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Hi All,

I learned about a new med from my MCAD support group. There is much overlap between mast cell disorders and autonomic dysfunctions. Thought this might be helpful:

Droxidopa is an orally active synthetic precursor of norepinephrine currently approved and marketed in Japan for the treatment of orthostatic hypotension. By replenishing depleted norepinephrine via endogenous enzymatic pathway, Droxidopa allows for re-uptake of norepinephrine into peripheral nervous system neurons ? stimulating receptors for vasoconstrinction and providing physiological improvement in symptomatic neurogenic orthostatic hypotension patients.

http://www.chelseatherapeutics.com/pipelin.../droxidopa.html

http://www.chelseatherapeutics.com/pipelin...opa/orphan.html

The compensatory mechanisms that regulate blood pressure upon standing are dysfunctional in subjects with orthostatic hypotension (OH), a condition that may lead to inadequate cerebral perfusion with accompanying symptoms of syncope, dizziness or lightheadedness, unsteadiness and blurred or impaired vision, among other symptoms.

http://clinicaltrials.gov/ct2/show/NCT00004478

We see many patients at the [Vanderbilt] Autonomic Dysfunction Center who can be given a fairly definitive diagnosis, e.g., Orthostatic Intolerance, Pure Autonomic Failure, Multiple System Atrophy, and Baroreflex Failure. However, some patients present with a unique constellation of symptoms of autonomic dysfunction so that they do not fit into a diagnostic category. We hypothesize that a genetic cause exists in some of these patients. We further propose that our comprehensive evaluation of these patients will provide us with information on the pathophysiology of their condition and assist us in optimizing their treatment.

http://www.ncbi.nlm.nih.gov/pubmed/12885750?dopt=Abstract

http://circ.ahajournals.org/cgi/content/full/108/6/724

http://circ.ahajournals.org/cgi/reprint/108/6/724t

Circulation. 2003 Aug 12;108(6):724-8

Norepinephrine precursor therapy in neurogenic orthostatic hypotension

Kaufmann H, Saadia D, Voustianiouk A, Goldstein DS, Holmes C, Yahr MD, Nardin R, Freeman R

Mount Sinai School of Medicine, Box 1052, New York, NY 10029, USA. Horacio.Kaufmann@mssm.edu

In patients with neurogenic orthostatic hypotension (NOH), the availability of the sympathetic neurotransmitter norepinephrine (NE) in the synaptic cleft is insufficient to maintain blood pressure while in the standing posture.

We determined the effect of oral administration of . . .L-DOPS . . . , which is decarboxylated to NE by . . . decarboxylase (L-AADC) in neural and nonneural tissue, on blood pressure and orthostatic tolerance in 19 patients with severe NOH

After L-DOPS, blood pressure increases were closely associated with increases in plasma NE levels.

. . . from conversion of L-DOPS to NE outside the central nervous system.

http://circ.ahajournals.org/cgi/reprint/108/6/724

Clin Auton Res. 2004 Dec;14(6):363-8

Clinical pharmacokinetics of the norepinephrine precursor L-threo-DOPS in primary chronic autonomic failure

Goldstein DS, Holmes C, Kaufmann H, Freeman R

Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke National Institutes of Health, Bethesda, MD 20892-1620, USA. goldsteind@ninds.nih.gov

Edited by Sunfish
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This med is currently in trials here (see all links above) and I know one person w/ autonomic dysfunction who is loving it...she was just accepted for the longer trial next - 12 months - and so far is having pretty good results. Hopefully it won't be too long before it gains approval...it's been used in other countries.

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I was thinking of participating in the research study for this and receive information from a local neurology group, but I decided not to because I would have to be off the midodrine for about a week before the study and I can't function without it. I can't get out of bed without midodrine and I would have to report to the Doctor's office several times. Also, they may put the patient on a placebo part of the time. I just thought it would be too much for me.

I think this drug would be perfect for me (hopfully) since I have pure autonomic failure. I'm hoping the drug will be approved soon and I'm really getting my hopes up that it will help me.

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I think it's also used for Parkinson's, because I remember reading about it when I did work for a biotech company developing a Parkinson's treatment. I think any potential new treatment for POTS is a great thing! Thanks for the post.

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  • 2 weeks later...

This says the Phase III trial will be finished in January of 2010. A little less than a year!

On the other hand, does anyone have any thoughts on how much this drug will cost when it hits the market? Chelsea will have exclusive rights to it for seven years. I pay 400 $ a month for provigil. I guess Droxidopa will be about the same? Maybe more?

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There is a broker's report on the Internet which says the price in Japan (where it is already available) is about $4 a day, but they would obviously like to charge more in US/Europe e.g. $16. The $16 was a number plucked out of the air and, of course, this is in the context of influencing stock prices so one would hope it is top end.

Mind you, I don't understand why there is such a difference in drug prices around the world when they can be imported. At least fludrocortisone and midodrine (not ProAmatine brand) are very cheap.

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There is a broker's report on the Internet which says the price in Japan (where it is already available) is about $4 a day, but they would obviously like to charge more in US/Europe e.g. $16. The $16 was a number plucked out of the air and, of course, this is in the context of influencing stock prices so one would hope it is top end.

Mind you, I don't understand why there is such a difference in drug prices around the world when they can be imported. At least fludrocortisone and midodrine (not ProAmatine brand) are very cheap.

I don't understand this AT ALL! Why can't we just have Droxidopa shipped from Japan?

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Hi,

I just wanted to clarify that Droxidopa is different than L-DOPA (Levadopa) that is commonly used for Parkinson's disease. Droxidopa is used for Parkinson's disease as well, but to treat orthostatic hypotension. Parkinson's was mentioned in previous posts and I just didn't want anyone to get confused... :blink:

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  • 4 months later...

Oh...my insurance doesn't cover anything that's not generic. It's so painful if there is something that's really helpful. (Hoping for National Healthcare).

I haven't found a drug yet that is not available in generic that'd be helpful, but this looks like one! Let's hope it's affordable and useful for us all!

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I think the major concern with droxydopa would be for 'hyperadrenergic' POTS - although the understanding of this type of POTS is a little murky still.

But from what I understand it has a lower side effect profile than other alpha agonists and its basically just a precursor for norepinephrine. I spoke to a guy with POTS in facebook that said it worked wonders for him.

Other reports on it in POTS have been iffy.

Definately works in patients with NCS and NMH - Orthostatic hypotension.

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Dont worry too much - it might be helpful even in those forms of POTS - as particularly in NET disfunction (that is reduced reuptake of norepinephrine) patients often demonstrate signs of both reduced and excessive norepinephrine simultaneously. I think Dr Blair Grubb said that these patients run out or deplete their norepinephrine stores and then get symptoms. So it might be helpful.

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Dont worry too much - it might be helpful even in those forms of POTS - as particularly in NET disfunction (that is reduced reuptake of norepinephrine) patients often demonstrate signs of both reduced and excessive norepinephrine simultaneously. I think Dr Blair Grubb said that these patients run out or deplete their norepinephrine stores and then get symptoms. So it might be helpful.

Wow, thanks for this info. I'll mention this tomorrow. I feel very blessed that the doctor I have seems to really want to help. And, I don't get the feeling that he would just balk if he didn't know how to help me. He seams humble enough to admit if he's not sure or thinks I should ask another specialist.

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Well, I signed consent for the trial on Thursday. I go in Tuesday for my first visit and will have a physical and lab work done as well as orthostatic vitals (referred to as the standing test). I have to start the med within 7 days of this appt and return daily (for up to 6 days) for dose titration. Once the dose is at a therapeutic level for me, I'll stay on it for 7 days. After 7 days of active treatment, I will discontinue med for 7 days. I will then return for either a 7-day supply of the Droxidopa or placebo (double-blind) and return after those seven days are over. I will have more testing and this will conclude the study.

If I do not get improvement of symptoms after dose titration up to max allowable dosage, I will be removed from the study. If I do have improvement and wish to remain on the medication following the study, I can enroll in an extended study. I would be on the med for 12 months while they followed me for long-term side effects and by then the FDA should grant approval.

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Yes please let us know - saw my neuro today and he wants me to enroll in the study as well. Need to go back to get the 'official' testing to see if I qualify. I hope I do because he says he's seen great results.

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  • 1 month later...

Hi, I'm new to this forum but would love to hear from others who are taking part in the Droxidopa trials.

I have been diagnosed as having Dysautonomia, not POTS. Orthostatic hypotension is a major problem as well as fatigue and headaches etc. I was unable to take Fllorinef because of the headaches. Was on DHE oral and injectable for months which helped a little but not enough.

My doctor thought that the LDops would be just the thing for me and would basically restore me to be able to participate in life again and he was very excited about it which gave me hope.

I have been taking part in the Droxidopa trial in Melbourne since May of this year, and it has not been quite as straight forward as I had hoped.

How are other people finding it?

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  • 2 weeks later...

LDops Update:

I got into a mess after the 'double blind' part of the trial. Couldn't seem to get back on the med. After stopping everything for a few days because of severe headaches I began very slowly with 100mgs.

Having been on no medication for a few days I really was able to see the difference. Off meds and I was unable to cook a meal without sitting down every few minutes and I felt lousy all the time, most of you can relate to that.

Because of the way my body seems to reject medication I decided to go very slowly with the LDops and have just been on the 100mgs for a few weeks, my body has taken it well and I feel okay when I am just sitting which as many of you know is in itself huge.

Because of having surgery for another issue I will leave the LDops at the 100mgs level for the moment, I will have to increase it because I am still unable to walk far or do very much on the 100mgs, but just feeling okay when I sit at the computer or read a book is a relief for me.

So I would like to be encouraging about Droxidopa, like many things it needs to be worked out for each individual and I think once it is released for general use there will be more flexibility for that, but I am finding it a help.

Have a good day

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