 360 days of open-label treatment with nebivolol and valsartan.

The safety of the 5 mg/ 80 mg dose of nebivolol/valsartan was evaluated during the first 4 weeks of an 8-week placebo-controlled trial. During the 4 week period, the overall incidence of adverse events on therapy with BYVALSON 5 mg/ 80 mg was similar to placebo and the individual components (nebivolol 5 mg and valsartan 80 mg). Discontinuation of therapy due to a clinical adverse event occurred in 2.0% of patients treated with BYVALSON 5 mg/ 80 mg versus 3.2% of patients given placebo and approximately 1% of patients given nebivolol 5 mg or valsartan 80 mg as monotherapy.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of either nebivolol or valsartan. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions have been reported in post-marketing experience:

Cardiac: atrioventricular block (both second and third degree), myocardial infarction

Central Nervous System: somnolence, syncope, vertigo

Circulatory: Raynaud's phenomenon, peripheral ischemia/claudication, thrombocytopenia

Dermatologic: pruritus, psoriasis, various rashes and skin disorders

Digestive: vomiting

Hepatic: Abnormal hepatic function (including increased AST, ALT and bilirubin)

Hypersensitivity: hypersensitivity (including urticaria, allergic vasculitis and rare reports of angioedema)

Renal: acute renal failure Respiratory: acute pulmonary edema, bronchospasm

Sexual Dysfunction: erectile dysfunction

The following additional adverse reactions have been reported in post-marketing experience:

Hypersensitivity: Angioedema.

Digestive: Elevated liver enzymes, hepatitis

Renal: Impaired renal function, renal failure

Clinical Laboratory Tests: Hyperkalemia

Dermatologic: Alopecia, bullous dermatitis

Blood and Lymphatic: thrombocytopenia

Vascular: Vasculitis