Nebivolol (Bystolic), the uniquely well-tolerated beta-blocker, is now available as a cheap generic

There is good news for those patients taking the beta-blocker drug Bystolic: it is now available as a generic (nebivolol) at a substantially lower price. Given nebivolol’s uniquely low side effect profile, many patients suffering beta-blocker side effects (fatigue, erectile dysfunction, shortness of breath, weight gain) may benefit from switching to it now without concern about high costs.

A patient alerted me to this development and shared with me his pharmacy summaries of the generic versus brand name costs of the drug.

Brand name Bystolic $62 for 30
generic nebivolol $10 for 30

My patient also noted that AbbVie (ABBV) the current maker of Bystolic has already started lowering the price and offering coupons, presumably due to the generic competition. Previously he would pay $200 for 30 Bystolic tablets. His nebivolol is coming from ANI pharmaceuticals whose website mentions that Bystolic” has a current annual U.S. market of about $1.05B.

Beta-blockers are used frequently in cardiology for abnormal cardiac rhythms (atrial fibrillation, PVCs, PACs, ventricular tachycardia) angina, heart failure and hypertension. Although nebivolol showed some promise in the treatment of heart failure it did not achieve an indication for that diagnosis.

Here is a 2017 chart of the most popular beta-blockers. The top 9 with the exception of Bystolic are all generic and therefore relatively inexpensive. Toprol XL is the brand name version of the long-acting, once-daily version of metoprolol but since there are generic versions of this drug (Metoprolol Succinate) I use those rather than Toprol XL.

https://www.definitivehc.com/blog/beta-blocker-prescription-patterns

Why Bystolic Is Important

There is much I can say about Bystolic. I’ll save specific discussion on its pharmacology and history for a subsequent post. Full disclosure: prior to becoming the skeptical cardiologist and eliminating pharmaceutical rep interactions in order to eliminate the bias such interactions create, I gave paid talks in 2008 for Forest Pharmaceutical on the drug when it was first released. Like all drug company speakers I spent a weekend receiving indoctrination into the wonders of the drug and I was paid handsomely to convey those wonders to physicians who were often eating free steaks while I spoke.

I am not proud of that work and I now scrupulously avoid sources of bias. Heretofore I avoided writing about Bystolic (because of concerns that lingering pharma influence would taint my opinions) but with a decade of experience with the drug and now that a generic is available I think it is important that doctors and physicians recognize its benefits within the family of beta-adrenergic blocking medications.

I’ve successfully switched lots of patients who were having side effects on other beta-blockers to Bystolic. I take the drug myself and it has worked well without any side effects for my hypertension and my hypertrophic cardiomyopathy (more on that also in a subsequent post.)

Here’s a summary description of the drug from the introduction to a recent Korean observational study (which showed it works as well in an Asian population as a white one)

Nebivolol is a third-generation vasodilatory β1-adrenergic receptor antagonist, which induces nitric oxide-mediated vasodilatory effects via β3 receptor agonism. Nebivolol has been shown to have similar or better treatment response and BP control compared with other antihypertensives or their combinations, with significantly better tolerability. Nebivolol was also effective in reducing SBP and DBP in patients with hypertension as an add-on to or as a fixed-dose combination with other antihypertensive agents Furthermore, in patients with hypertension with comorbidities, nebivolol has been reported to be lipid neutral, did not produce detrimental metabolic effects, and demonstrated a potentially positive effect on HDL

A few years ago I described another approach to consider in the patient with beta-blocker side effects: stopping beta-blockers altogether. I wrote a post (Is an unneeded beta-blocker making you feel logy?) several years ago about a patient who had undergone stenting of a coronary artery after presenting with chest pain diagnosed as a heart attack (non ST elevation MI or NSTEMI) a year earlier.

He was put on the beta-blocker carvedilol (brand name Coreg) and ever since then he had felt “logy”, his term for fatigue or lack of energy. After reviewing the literature I concluded that I could safely remove post-MI patients like him from beta-blockers if their left ventricular function was normal. A session at the recent AHA conference was devoted to discussing this same issue.

A meta-analysis of nebivolol trials from 20018 concluded:

 This meta-analysis showed that nebivolol 5 mg achieved similar or better rates of treatment response and BP normalization than other drug classes and other antihypertensive drugs combined, with similar tolerability to placebo and significantly better tolerability than losartan, CCAs, other beta-blockers, and all antihypertensive drugs combined. Although not definitive, this meta-analysis suggests that nebivolol 5 mg is likely to have advantages over existing antihypertensives and may have a role in the first-line treatment of hypertension.

Whether nebivolol should be a first-line agent for hypertension is debatable but any patient who requires a beta-blocker for cardiac conditions other than heart failure or hypertension, I will now consider it as my first choice, especially in patients who have underlying lung disease/bronchospasm, peripheral vascular disease, erectile dysfunction, or fatigue.

Antiadrenergically Yours,

-ACP

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36 thoughts on “Nebivolol (Bystolic), the uniquely well-tolerated beta-blocker, is now available as a cheap generic”

  1. I have been taking Bystolic for 9 years for heart palpitations and high blood pressure with little to no side effects. Bystolic was by far the best of all the other beta blockers i have tried. I tried the generic Bystolic produced by Ani but experienced increased heart palpitations and increased blood pressure taking it. My Question: Is there any data indicating which generic drug is more akin to the brand Bystolic? I don’t really want to do a trial and error test period again. Not to mention that since the generic versions were released, my monthly cost of brand Bystolic has increased from $30 to $90. The $90 is only with a manufacturer’s coupon which lowers the original cost from $160.00 month. I very much appreciate your thoughts.

    Reply
  2. Hi Dr. P – thanks for your comments. I very recently had a 20 second long atrial fibrilation caught on an event monitor during a workout, which resulted in multiple phone calls from my doctor’s office within an hour and prescription for metoprolol before noon. I have an appointment with an EP next week to discuss treatment options, and I’m trying to think through questions to ask. So far, I can tell that metoprolol (25mg ER) is having an effect that would substantially reduce my performance during my workouts.

    Do you think Bystolic could hypothetically be an option worth discussing with an EP for a person in their 30s who experiences infrequent (1-2x annual) self-terminating atrial fibrilation and still wants to do heavy squats and deadlifts?

    Reply
    • Ryan,
      Yes. It would definitely be worth discussing and giving it a trial.
      I have a very cynical theory about EPs (many).
      I believe that they utilize medications which guarantee the failure of medical treatment of atrial fibrillation either because they are ineffective or because they have unacceptable side effects.
      Let me know how things go.
      Dr P

      Reply
      • Thanks for the response Dr. P!

        Shall I infer that your cynicism regarding some EPs is that they’re pushing ablations, perhaps unnecessarily?

        Reply
        • Ryan,
          You may infer that.
          I can state it explicitly. Many EPs (like the man with a hammer) have an unjustified belief in the benefits of AFIB ablation and minimize its risks, therefore perform them on many patients with Afib who have not had a proper trial of medical therapy.
          Some of this comes from hubris, some from ignorance, some is financial.
          Dr. P

          Reply
          • Good news for me – EP says that my referring physician misdiagnosed my issue as AFib. Says it was PSVT, and said that doing nothing was a fine approach at this juncture given the short and self terminating nature of my issues.

            Reply
            • Excellent! Medical therapy works well for many with PSVT but I have a much lower threshold for referring to EP with the most common form of PSVT, AVNRT, as it is very easy to ablation , success rates are high, and complications low.
              Dr. P

              Reply
  3. Hi, Today I picked up my first generic version of Bystolic. Manufactured in India, Aurobindo Pharmaceuticals. (They have had 2 recalls and a letter last summer fromthe FDA.) First I had heard a generic was available. I have reached this website while searching for information on this exact subject. I am leary of using it. But have decided to try. I have 45 5mg in which I cut them in half for 90 day count. When finding Bystolic after 2 other low dose BP meds, Iloved it. No noticeable side effects. Scared to get depressed again. Or allergic to some additive, in which they never tell you what they are and yet say. “Don’t use if you are allergic”. Just venting! Thanks.

    Reply
  4. I always thought of Bystolic as something for hypertension. I take a small dose of metoprolol to keep PVCs at bay, and it does work. I wonder if Bystolic could also be an option? I don’t have hypertension, and I wouldn’t want to drop my BP too much. The metoprolol is a rather small dose, and really doesn’t affect my BP.

    Reply
    • Bystolic and metoprolol are used for hypertension and for control cardiac rhythm.
      So Bystolic is an option for individuals with PVCs, or atrial fibrillation, or ventricular tachycardia.
      If doing strength is equal they have similar effects on BP

      Reply
  5. Curmudgeonly comments on Christopher’s conundrum:

    My experience (N of 1):
    Ten years ago, after years of quite intense aerobic and anaerobic activities, I had increasing symptomatic paroxysmal AF. Neither flecainide nor propafenone helped. On (nasty) warfarin at the time.
    Opted for 2nd generation cryo ablation, thinking that a continuous full thickness circumferential scar from freezing around each Pulmonary Vein would be better than the dotted line of RF burns.
    Success, in that I’ve not had any AF since!
    However, one should not expect to get away with no consequences. The risk of acquiring phrenic nerve palsy (temporary paralysis of 1/2 of the diaphragm) was deemed a fraction of a percent at the time. Well, it was a challenge to breathe properly for the six months it took for that to clear up. (All the risk calculations and decision making in the world won’t change the fact that, for the individual, you either got it or you don’t.)
    There are also ganglia near the ablation site that can be compromised. This apparently explains my resting heart rate increase from the high 50s to the low 70s. At the time, it was protocol to do two freezes for each PV. Now it’s one. Perhaps now there are fewer side-effects?
    Arrhythmias other than AF can then present: atrial flutter and various sorts of atrial tachycardia.
    After a total of four ablations, I find that I cannot engage in those exercise/work activities to the extent I’d been used to. Perhaps the forced moderation is a benefit?
    I’m now on 50 mg flecainide, standard dose Eliquis, and losartan. I do wonder if nebivolol would be an improvement.

    All of that experience notwithstanding, I’m extremely grateful to my EP and his technology to now be arrhythmia free!
    My father died at the age of 75 in the electrophysiological dark age of 1973 from an AF induced stroke. I’m two years older than he ever got to be.

    Reply
  6. I currently take 100 MG of Flecainide BID and 3.125 MG of Carvedilol BID to control my paroxysmal Afib. It works well and I have had no recorded episodes of arrhythmia since using daily rhythm and rate control. I have a severely enlarged left atrium from decades of high intensity aerobic exercise.

    I find the following medication side effects intolerable from what I think is the beta blocker. I have tried 25 MG Metoprolol succinate as well at 12.5 MG half doses to no avail. I also tried Diltiazem and Digoxin in lieu of a beta blocker as well and the side effects were even worse.

    Increasingly lowered tolerance to exercise
    14 pound weight gain despite consistent exercise and monitoring of caloric intake
    Chronic insomnia
    Daytime sleepiness
    Systolic blood pressure increase to an average of 138/80 (about 20 point increase). This increase happened recently after switching to Carvedilol from Metoprolol.
    Hand tremors (possibly from Flecainide after the first month of therapy). My neurologist has no other explanation for the tremors.

    Questions:
    1. Is this the point where it may be advisable for me to consider an ablation?
    2. If so, can an ablation be successfully performed if there is no incidence of paroxysmal Afib during the procedure?
    3. Can rate and rhythm control medication normally be stopped after a successful ablation? I have no problem with continuing Eliquis.

    Reply
      1. You could consider an ablation which can be performed successfully if in NSR.
        Be aware that ablation is not a cure and AF recurrence is the norm.
        Depending on the EP, both the rhythm and rate control drugs typically stopped after 3-6 months if no recurrence.
      2. A few things I would discuss if I had a patient like you. One is a trial of low dose (2.5 mg) nebivolol and/or a trial of lower dosage flecainide at 50 or 75 BID. In my experience nebivolol at lower dosages is a better antihypertensive than other beta-blockers.
      Reply
  7. Thank you Dr. Pearson for your excellent columns. I have been taking branded Bystolic for 7 years after having unsatisfactory results with some generic BBs. I switched to generic Nebivolol last month and after several weeks noticed that it was not as effective as the Bystolic had been in controlling systolic BP. I’ve switched back to Bystolic and am accumulating data before I can do an honest comparison to see how big the effect is. If you are interested in cost, I can share my invoice costs with Humana Pharmacy (on a Medicare Part D plan): Bystolic 2.5mg 90ct – $497.95 cost before insurance; Nebivolol 2.5mg 90 ct – $228.65 cost before insurance. (My copays are roughly in the same ratio as these list prices). I would call Nebivolol a less expensive generic but certainly not a cheap generic.

    Humana pharmacy standard packaging does not indicate the name of the manufacturer nor the country of origin. I know the Bystolic samples I was given some years back were manufactured by Forest in Belgium and licensed from Mylan Labs.

    Reply
    • Henry,
      Thanks for this information. It is best in this kind of situation for each patient to do as you did and perform an n of 1 experiment with the nebivolol versus the Bystolic. Although the experiment is not blinded, the BP is typically not influenced by placebo effect.
      Please share your long term data as you accumulate it.
      Dr P

      Reply
  8. Dan asked my question about the safety and efficacy of generics? Can you shed some insight on how to know where the generic will be produced and how it is tested to be a match to Bystolic? Although Bystolic is expensive, it does a terrific job without side effects. Thanks for prescribing it when I need BP help, Dr. P.

    Reply
    • Celeste,
      I’m not sure where the brand name Bystolic is made. ANI is respected generic drugmaker headquartered in Baudette, MN and their information suggests at least some of the nebivolol they make will come from the MN plant.
      That being said, if you have done well on Bystolic and the cost to you is not that bad (and this cost after the emergence of generics is definitely going down) then probably best to stay on it. Most of my patients self-monitor BP and for those who make this switch for cost reasons we will be closely monitoring before and after BPs and side effects to verify equivalence.
      If any pharmacist or patient readers have info on this please chime in.
      Dr P

      Reply
  9. This is good news, however, given the light that has been shed on the quality of generics and what appears to be offshore production of such drugs, is it better healthwise to stick with the brand name vs going generic (ie, cost is not a factor)? Note I have been buying brand name bystolic via a Canadian online pharmacy. The price is much lower than US pricing, and no issues with the shipping.

    Reply
    • dan,
      See my response to celeste’s similar question on the quality of the generics.
      Could you provide more info on the Canadian online pharmacy bystolic purchases?
      It is something I haven’t looked into although i know my father at times utilized one (perhaps for bystolic which he also took)
      Perhaps you could provide us with the pros and cons of the Canadian online pharmacy approach.?
      Dr P

      Reply
      • Dr P

        I started to use a Canadian online pharmacy after my insurance company dropped Bystolic from coverage. I explored a few options and decided to try https://www.canadapharmacyonline.com/ which was recommended by a doctor that I know. I checked pricing today for Bystolic (Canada origin) and 90 day supply was $210. To date, I probably have ordered in this quantity for about one year and have had no issues. thus can recommend.

        Note that another doctor that I know recommend a US based online pharmacy https://www.valisure.com/. This company does chemical composition analysis of generic drugs prior to shipping to consumers (they do random sampling, not each prescription filled). So I feel somewhat more at ease when ordering generics from this company and have done so for about two years. No issues and thus can recommend if one is interested in an increased level of scrutiny concerning generics.

        Note I have no ties to either company mentioned and am not in the pharma field. I offer this info to fellow readers of your very informative and well written blog and appreciate the info that you provide to the community.

        dan

        Reply
        • Dan,
          Thanks for that great information.
          I have been looking at Valisure for the last couple of years and agree with your assessment. I used it myself and was pleased with the process, however, it is much simpler (and sometimes cheaper) to deal with Express Scripts for all my medications so I haven’t used Valisure routinely.
          They deserve major kudos for identifying the carcinogen in generic ARBS among a host of issues they have identified.
          Dr P

          Reply
          • This is some info I bookmarked from Valisure.
            * Outcomes are everything — Our pharmacy team is fully staffed and operates much like your local bricks and mortar pharmacy. Like you, we are very focused on outcomes, which in the pharmacy world means getting the right medicine to the right patient at the right time so they can take their important medications without interruption
            * Batch-validation is unique — We know of no other online or physical pharmacy with Valisure’s ability to batch-validate medicine and publish data on active and inactive ingredients, impurities, etc. Unfortunately, the length of testing does create occasional backlogs in our system and sometimes we are unable to fill prescriptions immediately. Over time, we expect to narrow our purchasing strategy and accelerate our ability to ship all requested medicines within 1-2 days.
            * Every order is essential — My team is engaging with physicians and patients every day to make sure questions are answered in a professional manner and the patient gets the medication they need.
            * Refills — We follow up with customers via phone for each refill.
            * Cost – Prescribers and customers always ask – “are you charging more for your service?” The answer is no. We are investing in our unique value proposition and are able to batch-validate in a way that does not impact the consumer price. This is especially helpful to our customers who have insurance that does not currently cover Valisure. The price for generic medicines are competitive to their insurance co-pay. Sometimes the generic price is even lower than the co-pay!

            Reply
  10. Really look forward to your reflections on hypertrophic cardiomyopathy versus/and ‘athletes heart’ and what restriction you have on your exercise– as an symptomatic heart issue life long athlete currently undergoing examination for this I am eager to hear your views on this!!!

    Reply
  11. In school I thought it was interesting that 2nd generation beta blockers like metoprolol and nebivolol had much higher affinity for b1 (cardiac) receptors than their 1st generation non selective counterparts like carvedilol. For those with asthma these 2nd generation b blockers became viable inotropic and chronotropic agents without exacerbating their asthma. I am curious though, if your patients develop dyspnea from CHF or have chronic issues like COPD, do you think 1st gen agents like carvedilol exacerbate their dyspnea?

    Reply
    • Nebivolol at low doses is the most beta 1 selective BB. Non selective BBS exacerbate definitely worsen suspense all the the time in COPD and asthma patients

      Reply
      • Can you translate this for a lay person? I have tried BBs in the past and could not tolerate them due to my asthma. Is Nebivolol better tolerated by asthma patients compared to other BBs?

        Reply
  12. I was prescribed valsartan and then switched to losartan when valsartan was recalled a while back. Add on verapamil. These are supposedly kidney friendly for those of us with less than optimal kidney function.

    How’s nebivolol? Would my nephrologist be pleased?

    What you describe suggests that maybe its not advancing age getting me down, but the combined side effects of losartan and verapamil.

    Reply
  13. The captioning of the pharmacy summaries “generic nebivolol $10 for 30” and “Brand name Bystolic $62 for 30” overlooks the difference in dosages.

    Reply
    • Price is the same for 2.5 and 5 mg tablets per my patient.
      If other readers can report their price differential that would be good

      Reply
  14. Thank you so much Dr Pearson for these good news.
    I do hope that generic nebivolol will become available soon in Canada.
    It is a great drug, that my cardiologist prescribed when I realized my symptoms of depression and brain fog were related to metoprolol. My tolerance to nebivolol is just fine, and it works well for me to lower my BP and possibly prevent arrhythmia. Howvere, it is still quite expensive.
    Great news! 🙂

    Reply

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