Horizant: The Second Coming of Gabapentin (Neurontin)

June 10, 2011

Horizant: The Second Coming of Gabapentin

In keeping with the religious notion of reincarnation, apparently some drugs are destined to be reborn, redesigned, and re-packaged for brand new indications. There are other drugs-- Silenor for instance-- that have been re-tweaked and renamed for newer (and larger) markets. Silenor is actually low dose Doxepin is a tricyclic antidepressant rarely used (although has enjoyed a bit of a resurrection since docs have shied away from SSRIs and SNRIs). It is being marketed as a sleep aid for this with insomnia. You can expect the typical physiological dependence associated with tricyclics. The up side of this is that tricyclics were always simpler to get off than the later generations of antidepressants. But I digress.

In early April, the FDA granted its approval to yet another " new " agent (that's " new " with an asterisk, mind you), Horizant, developed by GlaxoKline (GSK) and Xenoport. Horizant is a name-brand version of gabapentin, also known as Neurontin. But instead of simply re-labeling gabapentin and introducing it with a new name, GSK made some subtle changes to gabapentin that may provide advantages over the already-available alternative. But the question is: at what cost? And for what, exactly?

Gabapentin was first approved in 1994 and is marketed as Neurontin. It's approved for the treatment of partial seizures and post-herpetic neuralgia (although its manufacturer, Pfizer, got into some serious trouble for extensive off-label marketing of this compound—seems to happen a lot these days). Gabapentin is actually quite widely used by neurologists and psychiatrists, not just for seizures, but also for chronic pain syndromes, anxiety, mood stabilization (where it's not particularly effective), and even for alcohol dependence.

Gabapentin's bioavailability—the proportion of drug that enters the bloodstream when taken as an oral dose—is rather low (and, paradoxically, decreases as the dose is increased) and the duration of its action is quite short, which means that users need to take this drug three or four times daily. The key advantage of Horizant is that it is a " pro-drug. " Technically it's gabapentin enacarbil, and the " enacarbil " refers to a molecule added to the drug which allows it to be absorbed along the entire GI tract, resulting in greater blood levels for a longer period of time.

Interestingly, in early 2010 the FDA rejected Horizant's first request for approval, citing a small but significant risk of cancer. They relented, however, and approved it this year after " reconsidering the risks and benefits. " (Specifically, GSK argued that the large number of pancreatic tumors found in rats taking Horizant may have occurred spontaneously, and human data don't show a compelling link between cancer and gabapentin use.)

So who might use Horizant? Well, GSK and Xenoport probably hope that anyone who currently uses Neurontin (and there are a lot of them) is a potential patient. Officially, though, Horizant was approved only for the treatment of restless legs syndrome (RLS).

June 22, 2011

Horrifying, it just goes on and on and on. I recommend the book " Our Daily Meds "

by Melody , which contains a chapter " Neurontin for Everything. " A

readable account of the deliberate strategy developed and carried out by the

mfgr. of gabapentin to get it prescribed for practically ....everything, how

that saga finally came to an end through the courageous decision of an employee

to blow the whilstle, and how after the company was forced to pay nearly half a

billion $$s in fines, the story is still not over, because doctors who were

hoodwinked and brainwashed the first time around continue to prescribe Neurontin

for everything. Cate

>

> >

> > Horizant: The Second Coming of Gabapentin

> >

> > In keeping with the religious notion of reincarnation, apparently some drugs

are destined to be reborn, redesigned, and re-packaged for brand new

indications. There are other drugs-- Silenor for instance-- that have been

re-tweaked and renamed for newer (and larger) markets. Silenor is actually low

dose Doxepin is a tricyclic antidepressant rarely used (although has enjoyed a

bit of a resurrection since docs have shied away from SSRIs and SNRIs). It is

being marketed as a sleep aid for this with insomnia. You can expect the

typical physiological dependence associated with tricyclics. The up side of

this is that tricyclics were always simpler to get off than the later

generations of antidepressants. But I digress.

> >

> > In early April, the FDA granted its approval to yet another " new " agent

(that's " new " with an asterisk, mind you), Horizant, developed by

GlaxoKline (GSK) and Xenoport. Horizant is a name-brand version of

gabapentin, also known as Neurontin. But instead of simply re-labeling

gabapentin and introducing it with a new name, GSK made some subtle changes to

gabapentin that may provide advantages over the already-available alternative.

But the question is: at what cost? And for what, exactly?

> >

> > Gabapentin was first approved in 1994 and is marketed as Neurontin. It's

approved for the treatment of partial seizures and post-herpetic neuralgia

(although its manufacturer, Pfizer, got into some serious trouble for extensive

off-label marketing of this compound—seems to happen a lot these days).

Gabapentin is actually quite widely used by neurologists and psychiatrists, not

just for seizures, but also for chronic pain syndromes, anxiety, mood

stabilization (where it's not particularly effective), and even for alcohol

dependence.

> >

> > Gabapentin's bioavailability—the proportion of drug that enters the

bloodstream when taken as an oral dose—is rather low (and, paradoxically,

decreases as the dose is increased) and the duration of its action is quite

short, which means that users need to take this drug three or four times daily.

The key advantage of Horizant is that it is a " pro-drug. " Technically it's

gabapentin enacarbil, and the " enacarbil " refers to a molecule added to the drug

which allows it to be absorbed along the entire GI tract, resulting in greater

blood levels for a longer period of time.

> >

> > Interestingly, in early 2010 the FDA rejected Horizant's first request for

approval, citing a small but significant risk of cancer. They relented,

however, and approved it this year after " reconsidering the risks and benefits. "

(Specifically, GSK argued that the large number of pancreatic tumors found in

rats taking Horizant may have occurred spontaneously, and human data don't show

a compelling link between cancer and gabapentin use.)

> >

> > So who might use Horizant? Well, GSK and Xenoport probably hope that anyone

who currently uses Neurontin (and there are a lot of them) is a potential

patient. Officially, though, Horizant was approved only for the treatment of

restless legs syndrome (RLS).

>

> shelley@...

June 22, 2011