Reducing sudden dropoff of Pyridostigmine/Mestinon therapeutic effect
 

Hi everyone, I'd really appreciate your constructive advice.

A close friend is currently being treated with Pyridostigmine / Mestinon. She was originally on a generic brand but is now using name-brand Mestinon with generally positive effects.

Her current regimen is to take 1/2 a tablet every 3 hours. At or around the 3 hour mark, the improvement often has a sudden dropoff. The effictiveness during the ~3-hour period with name-brand Mestinon appears better but this sudden falloff in efficacy is even more pronounced.

This is generally effective and works well. However, in a work environment one can't always excuse themselves from a slightly extended business meeting or videoconference when the effects suddenly drop off and another dose is required. Additionally, it can be uncomfortable to communicate this need since the onset is sudden and can affect speech.

I understand that MG and the treatment thereof can vary widely from person to person and be trial-and-error, but with this situation in mind, I was wondering whether anyone had any similar experience, and I also had an idea that I suspect may be effective, and would like to know whether anyone has tried something similar or knows of a good reason why this should not be done.

The idea I had is that instead of taking 1/2 a tablet every 3 hours, to divide that dose again and simultaneously take:
- 1/4 a tablet
- 1/4 a tablet inside a do-it-yourself vegetarian cellulose capsule

My understanding is that the it takes 20-30 minutes for the cellulose capsules to dissolve (vs. 2-5 minutes for a gelatin capsule), so my instinct is that this would extend some of the positive effect for another 20 minutes. So, instead of being faced with an "oh no - it completely stopped working - and it's now uncomfortable to speak to communicate this" situation, she might have 10 minutes of feeling a more gradual dropoff and be able to excuse herself to take the next dose.

Reasons that I think this might work are:
- No change in schedule and no chance of forgetting to take an additional part-tablet
- The dosage rate itself (in mg / hour) is not changing
- It should be a minimal change to what we know is a generally effective regimen
- Some of the dose is still absorbed pretty much immediately and should hopefully start being effective quickly
- Sustained release versions of Mestinon exist, indicating that it is OK for it to be absorbed in the small intestine
- The time to dissolve the cellulose capsule (about 30 minutes according to what sources I could find) seems to be long enough to make a difference. According to simulations using a 1.75hr half-life, the concentration normally hit at ~3hrs is extended to ~3hrs15min. Other options to play with this delay period might be to use gelatin capsules and/or cellulose capsules in a Babushka doll/Nesting doll fashion.

I appreciate your advice and help!

Aaron

Aaron, Hi and welcome!

The dosing of Mestinon can be tricky and hard to get used to. What you are proposing, however, could get your friend into trouble. Too much overlapping of doses can actually cause her to have too much acetylcholine, making her weaker.

Has she had a conversation with her neurologist about this? There are two things a person can "tweak" with Mestinon: The dose amount and the dose timing. Sometimes people are allowed to take Mestinon every 2-1/2 hours. But, again, she needs to talk to her doctor about that first. The dose for her might not be high enough. For example, I'm on 90 mg. (Mestinon Syrup) every 3 hours, round the clock. There are times I might need a little less or a little more. I can go up to 100 mg. Some studies have shown that anything over 100 may flood the neuromuscular junction with too much acetylcholine. Some MG patients are on more than that.

This is a tricky issue. She doesn't want to go up too high on Mestinon or too quickly and end up in the ER with a cholinergic crisis (too much acetylcholine). Maybe talk about increasing the dose amount slightly, like from 30 to 60, and on the weekend when she can see how she'll do. No, I'm not suggesting she do that without her neuro's permission! ;)

Mestinon is simply not enough for some people, especially if they want to keep working. It has finite possibilities for keeping you strong. While your idea sounds good on paper, in practice it may not provide the help she needs. I get only two "good" hours from Mestinon. It kicks in after about 30 minutes and wears off after 2-1/2 hours of taking it.

Only your friend and her doctor can decide what to do. I would not recommend that she try your idea. It's not that it's a bad idea but playing around with meds can be dangerous. It can also loose it's effectiveness if you change the form it comes in. For example, Mestinon cannot be put in the fridge. There's a lot to think about here and she needs to talk to her neurologist.

It's very nice that you are trying to help her. MG is an unpredictable disease and even with changes in a treatment regimen, it can still get worse. It completely sucks! Maybe she could log on and talk about it too. I hope she gets it all figured out.

Annie

Aaron, why not use the Timespan (the sustained release version)?

Abby

Aaron, unless your friend is "hiding" her condition from her co-workers, I suggest that she take a half tablet and put it under her tongue at the 2 hours and 50 minute mark. Mestinon used sublingually takes about 10 minutes to start acting (at least for me). OF COURSE she should run this by her doc, FIRST! (Or do it at the 3 hour mark if she'd rather NOT ask her doc -- her symptom recovery will be 10 minutes as opposed to 30 minutes.)

Mestinon melts fairly quickly under the tongue and does not have an unpleasant taste.

I agree with what everyone has said but would add that in addition to time and dose, STRESS can have a huge impact on MG. There are pleasant - and unpleasant - business meetings...so I know how much STRESS can build up in a difficult meetings with difficult clients!!

Very hard to hit the right dose for the tough meetings.

Aaron,

Mestinon can't do magic...sounds like your friend was in a similar situation as I was.

I was trying to work and tried taking 1/4 of a pill at shorter time periods (after talking to my neuro, he said is was ok for me to take any size dosage as long as I didn't go over the total amount he recommended per day).

It worked for a while, but MG is a strange thing to deal with. I ended up crashing big time and was unable to work and barely able to even care for myself for about three months last year. I crashed not because of the change in dosage but because i was pushing myself too hard.

Personally, I don't recommend using Mestinon to push oneself when you have MG. I learned that the more Mestinon I take, the harder I am going to crash later on. I haven't been able to return to work since pushing myself too hard last year. I overdid it because the Mestinon made me feel strong...

Going by my own experiences, I'd recommend your friend listen to her body and taking a break when she gets weak. Please don't try to help her push herself even more. MG has a way of punishing us for overworking. What she is experiencing, the sudden dropoff, if that were me, and it was me, would be a sign that I must take a break, not take more Mestinon. I no longer try to push myself or take extra Mestinon to do more (even though my neuro says that is okay, lol) because I was going downhill until I stopped working. Now I may be poor financially, but at least I am not experiencing those sudden crashes.

Of course, all that said, we are all different, and your friend may find help by adjusting her dosage timing (after talking to her doctor).

I replied because I was in a similar position, with people around me expecting the Mestinon to be a miracle cure so I could live a normal life, and work normally, and they were recommending similar things to me as you are suggesting to your friend. I felt pressured...and honestly, I wish I had more people around me that were supportive and could work around my weakness without pressuring me to push myself.

I wish your friend the best. She may find support by joining this forum. I think you should recommend it.

~DesertFlower

Hi Aaron,
How about taking ONE 60 mg pill and see when the drop-off occurs?
Maurice.

I had forgotten.........may I blame it on my dementia?? :rolleyes:

I did the same thing -- giving myself more and more Mestinon so that I could continue to perform my duties as a teacher (with my physician's approval) -- and I WAS able to continue -- to a point -- when I finally collapsed into an awful exacerbation -- and had to yell "uncle" and apply for disability.

Thanks for reminding me. MG "ain't" nothing to play around with!!!:hug:

I'd just like to say a huge "thank you" to everyone for sharing their experience. I really, really appreciate your helpful comments and kind words. I'm sure that my friend would benefit from your input and from a supportive, kind group of people such as you have demonstrated yourselves to be. Thank you so much!

:hug:

Annie: Thank you so much for your constructive input, your response was very informative and helpful. My friend will be discussing things with her doctor, and seeing what he thinks. As I understand, 60mg was too much, but it's something that they can perhaps adjust. I don't believe she has been given the syrup as an option so I'll let her know that is an alternative, too (it might make it easier to make slight adjustments to the dose) and she can discuss that at her upcoming appointment.

Abby: Thank you for the suggestion. From what research I have performed, it sounded like the sustained release version is OK for using while sleeping or on an uneventful day, but i've seen quite a few accounts that say it's not accurately dosed enough (or easily manipulated enough) to support people working through the day.

Jana: Thank you for the suggestion about dissolving the tablet under her tongue for faster rate of action, I will definitely pass it on. I don't believe that the rate of efficacy is the constraining factor however, but rather that the occasional sudden dropoff of efficacy of the previous dose. Also, thank you for sharing your experience about pushing things too much.

suev: Thank you, I can see how stress can be a big factor, and indeed, thinking about whether symptoms will exhibit themselves within a meeting can be stressful. Adjusting the dose slightly based on the stress involved with the activity is something that my friend can discuss with her doctor, so thank you for the input!

DesertFlower: Thank you for sharing your experience with shortening the time between doses - that is very valuable knowledge. I know my friend has adjusted her expectations and been careful about managing what energy and strength is available and resting when needed, but your experience really does reinforce how important this can be. Thank you very much.

Maurice: Thank you, I am sure my friend will be discussing this and dosing in general with her doctor.

Thank you!
 

My most awesome friend, Aaron, shared your responses with me. I've been diagnosed with a mild case of MG and as Aaron mentioned, I'm trying to get Mestinon, life, work on track. The common thread amongst all of your extremely helpful posts is the importance of rest. You hear it so much: rest when you have a cold; catch up on rest over the weekend; rest when you feel overworked or stressed. It becomes just another word but I think for Myasthenics, it's THE MOST IMPORTANT WORD. Does anyone also suffer from headaches? My doctor feels that my frequent headaches are a result of my blurry vision and too much computer work. Just wondering if anyone out there has a similar symptom? Also, I have weakness in one arm and hand. Is this common?

Hi and Welcome!

I don't get dv or headaches, but my original complaint was my 'weak with use' right arm. I'm a golfer and used to be pretty good....until my right arm wouldn't help me control the club half way through my round!!

Even today (after a few years of Mestinon) the right arm is almost always the first thing to get weak. Kind of my 'tell' on what's coming if I don't slow down for a bit.

Headaches -- yes, ARRRGGGHHH!!! I've always suffered from migraines -- but, they were under control until this past July. My vision started going "wonky" about that time (blurry) -- I ended up with severe double vision during September and October -- it started again during December and still hasn't gone away.

I complained mightily about my increasing headaches (up from 2 or 3 a month to 20 days per month) -- but, until I saw an optometrist a couple of weeks ago, no one seemed to "catch" the double vision/headache connection. My migraine neuro had recently upped my Topamax and renewed my Maxalt -- and it did help -- but, a slight daily residual headache remained. This past week I saw a neuro-ophthalmologist and got stick-on prisms!! I can SEE again!! My head already feels better. So, YES, I NOW firmly believe in the "eye-headache" connection that I ALWAYS heard about as a child!

Hmmmm -- just ONE arm/hand is weak?? I've had BOTH weak -- but, honestly, with MG you can expect the oddest symptoms. Like Annie, I'm having back issues right now -- MG can do AWFUL things to your back and neck muscles -- and if certain muscles got weak and didn't give proper support to certain vertebrae, I could imagine how a nerve (or something) might get pinched causing just one arm/hand to be weak.

BE careful -- I really hope that you CONTINUE to have "mild" MG. I was diagnosed with "mild" MG -- but, it only stayed "mild" for about 15 months.

BTW, I AGREE that rest is EXTREMELY important for MGers -- but, for me, avoiding STRESS is even MORE important. NOT easy to do -- but, essential for breathing, ya know?

Jana, I read all the posts here, and I'm sure I'm getting people's details mixed up with each other, but are you the one who has brain-fog, or some mental symptoms like that? I ask because you mentioned you're on Topamax, which has a reputation of doing awful things to your mind. I got a prescription for it once (for migraines) and didn't dare to take it, after reading about the mental side effects. People say that it makes them unable to think clearly, especially unable to think of words.

You probably know all this. I always figure it's better to risk being a little annoying by telling people things they already know, than to risk not telling them what they need to know!

Abby

Abby, you are SOOOOOO sweet -- and wow, WHAT a memory YOU have!!

Yes, I've got "brain fog" that sometimes drive me C-R-A-Z-Y!!! And, YES, my docs think that "some" of it may be attributed to the Topamax. But, I started having my demented "moments" about 6-9 months (??) BEFORE I started taking the Topamax -- ARRRGGHHHH -- so, I can't place all blame there. *sigh* A very astute resident that I saw at one of my appointments also noticed that I was taking Zyrtec (I was rotating off of Claritin) and he said that Zyrtec also had a reputation for doing the "brain fog" thing in some people. (I'm BACK on Claritin, now!)

I lowered my Topamax dosage about a year ago (just to see if my IQ shot back up -- LOL) -- and the ONLY thing that I (and my family) could tell is that my spelling and "grabbing" words improved. Other than that, I was about the same.

My brain fog seems to be worse on my BAD MG days -- and when my MG is "behaving", I still seem to be able to handle MOST of the difficult math problems that I taught as a high school teacher. :D I was ALWAYS the "encyclopedia" of the family -- the one who knew everything -- remembered where everything was -- and although I still seem to remember more than some of the others, I remember LESS than the OLD me -- so, deep in my heart, I somehow feel that MG is to "blame". I'm just not OLD enough for OLD AGE to be the cause of this, yet.

So, "in short" (hahahahahahaha -- as I've written a book), for ME at least, you are RIGHT!! Topamax seems to bring problems with WORDS -- spelling and finding synonyms. Since talking is my WORST symptom -- and I don't get out in public much anyway -- I don't consider this much of a big deal. The Topamax is a WONDER drug in getting rid of my migraines -- at least the ones NOT caused by double vision! ;)

:hug:

Thanks!

Sorry to hear about your golf game. Do you also have trouble with your right hand? Difficulty writing? Do you take anything other than Mestinon? Do you notice a difference between the name brand and the generic?

So many questions!!!

Thanks for all the advice - very helpful! I'm especially intrigued about the neuro-ophthalmologist and stick-on prisms. My vision is blurry too and the headaches come after too much computer work. I know what you mean about stress. For me the reaction is a tightening in my throat which stops me from speaking. Sorry to hear that you went from mild to not-so-mild. I'll definitely stay aware!

I just HATE when my voice "squeaks" to a halt. And, if stress can stop your voice -- beware -- it might eventually affect your breathing. Unfortunately, this might just come on SUDDENLY one day -- without ANY warning. You won't have a clue what is going on -- you just won't be able to "grab" air. Make sure you have emergency info in your purse -- so that someone in an ambulance/ER will know what you have and what to do. Better to BE prepared and NOT need it -- than to need it and NOT be prepared, right??

To see if your "blurry" vision is "early" double vision, cover one eye. If the blurriness goes away.......you have DV.

Something I LEARNED from the tech at my neuro-ophthalmologist's office -- put that "cloudy" looking Scotch transparent tape over one lens of a pair of reading glasses -- your NON-dominant eye. It doesn't look as "freaky" as a patch :D -- and sufficiently keeps that eye from focusing -- thus eliminating DV. If you do NOT need reading glasses, just get an el cheapo pair (like at Dollar Tree) and knock the lens out of the side you WANT to see through -- putting the tape on the OTHER side (if this makes any sense).

I did NOT know this thing about blurry vision and DV -- even though countless MGers had posted about it. I just thought that my presbyopia was getting worse RAPIDLY!! Eventually, I DID see TWO distinct objects -- and experienced the dizziness, nausea, tripping, almost falling, and soooooo much fun. :cool:

tperillo - you are right...my handwriting gets very bad in a fairly short period of time...to the point where I have to stop and take a break because the words aren't legible. I also notice deterioration when I need to stir stuff, or cut up a bunch of veges (needless to say I have to be very careful with knives since they can easily twist or fall out of my hand on the fifth or sixth carrot!!)

I only take Mestinon and its the generic. It works and luckily does not cause any side effects for me.

Jana - thanks for the warning about stress and voice. Odd that when I'm on phone for a bit my voice gets tired and cracky...but when I'm upset enough to want to 'spit my words out' absolutely nothing happens. It's like my throat gets stuck on pause!! Both of these are new for me so I appreciate the confirmation and the heads up!

Sue, ya know, I'm NEVER left alone. *sigh* But, if I WAS in a situation, say, where I might get mugged or something................I feel sure that I wouldn't be able to SCREAM (cause of my voice disappearing during stress). I've often thought that I should get an air horn or something to keep in my purse. A whistle would be good -- but, I tried and my lips won't fit around it enough to blow -- in the same way that I can no longer blow up a balloon. Of course, my lips were the FIRST part of me to stop working. :p

I would like to comment that those of us who think/thought we have mild MG, because we haven't had a crisis yet, may have no idea about how much the disease is interfering in our lives. It sounds like you are progressing in your illness and Mestinon may not be enough, and something more may be necessary to treat the actual disease process. I don't know what your problem is with taking larger doses, I had horrid stomache ache to start with, but now up to 60 every 4 hours. But one thing I found was that chewing and not swallowing not only got into the system quicker, but bypassed the stomach ache. So if I have to take 60 without food now I take the first 30 under the tongue and the other 30 with water. (After a number of months, I could finally take 60 with food which prolongs the maximum blood level and enabled me to spread out the Mestinon to every four hours.) nc