Formulary recommendations for an MAPD plan, based on the evaluation of its clinical benefits & possible place in therapy amongst other beta blockers

1. BYSTOLIC
NEBIVOLOL

2. Pharmacological Characteristics of Commonly
Used β-Blockers
1
Table 1.
Price Per Month8
Selectivity Vasodilation ISA Dosing
Β-blocker
(max frequency)
$
Acebutolol Cardioselective No + qd/bid 33
Atenolol Cardioselective No - qd 13
Bisoprolol Cardioselective No - qd 35
Bystolic (Brand) Cardioselective Yes - qd 56
Coreg CR (Brand) Nonselective Yes - qd 123
Carvedilol bid 30
Labetalol Nonselective Yes + bid 21
Metoprolol Cardioselective No - qd 35
Succinate
Propranolol Nonselective No - bid 26

3. HIGHLIGHTS
Bystolic is a Beta-adrenergic blocking agent with high β-1 selectivity no ISA or alpha-
,
adrenergic blocking effects, and nitric oxide mediated vasodilatory effects. 2
Demonstrates efficacy in a broad range of patient populations, including African
Americans, who often have reduced levels of nitric oxide. 3
The nitric oxide mediated vasodilatory effect improves arterial stiffness and endothelial
dysfunction which may be useful for heart failure, diastolic dysfunction, and reducing
cardiovascular risk. 3
Decreases systemic vascular resistance & increases stroke volume while maintaining
cardiac output. 2
Well tolerated and may be effective in reducing the morbidity and mortality in patients of
age>70 years with heart failure regardless of the initial ejection fraction.4
Effective for isolated systolic hypertension. 3
Convenient once daily dosing with fewdrug interactions and side effects. 2

4. Lower incidence of side effects commonly associated with the
use of β-blockers (fatigue, ED, bradycardia, depression)1
Does not negatively affect lipid profile, insulin sensitivity or
,
glycemic control.4
Lowrates of bronchoconstriction & peripheral vasoconstriction.1
Tolerability is similar to that of placebo and may improve patient
compliance.4 (Table 2)
Treatment Placebo
Table 2.2
Headache 6-9% 6%
Fatigue 2-5% 1%
Dizziness 2-4% 2%
Nausea 1-3% 0%
Diarrhea 2-3% 2%
Bradycardia 0-1% 0%
Dyspnea 0-1% 0%

5. TIER 1 ALTERNATIVE
METOPROLOL SUCCINATE (TOPROL XL)
Currently the highest prescribed β-Blocker within your plan: 39%
of total β-Blocker claims for 20075
β-1 Selective6
JNC7 Guidelines recognize this agent as being cardioprotective7
Approved for use in CHF. Shown to reduce morbidity & mortality
in patients with CHF. 5
The incidence of adverse events commonly associated with β-
Blockers for Metoprolol Succinate is low Toprol XL Prescriber
.
Information contains the following information regarding adverse
events:6
Serious adverse events and adverse events leading to discontinuation of study medication in MERIT-HF at an
incidence >1% in the group receiving TOPROL-XL and greater than placebo by more than 0.5% were
dizziness/vertigo (1.8% vs 1.0%), bradycardia (1.5% vs 0.4%), and accident and/or injury (1.4% vs 0.8%)
Other adverse events with an incidence >1% on Toprol XL and as common on placebo (within 0.5%)
included myocardial infarction, pneumonia, cerebrovascular disorder, chest pain, dyspnea,
dyspnea/aggravated syncopy coronary artery disorder, ventricular tachycardia/arrythmia aggravated,
,
hypotension, diabetes mellitus/aggravated, abdominal pain and fatigue.
QD Dosing6
Monthly cost: ~$358

6. RECOMMENDATIONS
Bystolic may be beneficial in these populations:
Elderly (Higher incidence of falls and comorbidities)
African Americans (Less responsive to other β-blockers & often have
reduced levels of nitric oxide)
Patients intolerant to side effects common to other beta blockers
(fatigue, dizziness, bradycardia, bronchoconstriction, hyperglycemia)
Possibly useful for patients with heart failure (↓SVR, ↑SV, ↔CO)
Patients on optimized conventional therapy with uncontrolled HTN
(Approved as add on therapy for the treatment of HTN)
Formulary Considerations
Monthly cost ~$568
Tier 2 with Step Therapy
Must have been on at least one other β-blocker
Tier 3

7. REFERENCES
Forest Laboratories, Inc. Product Monograph ‘Bystolic’. 2007
1.
Miko, Leandra. Bystolic – Nebivolol. www.gahec.org/pharmupd/Bystolic.ppt.
2.
01/24/2008
Cockcroft, John. A review of the safety and efficacy of nebivolol in the mildly
3.
hypertensive patient. Vascular Health and Risk Management 2007:3 (6) 909-917
Rosei, Enrico Agabiti. Rizzoni, Damiano. Metabolic Profile of Nebivolol, a
4.
Adrenoceptor with Unique Characteristics. Drugs 2007;67 (8) 1097-1107
Medinitiatives.com
5.
Astra Zeneca. Prescribing Information. http://www1.astrazeneca-us.com/pi/toprol-
6.
xl.pdf. 2007
U.S. Department of Human and Health Services. The Seventh Report of the Joint
7.
National Committee on Prevention, Detection, Evaluation, and Treatment of High
Blood Pressure. http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.htm.
2004
http://www.drugstore.com/
8.