Gilenya and VO2max, exercise tolerance

[pawpaw]

In mid-December I started Gilenya. The 6 hour observation went well- about a 6 point drop in my heart rate- from 60 to 54.
In November cycling season was over (my main sport) so I started a fairly aggresssive weight lifting program to gain strength over the winter. I continued some cardio, but didn't focus on this.
Fast forward to February. I started riding the bike on the trainer, but noticed that I was very short of breath at a lower heart rate than usual. I can pretty much tell what my heart rate is by how I feel and how I am breathing. Not now! Thinking I am a wimp and just need to be back in shape I train hard but find that I am very short of breath and can not get my heart rate up to my usual range no matter how hard I try.
So, at the end of February, I see my exercise physiologist who is also a cyclist. He puts me on a trainer to figure out my exercise zones and my lactate threshold. My VO2 max has fallen by 20% and my max heart rate is 10 points lower.
My neurologist has checked around and he hasn't found any information stating that this may be an issue. Cardiac conduction is affected by the drug, so this may part of the problem. He thinks there are so few very active MSers on the drug that there will be no data.
Has anyone else experienced decrease in exercise tolerance or decreased max heart rate?

Pell

[msma]

I've been on Gilenya for just over a month. No problems yet, but I'm not a serious athlete either. I know that shortness of breath shows up as one of the potential side effects:

http://www.pharma.us.novartis.com/pr...ilenya_pmg.pdf

[pawpaw]

I spoke with the pharmacist at the specialty pharmacy that dispenses my Gilenya about the heart rate and exercise tolerance issues. She checked the available literature and found nothing. She called Novartis and spoke with a nurse navigator who was basically very short with her and told her that there is no problem like mine documented and that they wouldn't tell her if there was! Reassuring.
I have noticed that the effect on my heart rate is less the longer it has been since my last dose. I rode my bike last night and on one particular hill I hit 152 heart rate. This morning I rode the same hill again and hit 137. I take my meds at night so it was a 10 hours interval since my dose this morning and 18 hours last night.

[AMFADVENTURES]

Went to see the Neuro last week and asked about Gilenya. I brought up the things I’m hearing from you guys. He wasn’t surprised about the shortness of breath and when I started talking about heart rates, he mentioned the reduction in max hr before I could. It appeared my Neuro had been hearing the same things from other people. That’s understandable since I know my Neuro works with a number of physically active MSers. It certainly makes the pharmaceutical company’s response (or lack of) more interesting.

Anyway, hope you guys keep talking about the experience, Gilenya may be in my future in another year so I am paying close attention to what you have to say.

[Marinadca]

Its interesting that you bring this up.... I started Gilenyia at the end of November. I didn't really think I was having any side effects...but while riding this weekend I found I got out of breathe too easily at too low of a heart rate. I was wondering if I had developed exercise induced asthma, or was just super out of shape....but this is another thing to be thinking about.

I don't have a HRM but thinking it might be a good investment, to figure out what is going on.

[pawpaw]

Marina- You sound exactly like me a few months ago when I started riding my bike again. I am still not sure that I don't have something going on with my breathing, but with exercise induced asthma our HR should be higher, not lower.
I hope you do get a HRM and look forward to your findings.

[ActiveMSers]

I talked with a rep from Gilenya who said HR issues should resolve over time (like two months) but this sounds different. Cardiac issues were discussed at the AAN meeting last week according to this story. It's so new, docs aren't sure exactly what is going on, as the FDA is focused on low heart rate after the first dose....

-----------------------

The cardiac issue has neurologists "nervous," according to Benjamin Greenberg, MD, of the University of Texas Southwestern Medical Center at Dallas, who was not part of the study, but who moderated the session at which it was presented.

"Some are still not prescribing it," he told MedPage Today, because they are not sure how best to protect patients -- and themselves -- from possible cardiac risks.

The drug was approved late last year, but the FDA mandated monitoring patients for six hours after the first dose, taking vital signs during that period, and watching for cardiac symptoms.

On the other hand, Greenberg noted, the FDA said nothing about screening patients by electrocardiogram or keeping an eye on cardiac changes with a Holter monitor.

The absence of such guidelines has "left neurologists across the country with a lot of concern," Greenberg said, "that they will be medically liable" if patients have an adverse event.

http://www.medpagetoday.com/MeetingCoverage/AAN/25965

[laacevedo625]

Effects from Starting Gilenya

I'm on day 12 of Gilenya. First day - took the pill at 8:30 am - felt fine for a while. Around 1 pm couldn't think straight. I was aware of things but not understanding much. Around 2pm my walking started to be like to drunken walking. Good thing my husband came to pick me up. I couldn't even remember how to get from the clinic to the elevator which was just around the corner. By 4 pm I was not feeling so good. My heart rate and BP were very low and breathing felt close to short breath. I didn't have much appetite and barely ate all day. By about 8 or 9 pm my HR and BP were coming back up and I was starting to feel better. I think the muscle relaxant I take (Soma) might have made it a little worse. I have not had shortness of breath but have felt like I'm on the verge of it. I have gained a couple of pounds but it could be due to lack of exercise - I'm slowly and carefully getting back into it. I had a lot of issues from my relapse before starting Gilenya and am not able to do very much cardio right now.

[TonyTony]

Gilenya and Exercise

Hi,

I'm on G for about 4 months now and I'm convinced it has shifted my heart rate training zones down by 10 beats and limits my max effort.
Anyone else any experience with this?

PawPaw, how are things 2 years on?

Thx
Tony

[TonyTony]

HR + Gilenya

Hi all,

I'm noticing the same effects with G. I'm convinced my training zones are lower and my max heart rate is lower. I wonder are there any long term consequences ?

TonyTony

[Marinadca]

Tony - I found that same thing for awhile but it seems to have resolved for me as time went on. I have been on Gilenya for almost four years and find that my HR zones are back to my pre-G days.

I tried not to worry too much about it, and just adjusted my Garmin zones

[bethslast]

heart rate

I started gilenya about a month ago and I noticed that when I exercise I can't get my heart rate up. I go to a gym called Orange Theory fitness and have been going for a year. Ever since starting Gilenya I am working out really hard, just like before, but my heart rate will not go up like it did before. Has anyone heard anything new since these posts? I want to be careful not to over work my heart. Thanks!

[ActiveMSers]

Here is a study that was just published on heart function and Gilenya. Although researchers say "no clinical consequences" I wonder if that includes athletes who enter the cardio zone for a sustained period of time. - Dave

Fingolimod effects on left ventricular function in multiple sclerosis

Vittorio Racca
Cardiology Rehabilitation Department, Santa Maria Nascente Institute IRCCS, Don Carlo Gnocchi Foundation, Italy
Marco Di Rienzo
Technology Centre, Santa Maria Nascente Institute IRCCS, Don Carlo Gnocchi Foundation, Italy
Rosella Cavarretta
Multiple Sclerosis Centre, Santa Maria Nascente Institute IRCCS, Don Carlo Gnocchi Foundation, Italy
Anastasia Toccafondi
Cardiology Rehabilitation Department, Santa Maria Nascente Institute IRCCS, Don Carlo Gnocchi Foundation, Italy
Emanuele Vaini
Technology Centre, Santa Maria Nascente Institute IRCCS, Don Carlo Gnocchi Foundation, Italy
Maurizio Ferratini
Cardiology Rehabilitation Department, Santa Maria Nascente Institute IRCCS, Don Carlo Gnocchi Foundation, Italy
Marco Rovaris
Multiple Sclerosis Centre, Santa Maria Nascente Institute IRCCS, Don Carlo Gnocchi Foundation, Italy
Cardiology Rehabilitation Department, Santa Maria Nascente Institute IRCCS, Don Carlo Gnocchi Foundation, Via Capecelatro 66, Milan, 20148, Italy’

Abstract

Background: Cardiovascular side effects such as bradycardia and atrioventricular block were observed during the early clinical trials of fingolimod in multiple sclerosis, and one cardiovascular- linked death has been reported in the post-marketing period.

Objective: To investigate the medium-term effects of fingolimod on heart function in order to obtain further insights into its cardiac safety profile.

Methods: The study involved 53 patients starting treatment with fingolimod 0.5 mg daily and 25 patients treated with natalizumab 300 mg monthly. Cardiac function was assessed by means of echocardiography at baseline (T0), and after one (T1), six (T6), and (in the case of the fingolimod group) 12 months (T12).

Results: Mean left ventricular ejection fraction significantly decreased and end-systolic volume increased from T0 to T1 (p=0.005) and T6 (p=0.0001) in the fingolimod but not the natalizumab group, although a slight increase was observed at T12. A similar decrease in ejection fraction was also observed after six months in nine patients switched from natalizumab to fingolimod.

Conclusion: Fingolimod significantly reduces left ventricular systolic function in MS patients. This effect has no clinical consequences in subjects without previous cardiac disorders, but suggests that more caution is required in patients with current or previous heart failure.

[ActiveMSers]

BartsMS, an MS research blog I highly respect, just posted this:

"The following study shows that fingolimod affects the function of the heart in MSers. In essence fingolimod reduces the amount of blood ejected from the heart with each heart beat; we call this the ejection fraction. In comparison, natalizumab had no effect on heart function in MSers. However, when MSers were switched from natalizumab to fingolimod there was a reduction in ejection fraction. The drop in ejection fraction is small and is probably not clinically significant unless there is an underlying cardiac disease or the MSers' concerned participate in elite or endurance sports. This finding is clearly worrying and further studies are required to reproduce these findings and to ascertain the long-term effects of fingolimod on heart function. I would be interested to know if any of you who are on fingolimod have noticed a change in your exercise tolerance or endurance?"

Perhaps a few of our members—among the first patients to notice this issue—would like to participate in their survey....

http://multiple-sclerosis-research.b...is+Research%29

[garyp]

Still impacted by this 4 years after starting Gilenya

Thanks Dave. Just completed the survey.

Quick update on my experience with this...

Prior to starting Gilenya 4 years ago now, my max HR when exercising was 140. Shortly after I started Gilenya, went down to 120. Has climbed back to 130 slowly over the 4 years. Measure myself using a modified Astrand technique. Yes, this is not done in a truly scientifically clean way, but the testing is consistent each time (same equipment and settings etc..). And I know my body. I get more winded when playing indoor soccer than before...so my testing backs up what I am experiencing when running around a indoor soccer field.