What to do about Mestinon side effects?

[Elli]

Hello everybody!

I have hyperadrenergic and neuropathic POTS. I was prescribed Mestinon. At first, it went well, no side effects, and it helped with the POTS a lot. Then the side effects started at 50mg (in 5 doses over the day): severe (!) diarrhea, severe stomach issues/gastritis symptoms, burning eyes. I can't live with these side effects. So I stopped and started with a lower dose again (10-5-5), but I get these side effects again. Ok, so I thought to stop again, and to try tiny doses of 0,2mg or so, and then increasing very slowly. Since it helped with the POTS, I feel sad about letting it go... My doctor said if reducing the dosage doesn't help, I need to stop. But people with Myasthenia don't just "give up" if they can't tolerate Mestinon, or do they? What do they do in such cases? I can't find anything...

Is here anyone with the same experiences? What can be done? Or do I just have to stop taking it? Are there alternatives? (Will ask the doctor, too...)

Many thanks for any reply!

[Pistol]

@Elli - I am so sorry that you are in this situation!! Here is what I have found throughout the years of trying meds for POTS: sometimes meds work and then stop working or suddenly we no longer tolerate them. It sounds like the high dose of Mestinon was too much and therefore may have caused the side effects. I agree with your doctor - if a decrease in dosage does not improve your symptoms then you really should stop the med - these are serious side effects that can make you sicker than before. Even in people with myasthenia gravis - if a med makes you sick you cannot take it. Doctors always weigh the risks and benefits of medications and continouing mestinon despite the side effects would not be of benefit for you. There are many other medications that your doctor can try. Be well!!!!!

[p8d]

I agree with @PistolWhen I first got sick we tried mestinon and I had very similar side effects.  I won’t go into detail but I ended up hospitalized and even more ill than before.  These side effects are *nothing* to mess around with.  I was switched to midodrine, which I couldn’t tolerate either before we settled on fludricortisone.  That worked for a few years until my BP became too high and we stopped it.  There are other drugs and it’s trial and error so don’t give up but do stop this drug.  I don’t want anyone to go through what I did.  My neurologist was seriously concerned about me to the point of calling twice a week to see how I was doing.  If you want the gory details send me a message and I will tell you.

[bombsh3ll]

Hi Elli,

The GI and eye side effects you mention can probably be mitigated with other medications/eye drops. I would speak to your doctor about options for this since it was helpful for your POTS. 

Mestinon is something I am thinking of trying again. I tried it briefly in the past but it only helped with constipation, & I have other laxatives for that. 

When you say it helped your POTS, do you mean it helped you stand & function or just the numbers?

I hope you find a way to make it work.

B xx

[Elli]

Hey, thank you everybody for your helpful replies!

18 hours ago, Pistol said:

It sounds like the high dose of Mestinon was too much and therefore may have caused the side effects.

Yes, increasing to 60mg caused the side effects, but then going back to 50mg didn't stop them (that's why I think it would have happened with 50mg, too, just maybe a bit later). Yesterday I tried 5mg-5mg-5mg, which was ok (no stomach issues, only a bit of gut issues). I am careful though and I see the potential risks. Thank you @p8d for extra cautioning me. (And yes, I'd be interested in your Mestinon experience.)

18 hours ago, Pistol said:

There are many other medications that your doctor can try.

My understanding is that hyperadrenergic POTS is difficult to treat. My doctor gave me the impression Mestinon is the only shot. I have other diseases, too, and it seems they exclude other meds. (I will ask about alternatives nonetheless...)

@bombsh3ll, yes, I treat the burning eyes with drops which works. The diarrhea wasn't funny though, so I decreased the dosage to the already mentioned 5-5-5. I already have low body water, so losing more via diarrhea might be problematic (besides not getting the nutrients you need). This dosage gives barely side effects and helps a bit with the POTS. But I still consider lowering the dosage/stopping. But:

11 hours ago, bombsh3ll said:

When you say it helped your POTS, do you mean it helped you stand & function or just the numbers?

Both. That's why I don't want to give up. I felt nearly normal. It felt like I could do things I couldn't do before because being upright causes so much trouble. I have to take IGG, and afterwards POTS gets much worse, which was much better with Mestinon. If I eat "too much" (especially carbs), the POTS gets worse, and Mestinon helped with that, too. I imagine if I had been able to increase Mestinon, that might have disappeared altogether. It's not like I was like healthy again, but it was like "Oh I have POTS? Really? I nearly forgot about that." There are some more "subtle" POTS symptoms of course...

Re. numbers: Without Mestinon my HR was 145 after 1min of standing; I had to stop a poor-man's-TTT (Schellongtest) after 7min latest because I felt like fainting. With Mestinon, HR rised to 120 after 5min, which still isn't grand, but!, and although I wasn't symptom-free, I could finish the test.

There's only one downside (besides the side effects): During sleep my HR is already low with ~45 bpm, 50mg Mestinon lowered that slightly more to maybe 38-40bpm.

 

[Pistol]

2 hours ago, Elli said:

My understanding is that hyperadrenergic POTS is difficult to treat. My doctor gave me the impression Mestinon is the only shot. I have other diseases, too, and it seems they exclude other meds. (I will ask about alternatives nonetheless...)

I have hyperadrenergic POTS and tried many, many medication y specialist ordered: mestinon, different BB's, clonidine, Ritalin, guanfacine, diltiazem, Lexapro … I can't even remember them all. Yes - it IS difficult to treat but there are many options. Below is a section of the article about hyperadrenergic subtype from this web site:: 

QUOTE:

There are many medications that have been effective in symptom improvement, however, there are no FDA approved drugs for the treatment of this type of POTS. The treatment is highly individual, which means some meds will help one patient but not the other. This can create a frustrating process of trial-and-error but often will lead to the discovery of the right combination.

Some of the medications that have been found helpful are:

• Adderall, Ritalin
• Florinef
• Clonidine
• Beta-blockers (especially the combination of Carvelidol and Labetaiol)
• Midodrine
• SSRI/SNRI
• Modafinil
• Methyldopa

One of the more significant findings in the treatment of hyperPOTS is the general observation that centrally acting sympatholytics (Clonidine, Methyldopa & others) and beta-blockers seem to work better to manage symptoms in people with hyperPOTS than patients with neuropathic POTS. (Grubb, et.al) 

END QUOTE

So - as you see there are more meds than just mestinon. Having said that - if you have other conditions ( as you mentioned in your post ) you might be limited if these options are contraindicated for you. For example - I cannot take midodrine or florinef due to the type of hyperadrenergic POTS I have. Since you have hyperadrenergic AND neuropathic POTS I could see that this is extra difficult. ---- Has your doctor ever tried IV fluids? They are a very effective treatment for both types of POTS and have shown to bring relief of most symptoms, especially tachycardia and orthostatic intolerance. I have found great improvement from weekly IV fluids and in the past used them during flares. --- Wishing you the best - be strong!!!!!

 

 

[bombsh3ll]

3 hours ago, Elli said:

The diarrhea wasn't funny though, so I decreased the dosage to the already mentioned 5-5-5. I already have low body water, so losing more via diarrhea might be problematic (besides not getting the nutrients you need).

There are specific meds that can help with this such as hyoscine, loperamide, amitriptyline, codeine etc that you could ask your doctor about if it would help you keep a valuable med. 

I too am severely hypovolaemic (from polyuria though not diarrhoea) and also have low sleeping HR.

B xxx

[Elli]

21 hours ago, Pistol said:

Has your doctor ever tried IV fluids? 

Again thank you @Pistol! My GP (who would have to make the infusions) thinks saline IV is useless because the water disappears again very fast. This may be correct, also because I seem to pee more than I drink. (This is being looked at in the sense that my GP says a one-time measurement is not enough - which I did - so now I will do a week. If the amount in is still smaller than the amount out, he wants me to go to a Nephrologist. But I will speak about that with the POTS doctor, too.) But whatever, he is not willing to do it...although my immunologist who also knows POTS recommended it. 

20 hours ago, bombsh3ll said:

I too am severely hypovolaemic (from polyuria though not diarrhoea) and also have low sleeping HR.

This is interesting. What do you do against polyuria? I think it's a huge problem re. POTS. Is it a consequence of dysautonomia? (I suspect so. That's why I think a Nephrologist will not be helpful.)

Ah, I forgot: My GP thinks I should lower the Mestinon dosage until I don't get side effects anymore and from there increase very slowly over weeks. Maybe it'll work. If not, I will have to ask for alternatives, but as I said the before the POTS doctor sounded very much like "nothing I can do in your case but we can try Mestinon". (@Pistol, many meds on that list are contraindicated, and I remember the POTS doctor excluded others, too, but still I will ask.)

[bombsh3ll]

1 hour ago, Elli said:

This is interesting. What do you do against polyuria? I think it's a huge problem re. POTS.

Unfortunately there is nothing I can take for this as I had horrible side effects with fludrocortisone, which is the only synthetic replacement for aldosterone. I cannot take desmopressin because I am already prone to low sodium due to the mineralocorticoid deficiency. 

I drink lots of electrolyte mix, which may help marginally, & am always drinking water too. For about a year I had great benefits from licorice root, which basically tricks your own cortisol into acting like aldosterone, but the effects wore off over time.

I have tried IV fluid but lose it just as quickly as I lose oral fluid, so it is not worth a central line for me. 

Still looking for the answer! There is a study going on in Canada just now into IV albumin instead of saline which has a much longer volume expanding effect, which I would really like to try if this shows positive results & I can get someone to listen.

What is odd though is that all my life I've been a drink-a-lot, pee-a-lot person but never had POTS until five years ago (sudden onset after a forceful Valsalva).

Good luck with the nephrologist. They may be able to look into antidiuretic meds for you like the ones above if you haven't already tried them, although normally it would be an endocrinologist for that. 

B xxx 

[Pistol]

@bombsh3ll and @Elli -- I used to have the problem with polyuria and NSS did nothing for that. Only once we used Lactated Ringers solution instead of saline did the issue improve. I pee a whole lot - which is why oral fluids do nothing for me. But the LR does not cause me to urinate, I actually pee much LESS with the infusions. LR has a certain combination of electrolytes which keeps the fluid within the vascular System, sort of like a volume expander. This is the reason they use LR during surgery rather than NSS. My sister also gets infusions for her POTS and did great on LR but was switched to NSS and it causes her polyuria, high BP and the effects are short-lived. They are considering switching her back to LR.  

[bombsh3ll]

1 hour ago, Pistol said:

Only once we used Lactated Ringers solution instead of saline did the issue improve. I pee a whole lot - which is why oral fluids do nothing for me. But the LR does not cause me to urinate, I actually pee much LESS with the infusions. LR has a certain combination of electrolytes which keeps the fluid within the vascular System, sort of like a volume expander. This is the reason they use LR during surgery rather than NSS.

That's really interesting, I will look into accessing that here but it is hard enough to get saline!

B xxx

[Elli]

6 hours ago, bombsh3ll said:

 I cannot take desmopressin because I am already prone to low sodium due to the mineralocorticoid deficiency. 

So you have low cortisol? Why does that lead to low sodium? Well, again side effects... ☹

7 hours ago, bombsh3ll said:

There is a study going on in Canada just now into IV albumin instead of saline

Interesting! Do you have a link maybe? Because this could be something my GP might consider.

I will not get antidiuretics without indication, so I can't just try them. It's ok. I want to be sure I really pee too much water before trying something like that. But it takes longer.

5 hours ago, Pistol said:

Only once we used Lactated Ringers solution instead of saline did the issue improve.

This is very interesting, too. Actually maybe a very good option to antidiuretics? I will suggest that to my GP. Maybe... 😊

 

[RecipeForDisaster]

I'm hoping to try LR, too, but I have enough trouble getting saline myself. The doctor who writes my Rx for saline doesn't want to try LR for some reason and I'm grateful to have ANYthing, so....

 

I use DDAVP as a last ditch BP increaser because I am very low and not much helps it. I use it as little as possible and take 15gm salt daily. I haven't had my urine volume measured, but my sodium excretion was normal. I don't think I urinate more than I drink. I'm going to see a nephrologist next. Endocrinology was not interested. If not for saline and DDAVP, I'd be stuck on the floor at least one day a week these days.

[bombsh3ll]

38 minutes ago, Elli said:

So you have low cortisol?

No I've got tons of cortisol, I just don't produce aldosterone. I do not think it is an adrenal problem though, as my renin is non existent too, which the kidneys are responsible for producing. Renin stimulates the production of aldosterone via a complex series of interactions, but basically I have hyporeninemic hypoaldosteronism. 

Here is the study on albumin. https://clinicaltrials.gov/ct2/show/NCT03365414 Looks like they have yet to start it though, that is frustrating! I wish I could be one of their patients!

42 minutes ago, Elli said:

I will not get antidiuretics without indication

Both fludrocortisone and desmopressin are used off label for POTS, without urine measurements. Some people find one or both really helpful.

B xxx

[Pistol]

33 minutes ago, RecipeForDisaster said:

The doctor who writes my Rx for saline doesn't want to try LR for some reason

This is most likely b/c LR has potassium and calcium in it and they are afraid that this might make your level of these electrolytes too high. I get 1 l weekly ( rarely more ) but my CMP ( electrolyte panel ) is always normal, so no exccesive readings. I truly believe that the medical community needs to take a serious look at this issue - so many of us only get approved for NSS - yet those of us that ARE getting LR have much better results. 

[Elli]

1 hour ago, RecipeForDisaster said:

I'm going to see a nephrologist next. Endocrinology was not interested. If

Best wishes for you!

Thanks @bombsh3ll for the link. I wish the study was already finished. 😊

50 minutes ago, bombsh3ll said:

Both fludrocortisone and desmopressin are used off label for POTS, without urine measurements. Some people find one or both really helpful.

I meant antidiuretics for supposed polyuria - polyuria is not proven yet, there is an indication. My GP wouldn't prescribe antidiuretics for polyuria. POTS is an indication, and my GP would prescribe fludrocortisone, I think. I'm not sure with the desmopressin, though. (I didn't know that fludrocortisone is an antidiuretic and that desmopressin is used for POTS, although my GP explained that corticosteroids tend to increase body water.)

27 minutes ago, Pistol said:

This is most likely b/c LR has potassium and calcium in it and they are afraid that this might make your level of these electrolytes too high.

Oh, this is a good point. 

[RecipeForDisaster]

My CMP is always fine, too... potassium and sodium actually on the low side despite supplementation. I'd love to at least get the first liter LR and the rest NS... not like I want to run 6L LR weekly or anything.

 

DDAVP isn't super common for this sort of thing... I know for me it was one of the last chance drugs, and most of my docs didn't want to prescribe it. No alternative was available - I can't ruin my veins nor can I always lug an IV pole around for 12 hours, and sometimes I'm too shocky to even get an IV.

[Elli]

I've had some thoughts - since this is a bit of speculation, I am thankful for corrections or new facts.

I found it interesting that I seem to tolerate Mestinon in the morning better than in the evening. (Are there others who share that experience?) So right now I take max. 2mg of Mestinon in the evening without having side effects, and 6mg in the morning without side effects.

I have neuropathies. These usually are much worse in the evening. There are indications that the vagus nerve is somehow affected, too. The vagus nerve is part of the parasympathicus, which is one regulator of the autonomous nervous system. Mestinon is cholinergic and therefore - as I understood - "stimulates" the parasympathicus (a researcher who specializes in the vagus nerve mentioned Mestinon as a "vagus stimulator", so it seems to have some effect on the vagus). I observe in me that whenever the vagus gets "tickled" (there are certain "triggers"), symptoms like the side effects I got from Mestinon appear or get worse. So almost anything that's supposed to stimulate the vagus nerve makes me worse. Also, if I take anticholinergic drugs (e.g. Vomex; H2-blockers like Ranitidin help with stomach issues alone) the Mestinon side effects get better or disappear (but this seems trivial to me; I assume the entire effect of Mestinon is neutralized then). I wondered if there is any connection between neuropathies (which may cause dysautonomia) and tolerance of Mestinon?