FDA reviewers say Titan drug dose may be insufficient

Jabberwocky

Jabberwocky

Frumious Bandersnatch
Joined
Nov 3, 1999
Messages
1,220
Location
Looking-Glass Land
Toni Clarke said:
Tue, Mar 19 2013

(Reuters) - Titan Pharmaceuticals Inc's experimental drug to treat opioid addiction was shown to be more effective than placebo in a clinical trial, but patients' response suggested that the proposed dosage might be too low, reviewers for the U.S. Food and Drug Administration said in documents published on Tuesday.

The commentary was published on the FDA's website ahead of an advisory panel meeting to be held on Thursday and sent the company's stock down 42 percent to $1.19 in over-the counter trading.

The reviewers said they would ask the advisory panel whether Titan should explore dosing further before the product is approved.

The drug, Probuphine, is a long-acting version of buprenorphine, a drug sold by Britain's Reckitt-Benckiser Group Plc under the brand names Subutex and Suboxone.

Unlike Subutex and Suboxone, which are dissolved daily under the tongue, Titan's drug is implanted under the skin of the upper arm during a 10-15 minute office procedure and delivers a continuous supply of buprenorphine for six months.

"Overall, the response was not what one might hope for, given that the product ensures compliance with the medication for six months," the reviewers said. "It prompts speculation that the dose is simply not high enough."

While the safety of Probuphine appears largely in keeping that of other buprenorphine products it presents an additional safety concern, reviewers said. It must be implanted, potentially leading to surgery-related complications. The reviewers said the product is in some ways similar to Norplant, an implantable, progestin-releasing contraceptive which is no longer marketed in the United States.

Even though insertion and removal of Norplant was performed by trained health-care providers, there were cases of implantation and removal-related of complications, some with disabling consequences, the reviewers said. They will ask the advisory committee whether it believes the company has adequately addressed these concerns under its proposed risk mitigation plan and whether the drug's benefit is enough to outweigh the potential risks.

In December, Titan licensed the U.S. and Canadian rights to Probuphine to Braeburn Pharmaceuticals, a company owned by the venture capital firm Apple Tree Partners. Titan received an up-front payment of $15.75 million and will receive up to $50 million if Probuphine is approved.

(Reporting by Toni Clarke in Washington; Editing by Gerald E. McCormick and Alden Bentley)
Click to expand...
http://www.reuters.com/assets/print?aid=USBRE92I0L120130319

Fuck. That. Shit.

I would never agree to this form of bupe treatment.
 
Titan's drug is implanted under the skin of the upper arm during a 10-15 minute office procedure and delivers a continuous supply of buprenorphine for six months.
Click to expand...

^ this sounds awful

Not so much for the people like me who enjoy buprenorphine (it would still be awful for me), but specifically because some people feel really bad on Suboxone, have allergic reactions, have precipitated withdrawal due to dosing at an incorrect time, or relapse constantly (making it a poor choice for ORT for such individuals).

Could you imagine not having a choice to be on bupe or not? 8( I can't.
 
Re-distributed said:
What would the outcome be if someone with this implant decided to try to dose opiates again?
Click to expand...

They would either get high (if the dosage of buprenorphine wasn't sufficient; it sounds like it isn't going to be due to this article), or they wouldn't due to a buprenorphine blockade (if the dose was high enough).

It is also important to remember that at the blockade dosage of buprenorphine (which is like, 8 to 16 milligrams, or more depending on the individual, taken sublingually), that while it will block heroin/opiates, it'll also cause a higher incidence of side effects like insomnia, irritability, anxiety, etc. which I have even noticed myself when taking too much buprenorphine.

I like knowing that I make a daily, conscious decision to take buprenorphine, and not relapse on heroin. If my power to say no was taken away from me, I'd probably relapse out of spite to regain a sense of self control!

Fuck... this is a disaster waiting to happen. Sure, it might not be that big of a disaster compared to naltrexone implants (cue a series of threads where the OP is begging for advice on how to surgically remove their implant on their own in not perfectly sanitary conditions, and an even longer series of threads asking when they can use heroin again), but it will be a disaster nonetheless.

If anything, a bupe implant would just enable addicts to be able to not have to use heroin every day, and not really go through real withdrawals - in a sense this would be encouraging addiction and it wouldn't be encouraging sobriety.

With regular Suboxone taken externally of the body, you have to go through induction on your own again, which can be painful due to having to return to acute withdrawal, or especially hellish if you accidentally go through precipitated withdrawal. An implant would eliminate both of these painful circumstances, virtually eliminating most of the down-sides to relapsing (which really need to be there for the user to want to quit IMO).

mark my words...

Honestly though... if this helps one person get off opiates/heroin, it's worth it. I just hope that this isn't pushed onto opiate addicts like naltrexone implants were, because that is a disturbing trend I have noticed over the years (forcing people to quit drugs or encouraging them to get an implant/pills to try to quit when the person isn't ready to quit for their own reasons).
 
Hey Captain, you mentioned that an implant user might not feel the typical "roller coaster" effect that those of us who use Subs when completely out of DOC experience. Why is that? Say they do a large enough shot of Heroin to break through the blockade effect, wouldn't the continuous dose then kick the Heroin off after awhile or at the next dose interval?

I've also always wondered, Say I took an 8mg Sub and tried to shoot some Heroin later in the day and I obviously do not feel it all because the Bupe is blocking it. If I dosed another 8mg of Sub AFTER the unsuccessful Heroin shot, would it send me into precipitated withdrawals or would I be fine due to the H not attaching to the receptors in the first place?
 
I wonder what the actual daily dose works out to be, must be pretty small if it's supposed to last for 6 months, how much buprenorphine can they possibly fit into a single implant?

Anyway it sounds like a horrible idea, someone should always have the right to decide whether they take a medication or not, this is nothing more than robbing people of their freedom to choose what goes into their body under the name of 'patient compliance.'
 
burrito10 said:
Hey Captain, you mentioned that an implant user might not feel the typical "roller coaster" effect that those of us who use Subs when completely out of DOC experience. Why is that? Say they do a large enough shot of Heroin to break through the blockade effect, wouldn't the continuous dose then kick the Heroin off after awhile or at the next dose interval?

I've also always wondered, Say I took an 8mg Sub and tried to shoot some Heroin later in the day and I obviously do not feel it all because the Bupe is blocking it. If I dosed another 8mg of Sub AFTER the unsuccessful Heroin shot, would it send me into precipitated withdrawals or would I be fine due to the H not attaching to the receptors in the first place?
Click to expand...

This just depends on you. IME I can use bupe like normal (say taking 8mg/day) and, even if I take my bupe the next morning, if I use enough dope I can get high. How long will the high last? I can't tell you (for me it lasted like it always has, by the next day it was gone, although the side effects of high dose dope use begin to get very pronounced when you do this - e.g. nausia - even with the bupe's increase in tolerance) how heroin or any other full agonist will make you feel. It'll probably be a lot like it used to be, except like I said with those high-dose negative side effects more pronounced.

Precipitated w/d does not generally become a problem as long as there is some bupe in your system. So that means, if you've been taking it for a while, then do a shot of dope, you won't go into precipitated w/d (even if you were to get high from your shot having broken through the blockade dose of bupe, you still won't go into precipitated w/d).

Crankinit said:
I wonder what the actual daily dose works out to be, must be pretty small if it's supposed to last for 6 months, how much buprenorphine can they possibly fit into a single implant?
Click to expand...

Technically speaking, they could fit a LOT of bupe into this. Technically speaking, you could fit a LOT of bupe into a very small space (see: http://www.drugbank.ca/drugs/DB00921). So the problem isn't getting enough bupe into this to deliver a therapeutic or blockade dosage for up to six months, the problem is how it's regulated and introduced into one's system over those six months... E.g. The challenge is in finding a way to get the mechanism to deliver a reliable daily (or equivalent) amount of bupe per day), whether 16mg/day, 8mg/day or 4mg/day, it's got to be consistent.

Mass08 said:
Wouldn't anyone who had this implanted done it by choice?
Click to expand...

I'd would hope that no one has this implanted in them without their consent, but you never know. Plus, some people are often coerced to do certain things via family/loved ones. So there are a lot of problems with someone like this on a basic fundamental level. And on another level, even consent isn't everything (e.g. using that as an excuse as to why this product is okay isn't ever a good argument on a philosophical level - unless you're a hardcore libertarian I mean).

At the very least, this should never be used one someone who hasn't begun their treatment with sublingual bupe via pills or strips in a medical setting so that them and their doctors know how they react to bupe. This would require a "pre-treatment" phase of up to a number of months, because it takes a while for patients to figure out what dose of bupe they need (i.e. to adjust their dose, as almost everyone I know who has taken bupe successfully has required different dosages) and how they'll react to it generally speaking (again, that's the biggest downside to this implant is not being able to change it on the fly).

Re-distributed said:
What would the outcome be if someone with this implant decided to try to dose opiates again?
Click to expand...

In terms of using opioids while this is implanted, I'm sure capt'n covered it, but I'll give it a quick overview too ;)
1) If there is enough bupe in one's system (8-16mg) that would otherwise (regardless of ROA) be considered a blockage dose, little would happen when normal dosages of full agonist opioids (heroin). E.g. If you are used to smoking heroin and you try to smoke some after this is implanted, you won't feel much if anything from the heroin. But nothing else will happen.
2) There will still be some "opioids" that you can get high from because bupe does not effect them - Tramadol and loperamide - but these aren't really traditional opioids and their high is something most people don't seek out
3) To get any effect from opioids while on bupe, especially a "blockade" dose, you'd have to use a lot more. That means the most effective ROA (if you used to smoke or sniff your heroin, you gotta start injecting it for anything to happen - although try smoking or snorting again on the bupe first). Also means using a lot more of the full agonist opioid than you might have been used too (e.g. 1g shots are not uncommon with even medium quality dope just to get over the blockade effects of bupe)

There are a lot of problems with using full agonists to get high on bupe, regardless of whether it's bupe from an implant like this or some pills or sublingual strips. First, a big problem has to do with the method of use, such as those that come with using Needles. Second, and maybe even more so, the dose required is a lot larger, so OD is more of a risk. The OD risk applies more to non-implant bupe, but then again after seeing this article, it could apply to the implant too (as it seems the amount of bupe delivered by implant can be inconsistent) as you don't really know what amount of bupe is in your system at any given time.

----------------------------------------------------------------------------------------------

Anyways, there is really very, very little that is gained over using the implant over strips or pills. Complications from surgery aside (and this is a big deal in itself), this sort of thing seems appropriate only for people who really have no self control. I mean, like for people who for whom strips and pills have already shown to be ineffective because they sell them to buy dope or take them impulsively so they run out after a couple days. These are extreme cases though.

I'm about as excited about this product coming out, whether from a HR, medicinal or recreational standpoint, as I am the medical establishment releasing an "electric shock treatment" implant that comes with a remote allowing SWIM (doctor, parents, wife, kids, strangers....) to deliver an electric shock whenever the patient within whom it is implanted dose something deemed serious enough to require negative reinforcement - e.g. an electric shock!...

And like I said, all my complaints don't even begin to address the problems of having this surgically implanted within someone. It's just asking for the surgeon to fuck up. Or the patient to try and "surgically" remove it themselves (especially if this has been decided upon without first taking a few months to get inducted to bupe treatment in a medical setting w/ sublingual bupe via strips or pills). It's a disaster waiting to happen...

really, that's about what I see this bupe implant as. then again, I was never a big fan of shock collars for dogs either.

Seriously this is some really 1984 shit
 
Last edited by a moderator:
With an implant like this around, I don't know why they don't just decriminalize heroin use. With a 6 month implant you are still an addict, just to the medical system instead of street product. The only difference is where the money is going.
 
Foreigner said:
With an implant like this around, I don't know why they don't just decriminalize heroin use. With a 6 month implant you are still an addict, just to the medical system instead of street product. The only difference is where the money is going.
Click to expand...

That's like saying that, since methadone is easily and legally available to people who are dependent on (or can fake it) opioids they should decriminalize heroin use...

Not saying I disagree, just that it misses the whole point of why heroin is illegal (it's not illegal cause it causes addiction or is bad for you or supposedly has "no medical or therapeutic" value - there are a lot of things that (a) cause just as severe if not more severe addiction such as nicotine and ethanol, (b) are bad for you - cigarettes/nicotine, ethanol and McDonalds etc, and (c) have no medical or therapeutic value - nicotine etc [plus heroin dose have legit medical/theraputic value, as dose nearly every other opioid, but I won't get into that]).

To learn why heroin (and other drugs like weed and coke) is illegal I'd suggest you look up the book: The Birth of Heroin and the Demonization of the Dope Fiend. Good read :)

Heroin (and other opioids) should be decriminalized, regardless if they are legalized or not, just for different reasons...

Or am being too gullible today again? :\
 
toothpastedog said:
That's like saying that, since methadone is easily and legally available to people who are dependent on (or can fake it) opioids they should decriminalize heroin use...
Click to expand...

I would feel the same if it were a methadone implant. You can't taper a person's opiate intake with a 6 month implant that delivers the same dose at constant levels. You're really just staving off withdrawals by giving them a legal opiate, yet if they still took heroin regularly to achieve the same end they could end up in jail on felony possession. It's a double-standard. One has you sucking the tit of big pharma and the other has you giving your money to the black market.
 
^Well i guess they're just becoming more and more brazen and openly insulting the public's intelligence more and more.

Hell, we all know it. What percentage of the general population do you think are clued in? I'd say most who possess an iota of critical thinking. The powers that be simply know that the majority will just accept their "wisdom" and do jack shit about it, even while fully conscious of it.

It's a matter of "We've got you by the balls and you know it"
 
You must log in or register to reply here.
Top