Nadolol and Low Heart Rate

[Nina Mae]

I just started Epclusa/Ribavirin on March 1; I take Nadolol 40 mg for the esophagael varix.  Since it's a beta blocker, I know my heart rate will be slower and it was really beating me up before I finally acclimated.

After walking the dog yesterday, I was wiped out and felt a bit lightheaded, dizzy, and faint so I rested and fell asleep (not sleeping so hot at night which I know is a side effect).  Anyway, while napping, my Apple Watch notified me three times that my heart rate was 38 bpm for about ten minutes starting at 3:48 pm.  (Cool feature on the watch).  Finally, I figured I'd better get up slowly and just try walking around inside to get my bearings.  I was quite weak and 'woozy' for about 10-15 minutes.

I emailed my nurse practitioner and she promptly replied that she'd tell my dr. and hopefully get a response soon.  Update: Dr suggests to split nadolol in half and see how that works.  It's the Epclusa that intensifies the beta blocker and it's rare (of course, it happened to me because my life is like a reverse lottery winner).

Plus, I'm losing weight too fast.  I spoke with nurse practitioner about this; in 5 days, I've lost over 3.5 lbs and in the past 6 weeks, I lost 11 lbs and it's not water weight (I'm on lasix) and I'm tiny to begin with (5'1" and weighed 127 for quite some time).  Now I weigh 116 lbs.

It's not a known side effect so I asked if perhaps, we should do a biopsy...she suggested another ultrasound instead and take it from there.

Has anyone have any feedback about any of this?

Anyway, if you read this, thanks.  I just needed to vent, I suppose.

Chin up always! 

[lporterrn]

Hi Nina,
Of course you needed to vent - that's a lot. Mostly I want to say that letting your doctor know was the right thing to do, so good for you!

Ribavirin is the culprit here - it explains everything - the sleeplessness, lightheartedness, dizziness, fatigue, loss of appetite, the lowered heart rate.

That said, how sure are you that it isn't water weight that you lost or losing weight as a result of having cirrhosis? I ask because you've only been on the treatment for 6 days but you lost weight in the past 6 weeks.

As for a biopsy, I am not sure why you suggested that, but since you already have varices, I'm guessing that your doc would not want to do a biopsy.

Sadly, it isn't likely to get better until you are about 1 to 2 months off of ribavirin, and it could get worse as ribavirin lowers the red blood cell count, hemoglobin, etc.
I went through a year of treatment with ribavirin and then another 12 weeks of it on the combo that cured me. I love being free of hep C, but I know what price you are paying.

Hang in there and keep us up to date.

[Nina Mae]

Thank you, Lucinda, for your kind words and support.

I spoke with my nurse practitioner who said that it's a rare but known side effect between Epclusa and Nadolol which surprised me as I thought oit was the ribavirin also.  She said that she knew about it and didn't say anything to me about it because it is so rare.  Anyway, dr said to split the dosage from 40 mg to 20 mg and see how that works.

The weight loss:  When I became acutely ill in Sept/Oct, I hadn't been dx'ed yet as I thought I hd a flu of some sort (vomiting but with such force, I threw my hip out and diarrhea, you know, the fun stuff).  But then the edema started in my legs and stomach and I had no idea what was going on...then tests were done and here we are. 

I'm a bit paranoid about cancer as I'm a survivor of Stage 3 Inoperable Infiltrating Lobular Breast Cancer and that cancer didn't show up on any imaging tests...mammogram was normal, Petscan, cat scan, ultrasounds showed nothing but you could see the lump and you could feel the lump and I insisted on a needle biopsy because I had to know what it was....the surgical oncologist was very reluctant to do it until I asked him what he'd tell his wife or daughter to do if they were me.

Ended up proving I was positive for cancer and I fear the same with my liver.  It may very well be the cirrhosis but I'd rather be proactive now because if I do have cancer again, I need to deal with that now!  I don't have a loss of appetite at all; I eat 6 small meals a day because it seems I'm painfully hungry frequently and if I don't eat something when I start feeling hungry, it creates havoc for me for the rest of the day.  My portions are smaller but more frequent and that seems to work.

This weight loss has nothing to do with HCV treatments as I've been losing weight rapidly even before I started meds....well, it may be accelerating it, I'm not sure.  But it seems that every single day, I drop another lb.

I have one varix that is not bleeding (yet).  Do esophagael varices indicate cancer?  What is the correlation between the varices and biopsy?  I know varices, umbilical hernias, ascites all determine whether the liver is compensated or decompensated but are any of these markers for cancer?

My nurse practitioner is looking into bumping up an ultrasound for me...but again, I fear imaging in my experience with cancer in the past.

It's a tough journey ahead, I know.  And I fear relapse because of my advanced disease but whatever it takes, I'll get through this. 

My breast cancer chemo was adriamycin/cytoxin for 4 sessions and 4 sessions of taxol. I understand that more and more women who were administered adriamycin are now having liver problems including cancer so there's a 2nd etiology...first was from a lousy attempt of donating blood back in 1983 (long story).  Then bilateral mastectomy, the 28 radiation treatments...that was back in 2003 and I'm still here typing about it.

Again, thanks, for your kind words, wisdom, and support.  Congrats on being Hep C free!!! 
 
That's a good club to join:)

[lporterrn]

The varices are not an indicator of cancer - generally, they are the result of hypertension (pressure) in the venous system that the liver is connected to. To answer your indirect question, I assume you have decompensated cirrhosis, because you have varices (and perhaps ascites?). Here's some info on the difference between compensated and decompensated cirrhosis - https://www.hepmag.com/basics/hepatitis-c-basics/cirrhosis

Cirrhosis raises your risk for liver cancer. The common cancer surveillance protocol uses ultrasounds and blood tests: https://www.hepmag.com/basics/hepatitis-c-basics/life-hepatitis-c-treatment Some docs do more frequent ultrasounds, esp with a prior cancer history. Liver biopsy is NOT appropriate for screening for liver cancer.

As for the nadalol, I am not convinced that this is solely an interaction, albeit it is important to consider the possibility. Your "wait and see" strategy will serve you well. When we are on treatment, it is a bit like being a scientist living in a body that is it's own experiment. Curiosity and patience are hard to maintain when we don't feel well, but if you can develop these, it helps. I found that keeping written records is very helpful. I will not lie to you - because you are on ribavirin, you have harder days ahead. I know you can do this, especially with support (and drink lots of water).

[Nina Mae]

Once again, thank you for your support, Lucinda.  Those links you attached add more pieces to the puzzle.

I'm a journal keeper type person and I've started a spreadsheet for now...as things progress or change, I'll adapt it.

I do know that the ribavirin comes along with some really intense side effects and thus far, I'm experiencing the 'Riba Rage' and I'm sad...not depressed, I don't think...just sad, and I cry easily which is not a side effect of the ribavirin but a side effect of being dx'ed with all this.  I'm not into 'pity parties'; I'm generally a tough old bird (66 yo) but I'm finding it so difficult to 'sustain' a positive attitude; I've been through so many health challenges (each one serious) and I'm getting sick and tired of being sick and tired...from my Stage 3 Breast Cancer in 2003, to an MI with a stent implanted in my LAD in 2009, to a BRAO in 2014 (branch arterial retina occlusion), and now all this.

I'll be okay...it's just a 'moment'.

Lucinda, you said you're not convinced that the nadolol is solely an interaction.  Can you elaborate on that?  I'd love to hear your take on it.

I"m sorry about rambling, I really am.  I'm just having a 'moment' and again, I needed to vent.  The weather is disgusting today, snow rain mix, the 15 yo dog doesn't even want to go out, and here I am.

[lporterrn]

Here's my elaboration on the nadolol: I think we don't have enough data and I am hoping that researchers do a study to see if there really is a drug interaction between sofosbuvir (one of the drugs in Epclusa) and nadolol or if the problem is that sofosbuvir lowers heart rate. (I have a long story behind this - not just a whim)

Also, I think that sometimes doc underestimate how intense and extensive ribavirin's side effects are.

It helped me to know that the mood-altering side effects of ribavirin would eventually pass.The second time around (but 3rd treatment) I tried not to fight them. Humor, water, walks, and the Forum really helped. No downer movies or books or people.

[Nina Mae]

Lucinda, I think you're right about the possibility that dr's underestimate the intensity of the effects of nadolol and epclusa.  Apparently, since you have your own story, how 'very' rare is that side effect that I wasn't pre-warned that there's a slim possibility of it happening?

Since dropping the dose of Nadolol from 40 mg to 20 mg, it seems that I'm tolerating that with a resting heart rate of 48-51 bpm. 

My weight loss is starting to level off with normal fluctuations.  I'm now 117.4.  I think I'm a bit OCD about this weight loss:  when I was acutely ill in Sept, I was 133.  Then 127 on Jan 14.  Now 117.4 today.  If I go below 115, I'll discuss with my GP.

They've booked an ultrasound for March 30.  Though I'm not as panicky about weight loss as I was when I saw 116 last week...I'm more paranoid that this could be another issue unrelated to HCV and cirrhosis but I decided I if I go down to 110, that's where I draw the line...BMI chart or not.  (Turning into a true hypochondriac)

All my life I had a weight problem...I was always on the chubby-obese side so this is really very disturbing for me.

It IS good to know about the moodiness, emotional side effects from Ribavirin...though I was rather depressed and overwhelmed when dx'ed which I'm certain all of us go through.

That 'Riba Rage' is no joke...it's only happened once where I went 'unhinged' but managed to avoid the 2nd one in the pharmacy when I started to get enraged, I didn't answer the next stupid comment and walked out; had I stayed, it would have been a scene.  Stupidity always annoyed me but now, I need to keep myself in check seriously.  I'm starting to chant inwardly, "it's the meds.  Take it easy..nice and easy'...it helps until the next event (lol). 

[To quote one member (forgot their handle), turning into a "grouchy hepper"]

Today is Day 14 so I get my first of the 'every two weeks' lab work.  Busy day today...tired but what else is new.  I'll be interested to start monitoring my own lab results...

Thanks for reading this boring ramble...

Taking it nice and slow...doing what I know to do...

Chin up...always.   

[lporterrn]

Hi,
My heart goes out to you. Go easy on yourself re the riba rage - it helped me to think of it like having temporary Tourette's. It's largely outside of your best intentions to control. However, try to control what you can to minimize the risk of rage - get as much sleep as you can, as much humor and playtime as you can, as much help as you can, and know that this is temporary.

As for weight loss, perhaps use your OCD to try to bulk up your calories with high-density nutrients - sneak in calories wherever you can with things you can tolerate. Now is the best time to do this because you are likely to lose even more of your appetite later. A dietitian can help if your doc doesn't have enough resources to help you directly.

Remember, if you can't complain here, where else can you! Complain all you want - lots of people here from the old ribavirin days!
 

[Nina Mae]

I thank the internet gods for this forum.  And I'm very sorry for all of us who have this horrible disease.

Diet:  If I don't eat something every two-three hours, I get not just 'hunger pains' but actually 'painfully hungry' which creates a whole other problem because I'll get nauseated as a result of not eating something along with a protein.

I eat 6 small meals a day but what I'm challenged with is finding high caloric foods with low sodium.

I'm maintaining 10k+ steps (unless weather isn't cooperative).  I was vegetarian before dx but now, I'm pescatarian eating baked salmon daily.

Thank you for understanding; I suppose we all do...it's just comforting to know that there are people unfortunately in similar conditions that can relate. 

I wonder...are there any documented cases of PTSD associated with Hep C, treatments, liver disease.  I thought breast cancer was hard?  It was but this is off the charts creepy.

I find, in my short experience in dealing with hepatology professionals, they seem to be more clinical and though I do appreciate the bare basics, I do appreciate a little more empathy.  Breast cancer oncologists, radiologists, nurses, techs were all so awesome with always an encouraging word. 

Who knows...it could be just me reacting to a very scary disease with a poor prognosis.

I'll stop here before I start crying...

Deep breathing helps too!   

[lporterrn]

Hi,
There is documentation re PTSD and post-liver transplant. As for what you are experiencing, I can't over-stress how crazy the ribavirin ride is. I am not an alarmist, I rarely get ruffled, I rarely worry, and I am annoyingly peaceful - all that went to hell the 2 times I was on ribavirin.

But, I have tricks up my sleeves to share with you. This is the time to relax your rules. Your job is to beat hep C and we'll help you through it. Here are some more tips:
1) Lots of water
2) Talk to your doc about B12 supplementation (or general B supplement). You will likely show signs of anemia - don't self-supplement with iron unless doc advises - this is hemolytic anemia, not iron-deficiency anemia and you can get into trouble if you take iron without proper medical supervision.
3) If sleep or anxiety are a problem and you don't have addiction issues, perhaps your doc will prescribe something
4) Have you developed any itching? If so, hydroxyzine helps with the itching, helps with anxiety, helps with sleep and is non-addictive
5) Keep track of the timing of your ribavirin dosing - how much are you on? Sometimes a small change in when you are taking them or how the dose is divided can make a significant improvement in symptoms.

And finally,repeat this over and over: "This will pass."

[Nina Mae]

Lucinda, you made me actually laugh out loud !  You're absolutely correct to to relate riba rage to 'temporary Tourette's'.

These tips are very enlightening.  I'm too paranoid and 'scaredy catish' to self-medicate.  My GP had me on "Proferrin" which is a protein based iron supplement BEFORE I was dx'ed and the Hep C nurse knows I take it and said I can continue it.

Now I wonder if I should even bother taking them anymore which I'll discuss with GP because if they're not going to help my type of anemia, why buy them (they're expensive).  Of course, if it's decided I don't need to take them, I'll run that by the Hep C nurse before stopping them (paranoid).

No addictions (was a heavy smoker but quit in 2009 and haven't looked back); I'm already on ativan (1 mg) but I still can't sleep well.  I may get 5 hrs of broken sleep but rarely more than that.

No itching so far and very thankful for that.

Ribavirin:  200 mg. 

Epclusa/Ribavirin/pantoprazole dosage scheduled for 10 am (actual dosing times minor fluctuations, ie earliest time of dose 9:50 am; latest was 10:23 am. PM Ribavirin doses minor variances in PM in time from 9:40 pm to the latest being 10:10 pm.

To have to take ribavirin for two sets of treatments had to be so awful, Lucinda.  I admire you because I'm riba crazy now in just two weeks; I dread that it will get worse but at least I'm prepared, thanks to you and so many other caring, smart people on this forum.

I honestly don't know how you did two separate rounds of riba...they'd have to throw a net over my head, I'm sure.

You're right...this will pass...

 

[lporterrn]

Hi,
Glad I made you laugh - I compiled some ribavirin-related humor once - I'll see if I can find it.

You are on a low dose of ribavirin, so I doubt the hemolytic anemia has even begun, especially since you said your GP suggested supplementation prior to treatment - I highly suspect you need what you are on. Plus your hep C nurse is on board with it - sounds like you need it.

Ribavirin can be stimulating, and may be interfering with sleep. HOWEVER, taking it in the day may mean living with anxiety all day. I took 600 mg at night and 400 in the morning. I found it better to augment sleep with something my doc prescribed rather than take the larger dose in the day and live with anxiety.

One thing to keep in mind is that even healthy, unmedicated people who don't get enough good quality sleep can be grouchy. It may be that if you fix the sleep, you fix a lot of this. I find that meditation apps and podcasts help me sleep.

[Nina Mae]

I have to stop reading posts on this forum late at night.  I get too immeshed and the next thing I know, it's like 1 am and I naturally awaken through the night to pee multiple times.

Sleep was always a struggle for me (since breast cancer et al).

I suppose our BMI dictates the strength of ribavirin prescribed to us.  Nurse did say I'm on the lowest dosage.

All these symptoms of emotional stress:  the sadness, sleeplessness, and crying so easily were present before treatment.  The rage wasn't though...that flying off the handle stuff that is definitely attributable to the ribavirin...or is it the entire situation that angers me so.  Or is it so new and foreign to me yet to be bombarded with both dx's of Hep C, the influence of adriamycin and cirrhosis (including cancer in many women who were administered this chemo drug).

I didn't find out how advanced my cirrhosis is until March 1 when I met the Hep C nurse to get my first month of epclusa and ribavirin.  I knew I was sick but didn't know exactly 'how' sick I really am with such a poor prognosis. 

I think all this trauma is from all of the above...all immeshed now with ribavirin to just top it off and accentuate it all.

I'm using the free version of Headspace and that is excellent.  I'm just waiting for it to go on sale ($100+ USD).

Again, thank you, Lucinda.  I sure hope you have a great day and forthcoming weekend!

[Lynn K]

About poor prognosis. Well sure having a diagnosis of cirrhosis isn’t optimal (and I remember crying when my doctor told me) with Ute our livers will be able to heal at least partially. I’ve seen a couple of indications of some improvement since I was cured 4 years ago although not any change in my fibrosis score at least not yet.

I was diagnosed with cirrhosis 11 years ago and I’m still here. With cure I now have hope I didn’t have before these new drugs were approved I have the chance to have a future.

Hang in there we are not done yet!

[Nina Mae]

 

Thank you, Lynn, for your encouraging words.  I sure wish you didn't have to go through all this but you are obviously a strong willed woman...hats off to you! 

Like I told Lucinda, if it wasn't for this forum with so many caring, compassionate, and smart people like yourself, I really don't know what I'd do.

I've learned more from you guys than my entire care team has imparted.  This hepatology field...I don't know about them because they are so clinical, human factor with emotions are hardly their strong points.  I like them though and the fact that they're 'no nonsense or beating around the bush' but there's a way of telling people who are in our situations (and worse)...compassion and encouragement goes a long way.

You're right.  We are NOT done yet.  Today's a much better day for me in all facets.  Minor gastro side effects; it's just the ribavirin mood altering monster effects that's playing games with me.

Walking, taking deep breaths when overwhelmed, and telling myself that 'it's only 12 weeks and it will go fast' helps tremendously.

And I keep repeating...it will pass. 

As always, thank you for holding my hand.  Here's to many more good years, Lynn!  I believe you will defy whatever stats there are.  I defied advanced breast cancer 15 years ago so there you have it.  Each one of us are different with different circumstances...and if anyone is going to fight this battle with all their hearts, sounds like I found my twin   

[lporterrn]

Hi Nina Mae - Looks like you are a quick observer of cause and effect. Re the computer - my rule is computer and handheld devices off by 7 pm; TV off by 8:30 - this single rule has transformed my sleep. I was a lifelong problem sleeper for decades, and now sleep well on most nights. Headspace is great. So are Calm and 100% Happier. There are free meditations on various podcasts, such as 100% Happier. I haven't checked out the Insight Timer app, but that one looks good. All of these have sleep meditations. Calm has sleep stories which are very sleep-inducing.

[Nina Mae]

Hi Lucinda!

I'll tell you:  that one line of yours, 'think of it (re: riba rage) as temporary turrette's'!  Every time I think of that, I giggle to myself.

By golly, I think you cured me of those rages (for now, at least)!  But really, I haven't visited the forum or anything 'liver disease' related in a few days and I think that alone may be helping me in dealing with the anxiety of it all. 

I've been very fortunate as our weather is just lovely these past few days so I've been getting out more.  And distracting myself with house chores, etc.

I had my first of the every two week blood work and I have the results.  Though I don't have the baseline results, I can't see a trend (yet, my GP will give me that report, I'm sure).  According to nurse, she said, 'In love with the blood work! Numbers are going in the right direction.'

I'm using that 'Tracking Log' from this website to document and see my own trends.  Most abnormal results seem to be either slightly higher or slightly lower except the ALP.  ALP is off the chart with a result of 230.

Results Variations
AST:  43  (High)
Bili:    19 (High)
HGB:  108 (Low)
INR:    1.4 (High)
Hemoglobin, MCV, MCH, MCHC:  All low
RDW:  18.2 (High)
Monocytes:  0.9 (High)

I have a GP appt on the 27th; Week 4 blood work on the 28th; Ultrasound on the 30th.

Is the anemia attributable to the cirrhosis and can it improve after HCV treatment?  I believe I was anemic prior to starting DDA's.  Are there treatments for anemia as a symptom of cirrhosis and is it treatable as a chronic disorder? 

Inquiring minds...

Lucinda, you and Lynn K are a breath of fresh air!

I thank you again and again!

[lporterrn]

The anemia is likely from the cirrhosis and there is nothing more that can be done. However, if the DAAs do their job, you may see improvement about 2 months after you are off the ribavirin.

Good for you for giving yourself a break from the liver world!

[Nina Mae]

Yes, I kinda thought that though was hoping there may be cirrhotic specific meds or  something that can help even slightly.

Again, you're spot on.  I'll have to wait and see a few months or so after EOT for any improvements.  If it's going to improve, it will and that's all there is to it.

Do tell:  is the extremely elevated ALP of 230 significant to HCV or cirrhosis and will that improve after DDA?  Isn't the ALP and AFP the two blood tests that screen for HCC in conjunction with ultrasound?  Now I just made myself nervous...thanks, self.

[Lynn K]

ALP or Alkaline phosphatase is released in several circumstances including liver damage. It is elevated both with hepatitis c and liver cirrhosis.

https://en.m.wikipedia.org/wiki/Elevated_alkaline_phosphatase

AFP or Alpha-fetoprotein can be associated with liver cancer but it is an imperfect indicator which is why it should be used in concert with ultrasound or other imaging. AFP is often slightly elevated in hepatitis C

https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=alpha_fetoprotein_tumor_marker

[Lynn K]

There really aren’t any meds currently to treat liver cirrhosis. The meds commonly used in liver cirrhosis are to treat symptoms of advanced liver disease if/as they arise.

[Nina Mae]

Thanks, Lynn K.

I'm under the impression that both the AFP and ALP are used along with ultrasound for HCC screening? 

I know there aren't any meds  for cirrhosis; I suppose I phrased that wrong.  Are there specific supplements that can raise our RBC's being that we are cirrhotic?  Does this make sense?

I know that we can't 'treat' or 'cure' cirrhosis; just hoping there may be meds/supplements/nutrients that could help with our specific anemia?

I feel bloated and crampy today...weird.  It kind of feels like the 'once a month cramps' us women get (or used to get).  Sodium intake was low today (~1700-1800 mg)....I don't know so I'll blame the riba on it (why not...seems to be the culprit to so much as is).

[Lynn K]

I’ve never heard anything about using ALP as a reference to HCC only AFP and ultrasound nothing else except maybe an MRI if something suspicious was seen with ultrasound. Personally I’m not aware of any relationship with ALP (alkaline phosphatase) and HCC

ALP is just another liver enzyme like AST and ALT

I’m not a big fan of supplements personally many do little to noting and some can be dangerous to us with liver cirrhosis. I figure if there was something I could take my doctor would advise me to do so. I understand the desire to try to do something but really the best we can do is follow our doctors instructions try to eat a healthy diet and get some exercise as tolerated and permitted by our medical team.
If you do want to try any supplement make sure your doctor says it’s ok.

Cirrhosis can cause anemia. To improve HGB levels the solution is to eliminate the cause. So if the cause is cirrhosis then the liver needs to become less scarred.

With curing our hep c there is about a 50% chance our livers may begin to improve with time. This will depend on the amount of liver damage that has already occurred before being cured. For those who were cured and only recently had developed cirrhosis they will see improvement sooner than someone like myself who had advanced liver disease for a longer time and had symptoms of liver cirrhosis.

With cure our livers will no longer be under attack from hep c and our cirrhosis if hep c is the only cause of liver disease will not continue to worsen. Also being cured of hep c also means our risk of developing HCC is greatly reduced. We will still be at an increased risk vs someone who has no liver damage so we will still need to be monitored with blood tests and abdominal ultrasound every six months for early indications of HCC but we are at much less risk then had we not been cured.

Most recommendations for low HGB involve eating iron rich foods but the problem is because we have liver damage excessive iron load can be a problem for us. Iron overload can by itself cause liver damage so folks with cirrhosis are generally advised against taking supplemental iron.

If you want some safe ideas on how to improve your HGB levels I recommend you discuss this with your doctor.

Wish I had better news but with cirrhosis we’re kind of between a rock and a hard place. Darned if you do and darned if you don’t

Best of luck

[Lynn K]

Here is an article about HCC by the AASLD (American Association for the study of liver diseases) and a reference to monitoring for HCC

https://www.aasld.org/sites/default/files/AASLD_2018_HCC_Guidance_on_Diagnosis%2C_Staging_and_Management_hep_29913.pdf

“surveillance testing
1a. the aaSlD recommends surveillance of adults with cirrhosis because it improves overall survival (oS).
Quality/Certainty of Evidence: Moderate
Strength of Recommendation: Strong
1B. the aaSlD recommends surveillance using US, with or without aFp, every 6 months.”

So no reference to ALP only AFP and ultrasound every six months