MEXILETINE reduction

Five years ago I started mexiletine therapy for erythromelalgia. I’ve written about that here: MEXILETINE, 450mg. (In addition to mexiletine, I also take a once daily extended release propranolol, 60mg.)

For the first couple years of treatment I took 450 mg of mexiletine (150mg, three times daily). In 2017, I stepped down to 300mg (150mg, twice daily) for 2-3 months during summer. However, I ended up returning to 450mg for fuller symptom coverage.

I again reduced my dosage to 300mg (150mg, twice daily) in March 2019. I’ve been able to stay at that dosing for over a year now with no increase in symptoms.

The lone side effect I’ve experienced with mexiletine is occasional heartburn. In the past month that has become significant, perhaps due to the stress of the pandemic. As a result, I am now attempting to reduce my dosing of mexiletine to 150 mg, once daily.

Since mexiletine must be taken with a meal, reducing the dosing to once a day will allow me to simply take it with dinner. The lesser amount also will hopefully reduce acid reflux. I have some reason to believe the new dosing will remain effective, as when I started mexiletine therapy I began taking just 150mg once a day for a week and felt most benefit came from that single daily dose.

I am currently on day 2 at once a day. So far, so good.

I will update this post as warranted.


Best of luck Erik! Please keep us all updated on your progress.

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Hi Carter. That is very interesting. Do you know if you have primary or secondary EM please
All best

I don’t know for certain. However, I’ve had EM for 5 years and don’t have other illness to which it would be secondary.

Mex has a 1/2 life of 10-12 hours. To keep at least 1/2 in you, you may need to take 2x a day. I guess I’m lucky as I take 200mg 3x a day without side effects.

Half life cycles actually work a bit differently than that. Plasma concentrations drop by half each cycle. For instance, it’s 10-12 hours for plasma concentrations of mexiletine to drop to 50%, another 10-12 hours to drop to 25%, 10-12 hours more to drop to 12.5% and so on. It generally takes 5.5 half life cycles for a medication to be eliminated from your system. Thus, a single dose of mexiletine isn’t completely eliminated from your system for 55-66 hours.

Yes, I know how they work. But with a 1/2 life of 10-12 hours by the time they are ready for their next dose the effectiveness of Mex will be 25% or less which is probably not therapeutic. Personally if I only needed 150mg for the day I’d be tempted to try 2 75mg doses to keep a more consistent level. Unless you’re only flaring in the night than one night time dose might work. For me, I could tell when it started wearing off as I gradually built up on it. I can even tell the difference between 150mg and 200mg doses. I do best on 200 and I’m lucky I have no side effects on it.

A therapeutic dosage for me may simply be lower than others. My flaring stopped 36 hours after my initial 150mg dose. Up to that point I had been flaring multiple times a day. I took 150mg daily for the first week. It was quite noticeable when the flaring abruptly stopped. I didn’t really see much additional benefit when I went to 300mg and 450mg daily. It’s possible what benefit I did perceive from the increases was a placebo effect. The initial improvement from the 150mg daily dose was so dramatic, I expected more would be better.

That’s awesome a small dosage helps so much. I know several on Mex and you’re the only I’ve seen that gets 24 hr relief on one dose. Good for you. It doesn’t stop my flares completely but makes life at least livable again. Before I could barely do anything at all and still flared every evening and night.

Well, I think it’s still too early to know if a single daily dose is sustainable long term. Sunday was the most recent day I took mexiletine twice daily. So, its only been 5 days. I did have some paresthesia (burning sensation) in my feet on Tuesday and Wednesday. Caveat: I also restarted doing cardiovascular exercise (stationary bike) at the start of the week after about a month off. It’s possible my feet were adjusting to that.

My knees have always been the primary site at which I have erythromelalgia symptoms and they’ve been quiet so far. I’ve not had any change there.

UPDATE: It has been another month and I seem to have settled in relatively well to a single daily dose. After the first week I wasn’t sure it would work. I was having a regular burning sensation in my feet during the evenings, though without erythema most of the time. When I decided to switch the daily dose from dinner to lunch that seemed to help a lot. I figured that would give a higher plasma concentration of the medication in the early evening. I also stopped an antacid I was taking occasionally. I don’t know if it was interfering with the mexiletine or not. The paresthesia (pins and needles sensation) I get occasionally at my knees while sleeping may occur slightly more often and take twice as long to dissipate (30-40 seconds vs. 10-20 seconds). I can live with that. Otherwise, there hasn’t been any other change. These remain minor symptoms. The major flaring at my knees, for which I originally sought treatment, has not reactivated.


Thanks for the Mexiletine update Carter, I’m keeping this option on my radar.

If you ever need an option for the paresthesia, alpha lipoic acid (300mg twice a day) has helped me. Granted my feet still flare but I no longer feel the nerve related tingling/prickling sensation.

Your mention of antacids makes me think of my current experience with Propranolol, my tolerance for spicy food has completely plummeted ever since I started on it. (saw you have propranolol listed as one of your treatments)


That’s a great idea! For over a decade I took a creatine that had 250mg of alpha lipoic acid in it. Then I got injured, stopped taking the creatine, and not long after that my EM started. I’ve long looked at that creatine and wondered if there was something in it that might have been mitigating symptoms. It did have some undesirable vascular side effects (one reason I never restarted it) and has a bit of a mad scientist list of ingredients. Alpha lipoic acid was the one ingredient I thought maybe could have been beneficial. You’re the first person I’ve heard say they found it helpful. (Actually, I’m not sure I remember anyone else mention taking it before.) I’m going to give that a try. Thanks for the tip!

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The first thing I tried was Alpha Lipoic Acid per recommendation by a neurologist and worsened while taking it but had no idea why until I came across Dr. Cohen’s article on supplements. It suggests that those who worsen with Magnesium can potentially worsen with ALA (which makes sense because magnesium and CCB medications made me flare more frequently). With that being said, it definitely has its benefits but I thought I would add that it did make me worse since we both respond well to mexiletine and propranolol.

From his article: “Alpha Lipoic Acid (ALA) This supplement has been used for decades in Europe and now in America for neuropathies, the type of nerve injuries seen in diabetes. Because neuropathies are the underlying problem in most cases of EM, ALA can be beneficial for many of us. ALA is one of my main supplements. I have used it for ten years. Anyone helped by magnesium are likely to benefit from alpha lipoic acid. If magnesium makes you worse, use ALA carefully. Yet because ALA has other healthful properties for nerves, it still may help you.”

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You mention use of Alpha Lipoic Acid for neuropathies seen with Diabetes… I haven’t tried ALA yet, but recently stopped Magnesium, which I was taking initially for constipation… I will watch carefully to see if the EM flares slow down or hopefully stop. I am now taking Cymbalta, Lisinopril, Metformin, Piogliatzin, Gabapentin… I use the Neuropathy Frankincense and Myrrh rubbing oil once or twice a day on my feet when they flare and burn… I am unsure of what to try now, but my legs and ankles are tingling and feel heavy recently. I pedal on an exercise bike for a couple of miles almost every day, which is the only exercise I get now. I am 77 years old, feel like I’m 50, except for the painful feet and legs and difficulty getting a full night’s sleep. I’ve had EM for about 10 years and Diabetes for 2 years. The neuropathy also began about the same time as the EM… My hands and arms are becoming more affected lately… I’m concerned about my future and the possibility of autonomic neuropathy and hope to prevent it happening if at all possible… Thanks for all ideas and suggetions any of you may have for me…

If you’re susceptible to or already have acid reflux, alpha lipoic acid will only add to your gut problem. I could not take a second dose because I’m that sensitive to whatever is in there: just the alpha lipoic acid, a filler, a binding substance.

Primary erythromelalgia is one you’re born with. Me, for example. I had EM flares as a very young child. And both my kids have EM.

Secondary erythromelalgia comes as a side effect of another disease entity.

I don’t fit neatly into either category. However, the complete absence of any secondary disease entity 7 years on has led my doctor to conclude it is primary, hypothesizing it was triggered by a nerve injury that healed.

The best analogy for my experience is that it hit like a tsunami wave and then, over a period of years, receded like flood waters from said tsunami, returning to where it was originally — no longer present.

So many seem to experience an insidious disease progression. That wasn’t my experience at all.

NEW UPDATE: This week I decided to reduce my mexiletine dosing to 150mg every other day. My doctor is of the opinion I no longer need the medication at all. He says the 150mg per day dosing I’ve taken the past year is below the therapeutic threshold. Since I’m hesitant to stop it entirely, he advised every other day as an interim step to see how I do.

So far I’ve not noticed any discernible change after a few days. Since at 48 hours only around 5mg of mexiletine remains in the bloodstream, it appears he may be correct I no longer need the medication.

I no longer take propranolol either. So, if I stop mexiletine entirely, it will mean I’m no longer taking any medication for erythromelalgia and no longer having symptoms.


This is fantastic news! So happy for you.