Controversies
Pharmacology of side-effects
Several studies have suggested that nebivolol has reduced typical beta-blocker-related side effects, such as fatigue, clinical depression, bradycardia, or impotence. However, according to the FDABystolic is associated with a number of serious risks. Bystolic 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 (Child-Pugh > B) and in patients who are hypersensitive to any component of the product. Bystolic therapy is also associated with warnings regarding abrupt cessation of therapy, cardiac failure, angina and acute myocardial infarction, bronchospastic diseases, anesthesia and major surgery, diabetes and hypoglycemia, thyrotoxicosis, peripheral vascular disease, non-dihydropyridine calcium channel blockers use, as well as precautions regarding use with CYP2D6 inhibitors, impaired renal and hepatic function, and anaphylactic reactions. Finally, Bystolic is associated with other risks as described in the Adverse Reactions section of its PI. For example, a number of treatment-emergent adverse events with an incidence greater than or equal to 1 percent in Bystolic-treated patients and at a higher frequency than placebo-treated patients were identified in clinical studies, including headache, fatigue, and dizziness. FDA warning letter about advertising claims
In late August 2008, the FDA issued a Warning Letter to Forest Laboratories citing exaggerated and misleading claims in their launch journal ad, in particular over claims of superiority and novelty of action. History
Mylan Laboratories licensed the U.S. and Canadian rights to nebivolol from Janssen Pharmaceutica N.V. in 2001.
In the urinary bladder it is thought to cause relaxation of the bladder and prevention of urination.Due to enzymatic inhibition, fluvoxamine increases the exposure to nebivolol and its active hydroxylated metabolite (4-OH-nebivolol) in healthy volunteers. Vasodilator action
Nebivolol is unique as a beta-blocker. Unlike carvedilol, it has a nitric oxide (NO)-potentiating, vasodilatory effect via stimulation of β3 receptors. Along with labetalol, celiprolol and carvedilol, it is one of four beta blockers to cause dilation of blood vessels in addition to effects on the heart. Antihypertensive effect
Nebivolol lowers blood pressure (BP) by reducing peripheral vascular resistance, and significantly increases stroke volume with preservation of cardiac output. The net hemodynamic effect of nebivolol is the result of a balance between the depressant effects of beta-blockade and an action that maintains cardiac output. Antihypertensive responses were significantly higher with nebivolol than with placebo in trials enrolling patient groups considered representative of the U.S. hypertensive population, in black people, and in those receiving concurrent treatment with other antihypertensive drugs. Pharmacokinetics
Nebivolol plasma protein binding is approximately 98%, mostly to albumin and its half-life of low doses is 12 hours in extensive CYP2D6 metabolizers and 19 hours in poor metabolizers. Contraindications
Severe bradycardia
Heart block greater than first degree
Patients with cardiogenic shock
Decompensated cardiac failure
Sick sinus syndrome (unless a permanent pacemaker is in place)
Patients with severe hepatic impairment (Child-Pugh class B)
Patients who are hypersensitive to any component of this product. Side effects
Side effects might include headache, tiredness, dizziness, lightheadedness, reduced blood flow to extremities, bradycardia.