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Nebivolol (BYSTOLIC) was approved by the Food and Drug Administration (FDA) in 2007 to treat hypertension (high blood pressure).[1] It is a member of a class of drugs known as beta blockers. Although initially touted as a drug that was “beta-1 selective” and therefore purportedly not harmful to patients with asthma, chronic obstructive pulmonary disease (COPD) or other breathing problems, studies show that nebivolol, at all but the lowest doses, is not beta-1 selective and can potentially...
Nebivolol (BYSTOLIC) was approved by the Food and Drug Administration (FDA) in 2007 to treat hypertension (high blood pressure).[1] It is a member of a class of drugs known as beta blockers. Although initially touted as a drug that was “beta-1 selective” and therefore purportedly not harmful to patients with asthma, chronic obstructive pulmonary disease (COPD) or other breathing problems, studies show that nebivolol, at all but the lowest doses, is not beta-1 selective and can potentially lead to serious worsening of breathing in such patients.
In addition, unlike some other beta blockers (see Table, right), nebivolol is not FDA-approved to lower the risk of death or serious complications from coronary artery disease, heart failure or any other disease linked to high blood pressure. We therefore have designated this drug as Limited Use (our previous recommendation was that the drug should not be used in any patient until 2015, covering the first seven years after its approval).[2]
Beta blockers
Besides nebivolol, there are 12 other beta blockers available for oral administration. In addition to treatment of hypertension, some beta blockers are approved to treat angina (chest pain from coronary artery disease), heart attacks, heart failure or abnormal heart rhythms. One (propranolol [INDERAL]) is also used to decrease the frequency of migraine headaches. Nebivolol is not approved for any of these additional uses.
Beta blockers have been a mainstay of hypertension drug treatment. Yet the most recent evidence has shown that beta blockers do not work as well as other antihypertensive drugs in preventing stroke, other cardiovascular events or death, especially among smokers and patients older than 60 years.[3],[4],[5] This reduced benefit was seen even in studies where the beta blockers alone were equally as effective, on average, at controlling blood pressure itself as other antihypertensive drugs.[6]
Although these drugs remain useful for some patients, we now no longer recommend them as the starting treatment for hypertension except in special circumstances.
Beta-1 selectivity
Beta blockers work by blocking beta receptors in the body. Blocking beta-1 receptors decreases heart rate, reduces the force of heart muscle contractions and blocks the release of a hormone in the kidney that normally raises blood pressure.[7] Blocking beta-2 receptors narrows arteries, which can increase blood pressure; constricts the airways in the lungs, thus causing difficulty breathing in certain patients; and decreases blood glucose levels.
Nebivolol has been described in medical journal articles as being a beta-1 selective beta blocker,[8] similar to the drugs acebutolol (SECTRAL), atenolol (TENORMIN), betaxolol (generic only), bisoprolol (generic only) and metoprolol (LOPRESSOR, TOPROL XL). A beta-1 selective beta blocker specifically targets the beta-1 receptors in the heart and kidneys. Blocking beta-1 receptors results in a lower heart rate and lower blood pressure, which are desired effects in patients with hypertension.
Yet while nebivolol is described as selectively targeting beta-1 receptors, this selectivity only applies to low dosages of no more than 10 milligrams (mg) daily. At doses higher than 10 mg, nebivolol loses its selectivity and blocks the beta-2 receptors as well.[9] The FDA has approved dosages of nebivolol ranging from 5 mg to 40 mg daily.
This lack of selectivity is harmful for the following patients:
- Those with asthma or COPD because nonselective beta-blockers can have adverse effects on breathing. These drugs inhibit smooth muscle relaxation throughout the body, including in the airways of the lung, which may lead to wheezing and shortness of breath;
- Those with or at risk of high blood potassium levels, as non-beta-1 selective beta blockers can increase blood potassium levels;[10] and
- Those taking epinephrine, including for life-threatening allergies, as non-beta-1 selective beta blockers can severely raise blood pressure when given along with epinephrine.[11]
Other risks of nebivolol
In addition to its ability to cause breathing problems and high blood potassium levels in certain patients, nebivolol has several other risks:[12]
- Dangerously low blood pressure and heart rate in certain patients and if overdosed
- In diabetic patients, masking some of the symptoms of severely low blood sugar
- In patients with hyperthyroidism, masking some of the symptoms of high blood thyroid hormone levels
- In patients with peripheral vascular disease, causing or worsening symptoms of low blood flow to certain parts of the body
- Dangerous interactions with certain drugs, including digoxin (LANOXIN); the calcium channel blockers diltiazem (CARDIZEM, CARTIA XT, DILTZAC, TAZTIA XT, TIAZAC) and verapamil (CALAN, VERELAN); quinidine (NUEDEXTA); fluoxetine (PROZAC, SARAFEM, SELFEMRA); and paroxetine (BRISDELLE, PAXIL, PEXEVA)
- Potentially dangerously high concentrations of nebivolol in patients with kidney or liver impairment
- In patients with a rare hormonal disease known as pheochromocytoma, worsening symptoms of the disease
Orally Administered Beta Blockers Approved by the Food and Drug Administration
| Beta blocker | Beta-1 selective?* | BApproved Uses Other Than Hypertension? |
|---|---|---|
| acebutolol (SECTRAL) | Yes | Heart (ventricular) rhythm disorder |
| atenolol (TENORMIN) | Yes |
Chronic angina Acute heart attack |
| betaxolol (generic only) | Yes | No |
| bisoprolol (generic only) | Yes | No |
| carvedilol (COREG) | No |
Chronic heart failure Acute heart failure post-heart attack |
| labetalol (TRANDATE) | No | No |
| metoprolol succinate (TOPROL XL) | Yes |
Chronic angina Chronic heart failure |
| metoprolol tartrate (LOPRESSOR) | Yes |
Chronic angina Acute heart attack |
| nadolol (CORGARD) | No | Chronic angina |
| nebivolol (BYSTOLIC) | Yes (only at doses <10 mg daily) | No |
| pindolol (generic only) | No | No |
| propranolol (HEMANGEOL, INDERAL, INNOPRAN XL) | No |
Chronic angina Chronic heart failure due to a condition known as hypertrophic subaortic stenosis Migraine prevention |
| sotalol (BETAPACE, SORINE, SOTYLIZE)** | No | Heart rhythm disorders (ventricular rhythm disorders and atrial fibrillation/flutter) |
* According to FDA-approved label
** Sotalol is not approved for hypertension.
What You Can Do
Do not take nebivolol if you have asthma, COPD, other serious breathing problems, problems with elevated blood potassium levels, or if you carry an epinephrine injector for allergies. If you have any of these conditions and you require a beta blocker, you should use one that is truly beta-1 selective, such as acebutolol, atenolol, betaxolol, bisoprolol or metoprolol.
Do not take any beta blocker for hypertension unless you have unsuccessfully tried other types of antihypertensive drugs such as thiazides (chlorthalidone [generic only], hydrochlorothiazide [MICROZIDE]) and beta blockers work best for controlling your blood pressure. If you have chronic heart failure, angina, a prior heart attack, or heart rhythm disorder (atrial fibrillation/flutter or ventricular rhythm disorder), you should only take a beta blocker (not nebivolol) that is approved for treating such conditions.
If you are already taking nebivolol (or another beta blocker) for hypertension, have never been treated with other first-line drugs for hypertension and do not have one of the aforementioned conditions, talk with your doctor about slowly transitioning to another antihypertensive medication. Never stop taking your beta blocker abruptly because this can lead to deadly adverse effects, particularly in patients with coronary artery disease. To mitigate this risk, you should work closely with a doctor to gradually taper down the dose.
References
[1] Allergan. Drug label: nebivolol (BYSTOLIC). November 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf. Accessed January 31, 2018.
[2] New hypertension drug poses breathing risks. Worst Pills, Best Pills News. May 2013. /newsletters/view/849. Accessed January 31, 2018.
[3] Wiysonge CS, Bradley HA, Volmink J, et al. Beta-blockers for hypertension. Cochrane Database Syst Rev. 2017;1:CD002003.
[4] MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: Principal results. BMJ. 1992;304(6824):405-412.
[5] Khan N, McAlister FA. Re-examining the efficacy of beta-blockers for the treatment of hypertension: A meta-analysis. CMAJ. 2006;174(12):1737-1742.
[6] Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension: Is it a wise choice? Lancet. 2004;364(9446):1684.
[7] Klabunde RE. Cardiovascular Pharmacology Concepts: Beta-Adrenoceptor Agonists (β-agonists). http://cvpharmacology.com/cardiostimulatory/beta-agonist. Accessed January 31, 2018.
[8] Gupta S, Wright HM. Nebivolol: a highly selective beta1-adrenergic receptor blocker that causes vasodilation by increasing nitric oxide. Cardiovasc Ther. 2008;26(3):189-202.
[9] Allergan. Drug label: nebivolol (BYSTOLIC). November 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf. Accessed January 31, 2018.
[10] Podrid PJ. Major side effects of beta blockers. August 22, 2016. UpToDate. https://www.uptodate.com/contents/major-side-effects-of-beta-blockers. Accessed January 31, 2018.
[11] People on certain beta blockers should be wary of epinephrine. Worst Pills, Best Pills News. May 2009. /newsletters/view/636. Accessed January 31, 2018.
[12] Allergan. Drug label: nebivolol (BYSTOLIC). November 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021742s022lbl.pdf. Accessed January 17, 2018.
