Retigabine (Trobalt, Potiga) — General Discussion

[Martin69]

Hi all,

It does not make much sense writing a user report since I have not tested much.
Today I have catastrophic T. 16 kHz screaming at me. It sounds like the complete room is filled with the noise.
So I decided taking just one 100 mg of Trobalt. My first one.

Didn't do anything on my T. I got a little bit tired after 30 minutes, but this could also be due to something else (not great sleep last night). I can only say that no effect on T and no side-effects.

But I neded to admit that for my T today I would probably need dosage for an elephant.
I could get endless Trobalt supply since my friend visits Spain on regular base. Was no problem getting the stuff without any prescription.

So that's where I am right now, not much further.
I didn't expect my 10/10 T will be killed with one 100 mg pill.

 

[Danny Boy]

Hi all,

It does not make much sense writing a user report since I have not tested much.
Today I have catastrophic T. 16 kHz screaming at me. It sounds like the complete room is filled with the noise.
So I decided taking just one 100 mg of Trobalt. My first one.

Didn't do anything on my T. I got a little bit tired after 30 minutes, but this could also be due to something else (not great sleep last night). I can only say that no effect on T and no side-effects.

But I neded to admit that for my T today I would probably need dosage for an elephant.
I could get endless Trobalt supply since my friend visits Spain on regular base. Was no problem getting the stuff without any prescription.

So that's where I am right now, not much further.
I didn't expect my 10/10 T will be killed with one 100 mg pill.

400mg, is the correct dose. As I said, it's the dose to kill t.

 

[Martin69]

400mg, is the correct dose. As I said, it's the dose to kill t.

So how would you taper up?
One week 100 mg per day, one week 200 mg per day, one week 300 mg per day and then 400 mg?
Or what would be your plan?

 

[Danny Boy]

So how would you taper up?
One week 100 mg per day, one week 200 mg per day, one week 300 mg per day and then 400 mg?
Or what would be your plan?

I've taken 1200mg in one single dose...Just to see, it doesn't do anything different. My Advice is take 400mg as a one off and report back.

 

[Martin69]

@Danny Boy
Without tapering up?
Hmm.

 

[Danny Boy]

@Danny Boy
Without tapering up?
Hmm.

I said one single dose, just as a one off. If it doesn't lower your t, then it isn't gonna work for you sadly.

 

[MarioT]

This is what a quick google search did for looking up a dosage scheme:

https://www.medicines.org.uk/emc/medicine/24527

"
Posology

Trobalt must be titrated, according to individual patient response, in order to optimise the balance between efficacy and tolerability.

The maximum total daily starting dose is 300 mg (100 mg three times daily). Thereafter, the total daily dose is increased by a maximum of 150 mg every week, according to the individual patient response and tolerability. An effective maintenance dose is expected to be between 600 mg/day and 1,200 mg/day.

The maximum total maintenance dose is 1,200 mg/day. The safety and efficacy of doses higher than 1,200 mg/day have not been established.

If patients miss one dose or more, it is recommended that they take a single dose as soon as they remember.

After taking a missed dose, at least 3 hours should be allowed before the next dose and then the normal dosing schedule should be resumed.

When withdrawing Trobalt, the dose must be gradually reduced (see section 4.4).
"

 

[locoyeti]

This is what a quick google search did for looking up a dosage scheme:

https://www.medicines.org.uk/emc/medicine/24527

"
Posology

Trobalt must be titrated, according to individual patient response, in order to optimise the balance between efficacy and tolerability.

The maximum total daily starting dose is 300 mg (100 mg three times daily). Thereafter, the total daily dose is increased by a maximum of 150 mg every week, according to the individual patient response and tolerability. An effective maintenance dose is expected to be between 600 mg/day and 1,200 mg/day.

The maximum total maintenance dose is 1,200 mg/day. The safety and efficacy of doses higher than 1,200 mg/day have not been established.

If patients miss one dose or more, it is recommended that they take a single dose as soon as they remember.

After taking a missed dose, at least 3 hours should be allowed before the next dose and then the normal dosing schedule should be resumed.

When withdrawing Trobalt, the dose must be gradually reduced (see section 4.4).
"

this is the dosage scheme for epilepsy. the correct dosage for tinnitus is still an open question. i personally dont think tapering up slowly is effective. danny is right, although i would say try a 300mg pill first. before that you can even try a 200mg pill. please go back over my old posts on this thread for dosage recommendations.

 

[linearb]

I said one single dose, just as a one off. If it doesn't lower your t, then it isn't gonna work for you sadly.

I'm sorry, but respectfully, I don't think you or anyone else here has nearly enough data to make this sweeping an assertion.

That is, even if I accept that everyone who has tried Trobalt to date, who did not notice an immediate benefit, did not notice any benefit, that's hardly convincing proof that "people who do not notice an immediate benefit from trobalt, but do notice an effect after a period of use" is a zero-count population.

I also think it's highly inappropriate for people on this forum to be giving dosing recommendations at all. It's fine to say "I took X mg and noticed effects Y", but that's very different than saying "I advise you to take X mg". The latter is not something that should come from anyone besides a licensed MD with experience prescribing the drug.

400mg, is the correct dose. As I said, it's the dose to kill t.

What works for you and is safe for you, may not work or be safe for other people. Drug pharmacokinetics are extremely complex, and relate to at a minimum: body size, genetics, GI flora/fauna, liver enzyme function and kidney function.

There is a reason that 'simple' pharmacists spend six years getting trained.

 

[Danny Boy]

I'm sorry, but respectfully, I don't think you or anyone else here has nearly enough data to make this sweeping an assertion.

That is, even if I accept that everyone who has tried Trobalt to date, who did not notice an immediate benefit, did not notice any benefit, that's hardly convincing proof that "people who do not notice an immediate benefit from trobalt, but do notice an effect after a period of use" is a zero-count population.

I also think it's highly inappropriate for people on this forum to be giving dosing recommendations at all. It's fine to say "I took X mg and noticed effects Y", but that's very different than saying "I advise you to take X mg". The latter is not something that should come from anyone besides a licensed MD with experience prescribing the drug.

What works for you and is safe for you, may not work or be safe for other people. Drug pharmacokinetics are extremely complex, and relate to at a minimum: body size, genetics, GI flora/fauna, liver enzyme function and kidney function.

There is a reason that 'simple' pharmacists spend six years getting trained.

We estimated the therapeutic potential of Kþ channel openers in suppressing tinnitus-like activity by quantifying the responses in the auditory cortical networks. Retigabine had the highest therapeutic potential, with a therapeutic concentration of 7.4 mM – a concentration at which counteraction against induced- hyperactivity were effective – followed by NS1619 (15.2 mM), flupir- tine (23.3 mM), and isopimaric acid (30.0 mM). These values were well within the range of their effective concentrations against epilepsy (3–100 mM; Kobayashi et al., 2008), thus, possible off-label treatment for tinnitus is plausible (and safe). Clinical studies had calculated the free brain concentration of retigabine taken at 1200 mg/day to be

around 2.0 mM

 

[Sharpfire]

We estimated the therapeutic potential of Kþ channel openers in suppressing tinnitus-like activity by quantifying the responses in the auditory cortical networks. Retigabine had the highest therapeutic potential, with a therapeutic concentration of 7.4 mM – a concentration at which counteraction against induced- hyperactivity were effective – followed by NS1619 (15.2 mM), flupir- tine (23.3 mM), and isopimaric acid (30.0 mM). These values were well within the range of their effective concentrations against epilepsy (3–100 mM; Kobayashi et al., 2008), thus, possible off-label treatment for tinnitus is plausible (and safe). Clinical studies had calculated the free brain concentration of retigabine taken at 1200 mg/day to be

around 2.0 mM

These types of studies should be taken with caution when deciding the dosage of a drug to take. This paper is an in-vitro (outside the body) study thus does not account for the pharmacokinetics and side effects of a high dose, regardless of the predicted high therapeutic effects it has found. I say predicted because again, it's an in-vitro study, therefore effects in-vivo may not exactly be the same.

 

[Danny Boy]

These types of studies should be taken with caution when deciding the dosage of a drug to take. This paper is an in-vitro (outside the body) study thus does not account for the pharmacokinetics and side effects of a high dose, regardless of the predicted high therapeutic effects it has found. I say predicted because again, it's an in-vitro study, therefore effects in-vivo may not exactly be the same.

The clinical evaluator notes that the drug has a narrow therapeutic index and is concerned about some reports of cardiac arrhythmia (asystole or ventricular tachycardia) healthy subjects within 3 h of receiving a single 900 mg retigabine dose (below the maximum recommended total daily dose). The clinical evaluator suggests that minimisation of pharmacokinetic variability is important, particularly reducing variations that could increase the maximum plasma drug concentration (Cmax): control of the drug particle size might be important in this context.

Immediate release, film coated tablets in a wide range of strengths are proposed: 50, 100, 200, 300 and 400 mg. These are all made from a common granulate using conventional excipients (which are unlikely to react with the nucleophilic drug). The five strengths are distinguished by tablet markings, colour and/or shape. The proposed tablets are not scored.

Blister packs of 21 tablets (for 50 and 100 mg only), and 84 tablets or 168 tablets are proposed, as well as an initiation pack of 50 mg (21 tablets) + 100 mg (42 tablets).

The requested finalised product specification at release and expiry has been provided. This is acceptable.


Retigabine is rapidly absorbed and extensively metabolised. There is some metabolite activity. Excretion is chiefly renal. Pharmacokinetics are claimed to be linear. The absolute bioavailability of oral solution and capsule formulations (2 x 100 mg) has been measured (both solution and capsules ~60%, with bioavailability of capsules versus oral solution ~100%).

Eleven bioavailability/bioequivalence studies were included in the submission. Some have been evaluated and some summarised. Almost all the bioavailability studies used doses significantly lower than the apparently optimal effective dose (600 to 1200 mg/day).

 

[Sharpfire]

The clinical evaluator notes that the drug has a narrow therapeutic index and is concerned about some reports of cardiac arrhythmia (asystole or ventricular tachycardia) healthy subjects within 3 h of receiving a single 900 mg retigabine dose (below the maximum recommended total daily dose). The clinical evaluator suggests that minimisation of pharmacokinetic variability is important, particularly reducing variations that could increase the maximum plasma drug concentration (Cmax): control of the drug particle size might be important in this context.

This is from a different paper, and I have no idea what it has to do with my comment.

 

[Danny Boy]

This is from a different paper, and I have no idea what it has to do with my comment.

You're asking about the dosage and as it states it's between 600-1200mg. These are from clinical studies within humans.

 

[linearb]

You're asking about the dosage and as it states it's between 600-1200mg. These are from clinical studies within humans.

none of which in any way rebuts anything I said in the post you were responding to...

 

[Danny Boy]

none of which in any way rebuts anything I said in the post you were responding to...

Rebuts what? He can do a fast taper up 300mgx3 then taper up to 400.

 

[Hotspur]

Hi Danny,i recently done the autifony trial,didnt feel a great effect from it,and will never be told if i got the placebo

Was just thinking, might be an idea if i could try a 400mg trobolt as a comparison,im in the Uk ,how would i get hold of it?Or could i buy a one off from you?

 

[attheedgeofscience]

You're asking about the dosage and as it states it's between 600-1200mg. These are from clinical studies within humans.

I did not know that Trobalt had been evaluated in a clinical study involving humans and in relation to tinnitus.

[Please notice the missing question mark at the end of my sentence, above].

These types of studies should be taken with caution when deciding the dosage of a drug to take. This paper is an in-vitro (outside the body) study thus does not account for the pharmacokinetics and side effects of a high dose, regardless of the predicted high therapeutic effects it has found. I say predicted because again, it's an in-vitro study, therefore effects in-vivo may not exactly be the same.

An astute analysis. And the difference between science and those who think common sense will suffice in order to understand pharmacology.

Addendum: nor does the in vitro study referenced account for sub-types of tinnitus (as defined by inclusion criteria in a clinical trial) or the interactions of the various structures within the brain which - may or may not - influence therapeutic potential in some patients.

 

[Danny Boy]

I did not know that Trobalt had been evaluated in a clinical study involving humans and in relation to tinnitus.

[Please notice the missing question mark at the end of my sentence, above].


An astute analysis. And the difference between science and those who think common sense will suffice in order to understand pharmacology.

Addendum: nor does the in vitro study referenced account for sub-types of tinnitus (as defined by inclusion criteria in a clinical trial) or the interactions of the various structures within the brain which - may or may not - influence therapeutic potential in some patients.

I meant for epilepsy. Both are basically hyperactive neurons, therefore the dosage would be the same. And 400mg does work, for me, so there must be some truth in that.

 

[Danny Boy]

Hi Danny,i recently done the autifony trial,didnt feel a great effect from it,and will never be told if i got the placebo

Was just thinking, might be an idea if i could try a 400mg trobolt as a comparison,im in the Uk ,how would i get hold of it?Or could i buy a one off from you?

400mg would knock you out haha

 

[attheedgeofscience]

Both are basically hyperactive neurons, therefore the dosage would be the same.

If science - and especially the sub-field of human medicine - was so straightforward, there would be no need to do a clinical trial (for tinnitus)...

 

[Danny Boy]

If science was so straightforward, there would be no need to do a clinical trial...

Well, 400mg does work for me....Then again, I can't believe my body can tolerate trobalt, as other people can't manage 200 or 300...I'm gonna admit, I've done 1200mg in one single dose and it didn't have any different effect from 400mg. That's science lol

 

[Hotspur]

Oh ok,so what website can i get it from?

 

[Danny Boy]

Oh ok,so what website can i get it from?

There isn't one. If you go to Spain you can buy trobalt prescription free.

 

[Hotspur]

Is that what you done?And is it ok to bring through customs?

 

[linearb]

Well, 400mg does work for me....Then again, I can't believe my body can tolerate trobalt, as other people can't manage 200 or 300...I'm gonna admit, I've done 1200mg in one single dose and it didn't have any different effect from 400mg. That's science lol

no, that's an anecdote, which is the opposite of science. I admire your bravery and am thankful that you are being so diligent about sharing youtr results with us, but we need to be very careful about making extrapolations from tiny data sets.

 

[Dana]

@Martin69 @Danny Boy or @ anybody who knows
I may to go to Spain to get some Trobalt for myself, so I repeat Hotspur's question: no problems with the customs?

 

[linearb]

@Martin69 @Danny Boy or @ anybody who knows
I may to go to Spain to get some Trobalt for myself, so I repeat Hotspur's question: no problems with the customs?

this is going to depend a lot on where you're trying to bring it, and what its legal status there is. For instance, in the US, this is a prescription-only substance, and you might have difficulty bringing it back in without a valid prescription. Or you might not, it probably depends on the whims of the customs agents, but either way it would be technically illegal. On the other hand, drugs which are not available or scheduled at all in the US, are generally easy to import legally.

 

[Dana]

@linearb
Thanks for your answer.

 

[undecided]

For what it's worth, I went to Scotland for Christmas (from Greece) and took some Trobalt along (like 20 pills).
No problems with the customs whatsoever during departure or arrival.