Rx Product Profile: Byvalson

The FDA has approved byvalson (nebivolol and valsartan) tablets by Allergan for the treatment of hypertension (high blood pressure [BP]).¹ An estimated 30% of American adults have hypertension, about half of whom have not achieved their BP goals.² Two-thirds of patients with hypertension will require more than 1 medication to achieve BP control. Byvalson is the only fixed-dose combination of a beta-blocker and an angiotensin II receptor blocker available in the United States.² Lowering BP reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions (MIs). These effects have been seen in controlled trials of antihypertensive medications, including drugs in the classes to which the components of Byvalson belong; however, no controlled studies demonstrate risk reduction with Byvalson.^1,2

Pharmacology and Pharmacokinetics

Nebivolol is a beta-adrenergic receptor blocking agent. In most individuals and at doses ≤10 mg, it is beta-1 selective. Valsartan is an angiotensin II receptor blocker that blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. After an oral dose of Byvalson, peak plasma concentrations of nebivolol are reached in approximately 1 to 6 hours and valsartan in approximately 2 to 4 hours.¹

Dosage and Administration

When used as initial therapy and in patients who are not adequately controlled on valsartan 80 mg or nebivolol ≤10 mg, Byvalson should be dosed as a 5-mg/80-mg tablet orally once a day. In patients who are already using nebivolol 5 mg and valsartan 80 mg, Byvalson can be substituted for its components. The maximum antihypertensive effects of the medication are usually achieved within 2 to 4 weeks.¹

Clinical Trials

Byvalson was evaluated in a phase 3, double-blind, placebo-controlled, dose-escalating, 8-week study in 4161 patients with stage 1 or 2 hypertension. Patients using Byvalson demonstrated a statistically significant reduction from baseline in diastolic and systolic BP compared with monotherapy with either nebivolol or valsartan.^1,2

Contraindication, Warnings, and Precautions

Byvalson carries a boxed warning that it should not be used during pregnancy, as medications that work on the renin-angiotensin system can cause injury and death to a developing fetus. If pregnancy is detected during treatment with Byvalson, the medication should be discontinued immediately. Byvalson also is contraindicated in patients with severe bradycardia, heart block greater than first degree, cardiogenic shock, decompensated cardiac failure, sick sinus syndrome (unless a permanent pacemaker is in place), severe hepatic impairment, or hypersensitivity to any component of the product, and during treatment with aliskiren in diabetic patients.

Byvalson should not be abruptly discontinued in patients with coronary artery disease, as this may lead to an acute exacerbation of angina, MI, or ventricular arrhythmias. Patients with diabetes should monitor their glucose carefully, as beta-blockers may mask the symptoms of hypoglycemia. Renal function and potassium should be monitored in patients at risk of developing acute renal failure while using valsartan. Patients using Byvalson should not breast-feed.

Concomitant use of CYP2D6 enzyme inhibitors also should be avoided, as this combination may increase levels of nebivolol. In addition, use with reserpine or clonidine may produce excessive reduction of sympathetic activity, use with digitalis glycosides may increase the risk of bradycardia, and use in combination with verapamil- or diltiazem-type calcium channel blockers may cause excessive reductions in heart rate, BP, and cardiac contractility. Further, potassium-sparing diuretics, potassium supplements, or salt substitutes may lead to increased serum potassium, and concurrent use with nonsteroidal anti-inflammatory drugs may lead to increased risk of renal impairment and loss of the antihypertensive effect. Lastly, dual inhibition of the renin-angiotensin system may increase the risk of renal impairment, hypotension, and hyperkalemia, and use of Byvalson with lithium may cause increases in serum lithium concentrations and lithium toxicity.

No adverse reactions were reported more frequently in patients using Byvalson than in those using placebo.¹

Dr. Holmberg earned her PharmD from the University of Connecticut and completed an ambulatory care residency at the Phoenix VA Healthcare System. Her practice has also included pediatrics and inpatient mental health. She resides in Phoenix, Arizona.

References:

• Byvalson [package insert]. Irvine, CA: Allergan USA, Inc; 2016. allergan.com/assets/pdf/byvalson_pi. Accessed October 2016.
• Allergan announces FDA approval of Byvalson (nebivolol and valsartan) [news release]. Dublin, Ireland: Allergan; June 6, 2016. allergan.com/news/news/thomson-reuters/allergan-announces-fda-approval-of-byvalson-nebiv. Accessed October 2016.