Retigabine (Trobalt, Potiga) — General Discussion

[Juan Carlos]

Some external info about the company. Seems small company (1-5 workers), working since 2008, located in China
http://merrychemical.en.hisupplier.com/
http://www.tradekey.com/company/Hangzhou-merrychemical-co-ltd-4329900.html
http://merrychemical.en.ec21.com/company_info.jsp

 

[111]

The USA FDA has a document which shows companies approved to supply the us market with drugs and similar products. Not surprisingly 70% of the meds come from countries other than the USA, and the top two, India by a long way 23.7% of total then China !

So anyone maybe thinking of getting retigabine directly from a supplier could use the below spread sheet to find an approved supplier ?

Link to the FDA article
http://www.gmp-compliance.org/enews...-market--generic-drug-products-and-APIs-.html

And I have attached the spread sheet as well listing all approved sites, quite a large document but can be filtered

 

[locoyeti]

Hey @locoyeti, great find. You noticed they quoted Dr Large as the one who calculated concentration of Retigabine at 1200mg/day? No wonder he went after an alternative KCNQ modulator.

Technically he went to work on Kv3 channels (KCNC), but I get your point. Potassium channel modulators seem to offer us a bright future.

Thank you for finding the paper, @locoyeti ! Just a question on the data bolded above - if the effective therapeutic concentration is 7.4um and at 1200mg/day you only get to 2.0um, it seems that it would require 7.4/2.0 * 1200 = 4320 mg/day of retigabine to get the the therapeutic concentration. This would seem to conflict with the "plausible and safe" assessment above, as I don't believe retigabine has been tested at such high dosages in epilepsy trials. Am I misunderstanding something here?

Good question. 'Therapeutic concentration' seems to be a term specific to this report (couldn't really find anything by googling the term). The paper defines it as:
"The concentration at which hyperactivity was attenuated to the native level was considered the therapeutic concentration, at EC42 on the sigmoidal curve – calculated by the inverse of the relative increase under pentylenetetrazol"

So I think it is a value that is specific to the pentylenetetrazol treatment, which is just a model of tinnitus. I am sure that tinnitus hyperactivity varies from person to person, but probably does not correlate to 1.0 mM pentylenetetrazol (imagine what that graph would look like on 0.5 mM of pentylenetetrazol).

Also we don't know what effects a partial dampening of activity will do to how tinnitus presents. As I see it, the root problem is the DCN fusiform cells. This paper used the auditory cortex of mouse embryos, so I think that it is possible that resolving the hyperactivity in the DCN might have non-linear downstream effects. Taking even higher dosages than 1200mg/day might bring even further improvements to tinnitus levels, but I think it would be safer to not exceed that maximum recommended dosage.

 

[Zimichael]

@locoyeti ...Indeed, this paper you discovered is pretty amazing in that it directly addresses a number of the questions of most interest to us:
~ It covers the two Kv7 drugs we can get hold of (with Flup. only in Europe, etc.) - well supposedly get hold of!
~ The dose relationship.
~ The toxicity aspects.
On all fronts Retigabine looked pretty darn good except for the "super high dose" requirement for supposed efficacy to the 'native', non tinnitus (aka pentylenetetrazol induced) state.
However, the "reality" of this may be pretty different in the real live humans, as we have already noted that "results" have occurred for trialees at much, much lower doses that the Fig. 5 A graph would imply. Irrespective, the graphics are very clear about the trend-line with dose increase = T reactivity for both 'spikes' and 'bursts' goes down (despite the 'interesting' time bleed off in Fig. 1 A at the 5 uM concentration in particular).

So sorry rt. but I think my "intuitive sense" that you need more Retig troops to "kick the doors open" was right on the money .

To conclude, I think one of the main take-aways from this study (which was quite impressive in terms of equipment and method - man there are some smart people out there to figure this kind of stuff out!) is that the KV7's may be as legitimate in the T race as the Kv3's...though it would have been REALLY nice to have had a side-by-side here of a Kv.3 drug like AUT00063...as then it might have shown us why that was so much "better" than the Kv.7s...Does not look like Autifony is going to oblige there.
Also, that it may be worth considering the "slow taper up" in dose model is perhaps inappropriate for using Retigabine to treat tinnitus. It is not epilepsy. Though I would suspect that anyone with hidden epileptic tendencies may be at risk for potential 'unknown reactions' on a super fast taper up. So caution is always warranted!

For me, this study does a lot to make me reconsider another go at Retigabine/Trobalt in the future (once all my dental stuff is complete = a ways off) if we can get the supply situation dialed in, and I can figure out how to deal with my increased hyperacusis at higher doses. This last is a stickler, as I have to go out and get groceries in the noisy world, and even with plugs in it was an "intense experience" when I was at 600 mg/day total, so what might it be like at 1200 mg/day total......Mmmmmmmmmmmm???!!!

Again, excellent find locoyeti!

Best, Zimichael

 

[locoyeti]

Some news: I just got my prescription for retigabine a few days ago, and I am currently researching prices. It seems that online, both the canadapharmacyonline.com and blueskydrugs.com had the 84 pack of 300mg at $360, and I think they said it would take 15-19 days. I went to CVS (retail store) and got a quote for double the price, but it would be available the next day. It's kind of pricey but I think for the piece of mind I will go the CVS route, as it seems that you online buyers are having some issues with procurement. I don't want to have to taper down for lack of the drug. If anyone has any input or suggestions I would appreciate them. I live in the North East USA.

So I was going over the old posts to get a sense of Mpt's taper up dosage, and I don't think he ever explicitly wrote a post on it. I think he privately messaged his taper up to @Christian78 , which was a rather quick 100mg TID for 3 days, 200mg TID for 3 days, and then 300mg TID indefinitely after that. Here is that post:
https://www.tinnitustalk.com/threads/retigabine-trobalt-potiga-—-general-discussion.5074/page-16#post-58080

Then there is @benryu 's post on dosages, but the chart image is missing:
https://www.tinnitustalk.com/threads/retigabine-trobalt-potiga-—-general-discussion.5074/page-12#post-57648
I think it was a starting dose of 300mg TID, with weekly increases of 50mg TID.

I am thinking of tapering up faster, but I am not sure about going as fast as @Mpt. I was thinking of shortening the taper up from
50mg TID increase every 1 week
to
50mg TID increase every 5 days.

That still doesn't come close to @Mpt's taper up speed. There might only be one chance to get this right, if in fact a quick taper up is what is needed to 'kick down the doors'. I think I will do some more research on this, I would appreciate any input.

 

[Danny Boy]

Can anyone get me these? I am willing to pay the cost of shipping and of course the cost of the drug. Really am desperate and I don't want to die. My doctor won't prescribe me them and that is just killing me....

 

[rtwombly]

@locoyeti Any help from your health insurance? I have a $200 deductible on drugs, but I'm not sure if I'd have to pre-qualify.

 

[luigilo]

Courage @Danny Boy , brace yourself the cure is coming. Hold on, be strong !

 

[SoulStation]

Can anyone get me these? I am willing to pay the cost of shipping and of course the cost of the drug. Really am desperate and I don't want to die. My doctor won't prescribe me them and that is just killing me....

Danny. Please go get some help. We all hurt and understand that T is ultra painful. Don't do anything drastic. This may not be the golden ticket and you can really gain some relief with other drugs/therapy.

 

[rtwombly]

For Danny Boy and anybody else feeling close to the end of their patience: see your GP for a psychological referral. No, it won't stop your tinnitus at this time, but there are plenty of things that can be done to help bear it for as long as you need to - which may not be that long at all!

At my lowest point I lost my temper with my daughter, smashed a handful of plates in the sink and ran outside screaming like an animal. I informed my employers that I wouldn't be in for awhile and that same day saw a PA in my GP's office and a psychiatrist. The PA took my suggestion for an anti-depressant, mirtazapine, which is known as one of the safest for people with tinnitus. It's not a strong anti-depressant, mostly it helps you sleep, but sleep is SO important. When I wasn't sleeping, I wasn't me, end of story.

Four or five months later, I ran out of my last refill of mirtazapine and decided I didn't need it anymore. I've gone through a job loss and the stress of being unemployed (briefly!) but I'm now so much better than I was I wouldn't trade my current peace of mind for my old job even if they let me work at home and keep my health benefits.

Is my tinnitus better? Maybe. I can't honestly tell the difference between lower tinnitus and less emotional response to tinnitus. I'm either a bit better or more habituated. And honestly, I don't think it matters much. I still want a cure - I could tell the difference between what I've got and SILENCE - but I'm so much better off.

I used to go into my daughter's room to tuck her in at night and think, "I can't enjoy this anymore," and feel worthless, like I was a broken man who was no good to anybody. It's a quiet room, and I couldn't stop myself rushing out of there as quickly as I could, despite the pain I felt at not wanting to be there. Now I read to her nightly, taking my time and coming up with funny voices for the characters in her books until my wife has to tell me to get out of there and let my daughter sleep.

Don't give up. You will feel better. Don't try to do it on your own, get help! We're close to a cure - so close - but it's not a black and white world. Maybe you feel everything's ruined for you now, but it's not ruined. You're not ruined. You're walking through a tunnel. It's dark and cold and gloomy. But I swear, it doesn't go on forever. There's light at the end. Light and warmth and freedom. The only thing that can stop you getting there is if you stop walking.

Now, what was this thread about? Oh yeah. @locoyeti, I think 5 days to a 150mg increase is perfect. It's the schedule I'd follow if I could ever get a scrip. Don't cut pills if you can help it.

@benryu @Mpt come back, friends!

 

[111]

Then there is @benryu 's post on dosages, but the chart image is missing:

This was the chart you were looking for, shows slow taper up and only to max level of 600mg a day as well

 

[locoyeti]

@locoyeti Any help from your health insurance? I have a $200 deductible on drugs, but I'm not sure if I'd have to pre-qualify.

Looking into that, but I don't think health insurance will cover it.

 

[111]

That still doesn't come close to @Mpt's taper up speed. There might only be one chance to get this right, if in fact a quick taper up is what is needed to 'kick down the doors'. I think I will do some more research on this, I would appreciate any input.

Mate I am sure you know a lot more about me on this stuff as you are all over this like a rash, but I have attached a page from GSK's own document showing what dose levels they did during the testing phase in case this assists you at all.

The maximum total daily starting dose is 300 mg per day (100 mg three times daily). Thereafter, the total daily dose is increased by a maximum of 150 mg per day ( 50 mg increase three times a day ) every week onwards, according to the individual patient response and tolerability. An effective maintenance dose is expected to be between 600 mg/day and 1200 mg/day. The maximum total maintenance dose is 1200 mg/day. The safety and efficacy of doses higher than 1200 mg/day have not been established.

 

[bedouin]

I've gone through a job loss and the stress of being unemployed (briefly!) but I'm now so much better than I was I wouldn't trade my current peace of mind for my old job even if they let me work at home and keep my health benefits.

I can relate. Thanks for your post. I've also lost my job due to tinnitus and my inability to focus or concentrate anymore. I took the opportunity to do am101 (which i am grateful for, as i know a lot of people don't even have the chance of getting on). Unfortunately there has been no improvement but its still early days and i remain +ve that the 2nd injections might help. I guess I just wanted to re-affirm what rt says about anti-depressants and sleep. It is a lot easier to cope with the world (less suicidal thoughts) when you get support and take something to assist with mood, t-induced depression and sleep.

Before am101 trials i was taking meds and i can honestly say, things weren't as hard as the are now. Unfortunately, the trial pre-requisite is that you can't be on anti-depressants so i came off everything cold turkey just to get on. That edge is now back. I know it is temporary. If i get no improvement from am101, i will consider going back on ad's and something to assist with sleep. So for the benefit of others going through hell at the moment, you are not alone and if you can, try and get something to bring you back from the edge, as they will help. I'm still unemployed but I am too hoping that too will change god willing soon and that something comes up. Apologies for going off thread.

Thanks locoyeti for the info on Retigabine. Good to hear that you are in the chute to start using it. I hope it works for you.

 

[Zimichael]

Hey, some Canada news on Trobalt...It is now available c/o CanadaPharmacyOnline, so presumably Blue Sky Drugs as well as they both use Westlake Pharmacy in Hounslow, UK, as their source. They had email confirmation yesterday.
So if using them I would double order, or get your scrip made out for more re "refills" amount.

I don't think any US health insurance would pay up for Potiga unless a special exemption for epilepsy....and that only. Off label for tinnitus. I would say zero likelihood unless you are the president.

@locoyeti ...on dose rate going up. Well we know that the GSK and "Benryu table" are pretty much possible to ignore with seemingly no harm done. I think the slow taper makes much more sense for epilepsy as it is inherently an "unstable condition" (I mean geeez, how else could you describe it???) and you don't want goofy stuff happening. So for T I think you should just play it as it goes and see how you feel. I was surprised at how fast I could jump up with no 'other' real side effects of note than mild temporary headaches. The darn > hyperacusis aside that is!
I would say if you have the pills and the patience, that 150 mg jumps every 5 days are more than fine. I did 300 mg/day total to 600 mg/day total in two days...well the interval was two days at 450 mg then 600 mg on the third day.
So potentially this "Matt taper" of 300 mg in 3 days is feasible. But I was pushed for supply, so this may not be an issue for you and 150 mg every 5 days is very 'conservative' compared to that!
If you feel really good, you may consider as a compromise > 150 mg every 3 days as maybe the max I would think. But feel it out as you go.

Best, Zimichael

 

[SteveToHeal]

Does anyone else find it strange that @Mpt and @benryu are still MIA?

 

[lapidus]

Does anyone else find it strange that @Mpt and @benryu are still MIA?

Benryu was last seen october 8 so he has been here but not replied to anyone. I don't blame him though, there's gotta be 100 alerts for him and this thread is a mess to keep up with if you leave for a while. But he could just pop in and say hi. As for Mpt, I have no idea where he's at. He said he would keep us updated on his tapering down.

 

[Markku]

Mpt has been gone for a while due to breaking our netiquette on a continuous basis. The decision wasn't made lightly, as everyone in the staff knew very well Mpt's contributions and valued them greatly.

It should be noted that the staff understood the reasons / emotions behind Mpt's actions leading to the ban, but when we looked at it objectively (and after we had already given multiple warnings), we had to instate a temporary ban.

Hopefully we can now turn over a new leaf.

The ban has since been lifted, and this is Mpt's latest update via e-mail:

I would appreciate it if you would post something to the effect that I'm not posting as I was banned so that there isn't any speculation I quit because my tinnitus came back or because I'm well and no longer care, etc. I do plan to post to the forum again at some point in the future.

As for @benryu, he sent us a message a couple of weeks back and told that he's been busy after returning from his vacation. But he did say that he would be coming back as soon as possible.

 

[locoyeti]

This was the chart you were looking for, shows slow taper up and only to max level of 600mg a day as well

Hey, some Canada news on Trobalt...It is now available c/o CanadaPharmacyOnline, so presumably Blue Sky Drugs as well as they both use Westlake Pharmacy in Hounslow, UK, as their source. They had email confirmation yesterday.
So if using them I would double order, or get your scrip made out for more re "refills" amount.

I don't think any US health insurance would pay up for Potiga unless a special exemption for epilepsy....and that only. Off label for tinnitus. I would say zero likelihood unless you are the president.

@locoyeti ...on dose rate going up. Well we know that the GSK and "Benryu table" are pretty much possible to ignore with seemingly no harm done. I think the slow taper makes much more sense for epilepsy as it is inherently an "unstable condition" (I mean geeez, how else could you describe it???) and you don't want goofy stuff happening. So for T I think you should just play it as it goes and see how you feel. I was surprised at how fast I could jump up with no 'other' real side effects of note than mild temporary headaches. The darn > hyperacusis aside that is!
I would say if you have the pills and the patience, that 150 mg jumps every 5 days are more than fine. I did 300 mg/day total to 600 mg/day total in two days...well the interval was two days at 450 mg then 600 mg on the third day.
So potentially this "Matt taper" of 300 mg in 3 days is feasible. But I was pushed for supply, so this may not be an issue for you and 150 mg every 5 days is very 'conservative' compared to that!
If you feel really good, you may consider as a compromise > 150 mg every 3 days as maybe the max I would think. But feel it out as you go.

Best, Zimichael

Yea, I called my Doctor's nurse and they put in the pre-confirmation to see if my insurance would cover it, but they said they were 100% sure that the insurance would not cover it. Looks like I will have to pay out of pocket. The nurse said that I could get a better deal at Target or Wal-mart, so I suggest trying those places too. Target was a little cheaper than CVS, ($1350 vs $1500) but they also did not have it in stock, and there is no way of knowing how long it will take to get it since it is a manufacturing problem. There also may be state/regional variation in prices.

For those that are trying to get this prescription, I strongly suggest going for the 300mg pills as they are the most cost effective. Also try and get as many pills as possible, especially if you want to do the high dosage-short taper up. This will give you more leeway, should you decide to taper up faster, or go higher in dosage. I know that some of you object to cutting the pills, but I don't think it will be a big deal, and since I am going up to 900mg/day I won't have to cut after my taper up.

@Zimichael , I agree that the fast taper up is probably not too big a deal, I am considering now to do a taper up of 50mg TID increase every 3 days. I am getting an eye exam this weekend and will probably start early next week.

 

[rtwombly]

I am considering now to do a taper up of 50mg TID increase every 3 days. I am getting an eye exam this weekend and will probably start early next week.

Man, don't do the fast taper up AND pill cutting. I did a 180 on looking back at Z's experience. How do we know what his actual dosage was at any given time?

300mg pills -> 50mg pills = cutting one pill into six pieces. If each pill is +-5mg, that's a pretty big cumulative effect. I have a lot of experience cutting pills in half, and pretty much every day for the 7+ years I was doing it I would cut, take half, set the other aside for later, and inhale the powder left on the cutting surface, because I could tell I'd left a lot behind.

If you're going to cut, I think you need a 5-day spread between jump ups.

@Markku, may your sons be wealthy and your daughters tender-hearted. You are a gentleman and a scholar, sir.

 

[Christian78]

Can anyone get me these? I am willing to pay the cost of shipping and of course the cost of the drug. Really am desperate and I don't want to die. My doctor won't prescribe me them and that is just killing me....

Is it so hard? I may have 2 boxes of 200 and one of 50 mg that i can sell you, inside EU, price is 50 euro or was it 48 idk and these smaller they have their price....

 

[Zimichael]

Is it so hard? I may have 2 boxes of 200 and one of 50 mg that i can sell you, inside EU, price is 50 euro or was it 48 idk and these smaller they have their price....

Hesus Christian...I would be careful on this. Say the recipient has a "Hengist reaction" that does not dissipate???

Your call I guess.

Best, Zimichael

 

[tomm]

What sites are able to provide this without a prescription?

I wasn't even able to get the corticosteroid prednisolone from my local GP at the 72 hour mark or from an online UK GP consultation via 'pharmacy2u.co.uk', so retigabine prescription will be quite unlikely.

Be nice to have some lined up in case AM-101 doesn't work. *shudder* Perish the thought.

 

[locoyeti]

hey @Johno @SoulStation @Christian78 @undecided @Mpt can we get some updates please?

 

[Danny Boy]

What sites are able to provide this without a prescription?

I wasn't even able to get the corticosteroid prednisolone from my local GP at the 72 hour mark or from an online UK GP consultation via 'pharmacy2u.co.uk', so retigabine prescription will be quite unlikely.

Be nice to have some lined up in case AM-101 doesn't work. *shudder* Perish the thought.

Hope you get some...I tried to convince my GP which supporting documents the lot...All they did is write a letter to the ENT department to ask about advice about Trobalt...Seriously, she was telling me she could get sacked for prescribing this to me!? She said a specialist can though. Trust me, GP's are useless!

 

[tomm]

Hope you get some...I tried to convince my GP which supporting documents the lot...All they did is write a letter to the ENT department to ask about advice about Trobalt...Seriously, she was telling me she could get sacked for prescribing this to me!? She said a specialist can though. Trust me, GP's are useless!

The community could do with a stack of good evidence (trial results, papers, Dr endorsements etc) to take to doctors for each medicine/supplement/procedure to help stop the massive inconvenience of 'shopping' for a sympathetic doctor. Once enough people who want it get the prescription and record their experiences we start getting a good picture of what works and what doesn't that helps everyone.

@Dr. Nagler I know you are US based and this may not be relevant for the rest of the world, but can you recommend a template or format/content of documents that a patient could bring to you that would cause you to consider and take seriously a proposal for a prescription that is out of your usual field please? I think there is a lot of frustration at being stuck at the first hurdle for some if us and not being able to try potentially helpful medications under observation. Thanks.

If we have any other medical professionals on site, please weigh in!

 

[undecided]

@locoyeti I have not much to report, been off trobalt for a week, still waiting for my 300mg pills to arrive.
Seems like there was some post office mix-up and my prescription got lost ... somewhere on the way. I've resend my prescription, hopefully it will get to the UK withing the next decade.

I've been trying gabapentin for the past week, seems quite useless as it probably makes T slightly worse and has 0 effect on the associated anxiety. Benzos FTW.

 

[Danny Boy]

The community could do with a stack of good evidence (trial results, papers, Dr endorsements etc) to take to doctors for each medicine/supplement/procedure to help stop the massive inconvenience of 'shopping' for a sympathetic doctor. Once enough people who want it get the prescription and record their experiences we start getting a good picture of what works and what doesn't that helps everyone.

@Dr. Nagler I know you are US based and this may not be relevant for the rest of the world, but can you recommend a template or format/content of documents that a patient could bring to you that would cause you to consider and take seriously proposal for a prescription that is out of your usual field? I think there is a lot of frustration at being stuck at the first hurdle for some if us and not being able to try potentially helpful medications under observation. Thanks.

Dr. Nagler please do help us!

 

[65vwbus]

@tomm @Danny Boy I think in the UK you'd probably need to see a neurologist to get Trobalt. My GP admitted to me that they don't know much about epilepsy drugs, I had to see a neuro to get the 4 epilepsy drugs I tried. They can be dangerous if you get the dosage too wrong, I have a permanent tremor due to a prescription error with Topamax months ago.

 

[Zimichael]

@Danny Boy ...Danny, I'm not sure you have been taking to heart what people have been telling you on this thread. I know you are 'hurting' and most of us know that place really well. However you are "short term T" and there are numerous other options open to you! I would suggest you take a hard look at those and not pin your hopes on this stuff, especially if you cannot get a doc to sign off on it.
These docs out there are not just afraid of Retigabine for zero reason...they are on the line if it goes "Boom" in your face. They see no big, controlled trials for Retigabine and Tinnitus, and despite the small body of evidence we have accumulated here it is from a total of less than 10 people with zero "control" a la normal science. This is not a "valid" reason for a doctor to take a huge risk on an "off label" psych' med. that has some pretty scary warning profiles. I sure would not prescribe it unless I knew my patient and their history very, very well.

I would leave Dr. Nagler out of this. He has already made his position on this drug clear. We do not need to muddy the waters with that.

Again, please look at some of the great advice that has been offer to you already.

Best, Zimichael