[Dr. Smith]

Posted in Medications & Treatments

Doc

[mrsD]

This form of gabapentin had a huge problem passing the FDA. And as it is, it is not approved for pain, yet. (this means studies are lacking- and it has been YEARS in trials)

It is only a sustained release form of gabapentin, and therefore not new, exactly.

I haven't seen anyone here yet using it or commenting on it.
But I have my doubts about its value.

[mrsD]

Here is the FDA document explaining the limited approval of GSK's Horizant (new gabapentin):

https://docs.google.com/viewer?a=v&q...b-hRYGgitH9G-w

It has to do with cancer of the pancreas risk. And that parent company did not provide NEW data showing increased absorption was safe.

They noted that the rat tumors were of pancreatic acinar cells and that such tumors occur
spontaneously in the rat, whereas the majority of human of pancreatic tumors are ductal in
origin. They also opined that the rat is uniquely sensitive to gabapentin-induced pancreatic
acinar cell tumors, possibly because of greater uptake of gabapentin into the pancreas, as
evidenced by an unusually high spontaneous rate of these tumors in rats. They also posited
that male rats are particularly sensitive to gabapentin-induced pancreatic acinar cell tumors
because of differential effects of male and female sex hormones.

The pharmacology/toxicology review team did not find these arguments to be compelling.

The paper is long, and goes into some mathematical jargon typical of studies. But at the end they do suggest a 300mg size dose (going DOWN rather than UP), because of side effects, and suicide risk.

All in all it appear to be carefully worded to not include chronic pain patients at this time.

We'll just have to wait and see.

[Dr. Smith]

Originally Posted by mrsD

It has to do with cancer of the pancreas risk. And that parent company did not provide NEW data showing increased absorption was safe.

That's what I gathered. The original study (and risk) applied to gabapentin, which has not been approved for pain either, yet is still a first-line treatment for a number of neuropathic pain conditions which it has not been approved for.

Regarding the cancer risk, the paper also goes on to add:

....Gabapentin was approved .... in part because of the serious nature of the disease to be treated (epilepsy). Moreover, particular factors provided reassurance regarding the non-clinical findings: carcinoma were observed in only one sex, they were not locally invasive, and they neither metastasized nor shortened survival.
....
One of the difficulties in extrapolating this risk to humans is the rarity of this particular tumor type: the vast majority of human pancreatic cancers are ductal in origin; acinar tumors are rare. Although the difference in tumor type was appreciated by the review team, there was inadequate information to establish that these tumors were not clinically relevant. ....

From what I've gleaned from this article and others, it seems to boil down to gabapentin and gabapentin enacarbil having virtually the same risks.

It is only a sustained release form of gabapentin, and therefore not new, exactly.

What I read is that gabapentin enacarbil is a form of gabapentin with increased bioavailability with both immediate and extended (sustained) release formulations.
http://jcp.sagepub.com/content/48/12/1378

Horizant® is an extended (sustained) release form of gabapentin enacarbil.
http://www.medilexicon.com/drugs/horizant.php

I wasn't wondering so much about immediate vs. sustained release, but about the increased bioavailability (in part concerning people with absorption issues - e.g. IBD). If, for example, someone with PN who was taking 1800 mg. of gabapentin/day could get the same benefit from only 300 mg. of gabapentin enacarbil, might the associated risks, side effects, tolerance, etc. be reduced as well? (Proportionally reduced risk might also sway the argument for FDA approval.) Might the more bioavailable form work for someone whom gabapentin did not? Also, since the analgesic benefits of gabapentin "top out" at a certain level (beyond which higher doses don't yield appreciable benefit), might that limitation be modified to the patient's advantage? (I'm lacking the words to say that properly at the moment... )

The questions are rhetorical at this time, but yes, I'd be interested in any feedback from people who'd tried it. The whole concept of prodrugs seems intriguing on several levels.

I reluctantly agree we'll have to wait. Perhaps a similar prodrug version of pregabalin or something else.... Anything to increase efficacy, reduce adverse effects/risks, ameliorate the suffering....

Doc

[mrsD]

You can visit Cafepharma.com and read on the Glaxo board
several threads about this... from the sales reps point of view.

They hate it. They say doctors won't write for it. etc etc.
There are several threads there if you search "Horizant".

What the end of the article hints at is that the sedative effects are substantial. Hence FDA would like to see a SMALLER dosage form.

Gabapentin is not a great pain reliever anyway. Having a long acting form, would just extend the sedative aspects perhaps. It probably knocks those patients with RLS out, so they are basically unconscious! And note... this is a drug originally developed for epilepsy, and not one paper for the new form on this topic! Very strange. One would think a long acting product would be more stable for seizure patients. Duh?
I did a PubMed search and only one page came up ---6 entries.
And that is a very small set of published papers. I suspect the negative ones were not published at all! And the studies were very small compared to other drug studies.

One thread over at Cafepharma suggests that the RLS approval was just to get it on the market so that doctors could be persuaded to write for it "off label". In addition no insurance will pay for this drug off label..either. So it will be expensive!

I just don't see much happening with it. Appears to me to be a Big Pharma manipulation... is all.

Lyrica goes generic soon too! Unless some smoke and mirrors in courts, slated to go off patent Oct 2013.

[Dr. Smith]

Originally Posted by mrsD

Gabapentin is not a great pain reliever anyway.

It worked for me the few times I tried it before trying RLA. One of the articles I cruised mentioned it works for about 30% of PN patients who tried it - nothing on dosage, duration, etc., and I didn't think to save the link as I was running down the enacarbil form....

One thread over at Cafepharma suggests that the RLS approval was just to get it on the market so that doctors could be persuaded to write for it "off label".

Hmmmm... Why doesn't that surprise me?

Well... like I said (figuratively), I was hoping for some hope for others....

Doc